JP2002537757A - Secreted proteins and polynucleotides encoding them - Google Patents

Abstract

  (57) [Summary] Disclosed are novel polynucleotides and the proteins encoded thereby.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001] This application is a continuation-in-part of the following application, all of which are hereby incorporated by reference: (1) Provisional Application No. 60 / 097,638 (GI6908), August 24, 1998. (2) Provisional Application No. 60 / 097,659 (GI6909), filed on August 24, 1998; (3) Provisional Application No. 60 / 099,618 (GI6910), filed on September 9, 1998 (4) Provisional Application No. 60 / 102,092 (GI6912), filed on September 28, 1998; (5) Provisional Application No. 60 / 109,978 (GI6914), filed on November 25, 1998; 6) Provisional Application No. 60 / 113,645 (GI6916), filed on December 23, 1998; (7) Provisional Application No. 60 / 113,646 (GI6917), filed on December 23, 1998.

FIELD OF THE INVENTION [0002] The present invention relates to novel polynucleotides and proteins encoded by such polynucleotides, and therapeutic, diagnostic and research uses for those polynucleotides and proteins. .

BACKGROUND OF THE INVENTION [0003] Technologies aimed at the discovery of protein factors, including, for example, cytokines such as lymphokines, interferons, CSFs and interleukins, have grown rapidly in the last decade. did. Current conventional hybridization and expression cloning techniques rely on information "directly" related to the protein for which the polynucleotides were discovered (in the case of hybridization cloning, the partial DNA / amino acid sequence of the protein; expression). In the case of cloning, new polynucleotides are cloned in the sense of (activity of protein). The presence of currently well-recognized secretory leader sequence motifs, and the use of various PCR-based or low stringency hybridization cloning techniques to isolate DNA sequences, such as signal sequence cloning, and more recent "Indirect" cloning techniques are known to have biological activity due to their secreted nature in the case of leader sequence cloning, and due to cell or tissue origin in the case of PCR-based techniques. The availability of a large number of DNA / amino acid sequences for certain proteins has led to an advance in the state of the art. The present invention is directed to such proteins and the polynucleotides that encode them.

SUMMARY OF THE INVENTION In one aspect, the 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 nucleotides 638-934 of SEQ ID NO: 1; (c) a polynucleotide comprising the nucleotide sequence of the full length protein coding sequence of clone vb11_1 of ATCC Deposit No. 98846; (d) A polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb11_1 of ATCC Deposit No. 98846; (e) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone vb11_1 of ATCC Deposit No. 98846; ATC A polynucleotide encoding the mature protein encoded by the cDNA insert of clone vb11_1 of accession number 98846; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 2; (h) a SEQ ID NO: 2 A polynucleotide encoding a protein containing a biologically active fragment of the amino acid sequence of SEQ ID NO: 2 (provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 2); f) a polynucleotide which is an allelic variant of the polynucleotide; (j) a polynucleotide encoding a species homolog of the protein of (g) or (h) above; Polynucleotides that hybridize under stringent conditions to any of the defined polynucleotides And (l) hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (h) above, and has a length of at least 25% of the length of SEQ ID NO: 1. A polynucleotide having the formula:

[0005] Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 638 to 934 of SEQ ID NO: 1 or comprises the nucleotide sequence of the full length protein coding sequence of clone vb11_1 of ATCC Deposit No. 98846. Or the clone v of ATCC deposit no.
It contains the nucleotide sequence of the mature protein coding sequence of b11_1.
In another preferred embodiment, the polynucleotide is ATCC Deposit No. 98846.
Encodes the full-length or mature protein encoded by the cDNA insert of clone vb11_1. In a further preferred embodiment, the present invention provides
A polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 2 (provided that the fragment is
Q ID NO: 2, preferably comprising 8, more preferably 20, even more preferably 30 contiguous amino acids) or SEQ ID N
A polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of O: 2, wherein the fragment is SEQ ID NO:
2 comprising the amino acid sequence of two amino acids 37 to 46).

[0006] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 1.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 1 except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 1; and (ab) the nucleotide sequence of the cDNA insert of clone vb11_1 of ATCC Deposit No. 98846; ) Hybridizing the probe to human genomic DNA under stringent conditions of at least 50 ° C, of the order of 4XSSC; and (iii) isolating the DNA polynucleotide detected with the probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 1 except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 1; and (bb) the nucleotide sequence of the cDNA insert of clone vb11_1 of ATCC deposit no. 98846; ii) hybridizing the primers to human genomic DNA at stringent conditions of at least 50 ° C. of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated. Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: 1 containing the nucleotide sequence corresponding to the cDNA sequence, and
SEQ ID NO: from the nucleotide sequence corresponding to the 5 ′ end of Q ID NO: 1
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of NO: 1 (except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 1). Preferably, also, the polynucleotide isolated by the above method comprises S
It contains the nucleotide sequence corresponding to the cDNA sequence of nucleotides 683-934 of EQ ID NO: 1, and nucleotide 6 of SEQ ID NO: 1.
SEQ ID NOs: 83-934 from the nucleotide sequence corresponding to the 5 'end of the above sequence
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 683 to 934 of D NO: 1.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group that is essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 2; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 2 (provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 2)
And (c) the amino acid sequence encoded by the cDNA insert of clone vb11_1 of ATCC Deposit No. 98846. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 2. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 2, provided that the fragment comprises SEQ ID NO: 2.
A protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 2, preferably comprising 2, preferably 8, more preferably 20, even more preferably 30 consecutive amino acids. (However, the fragment contains the amino acid sequence of amino acids 37 to 46 of SEQ ID NO: 2).

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 3; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 63 to 482 of SEQ ID NO: 3; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 201 to 482 of SEQ ID NO: 3; (d) a clone vb12_1 of ATCC Deposit No. 98846; A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vb12_1 of ATCC Deposit No. 98846; (f) a clone vb12_1 of ATCC Deposit No. 98846 (G) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vb12_1 of ATCC Deposit No. 98846; (h) the amino acid sequence of SEQ ID NO: 4 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 4 (provided that the fragment is composed of the eight amino acids of SEQ ID NO: 4) (J) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (g) above; (k) a species homolog of the protein of (h) or (i) above. (L) a polynucleotide as defined in (a) to (i) above; A polynucleotide that hybridizes under stringent conditions to any of the nucleotides; and (m) hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above, and SEQ ID NO: A polynucleotide having a length of at least 25% of the length of 3.

[0010] Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 63 to 482 of SEQ ID NO: 3, or comprises
NO: 3 or the nucleotide sequence of the full-length protein coding sequence of clone vb12_1 of ATCC Deposit No. 98846, or ATCC Deposit No. 9884.
It contains the nucleotide sequence of the mature protein coding sequence of the six clones vb12_1. In another preferred embodiment, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone vb12_1 of ATCC Deposit No. 98846. In a further preferred embodiment, the present invention provides a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 4, provided that said fragment comprises SEQ ID NO: 4, preferably 8 , More preferably 20
Or even more preferably 30 contiguous amino acids) or S
A polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of EQ ID NO: 4 (provided that the fragment is
(Including the amino acid sequence of amino acids 65 to 74 of ID NO: 4).

[0011] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 3.

[0012] A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: (i) Prepare one or more polynucleotide probes that hybridize at 65 ° C. with 6 × SSC to a nucleotide sequence selected from the group:
aa) SEQ ID NO: 3, except for the poly (A) tail at the 3 'end of SEQ ID NO: 3; and (ab) the nucleotide sequence of the cDNA insert of clone vb12_1 of ATCC Deposit No. 98846; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 3 except for the poly (A) tail at the 3 'end of SEQ ID NO: 3; and (bb) the nucleotide sequence of the cDNA insert of clone vb12_1 of ATCC Deposit No. 98846; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: 3 containing the nucleotide sequence corresponding to the cDNA sequence, and
SEQ ID NO: from the nucleotide sequence corresponding to the 5 'end of Q ID NO: 3
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of NO: 3 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 3). Preferably, also, the polynucleotide isolated by the above method comprises S
It comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 63 to 482 of EQ ID NO: 3, and nucleotide 63 of SEQ ID NO: 3
From the nucleotide sequence corresponding to the 5 'end of the above sequence
NO: 3 is a sequence that extends continuously from the nucleotide sequence corresponding to the 3 ′ end of the above-mentioned sequence of nucleotides 63 to 482. Preferably, also, the polynucleotide isolated by the above method is nucleotide 2 of SEQ ID NO: 3.
The nucleotide sequence corresponding to the cDNA sequence of SEQ ID NOs.
From the nucleotide sequence corresponding to the 5 ′ end of the above sequence of nucleotides 201 to 482 of EQ ID NO: 3, nucleotides 201 to 4 of SEQ ID NO: 3
82, which continuously extends from the nucleotide sequence corresponding to the 3 'end of the above sequence.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group that is essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 4; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 4, wherein the fragment contains eight consecutive amino acids of SEQ ID NO: 4.
And (c) the amino acid sequence encoded by the cDNA insert of clone vb12_1 of ATCC Deposit No. 98846. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 4. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 4, wherein said fragment is SEQ ID NO: 4.
A protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 4, preferably comprising 8, preferably 20, more preferably 20, even more preferably 30 contiguous amino acids. (However, the fragment contains the amino acid sequence of amino acids 65 to 74 of SEQ ID NO: 4).

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 5; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 1195 to 1527 of SEQ ID NO: 5; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 1468 to 1527 of SEQ ID NO: 5; (d) the clone vb14_1 of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vb14_1 of ATCC Deposit No. 98846; (f) a clone v of ATCC Deposit No. 98846 a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of b14_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vb14_1 of ATCC Deposit No. 98846; (h) the amino acid of SEQ ID NO: 6 (I) a polynucleotide encoding a protein containing a biologically active fragment of the amino acid sequence of SEQ ID NO: 6 (provided that the fragment is composed of eight amino acids of SEQ ID NO: 6); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) as defined in (a) to (i) above A polynucleotide that hybridizes under stringent conditions to any of the polynucleotides described above; and (m) hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. And a polynucleotide having a length of at least 25% of the length of SEQ ID NO: 5.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 1195 to 1527 of SEQ ID NO: 5, or comprises
SEQ ID NO: 5 comprising the nucleotide sequence of nucleotides 1468 to 1527 of nucleotide No. 5, the nucleotide sequence of the full-length protein coding sequence of clone vb14_1 of ATCC Deposit No. 98846, or the mature protein of clone vb14_1 of ATCC Deposit No. 98846 It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide comprises A
It encodes the full-length or mature protein encoded by the cDNA insert of clone vb14_1 of TCC deposit number 98846. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 6, provided that said fragment comprises SEQ ID NO: 6, preferably 8 Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 6, more preferably comprising 20 and even more preferably 30 contiguous amino acids. The fragment comprises the amino acid sequence of amino acids 50-59 of SEQ ID NO: 6).

Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 5.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 5 except for the poly (A) tail at the 3 'end of SEQ ID NO: 5; and (ab) the nucleotide sequence of the cDNA insert of clone vb14_1 of ATCC Deposit No. 98846; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 5, except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 5; and (bb) the nucleotide sequence of the cDNA insert of clone vb14_1 of ATCC Deposit No. 98846; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated. Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: 5 containing the nucleotide sequence corresponding to the cDNA sequence, and
SEQ ID: SEQ ID NO: 5 from nucleotide sequence corresponding to the 5 ′ end of Q ID NO: 5
It extends continuously to the nucleotide sequence corresponding to the 3 'end of NO: 5 (excluding the poly (A) tail at the 3' end of SEQ ID NO: 5). Preferably, also, the polynucleotide isolated by the above method comprises S
SEQ ID NO: 5 contains the nucleotide sequence corresponding to the cDNA sequence of nucleotides 1195-1527 and SEQ ID NO: 5 from the nucleotide sequence corresponding to the 5 'end of the sequence at nucleotides 1195-1527 of SEQ ID NO: 5
It extends continuously from the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 1195 to 1527 of EQ ID NO: 5. Preferably,
In addition, the polynucleotide isolated by the above method has SEQ ID NO:
5 comprising the nucleotide sequence corresponding to the cDNA sequence of nucleotides 1468 to 1527, and nucleotides 1468 to 152 of SEQ ID NO: 5.
SEQ ID NO: 7 from the nucleotide sequence corresponding to the 5 'end of the above sequence of SEQ ID NO:
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of 5 nucleotides 1468 to 1527.

In another aspect, the present invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group that is essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 6; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 6 (provided that the fragment includes eight consecutive amino acids of SEQ ID NO: 6)
And (c) the amino acid sequence encoded by the cDNA insert of clone vb14_1 of ATCC Deposit No. 98846. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 6. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 6, wherein said fragment is SEQ ID NO: 6.
A protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 6, preferably comprising 8, preferably 8, more preferably 20, even more preferably 30 contiguous amino acids. (However, the fragment includes the amino acid sequence of amino acids 50 to 59 of SEQ ID NO: 6).

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 7; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 82 to 294 of SEQ ID NO: 7; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 109 to 294 of SEQ ID NO: 7; (d) a clone ve11_1 of ATCC Deposit No. 98846; A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vel1_1 of ATCC deposit number 98846; (f) a clone vell-1 of ATCC deposit number 98846. (G) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vell_1_1 of ATCC Deposit No. 98846; (h) the amino acid sequence of SEQ ID NO: 8 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 8 (provided that the fragment is composed of the eight amino acids of SEQ ID NO: 8) (J) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (g) above; (k) a species homolog of the protein of (h) or (i) above. (L) a polynucleotide as defined in (a) to (i) above; A polynucleotide that hybridizes under stringent conditions to any of the nucleotides; and (m) hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above, and SEQ ID NO: Polynucleotide having a length of at least 25% of the length of 7.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 82 to 294 of SEQ ID NO: 7, or comprises
NO: 7 or the nucleotide sequence of the full-length protein coding sequence of clone vell_1_1 of ATCC Deposit No. 98846, or ATCC Deposit No. 9884.
It contains the nucleotide sequence of the mature protein coding sequence of 6 clones vell_1_1. In another preferred embodiment, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone ve11_1 of ATCC Deposit No. 98846. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 8, wherein said fragment comprises SEQ ID NO: 8, preferably 8 , More preferably 20
Or even more preferably 30 contiguous amino acids) or S
A polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of EQ ID NO: 8, wherein the fragment is
Which comprises the amino acid sequence of amino acids 30 to 39 of ID NO: 8).

Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 7.

A further aspect of the present invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 7 (except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 7); and (ab) the nucleotide sequence of the cDNA insert of clone vell_1_1 of ATCC Deposit No. 98846; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 7, except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 7; and (bb) the nucleotide sequence of the cDNA insert of clone vell_1_1 of ATCC accession number 98846; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated. Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: 7 containing the nucleotide sequence corresponding to the cDNA sequence, and
SEQ ID NO: from the nucleotide sequence corresponding to the 5 'end of Q ID NO: 7
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of NO: 7 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 7). Preferably, also, the polynucleotide isolated by the above method comprises S
It comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 82 to 294 of SEQ ID NO: 7, and comprises nucleotide 82 of SEQ ID NO: 7
From the nucleotide sequence corresponding to the 5 'end of the above sequence
NO: 7 is a sequence that continuously extends from the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 82 to 294. Preferably, also, the polynucleotide isolated by the above method is nucleotide 1 of SEQ ID NO: 7.
Containing the nucleotide sequence corresponding to the cDNA sequence of
From the nucleotide sequence corresponding to the 5 ′ end of the above sequence of nucleotides 109 to 294 of EQ ID NO: 7, nucleotides 109 to 2 of SEQ ID NO: 7
It extends continuously to the nucleotide sequence corresponding to the 3 'end of the above 94 sequence.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 8; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 8 (provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 8)
And (c) the amino acid sequence encoded by the cDNA insert of clone ve11_1 of ATCC Deposit No. 98846. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 8. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 8, wherein said fragment is SEQ ID NO: 8.
A protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 8, preferably comprising 8, preferably 8, more preferably 20, even more preferably 30 consecutive amino acids. (However, the fragment contains the amino acid sequence of amino acids 30 to 39 of SEQ ID NO: 8).

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 9; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 22 to 468 of SEQ ID NO: 9; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 118 to 468 of SEQ ID NO: 9; (d) the clone vf2_1 of ATCC Deposit No. 98846; A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vf2_1 of ATCC Deposit No. 98846; (f) a clone vf2_1 of ATCC Deposit No. 98846 Maturity A polynucleotide comprising the nucleotide sequence of the protein coding sequence; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vf2_1 of ATCC Deposit No. 98846; (h) comprising the amino acid sequence of SEQ ID NO: 10 A polynucleotide encoding a protein; (i) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 10 (provided that the fragment is composed of eight contiguous sequences of SEQ ID NO: 10) (J) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (g) above; (k) encodes a species homolog of the protein of (h) or (i) above A polynucleotide; (l) a polynucleotide as defined in (a) to (i) above. A polynucleotide that hybridizes under stringent conditions to any of the reotides; and (m) hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above, and SEQ ID NO: Polynucleotide having a length of at least 25% of the length of 9.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 22 to 468 of SEQ ID NO: 9, or comprises
NO: 9 or the nucleotide sequence of the full-length protein coding sequence of clone vf2_1 of ATCC Deposit No. 98846, or ATCC Deposit No. 98846.
Contains the nucleotide sequence of the mature protein coding sequence of the clone vf2_1. In another preferred embodiment, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone vf2_1 of ATCC Deposit No. 98846. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 10, provided that said fragment comprises SEQ ID NO: 10, preferably 8 Or more preferably 20 and even more preferably 30 contiguous amino acids) or SE
A polynucleotide encoding a protein having a biologically active fragment of the amino acid sequence of Q ID NO: 10 (provided that the fragment is
Which comprises the amino acid sequence of amino acids 69-78 of ID NO: 10).

Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 9.

[0028] A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: (i) Prepare one or more polynucleotide probes that hybridize at 65 ° C. with 6 × SSC to a nucleotide sequence selected from the group:
aa) SEQ ID NO: 9 except for the poly (A) tail at the 3 'end of SEQ ID NO: 9; and (ab) the nucleotide sequence of the cDNA insert of clone vf2_1 of ATCC Deposit No. 98846; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 9 except for the poly (A) tail at the 3 'end of SEQ ID NO: 9; and (bb) the nucleotide sequence of the cDNA insert of clone vf2_1 of ATCC Deposit No. 98846; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: 9 containing the nucleotide sequence corresponding to the cDNA sequence and SE
SEQ ID NO: 9 from nucleotide sequence corresponding to the 5 ′ end of Q ID NO: 9
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of NO: 9 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 9). Preferably, also, the polynucleotide isolated by the above method comprises S
A nucleotide sequence corresponding to the cDNA sequence of nucleotides 22 to 468 of SEQ ID NO: 9, and nucleotide 22 of SEQ ID NO: 9
From the nucleotide sequence corresponding to the 5 'end of the above sequence
NO: 9 is a sequence that continuously extends from the nucleotide sequence corresponding to the 3 ′ end of the above-mentioned sequence of nucleotides 22 to 468. Preferably, also, the polynucleotide isolated by the above method is nucleotide 1 of SEQ ID NO: 9.
A nucleotide sequence corresponding to the cDNA sequence from 18 to 468, and
From the nucleotide sequence corresponding to the 5 ′ end of the above sequence at nucleotides 118 to 468 of EQ ID NO: 9, nucleotides 118 to 4 of SEQ ID NO: 9
It extends continuously to the nucleotide sequence corresponding to the 3 'end of the above 68 sequence.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) the amino acid sequence of SEQ ID NO: 10; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 10, wherein the fragment contains eight consecutive amino acids of SEQ ID NO: 10 And (c) the amino acid sequence encoded by the cDNA insert of clone vf2_1 of ATCC Deposit No. 98846. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 10. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 10, wherein said fragment is SEQ ID NO:
: 10, preferably 8, more preferably 20, even more preferably 3
A protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 10, wherein the fragment comprises the amino acid sequence of amino acids 69 to 78 of SEQ ID NO: 10. (Including).

In one aspect, the 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 nucleotides 124 to 1641 of SEQ ID NO: 11; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 262 to 1641 of SEQ ID NO: 9; (d) the clone vg2_1 of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vg2_1 of ATCC Deposit No. 98846; (f) a clone vg2 of ATCC Deposit No. 98846 (G) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vg2_1 of ATCC Deposit No. 98846; (h) the amino acid of SEQ ID NO: 12 (I) a polynucleotide encoding a protein containing a biologically active fragment of the amino acid sequence of SEQ ID NO: 12 (provided that the fragment is composed of eight amino acids of SEQ ID NO: 12); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) a polynucleotide as defined in (a) to (i) above. (M) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above; And a polynucleotide having a length of at least 25% of the length of SEQ ID NO: 11.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 124 to 1641 of SEQ ID NO: 11, or comprises
SEQ ID NO: 11 comprises the nucleotide sequence of nucleotides 262 to 1641, the nucleotide sequence of the full-length protein coding sequence of clone vg2_1 of ATCC Deposit No. 98846, or the mature protein of clone vg2_1 of ATCC Deposit No. 98846 It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide comprises ATC
It encodes the full-length or mature protein encoded by the cDNA insert of clone vg2_1 of C deposit number 98846. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 12, provided that said fragment comprises SEQ ID NO: 12, preferably 8 , More preferably 20 and even more preferably 30 contiguous amino acids
Or a polynucleotide encoding a protein containing a biologically active fragment of the amino acid sequence of SEQ ID NO: 12, provided that the fragment comprises the amino acid sequence of amino acids 248 to 257 of SEQ ID NO: 12. To provide.

Another embodiment provides a gene corresponding to the cDNA sequence of SEQ ID NO: 11.

[0034] A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 11 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 11); and (ab) the nucleotide sequence of the cDNA insert of clone vg2_1 of ATCC Deposit No. 98846; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize with 6XSSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 11 except for the poly (A) tail at the 3 'end of SEQ ID NO: 11; and (bb) the nucleotide sequence of the cDNA insert of clone vg2_1 of ATCC deposit no. 98846; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated. Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 11, and
From the nucleotide sequence corresponding to the 5 'end of EQ ID NO: 11, SEQ ID NO:
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 11 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 11). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 124 to 1641 of SEQ ID NO: 11, and nucleotides 124 to 1641 of SEQ ID NO: 11 From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 124 to 1641 of SEQ ID NO: 11. Preferably, also the polynucleotide isolated by the above method has SEQ ID
A nucleotide sequence corresponding to the cDNA sequence of nucleotides 262 to 1641 of SEQ ID NO: 11 and nucleotide 262 of SEQ ID NO: 11
From the nucleotide sequence corresponding to the 5 'end of the above sequence
NO: 11 is a nucleotide sequence continuously extending from the nucleotide sequence corresponding to the 3 'end of the above-mentioned sequence of nucleotides 262 to 1641.

In another aspect, the present invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group that is essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 12; (b) a fragment of the amino acid sequence of SEQ ID NO: 12 (provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 12); And (c) the amino acid sequence encoded by the cDNA insert of clone vg2_1 of ATCC Deposit No. 98846. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 12. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 10, wherein said fragment is SEQ ID NO:
: 12, preferably 8, more preferably 20, even more preferably 3
A protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 12 (provided that the fragment has the amino acid sequence of amino acids 248 to 257 of SEQ ID NO: 12). (Including).

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 13; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 380-892 of SEQ ID NO: 13; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 416-892 of SEQ ID NO: 13; (d) the clone vj1_1 of ATCC Deposit No. 98846; A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vj1_1 of ATCC Deposit No. 98846; (f) a clone vj1_ of ATCC Deposit No. 98846 A polynucleotide comprising the nucleotide sequence of one of the mature protein coding sequences; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vj1_1 of ATCC Deposit No. 98846; (h) the amino acid of SEQ ID NO: 14 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 14 (provided that the fragment is composed of eight amino acids of SEQ ID NO: 14); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) as defined in (a) to (i) above A polynucleotide that hybridizes under stringent conditions to any of the polynucleotides; and (m) hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above, And a polynucleotide having a length of at least 25% of the length of SEQ ID NO: 13.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 380-892 of SEQ ID NO: 13, or comprises
DNO: 13 or the nucleotide sequence of the full-length protein coding sequence of clone vj1_1 of ATCC Deposit No. 98846, or ATCC Deposit No. 98
846 contains the nucleotide sequence of the mature protein coding sequence of clone 846 clone vj1_1. In another preferred embodiment, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone vj1_1 of ATCC Deposit No. 98846. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 14, provided that said fragment comprises SEQ ID NO: 14, preferably 8 Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 14, more preferably comprising 20 and even more preferably 30 contiguous amino acids. The fragment comprises the amino acid sequence of amino acids 80 to 89 of SEQ ID NO: 14).

[0038] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 13.

A further aspect of the present invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 13; and (ab) the nucleotide sequence of the cDNA insert of clone vj1_1 of ATCC Deposit No. 98846; Hybridizing to DNA; and (iii) isolating the DNA polynucleotide detected with the probe; and (b) a method comprising the following steps: (i) a nucleotide sequence selected from the group consisting of: Prepare one or more polynucleotide primers that hybridize with 6XSSC in:
(ba) the SEQ ID NO: 13; and (bb) the nucleotide sequence of the cDNA insert of clone vj1_1 of ATCC Deposit No. 98846; Hybridizing to human genomic DNA; (iii) amplifying the human DNA sequence; and (iv) isolating the polynucleotide product of (iii) above. Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 13;
SEQ ID NO: 13 from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 13
It extends continuously to the nucleotide sequence corresponding to the 3 'end of DNO: 13. Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 380-892 of SEQ ID NO: 13, and nucleotides 380-892 of SEQ ID NO: 13. From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 380 to 892 of SEQ ID NO: 13. Preferably,
In addition, the polynucleotide isolated by the above method has SEQ ID NO:
SEQ ID NO: 13 comprising the nucleotide sequence corresponding to the cDNA sequence of nucleotides 416-892 of SEQ ID NO: 13 and the nucleotide sequence corresponding to the 5 'end of the above sequence of nucleotides 416-892 of SEQ ID NO: 13.
And extend continuously to the nucleotide sequence corresponding to the 3 'end of the above sequence of nucleotides 416 to 892.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 14; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 14 (provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 14) And (c) the amino acid sequence encoded by the cDNA insert of clone vj1_1 of ATCC Deposit No. 98846. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 14. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 14, provided that said fragment is SEQ ID NO: 14.
: 14, preferably 8, more preferably 20, even more preferably 3
A protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 14 (provided that the amino acid sequence comprises amino acids 80 to 89 of SEQ ID NO: 14). (Including).

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 15; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 62 to 1057 of SEQ ID NO: 15; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 659 to 1057 of SEQ ID NO: 15; (d) a clone v11_1 of ATCC accession number 98846; A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vll_1 of ATCC Deposit No. 98846; (f) a clone vll of ATCC Deposit No. 98846 (G) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vll_1 of ATCC Deposit No. 98846; (h) the amino acid sequence of SEQ ID NO: 16 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 16 (provided that the fragment comprises eight amino acids of SEQ ID NO: 16); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) a polynucleotide as defined in (a) to (i) above. A polynucleotide that hybridizes under stringent conditions to any of the polynucleotides described above; and (m) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. And a polynucleotide having a length of at least 25% of the length of SEQ ID NO: 15.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 62 to 1057 of SEQ ID NO: 15, or comprises
DNO: 15 comprising the nucleotide sequence of nucleotides 659 to 1057 of nucleotide 15 or the nucleotide sequence of the full-length protein coding sequence of clone v11_1 of ATCC deposit number 98846, or ATCC deposit number 9
It contains the nucleotide sequence of the mature protein coding sequence of the 8846 clone v11_1. In another preferred embodiment, the polynucleotide is ATCC.
It encodes the full-length or mature protein encoded by the cDNA insert of clone v11_1 under accession number 98846. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 16, provided that said fragment comprises SEQ ID NO: 16, preferably 8 , More preferably 20 and even more preferably 30 consecutive amino acids)
Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 16, provided that the fragment comprises the amino acid sequence of amino acids 161 to 170 of SEQ ID NO: 16. Is what you do.

Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 15.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize at 65 ° C. with 6 × SSC to a nucleotide sequence selected from the group:
aa) SEQ ID NO: 15, except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 15; and (ab) the nucleotide sequence of the cDNA insert of clone v11_1 of ATCC Deposit No. 98846; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 15 (excluding the poly (A) tail at the 3 'end of SEQ ID NO: 15); and (bb) the nucleotide sequence of the cDNA insert of clone v11_1 of ATCC Deposit No. 98846; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 15;
From the nucleotide sequence corresponding to the 5 ′ end of EQ ID NO: 15, SEQ ID NO:
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 15 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 15). Preferably, also the polynucleotide isolated by the above method comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 62 to 1057 of SEQ ID NO: 15, and nucleotides 62 to 1057 of SEQ ID NO: 15 From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 62 to 1057 of SEQ ID NO: 15. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO:
SEQ ID NO: 15 comprising the nucleotide sequence corresponding to the cDNA sequence of nucleotides 659 to 1057, and SEQ ID NO: 15
SEQ ID NO: 57 from the nucleotide sequence corresponding to the 5 'end of the above sequence
: Extending continuously from the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 659 to 1057 at 15:

In another aspect, the present invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 16; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 16 (provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 16) And (c) the amino acid sequence encoded by the cDNA insert of clone v11_1 of ATCC Deposit No. 98846. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 16. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 16, wherein said fragment comprises SEQ ID NO: 16.
: 16, preferably 8, more preferably 20, even more preferably 3
A protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 16 (provided that the fragment has the amino acid sequence of amino acids 161 to 170 of SEQ ID NO: 16). (Including).

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 17; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 74 to 529 of SEQ ID NO: 17; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 140 to 529 of SEQ ID NO: 17; (d) a clone vk2_1 of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vk2_1 of ATCC deposit no. 98838; (f) a clone vk2_1 of ATCC deposit no. (G) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vk2_1 of ATCC Deposit No. 98838; (h) the amino acid sequence of SEQ ID NO: 18 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 18 (provided that the fragment comprises the eight amino acids of SEQ ID NO: 18) (J) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (g) above; (k) a species homolog of the protein of (h) or (i) above. An encoding polynucleotide; (l) as defined in (a) to (i) above. A polynucleotide that hybridizes under stringent conditions to any of the polynucleotides; and (m) hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above, And a polynucleotide having a length of at least 25% of the length of SEQ ID NO: 17.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 74 to 529 of SEQ ID NO: 17, or comprises
NO: 17 or the nucleotide sequence of the full-length protein coding sequence of clone vk2_1 of ATCC Deposit No. 98838, or ATCC Deposit No. 988
It contains the nucleotide sequence of the mature protein coding sequence of 38 clones vk2_1. In another preferred embodiment, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone vk2_1 of ATCC Deposit No. 98838. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 18, provided that said fragment comprises SEQ ID NO: 18, preferably 8 , More preferably 2
A polynucleotide which encodes a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 18, or even more preferably 30 consecutive amino acids, provided that the fragment comprises
It includes the amino acid sequence of amino acids 71 to 80 of EQ ID NO: 18.
).

[0049] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 17.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 17 except for the poly (A) tail at the 3 'end of SEQ ID NO: 17; and (ab) the nucleotide sequence of the cDNA insert of clone vk2_1 of ATCC Deposit No. 988838; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 17 except for the poly (A) tail at the 3 'end of SEQ ID NO: 17; and (bb) the nucleotide sequence of the cDNA insert of clone vk2_1 of ATCC Deposit No. 988838; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 17;
SEQ ID NO: 17 corresponds to the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 17.
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 17 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 17). Preferably, also the polynucleotide isolated by the above method comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 74 to 529 of SEQ ID NO: 17, and nucleotides 74 to 529 of SEQ ID NO: 17 From the nucleotide sequence corresponding to the 5 'end of the above sequence
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 74 to 529 of EQ ID NO: 17. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO: 17
From the nucleotide sequence corresponding to the 5 'end of the above sequence of nucleotides 140 to 529 of SEQ ID NO: 17 from the nucleotide sequence corresponding to the cDNA sequence of nucleotides 140 to 529 of SEQ ID NO: 17 529, extending continuously from the nucleotide sequence corresponding to the 3 ′ end of the above sequence.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group that is essentially free of other mammalian proteins: (A) the amino acid sequence of SEQ ID NO: 18; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 18 (provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 18) And (c) the amino acid sequence encoded by the cDNA insert of clone vk2_1 of ATCC deposit number 98838. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 18. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 18, wherein said fragment comprises SEQ ID NO: 18.
: 18, preferably 8, more preferably 20, even more preferably 3
A protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 18 (provided that the fragment comprises the amino acid sequence of amino acids 71 to 80 of SEQ ID NO: 18). (Including).

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 19; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 174 to 3170 of SEQ ID NO: 19; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 1098 to 3170 of SEQ ID NO: 19; (d) the clone vb21_1 of ATCC accession number 98862 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vb21_1 of ATCC deposit no. 98862; (f) a clone of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of vb21_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vb21_1 of ATCC Deposit No. 98862; (h) a polynucleotide encoding the mature protein; A polynucleotide encoding a protein comprising an amino acid sequence; (i) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 20 (provided that the fragment is SEQ ID NO: 20-8). (J) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (g) above; (k) a species homolog of the protein of (h) or (i) above. (L) a polynucleotide encoding a body; a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in i); and (m) a stringent condition to any of the polynucleotides defined in (a) to (i) above. A polynucleotide that hybridizes underneath and has a length of at least 25% of the length of SEQ ID NO: 19.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 174 to 3170 of SEQ ID NO: 19, or comprises
ID No: 19, comprising the nucleotide sequence of nucleotides 1098-3170 of nucleotides, or comprising the nucleotide sequence of the full-length protein coding sequence of clone vb21_1 of ATCC Deposit No. 98862, or the mature protein of clone vb21_1 of ATCC Deposit No. 98862 It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide is
It encodes the full-length or mature protein encoded by the cDNA insert of clone vb21_1 of ATCC Deposit No. 98862. In a further preferred embodiment, the present invention provides a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 20, provided that said fragment comprises SEQ ID NO: 20, preferably 8 Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 20, more preferably 20 and even more preferably 30 consecutive amino acids. The fragment comprises the amino acid sequence of amino acids 494-503 of SEQ ID NO: 20).

Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 19.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 19, except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 19; and (ab) the nucleotide sequence of the cDNA insert of clone vb21_1 of ATCC Deposit No. 98862; ) Hybridizing the probe to human genomic DNA under stringent conditions of at least 50 ° C, of the order of 4XSSC; and (iii) isolating the DNA polynucleotide detected with the probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 19, except for the poly (A) tail at the 3 'end of SEQ ID NO: 19; and (bb) the nucleotide sequence of the cDNA insert of clone vb21_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at stringent conditions of at least 50 ° C. of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 19, and
SEQ ID NO: 19 corresponds to the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 19.
It extends continuously to the nucleotide sequence corresponding to the 3 'end of D NO: 19 (excluding the poly (A) tail at the 3' end of SEQ ID NO: 19). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 174-3170 of SEQ ID NO: 19, and nucleotides 174-3170 of SEQ ID NO: 19. From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 174 to 3170 of SEQ ID NO: 19. Preferably, also the polynucleotide isolated by the above method has SEQ ID
SEQ ID NO: 19, comprising the nucleotide sequence corresponding to the cDNA sequence of nucleotides 1098-3170, and SEQ ID NO: 19, nucleotide 10
SEQ ID NO: from nucleotide sequence corresponding to the 5 'end of the above sequence from 98 to 3170
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 1098 to 3170 of ID NO: 19.

In another aspect, the present invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 20; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 20, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 20 And (c) the amino acid sequence encoded by the cDNA insert of clone vb21_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 20. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 20, provided that said fragment is SEQ ID NO: 20.
O: 20, preferably 8, more preferably 20, even more preferably 30 contiguous amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 20. A protein comprising the amino acid sequence of amino acids 494 to 503 of SEQ ID NO: 20.

In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 21; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 74 to 1453 of SEQ ID NO: 21; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 224 to 1453 of SEQ ID NO: 21; A polynucleotide comprising the nucleotide sequence of the long protein coding sequence; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc35_1 of ATCC deposit no. 98862; (f) a clone vc of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the 35_1 mature protein coding sequence; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc35_1 of ATCC Deposit No. 98862; (h) the amino acid of SEQ ID NO: 22 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 22 (provided that the fragment is composed of eight amino acids of SEQ ID NO: 22); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) In the above (a) to (i) A polynucleotide that hybridizes under stringent conditions to any of the defined polynucleotides; and (m) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. A polynucleotide soybean and having a length of at least 25% of the length of SEQ ID NO: 21.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 74 to 1453 of SEQ ID NO: 21, or comprises
D NO: 21 or the nucleotide sequence of the full-length protein coding sequence of clone vc35_1 of ATCC Deposit No. 98862, or the mature protein of clone vc35_1 of ATCC Deposit No. 98862. It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide is AT
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc35_1 of CC deposit number 98862. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 22, provided that said fragment comprises SEQ ID NO: 22, preferably 8 Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 22, more preferably comprising 20 and even more preferably 30 consecutive amino acids. The fragment comprises the amino acid sequence of amino acids 225 to 234 of SEQ ID NO: 22).

Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 21.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 21, except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 21; and (ab) the nucleotide sequence of the cDNA insert of clone vc35_1 of ATCC Deposit No. 98862; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 21 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 21); and (bb) the nucleotide sequence of the cDNA insert of clone vc35_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 21;
SEQ ID NO: 21 from the nucleotide sequence corresponding to the 5 ′ end of SEQ ID NO: 21
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 21 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 21). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 74 to 1453 of SEQ ID NO: 21, and nucleotides 74 to 1453 of SEQ ID NO: 21. From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 74 to 1453 of SEQ ID NO: 21. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO:
: SEQ ID NO: 21 comprising the nucleotide sequence corresponding to the cDNA sequence of nucleotides 224-1453, and SEQ ID NO: 21
SEQ ID NO: 53 from the nucleotide sequence corresponding to the 5 'end of the above sequence 53
No .: 21 and continuously extending from the nucleotide sequence corresponding to the 3 ′ end of the above-mentioned sequence of nucleotides 224-1453.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of 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 (provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 22) And (c) the amino acid sequence encoded by the cDNA insert of clone vc35_1 of ATCC deposit number 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 22. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 22, wherein said fragment comprises SEQ ID NO: 22.
O: 22, preferably comprising 8, more preferably 20 and even more preferably 30 contiguous amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 22. A protein comprising the amino acid sequence of amino acids 225 to 234 of SEQ ID NO: 22.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 23; (b) (C) a polynucleotide comprising the nucleotide sequence of nucleotides 243-368 of SEQ ID NO: 23; (d) a polynucleotide comprising the nucleotide sequence of nucleotides 243-368 of SEQ ID NO: 23; A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc36_1 of ATCC deposit no. 98862; (f) a clone vc of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the 36_1 mature protein coding sequence; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc36_1 of ATCC Deposit No. 98862; (h) the amino acid of SEQ ID NO: 24 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 24 (provided that the fragment is composed of eight amino acids of SEQ ID NO: 24); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) In the above (a) to (i) A polynucleotide that hybridizes under stringent conditions to any of the defined polynucleotides; and (m) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. A polynucleotide that soybean and has a length of at least 25% of the length of SEQ ID NO: 23.

Preferably, such a polynucleotide comprises the nucleotide sequence from nucleotides 135 to 368 of SEQ ID NO: 23, or
DNO: 23, containing the nucleotide sequence of nucleotides 243-368, containing the nucleotide sequence of the full-length protein coding sequence of clone vc36_1 of ATCC Deposit No. 98862, or containing ATCC Deposit No. 9
It contains the nucleotide sequence of the mature protein coding sequence of 8862 clone vc36_1. In another preferred embodiment, the polynucleotide comprises ATC
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc36_1 of C deposit number 98862. In a further preferred embodiment, the present invention provides a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 24, with the proviso that
The fragment comprises SEQ ID NO: 24, preferably 8, more preferably 20, even more preferably 30 contiguous amino acids) or the amino acid sequence of SEQ ID NO: 24. It is intended to provide a polynucleotide encoding a protein containing a fragment having an activity, wherein the fragment contains the amino acid sequence of amino acids 34 to 43 of SEQ ID NO: 24.

Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 23.

A further aspect of the present invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize at 65 ° C. with 6 × SSC to a nucleotide sequence selected from the group:
aa) SEQ ID NO: 23, except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 23; and (ab) the nucleotide sequence of the cDNA insert of clone vc36_1 of ATCC Deposit No. 98862; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 23 except for the poly (A) tail at the 3 'end of SEQ ID NO: 23; and (bb) the nucleotide sequence of the cDNA insert of clone vc36_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 23, and
From the nucleotide sequence corresponding to the 5 ′ end of EQ ID NO: 23, SEQ ID NO:
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 23 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 23). Preferably, also the polynucleotide isolated by the above method comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 135 to 368 of SEQ ID NO: 23, and nucleotides 135 to 368 of SEQ ID NO: 23 From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 135 to 368 of SEQ ID NO: 23. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO:
SEQ ID NO: 23, comprising a nucleotide sequence corresponding to the cDNA sequence of nucleotides 243-368, and SEQ ID NO: 23.
SEQ ID NO: 2 from the nucleotide sequence corresponding to the 5 'end of the above sequence
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of 3 nucleotides 243-368.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 24; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 24, provided that the fragment includes eight consecutive amino acids of SEQ ID NO: 24 And (c) the amino acid sequence encoded by the cDNA insert of clone vc36_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 24. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 24, wherein said fragment comprises SEQ ID NO:
O: 24, preferably comprising 8, more preferably 20, even more preferably 30 contiguous amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 24. A protein comprising the amino acid sequence of amino acids 34 to 43 of SEQ ID NO: 24.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 25; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 370-1662 of SEQ ID NO: 25; (c) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vc38_1 of ATCC Deposit No. 98862; A polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc38_1; (e) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone vc38_1 of ATCC Deposit No. 98862; (f) an ATCC deposit No. 98862, a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc38_1; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 26; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 26; A polynucleotide encoding a protein containing a fragment having a biological activity in the amino acid sequence (the fragment contains eight consecutive amino acids of SEQ ID NO: 26); (i) the above (a) to (f) )) A polynucleotide that is an allelic variant of the polynucleotide; (j) a polynucleotide encoding a species homolog of the protein of (g) or (h) above; (k) a polynucleotide as defined in (a) to (h) above. Polynucleotides that hybridize under stringent conditions to any of the selected polynucleotides And (m) hybridizes under stringent conditions to any of the polynucleotides defined in (a)-(h) above and has a length of at least 25% of the length of SEQ ID NO: 25. A polynucleotide having the formula:

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 370-1662 of SEQ ID NO: 25, or comprises the ATCC
It contains the nucleotide sequence of the full length protein coding sequence of clone vc38_1 at accession number 98862, or contains the nucleotide sequence of the mature protein coding sequence of clone vc38_1 at ATCC accession number 98862. In another preferred embodiment, the polynucleotide is ATCC Deposit No. 988.
It encodes the full-length or mature protein encoded by the cDNA insert of 62 clone vc38_1. In a further preferred embodiment, the invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 26, provided that said fragment comprises SEQ ID NO: 20, preferably 8 , More preferably twenty,
And even more preferably those containing 30 consecutive amino acids) or SEQ.
Polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of ID NO: 26 (this fragment is
D NO: 26 comprising the amino acid sequence of amino acids 210 to 219).

[0073] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 25.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 25, except for the poly (A) tail at the 3 'end of SEQ ID NO: 25; and (ab) the nucleotide sequence of the cDNA insert of clone vc38_1 of ATCC Deposit No. 98862; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 25 except for the poly (A) tail at the 3 'end of SEQ ID NO: 25; and (bb) the nucleotide sequence of the cDNA insert of clone vc38_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

[0075] Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 25;
SEQ ID NO: 25 from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 25
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 25 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 25). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 370-1662 of SEQ ID NO: 25, and nucleotides 370-1662 of SEQ ID NO: 25. From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 370 to 1662 of SEQ ID NO: 25.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of 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, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 20; And (c) the amino acid sequence encoded by the cDNA insert of clone vc38_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 26. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 26, provided that said fragment is SEQ ID NO:
O: 20, preferably 8, more preferably 20, even more preferably 30 contiguous amino acids) or the amino acid sequence of SEQ ID NO: 26, A protein comprising the amino acid sequence of amino acids 210 to 219 of SEQ ID NO: 26.

In one embodiment, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 27; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 105 to 365 of SEQ ID NO: 27; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 147 to 365 of SEQ ID NO: 27; (d) the clone vc39_1 of ATCC Deposit No. 98862 A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc39_1 of ATCC deposit no. 98862; (f) a clone vc of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of 39_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc39_1 of ATCC Deposit No. 98862; (h) the amino acid of SEQ ID NO: 28 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 28 (provided that the fragment comprises eight amino acids of SEQ ID NO: 28) (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) In the above (a) to (i) A polynucleotide that hybridizes under stringent conditions to any of the defined polynucleotides; and (m) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. A polynucleotide soybean and having a length of at least 25% of the length of SEQ ID NO: 27.

Preferably, such a polynucleotide comprises the nucleotide sequence from nucleotides 105 to 365 of SEQ ID NO: 27, or
DNO: 27, comprising the nucleotide sequence of nucleotides 147 to 365 of SEQ ID NO: 27, the nucleotide sequence of the full-length protein coding sequence of clone vc39_1 of ATCC Deposit No. 98862, or ATCC Deposit No. 9
It contains the nucleotide sequence of the mature protein coding sequence of the 8862 clone vc39_1. In another preferred embodiment, the polynucleotide comprises ATC
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc39_1 of C deposit number 98862. In a further preferred embodiment, the present invention provides a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 28, provided that
Said fragment comprises SEQ ID NO: 28, preferably 8, more preferably 20, even more preferably 30 contiguous amino acids) or the amino acid sequence of SEQ ID NO: 28. It is intended to provide a polynucleotide encoding a protein containing a fragment having an activity, wherein the fragment comprises the amino acid sequence of amino acids 38 to 47 of SEQ ID NO: 28.

[0079] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 27.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 27, except for the poly (A) tail at the 3 'end of SEQ ID NO: 27; and (ab) the nucleotide sequence of the cDNA insert of clone vc39_1 of ATCC Deposit No. 98862; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 27 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 27); and (bb) the nucleotide sequence of the cDNA insert of clone vc39_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 27, and
SEQ ID NO: 27 from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 27
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 27 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 27). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 105 to 365 of SEQ ID NO: 27, and nucleotides 105 to 365 of SEQ ID NO: 27. From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 105 to 365 of SEQ ID NO: 27. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO:
: SEQ ID NO: 27 comprises the nucleotide sequence corresponding to the cDNA sequence of nucleotides 147-365, and SEQ ID NO: 27 nucleotides 147-365
SEQ ID NO: 2 from the nucleotide sequence corresponding to the 5 'end of the above sequence
7 and extend continuously to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 147 to 365.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) the amino acid sequence of SEQ ID NO: 28; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 28, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 28 And (c) the amino acid sequence encoded by the cDNA insert of clone vc39_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 28. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 28, wherein said fragment is SEQ ID NO: 28.
O: 28, preferably comprising 8, more preferably 20, even more preferably 30 contiguous amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 28. A protein comprising the amino acid sequence of amino acids 38 to 47 of SEQ ID NO: 28.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 29; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 35-1066 of SEQ ID NO: 29; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 128-1066 of SEQ ID NO: 29; (d) the completeness of ATCC Deposit No. 98862 clone vc40_1 A polynucleotide comprising the nucleotide sequence of the long protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc40_1 of ATCC deposit no. 98862; (f) a clone vc of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the 40_1 mature protein coding sequence; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc40_1 of ATCC Deposit No. 98862; (h) the amino acid of SEQ ID NO: 30 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 30 (provided that the fragment comprises eight amino acids of SEQ ID NO: 30); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) In the above (a) to (i) A polynucleotide that hybridizes under stringent conditions to any of the defined polynucleotides; and (m) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. A polynucleotide soybean and having a length of at least 25% of the length of SEQ ID NO: 29.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 35 to 1066 of SEQ ID NO: 29, or comprises
D NO: 29, comprising the nucleotide sequence of nucleotides 128 to 1066 of nucleotide 29, the nucleotide sequence of the full-length protein coding sequence of clone vc40_1 of ATCC deposit number 98862, or the mature protein of clone vc40_1 of ATCC deposit number 98862. It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide is AT
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc40_1 of CC deposit number 98862. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 30, provided that said fragment comprises SEQ ID NO: 30, preferably 8 A polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 30, or more preferably comprising 20 and even more preferably 30 contiguous amino acids. The fragment comprises the amino acid sequence of amino acids 167 to 176 of SEQ ID NO: 30).

[0085] Another embodiment provides a gene corresponding to the cDNA sequence of SEQ ID NO: 29.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 29, except for the poly (A) tail at the 3 'end of SEQ ID NO: 29; and (ab) the nucleotide sequence of the cDNA insert of clone vc40_1 of ATCC Deposit No. 98862; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize at 65 ° C. with 6 × SSC to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 29 (excluding the poly (A) tail at the 3 'end of SEQ ID NO: 29); and (bb) the nucleotide sequence of the cDNA insert of clone vc40_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 29, and
SEQ ID NO: 29 from the nucleotide sequence corresponding to the 5 ′ end of SEQ ID NO: 29
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 29 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 29). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 35 to 1066 of SEQ ID NO: 29, and nucleotides 35 to 1066 of SEQ ID NO: 29. From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 35 to 1066 of SEQ ID NO: 29. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO:
SEQ ID NO: 29 comprising the nucleotide sequence corresponding to the cDNA sequence of nucleotides 128-1066, and SEQ ID NO: 29.
SEQ ID NO: 66 from the nucleotide sequence corresponding to the 5 'end of the above sequence
: Extending continuously from the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 128 to 1066 of 29.

In another aspect, the present invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 30; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 30, wherein the fragment contains eight consecutive amino acids of SEQ ID NO: 30. And (c) the amino acid sequence encoded by the cDNA insert of clone vc40_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 22. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 30, wherein said fragment comprises SEQ ID NO:
O: 30, preferably 8, more preferably 20, even more preferably 30 contiguous amino acids) or the amino acid sequence of SEQ ID NO: 30. A protein comprising the amino acid sequence of amino acids 167 to 176 of SEQ ID NO: 30.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 31; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 38-553 of SEQ ID NO: 31; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 104-553 of SEQ ID NO: 31; (d) a clone vc46_1 of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc46_1 of ATCC deposit no. 98862; (f) a clone vc4 of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of 6_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc46_1 of ATCC Deposit No. 98862; (h) the amino acid sequence of SEQ ID NO: 32 (I) a polynucleotide encoding a protein containing a biologically active fragment of the amino acid sequence of SEQ ID NO: 32 (provided that the fragment is composed of eight amino acids of SEQ ID NO: 24); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) as defined in (a) to (i) above. A polynucleotide that hybridizes under stringent conditions to any of the polynucleotides described above; and (m) hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. A polynucleotide having a length of at least 25% of the length of SEQ ID NO: 31.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 38-553 of SEQ ID NO: 31, or comprises
NO: 31 contains the nucleotide sequence of nucleotides 104 to 553, or contains the nucleotide sequence of the full-length protein coding sequence of clone vc46_1 of ATCC Deposit No. 98862, or ATCC Deposit No. 98
862 containing the nucleotide sequence of the mature protein coding sequence of clone vc46_1. In another preferred embodiment, the polynucleotide is ATCC.
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc46_1 of accession number 98862. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 32, provided that said fragment comprises SEQ ID NO: 32, preferably 8 , More preferably 20 and even more preferably 30 contiguous amino acids
Or a polynucleotide encoding a protein containing a biologically active fragment of the amino acid sequence of SEQ ID NO: 32 (provided that the fragment contains the amino acid sequence of amino acids 81 to 90 of SEQ ID NO: 32). To provide.

Another embodiment provides a gene corresponding to the cDNA sequence of SEQ ID NO: 31.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 31 except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 31; and (ab) the nucleotide sequence of the cDNA insert of clone vc46_1 of ATCC Deposit No. 98862; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 31 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 31); and (bb) the nucleotide sequence of the cDNA insert of clone vc46_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

[0093] Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 31;
SEQ ID NO: 31 from the nucleotide sequence corresponding to the 5 ′ end of SEQ ID NO: 31
It extends continuously to the nucleotide sequence corresponding to the 3 'end of D NO: 31 (excluding the poly (A) tail at the 3' end of SEQ ID NO: 31). Preferably, also the polynucleotide isolated by the above method comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 38-553 of SEQ ID NO: 31, and nucleotides 38-553 of SEQ ID NO: 31. From the nucleotide sequence corresponding to the 5 'end of the above sequence
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 38 to 553 of EQ ID NO: 31. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO: 31
From the nucleotide sequence corresponding to the 5 'end of the above sequence of nucleotides 104 to 553 of SEQ ID NO: 31 from the nucleotide sequence corresponding to the cDNA sequence of nucleotides 104 to 553 of SEQ ID NO: 31 553 to the nucleotide sequence corresponding to the 3 ′ end of the above sequence.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 32; (b) a fragment of the amino acid sequence of SEQ ID NO: 32, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 32 And (c) the amino acid sequence encoded by the cDNA insert of clone vc46_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 32. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 32, provided that said fragment is SEQ ID NO:
O: 32, preferably comprising 8, more preferably 20, even more preferably 30 contiguous amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 32. A protein comprising the amino acid sequence of amino acids 81 to 90 of SEQ ID NO: 32.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 33; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 164-2548 of SEQ ID NO: 33; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 242-2548 of SEQ ID NO: 33; (d) the clone vc49_1 of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc49_1 of ATCC Deposit No. 98862; a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of vc49_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc49_1 of ATCC Deposit No. 98862; (h) amino acids of SEQ ID NO: 34 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 34 (provided that the fragment is composed of eight amino acids of SEQ ID NO: 34) (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) a polynucleotide encoding the above (a) to (i) A) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a); and (m) a polynucleotide that hybridizes to any of the polynucleotides defined in (a) to (i) above. And a polynucleotide having a length of at least 25% of the length of SEQ ID NO: 33.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 164-2548 of SEQ ID NO: 33, or comprises
SEQ ID NO: 33 comprising the nucleotide sequence of nucleotides 242-2548 of nucleotides, or comprising the nucleotide sequence of the full-length protein coding sequence of clone vc49_1 of ATCC Deposit No. 98862, or the mature protein of clone vc49_1 of ATCC Deposit No. 98862 It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide comprises A
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc49_1 of TCC deposit number 98862. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 34, provided that said fragment comprises SEQ ID NO: 34, preferably 8 Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 34, more preferably comprising 20 and even more preferably 30 contiguous amino acids. The fragment comprises the amino acid sequence of amino acids 392 to 401 of SEQ ID NO: 34).

[0097] Another embodiment provides a gene corresponding to the cDNA sequence of SEQ ID NO: 33.

[0098] A further aspect of the present invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 33, except for the poly (A) tail at the 3 'end of SEQ ID NO: 33; and (ab) the nucleotide sequence of the cDNA insert of clone vc49_1 of ATCC Deposit No. 98862; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 33, except for the poly (A) tail at the 3 'end of SEQ ID NO: 33; and (bb) the nucleotide sequence of the cDNA insert of clone vc49_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated. Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 33, and
SEQ ID NO: 33 from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 33
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 33 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 33). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 164-2548 of SEQ ID NO: 33, and nucleotides 164-2548 of SEQ ID NO: 33. From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 164 to 2548 of SEQ ID NO: 33. Preferably, also the polynucleotide isolated by the above method has SEQ ID
SEQ ID NO: 33 contains the nucleotide sequence corresponding to the cDNA sequence of nucleotides 242-2548, and SEQ ID NO: 33 contains nucleotide 242
From the nucleotide sequence corresponding to the 5 'end of the above sequence
NO: 33, which continuously extends from the nucleotide sequence corresponding to the 3 'end of the above-mentioned sequence of nucleotides 242-2548.

In another aspect, the present invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group that is essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 34; (b) a fragment of the amino acid sequence of SEQ ID NO: 34, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 34 And (c) the amino acid sequence encoded by the cDNA insert of clone vc49_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 34. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 34, wherein said fragment is SEQ ID NO.
O: 34, preferably comprising 8, more preferably 20 and even more preferably 30 contiguous amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 34. A protein comprising the amino acid sequence of amino acids 392 to 401 of SEQ ID NO: 34.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 35; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 150 to 776 of SEQ ID NO: 35; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 246 to 776 of SEQ ID NO: 35; (d) a clone vc50_1 of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vc50_1 of ATCC deposit no. 98862; (f) a clone vc of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of 50_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc50_1 of ATCC Deposit No. 98862; (h) the amino acid of SEQ ID NO: 36 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 36 (provided that the fragment comprises eight amino acids of SEQ ID NO: 28); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) In the above (a) to (i) A polynucleotide that hybridizes under stringent conditions to any of the defined polynucleotides; and (m) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. A polynucleotide soybean and having a length of at least 25% of the length of SEQ ID NO: 35

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 150 to 776 of SEQ ID NO: 35, or comprises
D NO: 35, containing the nucleotide sequence of nucleotides 246-776 of ATCC Deposit No. 98862, or containing the nucleotide sequence of the full length protein coding sequence of clone vc50_1 of ATCC Deposit No. 98862, or ATCC Deposit No. 9
It contains the nucleotide sequence of the mature protein coding sequence of the 8862 clone vc50_1. In another preferred embodiment, the polynucleotide comprises ATC
C, which encodes the full-length or mature protein encoded by the cDNA insert of clone vc50_1 of deposit number 98862. In a further preferred embodiment, the present invention provides a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 36, with the proviso that
The fragment comprises SEQ ID NO: 36, preferably comprising 8, more preferably 20, even more preferably 30 contiguous amino acids) or the amino acid sequence of SEQ ID NO: 36. The present invention provides a polynucleotide encoding a protein containing a fragment having an activity, wherein the fragment comprises the amino acid sequence of amino acids 99 to 108 of SEQ ID NO: 36.

Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 35.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 35, except for the poly (A) tail at the 3 'end of SEQ ID NO: 35; and (ab) the nucleotide sequence of the cDNA insert of clone vc50_1 of ATCC Deposit No. 98862; ) Hybridizing the probe to human genomic DNA under stringent conditions of at least 50 ° C, of the order of 4XSSC; and (iii) isolating the DNA polynucleotide detected with the probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize with 6XSSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 35 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 35); and (bb) the nucleotide sequence of the cDNA insert of clone vc50_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at stringent conditions of at least 50 ° C. of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

[0104] Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 35, and
SEQ ID NO: 35 from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 35
It extends continuously to the nucleotide sequence corresponding to the 3 'end of D NO: 35 (excluding the poly (A) tail at the 3' end of SEQ ID NO: 35). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 150-776 of SEQ ID NO: 35, and nucleotides 150-776 of SEQ ID NO: 35. From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 150 to 776 of SEQ ID NO: 35. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO:
: SEQ ID NO: 35, comprising the nucleotide sequence corresponding to the cDNA sequence of nucleotides 246-776, and SEQ ID NO: 35, nucleotides 246-776.
SEQ ID NO: 3 from the nucleotide sequence corresponding to the 5 'end of the above sequence
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of 5 nucleotides 246 to 776.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 36; (b) a fragment of the amino acid sequence of SEQ ID NO: 36, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 36; And (c) the amino acid sequence encoded by the cDNA insert of clone vc50_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 36. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 36, provided that said fragment is SEQ ID NO:
O: 36, preferably comprising 8, more preferably 20 and even more preferably 30 contiguous amino acids) or the amino acid sequence of SEQ ID NO: 36 having a biologically active fragment A protein comprising the amino acid sequence of amino acids 99 to 108 of SEQ ID NO: 36.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 37; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 139 to 1308 of SEQ ID NO: 37; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 211 to 1308 of SEQ ID NO: 37; (d) the clone vc51_1 of ATCC accession number 98862 A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc51_1 of ATCC Deposit No. 98862; (f) a clone of ATCC Deposit No. 98862 a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of vc51_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc51_1 of ATCC Deposit No. 98862; (h) the amino acid sequence of SEQ ID NO: 38 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 38 (provided that the fragment is composed of eight amino acids of SEQ ID NO: 38); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) a polynucleotide encoding the above (a) to (i) A) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a); and (m) a polynucleotide that hybridizes to any of the polynucleotides defined in (a) to (i) above. And a polynucleotide having a length of at least 25% of the length of SEQ ID NO: 37.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 139 to 1308 of SEQ ID NO: 37, or comprises
ID No: 37, the nucleotide sequence of nucleotides 211 to 1308, the nucleotide sequence of the full-length protein coding sequence of clone vc51_1 of ATCC Deposit No. 98862, or the mature protein of clone vc51_1 of ATCC Deposit No. 98862. It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide comprises A
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc51_1 of TCC Deposit No. 98862. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 38, wherein said fragment comprises SEQ ID NO: 38, preferably 8 Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 38, more preferably comprising 20 and even more preferably 30 consecutive amino acids. The fragment comprises the amino acid sequence of amino acids 190-199 of SEQ ID NO: 38).

[0108] Another embodiment provides a gene corresponding to the cDNA sequence of SEQ ID NO: 37.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 37 (excluding the poly (A) tail at the 3 'end of SEQ ID NO: 37); and (ab) the nucleotide sequence of the cDNA insert of clone vc51_1 of ATCC Deposit No. 98862; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 37 (excluding the poly (A) tail at the 3 'end of SEQ ID NO: 37); and (bb) the nucleotide sequence of the cDNA insert of clone vc51_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

[0110] Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 37, and
SEQ ID NO: 37 from the nucleotide sequence corresponding to the 5 ′ end of SEQ ID NO: 37
It extends continuously to the nucleotide sequence corresponding to the 3 'end of D NO: 37 (excluding the poly (A) tail at the 3' end of SEQ ID NO: 37). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 139 to 1308 of SEQ ID NO: 37, and nucleotides 139 to 1308 of SEQ ID NO: 37 From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 139 to 1308 of SEQ ID NO: 37. Preferably, also the polynucleotide isolated by the above method has SEQ ID
SEQ ID NO: 37 contains the nucleotide sequence corresponding to the cDNA sequence of nucleotides 211 to 1308, and SEQ ID NO: 37 contains nucleotide 211
From the nucleotide sequence corresponding to the 5 'end of the above sequence
NO: 37, which continuously extends from the nucleotide sequence corresponding to the 3 'end of the above sequence of nucleotides 211 to 1308.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 38; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 38 (provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 38) And (c) the amino acid sequence encoded by the cDNA insert of clone vc51_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 38. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 38, wherein said fragment is SEQ ID NO: 38.
O: 38, preferably comprising 8, more preferably 20, more preferably still 30 consecutive amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 38. A protein containing the amino acid sequence of amino acids 190 to 199 of SEQ ID NO: 38.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 39; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 21 to 1142 of SEQ ID NO: 39; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 114 to 1142 of SEQ ID NO: 39; (d) a clone vc52_1 of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc52_1 of ATCC Deposit No. 98862; (f) a clone v of ATCC Deposit No. 98862 a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of c52_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc52_1 of ATCC Deposit No. 98862; (h) the amino acid of SEQ ID NO: 40 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 40 (provided that the fragment has eight amino acids of SEQ ID NO: 40); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) the above (a) to (i) A polynucleotide that hybridizes under stringent conditions to any of the defined polynucleotides; and (m) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. A polynucleotide that soybean and has a length of at least 25% of the length of SEQ ID NO: 39.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 21 to 1142 of SEQ ID NO: 39, or comprises
D NO: 39, comprising the nucleotide sequence of nucleotides 114 to 1142 of nucleotide 39, the nucleotide sequence of the full-length protein coding sequence of clone vc52_1 of ATCC Deposit No. 98862, or the mature protein of clone vc52_1 of ATCC Deposit No. 98862. It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide is AT
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc52_1 of CC deposit number 98862. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 40, provided that said fragment comprises SEQ ID NO: 40, preferably 8 Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 40, more preferably comprising 20 and even more preferably 30 contiguous amino acids. This fragment comprises the amino acid sequence of amino acids 182 to 191 of SEQ ID NO: 40).

[0114] Another embodiment provides a gene corresponding to the cDNA sequence of SEQ ID NO: 39.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 39, except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 39; and (ab) the nucleotide sequence of the cDNA insert of clone vc52_1 of ATCC Deposit No. 98862; ) Hybridizing the probe to human genomic DNA under stringent conditions of at least 50 ° C, of the order of 4XSSC; and (iii) isolating the DNA polynucleotide detected with the probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize with 6XSSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 39 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 39); and (bb) the nucleotide sequence of the cDNA insert of clone vc52_1 of ATCC Deposit No. 98862; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has the SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 39, and
SEQ ID NO: 39 from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 39
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 39 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 39). Preferably, also the polynucleotide isolated by the above method comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 21 to 1142 of SEQ ID NO: 39, and nucleotides 21 to 1142 of SEQ ID NO: 39 From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 21 to 1142 of SEQ ID NO: 39. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO:
: Containing the nucleotide sequence corresponding to the cDNA sequence of nucleotides 114 to 1142 of SEQ ID NO: 39, and nucleotides 114 to 11 of SEQ ID NO: 39
SEQ ID NO: 42 from the nucleotide sequence corresponding to the 5 'end of the above sequence
: Extending continuously from the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 114 to 1142 of 39.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 40; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 40, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 40 And (c) the amino acid sequence encoded by the cDNA insert of clone vc52_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 20. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 40, provided that said fragment is SEQ ID NO:
O: 40, preferably comprising 8, more preferably 20, more preferably still 30 consecutive amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 40. A protein comprising the amino acid sequence of amino acids 182 to 191 of SEQ ID NO: 40.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 41; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 13-1416 of SEQ ID NO: 41; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 346-1416 of SEQ ID NO: 41; (d) the completeness of ATCC deposit number 98886 clone vc33_1. A polynucleotide comprising the nucleotide sequence of the long protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc33_1 of ATCC deposit number 98886; (f) a clone vc of ATCC deposit number 98886 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of 33_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc33_1 of ATCC Deposit No. 98886; (h) the amino acid of SEQ ID NO: 42 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 42 (provided that the fragment comprises eight amino acids of SEQ ID NO: 42); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) In the above (a) to (i) A polynucleotide that hybridizes under stringent conditions to any of the defined polynucleotides; and (m) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. A polynucleotide that soybean and has a length of at least 25% of the length of SEQ ID NO: 41.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 13 to 1416 of SEQ ID NO: 41, or comprises
D NO: 41, comprising the nucleotide sequence of nucleotides 346-1416 of nucleotides, the nucleotide sequence of the full-length protein coding sequence of clone vc33_1 of ATCC deposit number 98886, or the mature protein of clone vc33_1 of ATCC deposit number 98886. It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide is AT
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc33_1 of CC deposit number 98886. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 42, provided that said fragment comprises SEQ ID NO: 42, preferably 8 A polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 42, more preferably comprising 20 and even more preferably 30 contiguous amino acids. The fragment comprises the amino acid sequence of amino acids 229 to 238 of SEQ ID NO: 42).

[0120] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 41.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize at 65 ° C. with 6 × SSC to a nucleotide sequence selected from the group:
aa) SEQ ID NO: 41, except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 41; and (ab) the nucleotide sequence of the cDNA insert of clone vc33_1 of ATCC Deposit No. 98886; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 41, except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 41; and (bb) the nucleotide sequence of the cDNA insert of clone vc33_1 of ATCC Deposit No. 98886; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: 41 contains the nucleotide sequence corresponding to the cDNA sequence, and
From the nucleotide sequence corresponding to the 5 ′ end of EQ ID NO: 41, SEQ ID NO:
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 41 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 41). Preferably, also the polynucleotide isolated by the above method comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 13 to 1416 of SEQ ID NO: 41, and nucleotides 13 to 1416 of SEQ ID NO: 41 From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 13 to 1416 of SEQ ID NO: 41. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO:
SEQ ID NO: 41 comprising the nucleotide sequence corresponding to the cDNA sequence of nucleotides 346-1416, and SEQ ID NO: 41.
SEQ ID NO: 16 from the nucleotide sequence corresponding to the 5 ′ end of 16 of the above sequences
No .: 41 and continuously extending from the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 346 to 1416.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of 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, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 42 And (c) the amino acid sequence encoded by the cDNA insert of clone vc33_1 of ATCC Deposit No. 98862. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 42. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 42, provided that said fragment is SEQ ID NO: 42.
O: 42, preferably comprising 8, more preferably 20, even more preferably 30 contiguous amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 42. A protein comprising the amino acid sequence of amino acids 229 to 238 of SEQ ID NO: 42.

In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 43; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 232-1461 of SEQ ID NO: 43; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 280-1461 of SEQ ID NO: 43; (d) a clone vc34_1 of ATCC accession number 98886; A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc34_1 of ATCC Deposit No. 98886; (f) a clone of ATCC Deposit No. 98886 a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of vc34_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc34_1 of ATCC Deposit No. 98886; (h) the amino acid sequence of SEQ ID NO: 44 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 44 (provided that the fragment comprises eight SEQ ID NO: 44 amino acids; (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) a polynucleotide encoding the above (a) to (i) A) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a); and (m) a polynucleotide that hybridizes to any of the polynucleotides defined in (a) to (i) above. And a polynucleotide having a length of at least 25% of the length of SEQ ID NO: 43.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 232-1461 of SEQ ID NO: 43, or comprises
ID NO: 43, comprising the nucleotide sequence of nucleotides 280 to 1461, the nucleotide sequence of the full-length protein coding sequence of clone vc34_1 of ATCC deposit number 98886, or the mature protein of clone vc34_1 of ATCC deposit number 98886. It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide comprises A
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc34_1 of TCC deposit number 98886. In a further preferred embodiment, the present invention provides a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 44, provided that said fragment comprises SEQ ID NO: 44, preferably 8 amino acids. Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 44, more preferably comprising 20 and even more preferably 30 consecutive amino acids. The fragment comprises the amino acid sequence of amino acids 200 to 209 of SEQ ID NO: 44).

Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 43.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize at 65 ° C. with 6 × SSC to a nucleotide sequence selected from the group:
aa) SEQ ID NO: 43, except for the poly (A) tail at the 3 'end of SEQ ID NO: 43; and (ab) the nucleotide sequence of the cDNA insert of clone vc34_1 of ATCC deposit no. ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 43, except for the poly (A) tail at the 3 'end of SEQ ID NO: 43; and (bb) the nucleotide sequence of the cDNA insert of clone vc34_1 of ATCC Deposit No. 98886; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: 43 contains the nucleotide sequence corresponding to the cDNA sequence, and
SEQ ID NO: 43 from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 43
It extends continuously to the nucleotide sequence corresponding to the 3 'end of D NO: 43 (excluding the poly (A) tail at the 3' end of SEQ ID NO: 43). Preferably, also the polynucleotide isolated by the above method comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 232-1461 of SEQ ID NO: 43, and nucleotides 232-1461 of SEQ ID NO: 43. From the nucleotide sequence corresponding to the 5 ′ end of the above sequence to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 232-1461 of SEQ ID NO: 43. Preferably, also the polynucleotide isolated by the above method has SEQ ID
SEQ ID NO: 43 contains the nucleotide sequence corresponding to the cDNA sequence of nucleotides 280-1461, and SEQ ID NO: 43 contains nucleotide 280
From the nucleotide sequence corresponding to the 5 'end of the above sequence
NO: 43, which continuously extends from the nucleotide sequence corresponding to the 3 'end of the above-mentioned sequence of nucleotides 280 to 1461.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of 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, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 44 And (c) the amino acid sequence encoded by the cDNA insert of clone vc34_1 of ATCC deposit number 98886. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 44. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 44, wherein said fragment is
O: 44, preferably comprising 8, more preferably 20 and even more preferably 30 contiguous amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 44. A protein comprising the amino acid sequence of amino acids 200 to 209 of SEQ ID NO: 44.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 45; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 1922 to 2350 of SEQ ID NO: 45; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 2237 to 2350 of SEQ ID NO: 45; (d) the clone vc47_1 of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc47_1 of ATCC accession number 98886; (f) a polynucleotide encoding ATCC accession number 98886 (G) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc47_1 of ATCC Deposit No. 98886; (h) SEQ ID NO: 46 (I) a polynucleotide encoding a protein containing a biologically active fragment of the amino acid sequence of SEQ ID NO: 46 (provided that the fragment corresponds to SEQ ID NO: 46); (J) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (g) above; (k) a species of the protein of (h) or (i) above. A polynucleotide encoding a homolog; (l) the above (a) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (i); and (m) a polynucleotide that is stringent to any of the polynucleotides defined in (a) to (i) above. A polynucleotide that hybridizes under conditions and has a length of at least 25% of the length of SEQ ID NO: 45.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 1922-2350 of SEQ ID NO: 45, or comprises
SEQ ID NO: 45 comprising the nucleotide sequence of nucleotides 2237 to 2350 of nucleotide No. 45, the nucleotide sequence of the full-length protein coding sequence of clone vc47_1 of ATCC Deposit No. 98886, or the mature protein of clone vc47_1 of ATCC Deposit No. 98886 It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone vc47_1 of ATCC Deposit No. 98886. In a further preferred embodiment, the present invention provides a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 46 (
Provided that the fragment has SEQ ID NO: 46, preferably 8
More preferably, it comprises 20 or even more preferably 30 contiguous amino acids) or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 46. The fragment comprises the amino acid sequence of amino acids 66-75 of SEQ ID NO: 46).

[0132] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 45.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize at 65 ° C. with 6 × SSC to a nucleotide sequence selected from the group:
aa) SEQ ID NO: 45, except for the poly (A) tail at the 3 'end of SEQ ID NO: 45; and (ab) the nucleotide sequence of the cDNA insert of clone vc47_1 of ATCC Deposit No. 98886; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 45, except for the poly (A) tail at the 3 'end of SEQ ID NO: 45; and (bb) the nucleotide sequence of the cDNA insert of clone vc47_1 of ATCC Deposit No. 98886; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

[0134] Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 45, and
SEQ ID NO: 45 from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 45
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 45 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 45). Preferably, also the polynucleotide isolated by the above method is the cDNA of nucleotides 1922 to 2350 of SEQ ID NO: 45.
Contains the nucleotide sequence corresponding to the sequence and has SEQ ID NO: 45
From SEQ ID NO: 45 to the nucleotide sequence corresponding to the 3 'end of the above sequence of nucleotides 1922 to 2350 from SEQ ID NO: 45. is there. Preferably, also the polynucleotide isolated by the above method comprises SEQ.
SEQ ID NO: 45 comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 2237-2350, and SEQ ID NO: 45 from the nucleotide sequence corresponding to the 5 'end of the above sequence of nucleotides 2237-2350
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 2237 to 2350 of EQ ID NO: 45.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) the amino acid sequence of SEQ ID NO: 46; (b) a fragment of the amino acid sequence of SEQ ID NO: 46, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 46; And (c) the amino acid sequence encoded by the cDNA insert of clone vc47_1 of ATCC Deposit No. 98886. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 46. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 46, wherein said fragment is SEQ ID NO: 46
O: 46, preferably comprising 8, more preferably 20, even more preferably 30 contiguous amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 46. A protein comprising the amino acid sequence of amino acids 66 to 75 of SEQ ID NO: 46.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 47; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 111 to 1337 of SEQ ID NO: 47; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 246 to 1337 of SEQ ID NO: 47; (d) the clone vc54_1 of ATCC accession number 98886 A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc54_1 of ATCC Deposit No. 98886; (f) a clone of ATCC Deposit No. 98886 a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of vc54_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc54_1 of ATCC Deposit No. 98886; (h) the amino acid sequence of SEQ ID NO: 48 (I) a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 48 (provided that the fragment has eight amino acids of SEQ ID NO: 48); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) a polynucleotide encoding the above (a) to (i) A) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a); and (m) a polynucleotide that hybridizes to any of the polynucleotides defined in (a) to (i) above. And a polynucleotide having a length of at least 25% of the length of SEQ ID NO: 47.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 111 to 1337 of SEQ ID NO: 47, or comprises
SEQ ID NO: 47 comprises the nucleotide sequence of nucleotides 246 to 1337 of nucleotide 47, the nucleotide sequence of the full-length protein coding sequence of clone vc54_1 of ATCC Deposit No. 98886, or the mature protein of clone vc54_1 of ATCC Deposit No. 98886 It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide comprises A
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc54_1 of TCC deposit number 98886. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 48, provided that said fragment comprises SEQ ID NO: 48, preferably 8 Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 48, more preferably comprising 20 and even more preferably 30 contiguous amino acids. The fragment comprises the amino acid sequence of amino acids 199 to 208 of SEQ ID NO: 48).

[0138] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 47.

A further aspect of the present invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: (i) Prepare one or more polynucleotide probes that hybridize at 65 ° C. with 6 × SSC to a nucleotide sequence selected from the group:
aa) SEQ ID NO: 47 (excluding the poly (A) tail at the 3 'end of SEQ ID NO: 47); and (ab) the nucleotide sequence of the cDNA insert of clone vc54_1 of ATCC Deposit No. 98886; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 47, except for the poly (A) tail at the 3 'end of SEQ ID NO: 47; and (bb) the nucleotide sequence of the cDNA insert of clone vc54_1 of ATCC Deposit No. 98886; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

[0140] Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: contains the nucleotide sequence corresponding to the cDNA sequence of 47, and
SEQ ID NO: 47 from the nucleotide sequence corresponding to the 5 ′ end of SEQ ID NO: 47
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 47 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 47). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 111 to 1337 of SEQ ID NO: 47, and nucleotides 111 to 1337 of SEQ ID NO: 47. From the nucleotide sequence corresponding to the 5 ′ end of the above sequence to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 111 to 1337 of SEQ ID NO: 47. Preferably, also the polynucleotide isolated by the above method has SEQ ID
SEQ ID NO: 47 contains the nucleotide sequence corresponding to the cDNA sequence of nucleotides 246 to 1337, and SEQ ID NO: 47 contains the nucleotide sequence
From the nucleotide sequence corresponding to the 5 'end of the above sequence
NO: 47, continuously extending from the nucleotide sequence corresponding to the 3 'end of the above-mentioned sequence of nucleotides 246 to 1337.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) the amino acid sequence of SEQ ID NO: 48; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 48, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 48 And (c) the amino acid sequence encoded by the cDNA insert of clone vc54_1 of ATCC Deposit No. 98886. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 48. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 48, wherein said fragment is SEQ ID NO: 48.
O: 48, preferably comprising 8, more preferably 20, even more preferably 30 contiguous amino acids) or the amino acid sequence of SEQ ID NO: 48, A protein comprising the amino acid sequence of amino acids 199 to 208 of SEQ ID NO: 48.

In one aspect, the invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 49; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 189-1637 of SEQ ID NO: 49; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 270-1637 of SEQ ID NO: 49; (d) the completeness of ATCC accession number 98886 clone vc57_1. A polynucleotide comprising the nucleotide sequence of the long protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vc57_1 of ATCC Deposit No. 98886; (f) a clone v of ATCC Deposit No. 98886 a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of c57_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vc57_1 of ATCC Deposit No. 98886; (h) an amino acid of SEQ ID NO: 50 (I) a polynucleotide encoding a protein containing a biologically active fragment of the amino acid sequence of SEQ ID NO: 50 (provided that the fragment has eight amino acids of SEQ ID NO: 50); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) the above (a) to (i) A polynucleotide that hybridizes under stringent conditions to any of the defined polynucleotides; and (m) a polynucleotide that hybridizes under stringent conditions to any of the polynucleotides defined in (a) to (i) above. A polynucleotide that soybean and has a length of at least 25% of the length of SEQ ID NO: 49.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 189-1637 of SEQ ID NO: 49, or comprises
SEQ ID NO: 49 comprises the nucleotide sequence of nucleotides 270 to 1637 of nucleotide 49, the nucleotide sequence of the full-length protein coding sequence of clone vc57_1 of ATCC Deposit No. 98886, or the mature protein of clone vc57_1 of ATCC Deposit No. 98886 It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide comprises A
It encodes the full-length or mature protein encoded by the cDNA insert of clone vc57_1 of TCC deposit number 98886. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 50, provided that said fragment comprises SEQ ID NO: 50, preferably 8 Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 50, more preferably comprising 20 and even more preferably 30 contiguous amino acids. The fragment comprises the amino acid sequence of amino acids 236 to 245 of SEQ ID NO: 50).

Another embodiment provides a gene corresponding to the cDNA sequence of SEQ ID NO: 49.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the steps of: (i) Prepare one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group at 65 ° C. in 6 × SSC:
aa) SEQ ID NO: 49, except for the poly (A) tail at the 3 'end of SEQ ID NO: 49; and (ab) the nucleotide sequence of the cDNA insert of clone vc57_1 of ATCC Deposit No. 98886; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 49, except for the poly (A) tail at the 3 ′ end of SEQ ID NO: 49; and (bb) the nucleotide sequence of the cDNA insert of clone vc57_1 of ATCC Deposit No. 98886; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

[0146] Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: containing the nucleotide sequence corresponding to the cDNA sequence of 49, and
SEQ ID NO: 49 from the nucleotide sequence corresponding to the 5 'end of
It extends continuously to the nucleotide sequence corresponding to the 3 ′ end of D NO: 49 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 49). Preferably, also the polynucleotide isolated by the above method comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 189-1637 of SEQ ID NO: 49, and nucleotides 189-1637 of SEQ ID NO: 49 From the nucleotide sequence corresponding to the 5 ′ end of the above sequence to the nucleotide sequence corresponding to the 3 ′ end of the above sequence of nucleotides 189 to 1637 of SEQ ID NO: 49. Preferably, also the polynucleotide isolated by the above method has SEQ ID
A nucleotide sequence corresponding to the cDNA sequence of nucleotides 270-1637 of SEQ ID NO: 49 and nucleotide 270 of SEQ ID NO: 49
From the nucleotide sequence corresponding to the 5 'end of the above sequence
NO: It extends continuously to the nucleotide sequence corresponding to the 3 'end of the above sequence of nucleotides 270 to 1637 of 49.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (A) an amino acid sequence of SEQ ID NO: 50; (b) a fragment of the amino acid-producing sequence of SEQ ID NO: 50, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 50 And (c) the amino acid sequence encoded by the cDNA insert of clone vc57_1 of ATCC Deposit No. 98886. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 50. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 50, wherein said fragment is SEQ ID NO.
O: 50, preferably 8, more preferably 20, even more preferably 30 consecutive amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 50. A protein comprising the amino acid sequence of amino acids 236 to 245 of SEQ ID NO: 50.

In one embodiment, the present invention provides a composition comprising an isolated polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 51; (b) A polynucleotide comprising the nucleotide sequence of nucleotides 15 to 1934 of SEQ ID NO: 51; (c) a polynucleotide comprising the nucleotide sequence of nucleotides 1704 to 1934 of SEQ ID NO: 51; (d) the clone ve13_1 of ATCC deposit no. A polynucleotide comprising the nucleotide sequence of the full length protein coding sequence; (e) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone ve13_1 of ATCC accession number 98886; (f) a clone ve of ATCC accession number 98886 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of 13_1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone ve13_1 of ATCC Deposit No. 98886; (h) the amino acid of SEQ ID NO: 52 (I) a polynucleotide encoding a protein containing a biologically active fragment of the amino acid sequence of SEQ ID NO: 52 (provided that the fragment is composed of eight amino acids of SEQ ID NO: 52); (J) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (g); (k) a species homolog of the protein of (h) or (i) above (L) as defined in (a) to (i) above. And (m) hybridizing under stringent conditions to any of the polynucleotides defined in (a) to (i) above. A polynucleotide having a length of at least 25% of the length of SEQ ID NO: 51.

Preferably, such a polynucleotide comprises the nucleotide sequence of nucleotides 15 to 1934 of SEQ ID NO: 51, or comprises
D NO: 51, comprising the nucleotide sequence of nucleotides 1704 to 1934 of nucleotide 51, the nucleotide sequence of the full-length protein coding sequence of clone ve13_1 of ATCC Deposit No. 98886, or the mature protein of clone ve13_1 of ATCC Deposit No. 98886. It contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide comprises A
It encodes the full-length or mature protein encoded by the cDNA insert of clone vel3_1 of TCC deposit number 98886. In a further preferred embodiment, the present invention relates to a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 52, provided that said fragment comprises SEQ ID NO: 52, preferably 8 Or a polynucleotide encoding a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 52, more preferably 20 contiguous amino acids, and even more preferably 30 contiguous amino acids. The fragment comprises the amino acid sequence of amino acids 315 to 324 of SEQ ID NO: 52).

[0150] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 51.

A further aspect of the invention provides an isolated polynucleotide produced by a method selected from the group consisting of: (a) a method comprising the following steps: (i) Prepare one or more polynucleotide probes that hybridize at 65 ° C. with 6 × SSC to a nucleotide sequence selected from the group:
aa) SEQ ID NO: 51, except for the poly (A) tail at the 3 'end of SEQ ID NO: 51; and (ab) the nucleotide sequence of the cDNA insert of clone vel3_1 of ATCC Deposit No. 98886; ) Hybridizing said probe to human genomic DNA under stringent conditions of at least 50 ° C., of the order of 4 × SSC; and (iii) isolating the DNA polynucleotide detected with said probe; and (b) A method comprising the steps of: (i) preparing one or more polynucleotide primers that hybridize in a 6 × SSC at 65 ° C. to a nucleotide sequence selected from the following group:
(ba) SEQ ID NO: 51 (excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 51); and (bb) the nucleotide sequence of the cDNA insert of clone vel3_1 of ATCC Deposit No. 98886; ii) hybridizing the primers to human genomic DNA at least 50 ° C. under stringent conditions of the order of 4 × SSC; (iii) amplifying the human DNA sequence; and (iv) producing the polynucleotide of (iii) above. The product is isolated.

Preferably, the polynucleotide isolated by the above method has SEQ ID
NO: 51 contains the nucleotide sequence corresponding to the cDNA sequence, and
From the nucleotide sequence corresponding to the 5 ′ end of EQ ID NO: 51, SEQ ID NO:
It extends continuously to the nucleotide sequence corresponding to the 3 'end of D NO: 51 (excluding the poly (A) tail at the 3' end of SEQ ID NO: 51). Preferably, the polynucleotide isolated by the above method also comprises a nucleotide sequence corresponding to the cDNA sequence of nucleotides 15 to 1934 of SEQ ID NO: 51, and nucleotides 15 to 1934 of SEQ ID NO: 51. From the nucleotide sequence corresponding to the 5 'end of the above sequence to the nucleotide sequence corresponding to the 3' end of the above sequence of nucleotides 15 to 1934 of SEQ ID NO: 51. Preferably, also, the polynucleotide isolated by the above method has SEQ ID NO:
: SEQ ID NO: 51 comprising the nucleotide sequence corresponding to the cDNA sequence of nucleotides 1704 to 1934, and SEQ ID NO: 51 from nucleotides 1704 to 1934.
SEQ ID NO: from the nucleotide sequence corresponding to the 5 'end of the above sequence of 1934
NO: 51, extending continuously from the nucleotide sequence corresponding to the 3 'end of the above-mentioned sequence of nucleotides 1704 to 1934.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises an amino acid sequence selected from the following group, essentially free of 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, provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 52 And (c) the amino acid sequence encoded by the cDNA insert of clone vel3_1 of ATCC deposit number 98886. Preferably, such a protein is SEQ.
It contains the amino acid sequence of ID NO: 52. In a further preferred embodiment, the present invention relates to a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 52, provided that said fragment is SEQ ID NO: 52.
O: 52, preferably comprising 8, more preferably 20, even more preferably 30 contiguous amino acids) or a biologically active fragment of the amino acid sequence SEQ ID NO: 52. A protein comprising the amino acid sequence of amino acids 315 to 324 of SEQ ID NO: 52.

In one embodiment, the present invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 53; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 53 from nucleotide 240 to nucleotide 503; c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 53 from nucleotide 318 to nucleotide 503; (d) clone ve16_1 deposited with the ATCC under accession number 98886
A polynucleotide comprising the nucleotide sequence of the full-length protein encoding sequence of (e) clone ve16_1 deposited with the ATCC under accession number 98886
A polynucleotide encoding the full-length protein encoded by the cDNA insert of (f) clone ve16_1 deposited with the ATCC under accession number 98886
A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of: g) clone ve16_1 deposited with the ATCC under accession number 98886
A polynucleotide encoding a mature protein encoded by the cDNA insert of (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 54; (i) a sequence having biological activity A fragment of the amino acid sequence represented by SEQ ID NO: 54 [this fragment contains eight consecutive amino acids of SEQ ID NO: 54]
(J) a polynucleotide which is an allele variant of the above-mentioned polynucleotide (a)-(g); (k) species homology of the above-mentioned protein (h) or (i). (L) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) (a)- A polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (i) and has a length of at least 25% of SEQ ID NO: 53; A composition comprising a nucleotide is provided.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 240 to nucleotide 503 of SEQ ID NO: 53; nucleotide 3 of SEQ ID NO: 53
Nucleotide sequence from 18 to nucleotide 503; nucleotide sequence of the full length protein coding sequence of clone ve16_1 deposited at the ATCC under accession number 98886; or mature protein of clone ve16_1 deposited at the ATCC under accession number 98886 Contains the nucleotide sequence of the coding sequence. In another preferred embodiment, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone ve16_1 deposited with the ATCC under accession number 98886. In a further preferred embodiment, the present invention provides a biologically active fragment of the amino acid sequence of SEQ ID NO: 54, wherein said fragment preferably comprises 8 (more preferably 20, most preferably 3
0) contiguous amino acids], or a fragment of the amino acid sequence shown in SEQ ID NO: 54 that has biological activity [this fragment corresponds to amino acids 39 of SEQ ID NO: 54]. From amino acid 4
Up to 8 amino acid sequences].

[0156] Another embodiment provides a gene corresponding to the cDNA sequence shown in SEQ ID NO: 53.

Further embodiments according to the invention include: (a) (i) (aa) SEQ ID NO: 53 excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 53; and (ab) accession number 98886 Clone ve deposited with ATCC below
Preparing one or more polynucleotide probes that hybridize at 65 degrees Celsius in 6X SSC to a nucleotide sequence selected from the group consisting of: 16_1 cDNA insert; 4X SSC, hybridizing with human genomic DNA under conditions that are as stringent as 50 degrees Celsius; and (iii) isolating the DNA polynucleotides detected by the probe; and b) (i) (ba) SEQ ID NO: 53 excluding the poly (A) tail at the 3 'end of SEQ ID NO: 53; and (bb) clone ve deposited at the ATCC under accession number 98886
Preparing one or more polynucleotide primers that hybridize in 6X SSC at 65 degrees Celsius to a nucleotide sequence selected from the group consisting of: 16_1 cDNA insert; 4X SSC, hybridizing with human genomic DNA under conditions that are as stringent as 50 degrees Celsius; (iii) amplify the human DNA sequence; and (iv) the polynucleotide product of step (b) (iii) Isolating a polynucleotide produced by a method selected from the group consisting of:

[0158] Preferably, the polynucleotide isolated according to the above method is SEQ ID NO: 53
And continuously extends from the nucleotide sequence corresponding to the 5 ′ end of SEQ ID NO: 53 to the nucleotide sequence corresponding to the 3 ′ end of SEQ ID NO: 53, except that the 3 ′ end of SEQ ID NO: 53 Contains a nucleotide sequence that excludes certain poly (A) tails. Also preferably, the polynucleotide isolated according to the above method is a cDNA from nucleotide 240 to nucleotide 503 of SEQ ID NO: 53.
From the nucleotide sequence corresponding to the sequence and corresponding to the 5 'end of the sequence from nucleotide 240 to nucleotide 503 of SEQ ID NO: 53,
3 comprising a nucleotide sequence that extends continuously from the nucleotide 240 to the nucleotide 503 corresponding to the 3 ′ end of the sequence. Also preferably, the polynucleotide isolated according to the above method corresponds to the cDNA sequence from nucleotide 318 to nucleotide 503 of SEQ ID NO: 53 and 5 ′ of the sequence from nucleotide 318 to nucleotide 503 of SEQ ID NO: 53 From the nucleotide sequence corresponding to the terminus, nucleotide 3 of SEQ ID NO: 53
Includes nucleotide sequences that extend continuously from 18 to nucleotide 503 to the nucleotide sequence corresponding to the 3 'end of the sequence.

In another aspect, the present invention provides: (a) an amino acid sequence set forth in SEQ ID NO: 54; (b) a fragment of the amino acid sequence set forth in SEQ ID NO: 54 [this fragment comprises eight consecutive amino acids of SEQ ID NO: 54; And (c) clone ve16_1 deposited with the ATCC under accession number 98886
A composition comprising an amino acid sequence selected from the group consisting of: an amino acid sequence encoded by the cDNA insert of claim 1; Preferably, such a protein comprises the amino acid sequence of SEQ ID NO: 54. In a further preferred embodiment, the invention relates to a fragment of the amino acid sequence shown in SEQ ID NO: 54, which is preferably a biologically active fragment of 8 (more preferably 20, most preferably 30) of SEQ ID NO: 54 Or a fragment of the amino acid sequence represented by SEQ ID NO: 54 which has biological activity [this fragment comprises the amino acid sequence from amino acid 39 to amino acid 48 of SEQ ID NO: 54] ] Is provided.

In one embodiment, the present invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 55; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 55 from nucleotide 11 to nucleotide 1063; c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 55 from nucleotide 71 to nucleotide 1063; (d) a polynucleotide comprising the nucleotide sequence of the full-length protein-encoding sequence of clone vf3_1 deposited with the ATCC under accession number 98886; (E) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vf3_1 deposited at the ATCC under accession number 98886; (f) a clone deposited at the ATCC under accession number 98886 vf3 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of __1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vf3_1 deposited with the ATCC under accession number 98886; (H) a polynucleotide encoding a protein containing the amino acid sequence represented by SEQ ID NO: 56; (i) a fragment of the amino acid sequence represented by SEQ ID NO: 56 having biological activity [this fragment comprises eight fragments of SEQ ID NO: 56] Contains consecutive amino acids of
(J) a polynucleotide which is an allele variant of the above-mentioned polynucleotide (a)-(g); (k) species homology of the above-mentioned protein (h) or (i) (L) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) (a)- A polynucleotide which hybridizes under stringent conditions to any one of the polynucleotides specified in (i) and which has a length of at least 25% of SEQ ID NO: 55; A composition comprising a nucleotide is provided.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 11 to nucleotide 1063 of SEQ ID NO: 55; nucleotide 7 of SEQ ID NO: 55
A nucleotide sequence from 1 to nucleotide 1063; the nucleotide sequence of the full-length protein-encoding sequence of clone vf3_1 deposited with the ATCC under accession number 98886; or the clone v deposited with the ATCC under accession number 98886
Contains the nucleotide sequence of the mature protein coding sequence of f3_1. In another preferred embodiment, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone vf3_1 deposited with the ATCC under accession number 98886. In a further preferred embodiment, the present invention provides a biologically active fragment of the amino acid sequence of SEQ ID NO: 56, wherein said fragment is preferably 8 (more preferably 20, most preferably 30) of SEQ ID NO: 56
Or a fragment of the amino acid sequence shown in SEQ ID NO: 56 which has biological activity [this fragment comprises amino acids 170 to 179 of SEQ ID NO: 56]
Which includes the amino acid sequence of SEQ ID NO: 1).

[0162] Another embodiment provides a gene corresponding to the cDNA sequence shown in SEQ ID NO: 55.

Further embodiments according to the invention include: (a) (i) (aa) SEQ ID NO: 55 excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 55; and (ab) accession number 98886 Clone vf deposited with ATCC below
3_1 nucleotide sequence of the cDNA insert; preparing one or more polynucleotide probes that hybridize at 65 degrees Celsius in 6X SSC to a nucleotide sequence selected from the group consisting of: 3ii. 4X SSC, hybridizing with human genomic DNA under conditions that are as stringent as 50 degrees Celsius; and (iii) isolating the DNA polynucleotide detected by the probe; and b) (i) (ba) SEQ ID NO: 55 excluding the poly (A) tail at the 3 'end of SEQ ID NO: 55; and (bb) clone vf deposited with the ATCC under accession number 98886
Preparing one or more polynucleotide primers that hybridize to a nucleotide sequence selected from the group consisting of 3_1 cDNA inserts at 65 degrees Celsius in 6X SSC at a nucleotide sequence selected from the group consisting of: 4X SSC, hybridizing with human genomic DNA under conditions that are as stringent as 50 degrees Celsius; (iii) amplify the human DNA sequence; and (iv) the polynucleotide product of step (b) (iii) And providing an isolated polynucleotide produced according to a method selected from the group consisting of:

Preferably, the polynucleotide isolated according to the above method is SEQ ID NO: 55
And continuously extends from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 55 to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 55, except that the 3 'end of SEQ ID NO: 55 Contains a nucleotide sequence that excludes certain poly (A) tails. Also preferably, the polynucleotide isolated according to the above method is a cDNA from nucleotide 11 to nucleotide 1063 of SEQ ID NO: 55.
SEQ ID NO: 55 corresponds to the nucleotide sequence from nucleotide 11 to nucleotide 1
From the nucleotide sequence corresponding to the 5 'end of the sequence up to
5 comprises a nucleotide sequence extending continuously from the nucleotide 11 to the nucleotide 1063 corresponding to the 3 ′ end of the sequence. Also preferably, the polynucleotide isolated according to the above method corresponds to the cDNA sequence from nucleotide 71 to nucleotide 1063 of SEQ ID NO: 55 and 5 ′ of the sequence from nucleotide 71 to nucleotide 1063 of SEQ ID NO: 55. From the nucleotide sequence corresponding to the terminus, nucleotide 7 of this SEQ ID NO: 55
Includes nucleotide sequences that extend continuously from 1 to nucleotide 1063 to a nucleotide sequence corresponding to the 3 'end of the sequence.

In another aspect, the present invention provides: (a) an amino acid sequence set forth in SEQ ID NO: 56; (b) a fragment of the amino acid sequence set forth in SEQ ID NO: 56 [this fragment comprises eight consecutive amino acids of SEQ ID NO: 56 And c) an amino acid sequence encoded by the cDNA insert of clone vf3_1 deposited at the ATCC under accession number 98886, wherein the protein comprises an amino acid sequence selected from the group consisting of: A composition comprising a protein substantially free of mammalian proteins is provided. Preferably, such a protein comprises the amino acid sequence of SEQ ID NO: 56. In a further preferred embodiment, the present invention provides a biologically active fragment of the amino acid sequence of SEQ ID NO: 56, wherein said fragment preferably comprises 8 (more preferably 20, most preferably 30) of SEQ ID NO: 56 Or a fragment of the amino acid sequence represented by SEQ ID NO: 56 having biological activity [this fragment comprises the amino acid sequence from amino acid 170 to amino acid 179 of SEQ ID NO: 56] ] Is provided.

In one embodiment, the present invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 57; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 57 from nucleotide 542 to nucleotide 886; c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 57 from nucleotide 755 to nucleotide 886; (d) a polynucleotide comprising the nucleotide sequence of the full length protein encoding sequence of clone vj2_1 deposited at the ATCC under accession number 98886; (E) a polynucleotide encoding the full length protein encoded by the cDNA insert of clone vj2_1 deposited at the ATCC under accession number 98886; (f) a clone deposited at the ATCC under accession number 98886 vj2 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of J._1; (g) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vj2_1 deposited at the ATCC under accession number 98886; (H) a polynucleotide encoding a protein comprising the amino acid sequence represented by SEQ ID NO: 58; (i) a fragment of the amino acid sequence represented by SEQ ID NO: 58 having biological activity [this fragment comprises eight Contains consecutive amino acids of
(J) a polynucleotide which is an allele variant of the above-mentioned polynucleotide (a)-(g); (k) species homology of the above-mentioned protein (h) or (i) (L) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) (a)- A polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (i) and has a length of at least 25% of SEQ ID NO: 57. A composition comprising a nucleotide is provided.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 542 to nucleotide 886 of SEQ ID NO: 57; nucleotide 7 of SEQ ID NO: 57
Nucleotide sequence from 55 to nucleotide 886; nucleotide sequence of the full-length protein-encoding sequence of clone vj2_1 deposited at the ATCC under accession number 98886; or clone v deposited at the ATCC under accession number 98886
j2_1 contains the nucleotide sequence of the mature protein coding sequence. In another preferred embodiment, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone vj2_1 deposited with the ATCC under accession number 98886. In a further preferred embodiment, the present invention provides a biologically active fragment of the amino acid sequence of SEQ ID NO: 58, wherein said fragment is preferably 8 (more preferably 20, most preferably 30) of SEQ ID NO: 58
Or a fragment of the amino acid sequence shown in SEQ ID NO: 58 which has biological activity [this fragment comprises amino acids 52 to 61 of SEQ ID NO: 58] Which includes the amino acid sequence of SEQ ID NO: 1).

[0168] Another embodiment provides a gene corresponding to the cDNA sequence shown in SEQ ID NO: 57.

Further embodiments according to the invention include: (a) (i) (aa) SEQ ID NO: 57 excluding the poly (A) tail at the 3 ′ end of SEQ ID NO: 57; and (ab) accession number 98886 Clone vj deposited under ATCC below
2_1 nucleotide sequence of the cDNA insert; preparing one or more polynucleotide probes that hybridize at 65 degrees Celsius in 6X SSC to a nucleotide sequence selected from the group consisting of: 4X SSC, hybridizing with human genomic DNA under conditions that are as stringent as 50 degrees Celsius; and (iii) isolating the DNA polynucleotide detected by the probe; and b) (i) (ba) SEQ ID NO: 57 excluding the poly (A) tail at the 3 'end of SEQ ID NO: 57; and (bb) clone vj deposited at the ATCC under accession number 98886
2_1 nucleotide sequence of the cDNA insert; preparing one or more polynucleotide primers that hybridize at 65 degrees Celsius in 6X SSC to a nucleotide sequence selected from the group consisting of: 4X SSC, hybridizing with human genomic DNA under conditions that are as stringent as 50 degrees Celsius; (iii) amplify the human DNA sequence; and (iv) the polynucleotide product of step (b) (iii) Isolating a polynucleotide produced by a method selected from the group consisting of:

Preferably, the polynucleotide isolated according to the above method is SEQ ID NO: 57
And continuously extends from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 57 to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 57, except that the 3 'end of SEQ ID NO: 57 Contains a nucleotide sequence that excludes certain poly (A) tails. Also preferably, the polynucleotide isolated according to the above method is a cDNA from nucleotide 542 to nucleotide 886 of SEQ ID NO: 57.
From the nucleotide sequence corresponding to the sequence and corresponding to the 5 'end of the sequence from nucleotide 542 to nucleotide 886 of SEQ ID NO: 57,
7 comprising a nucleotide sequence that extends continuously from nucleotide 542 to nucleotide 886 to the nucleotide sequence corresponding to the 3 'end of the sequence. Also preferably, the polynucleotide isolated according to the above method corresponds to the cDNA sequence from nucleotide 755 to nucleotide 886 of SEQ ID NO: 57 and 5 ′ of the sequence from nucleotide 755 to nucleotide 886 of SEQ ID NO: 57. From the nucleotide sequence corresponding to the terminus, nucleotide 7 of this SEQ ID NO: 57
Includes nucleotide sequences that extend continuously from 55 to the nucleotide sequence corresponding to the 3 'end of the sequence from nucleotide 886.

In another aspect, the present invention provides: (a) an amino acid sequence set forth in SEQ ID NO: 58; (b) a fragment of the amino acid sequence set forth in SEQ ID NO: 58 [this fragment comprises eight consecutive amino acids of SEQ ID NO: 58; And c) an amino acid sequence encoded by the cDNA insert of clone vj2_1 deposited at the ATCC under accession number 98886, wherein the protein comprises an amino acid sequence selected from the group consisting of: A composition comprising a protein substantially free of mammalian proteins is provided. Preferably, such a protein comprises the amino acid sequence of SEQ ID NO: 58. In a further preferred embodiment, the present invention provides a biologically active fragment of the amino acid sequence of SEQ ID NO: 58, wherein said fragment preferably comprises 8 (more preferably 20, most preferably 30) of SEQ ID NO: 58 Or a fragment of the amino acid sequence represented by SEQ ID NO: 58 having biological activity [this fragment comprises the amino acid sequence from amino acid 52 to amino acid 61 of SEQ ID NO: 58] ] Is provided.

In one aspect, the present invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 59; (b) a polynucleotide comprising the nucleotide sequence of nucleotide 30 to nucleotide 344 of SEQ ID NO: 59; c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 59 from nucleotide 84 to nucleotide 344; (d) a polynucleotide comprising the nucleotide sequence of the full length protein coating sequence of clone vp7_1 deposited at the ATCC under accession number 98886; (E) c of clone vp7_1 deposited at the ATCC under accession number 98886
A polynucleotide encoding the full length protein encoded by the DNA insert; (f) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone vp7_1 deposited at the ATCC under accession number 98886; (g) a deposit at the ATCC C of clone vp7_1 deposited under accession number 98886
A polynucleotide encoding a mature protein encoded by the DNA insert; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 60; (i) an amino acid sequence of SEQ ID NO: 60 having biological activity A polynucleotide encoding a protein comprising a fragment comprising the eight contiguous amino acids of SEQ ID NO: 60; (j) an allelic variant of the polynucleotide of (a) to (g) above. (K) a polynucleotide encoding a species homolog of the protein of (h) or (i) above; (l) any one of the polynucleotides specified in (a)-(i) under stringent conditions. (M) in (a)-(i) Hybridize with any one stringent conditions noted polynucleotides, SEQ ID NO: 59 of the length of at least 2
A composition comprising an isolated polynucleotide selected from the group consisting of: a polynucleotide having a length of 5%.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 30 to nucleotide 344 of SEQ ID NO: 59; SEQ ID N
O: nucleotide sequence from nucleotide 84 to nucleotide 344 at 59; AT
Nucleotide sequence of the full-length protein coding sequence of clone vp7_1 deposited at the CC under accession number 98886; or accession number 9888 at the ATCC
6 contains the nucleotide sequence of the mature protein coding sequence of the clone vp7_1 deposited in No. 6. In another preferred embodiment, the polynucleotide is ATC
C encodes the full-length or mature protein encoded by the cDNA insert of clone vp7_1 deposited under accession number 98886. In a further preferred embodiment, the present invention relates to a fragment of the amino acid sequence of SEQ ID NO: 60 having biological activity, preferably 8 of SEQ ID NO: 60.
A polynucleotide encoding a protein comprising a fragment comprising (more preferably 20, most preferably 30) contiguous amino acid sequences, or a fragment of the amino acid sequence of SEQ ID NO: 60 having biological activity, comprising
Provided is a polynucleotide encoding a protein comprising a fragment comprising the amino acid sequence from amino acid 47 to amino acid 56 of Q ID NO: 60.

[0174] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 59. Further aspects of the invention include: (a) (i) at 65 ° C. in 6XSSC: (aa) SEQ ID NO: 59, where 3 ′ of SEQ ID NO: 59.
(Ab) one or more that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of a cDNA insert of clone vp7_1 deposited at the ATCC under accession number 98886. (Ii) hybridizing said probe with human genomic DNA at least as stringent as 4XSSC at 50 ° C .; (iii) singly detecting the DNA polynucleotide detected with said probe. (B) (i) at 65 ° C. in 6 × SSC (ba) SEQ ID NO: 59, where 3 ′ of SEQ ID NO: 59
(Bb) one or more that hybridize with a nucleotide sequence selected from the group consisting of the nucleotide sequence of a cDNA insert of clone vp7_1 deposited at the ATCC under accession number 98886. (Ii) hybridizing said primers with human genomic DNA at least as stringent as 4XSSC at 50 ° C .; (iii) amplifying the human DNA sequence; (iv) Providing an isolated polynucleotide produced according to a process selected from the group consisting of a step comprising isolating the polynucleotide product of step (b) (iii).

[0175] Preferably, the polynucleotide isolated according to the above process is SE
This corresponds to the cDNA sequence of Q ID NO: 59, and corresponds to the sequence of SEQ ID NO: 59.
A nucleotide sequence that extends continuously from the nucleotide sequence corresponding to the 'end to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 59, but does not include a poly (A) tail at the 3 'end of SEQ ID NO: 59 including. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
From the nucleotide sequence corresponding to the cDNA sequence from nucleotide 30 to nucleotide 344 of NO: 59 and corresponding to the 5 'end of the sequence from nucleotide 30 to nucleotide 344 of SEQ ID NO: 59, SEQ ID NO: 59
From nucleotide 30 to the nucleotide sequence corresponding to the 3 'end of said sequence at nucleotide 344. Further, preferably, the polynucleotide isolated according to the above process has SEQ ID NO:
: Corresponding to the cDNA sequence from nucleotide 84 to nucleotide 344 of 59;
From the nucleotide sequence corresponding to the 5 'end of the sequence from nucleotide 84 to nucleotide 344 of SEQ ID NO: 59 to the nucleotide sequence corresponding to the 3' end of the sequence from nucleotide 84 to nucleotide 344 of SEQ ID NO: 59 Includes a continuously extending nucleotide sequence.

In another aspect, the invention provides a composition comprising a protein, wherein the protein is: (a) an amino acid sequence of SEQ ID NO: 60; (b) a fragment of the amino acid sequence of SEQ ID NO: 60. Oh, SE
A fragment comprising the eight contiguous amino acids of Q ID NO: 60; and (c) c of clone vp7_1 deposited with the ATCC under accession number 98886.
The protein comprises an amino acid sequence selected from the group consisting of an amino acid sequence encoded by a DNA insert, wherein said protein is substantially free of other mammalian proteins. Preferably, such a protein is SEQ.
Contains the amino acid sequence of ID NO: 60. In a further preferred embodiment, the invention relates to a fragment of the amino acid sequence of SEQ ID NO: 60 having biological activity, preferably of 8 (more preferably 20, most preferably 30) of the contiguous SEQ ID NO: 60. A protein comprising a fragment comprising an amino acid or a fragment having the biological activity of the amino acid sequence of SEQ ID NO: 60, comprising a fragment comprising the amino acid sequence of amino acid 47 to amino acid 56 of SEQ ID NO: 60 is provided. .

In one aspect, the invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 61; (b) a polynucleotide comprising the nucleotide sequence of nucleotide 23 to nucleotide 757 of SEQ ID NO: 61; c) nucleotides 119 to 757 of SEQ ID NO: 61
(D) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vp8_1 deposited at the ATCC under accession number 98886; C of clone vp8_1
A polynucleotide encoding the full-length protein encoded by the DNA insert; (f) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone vp8_1 deposited at the ATCC under accession number 98886; (g) a deposit at the ATCC C of clone vp8_1 deposited under number 98886
A polynucleotide encoding the mature protein encoded by the DNA insert; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 62; (i) an amino acid sequence of SEQ ID NO: 62 having biological activity A polynucleotide encoding a protein comprising a fragment comprising the eight contiguous amino acids of SEQ ID NO: 62; (j) an allelic variant of the polynucleotide of (a) to (g). (K) a polynucleotide encoding a species homolog of the protein of (h) or (i); (l) any one of the polynucleotides specified in (a) to (i) and strictly Polynucleotides that hybridize under mild conditions; and (m) (a)-(i) An isolated polynucleotide selected from the group consisting of a polynucleotide that hybridizes under stringent conditions with any one of the specified polynucleotides and has a length of at least 25% of the length of SEQ ID NO: 62. A composition comprising a nucleotide is provided.

[0178] Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 23 to nucleotide 757 of SEQ ID NO: 61; SEQ ID N
O: nucleotide sequence from nucleotide 119 to nucleotide 757 of 61; A
Nucleotide sequence of the full-length protein coding sequence of clone vp8_1 deposited at the TCC under accession number 98886; or accession number 988 at the ATCC
86 contains the nucleotide sequence of the mature protein coding sequence of clone vp8_1 deposited at 86. In another preferred embodiment, the polynucleotide comprises A
It encodes the full-length or mature protein encoded by the cDNA insert of clone vp8_1 deposited at the TCC under accession number 98886. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 62
A fragment of the amino acid sequence of SEQ ID NO: 62
A polynucleotide encoding a protein comprising a fragment comprising 8 (more preferably 20, most preferably 30) contiguous amino acids, or a fragment of the amino acid sequence of SEQ ID NO: 62 having biological activity, comprising:
A polynucleotide encoding a protein comprising a fragment comprising the amino acid sequence from amino acid 117 to amino acid 126 of Q ID NO: 62 is provided.

[0179] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 61. Further aspects of the invention include: (a) (i) at 65 ° C. in 6 × SSC: (aa) SEQ ID NO: 61, where 3 ′ of SEQ ID NO: 61
Excluding the terminal poly (A) tail; (ab) one or more nucleotide sequences that hybridize with a nucleotide sequence selected from the group consisting of the nucleotide sequence of a cDNA insert of clone vp8_1 deposited at the ATCC under accession number 98886. Preparing a polynucleotide probe; (ii) hybridizing said probe with human genomic DNA at least as stringent as 4XSSC at 50 ° C .; (iii) simply detecting the DNA polynucleotide detected with said probe. (B) (i) at 65 ° C. in 6 × SSC, (ba) SEQ ID NO: 61, where 3 ′ of SEQ ID NO: 61
(Bb) one or more nucleotide sequences that hybridize to a nucleotide sequence selected from the group consisting of the nucleotide sequence of a cDNA insert of clone vp8_1 deposited at the ATCC under accession number 98886. Preparing a polynucleotide primer; (ii) hybridizing the probe with human genomic DNA under conditions as stringent as at least 4X SSC at 50 ° C .; (iii) amplifying a human DNA sequence; b) a process comprising isolating the polynucleotide product of (iii). An isolated polynucleotide produced according to a process selected from the group consisting of:

Preferably, the polynucleotide isolated according to the above process is SE
This corresponds to the cDNA sequence of Q ID NO: 61, and corresponds to the sequence of SEQ ID NO: 61-5.
A nucleotide sequence that extends continuously from the nucleotide sequence corresponding to the 'end to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 61, but does not include the poly (A) tail at the 3 'end of SEQ ID NO: 61. Including. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
From the nucleotide sequence corresponding to nucleotide 23 to nucleotide 757 of the cDNA sequence of SEQ ID NO: 612 and corresponding to the 5 'end of the sequence from nucleotide 23 to nucleotide 757 of SEQ ID NO: 61, SEQ ID NO: 61
From nucleotide 23 to the nucleotide sequence corresponding to the 3 'end of said sequence at nucleotide 757. Further, preferably, the polynucleotide isolated by said process has SEQ ID NO: 6.
SEQ ID N corresponds to the cDNA sequence from nucleotides 119 to 757 of SEQ ID NO: 1.
O: from the nucleotide sequence corresponding to the 5 'end of the sequence from nucleotide 119 to nucleotide 757 of 61, nucleotide 1 of SEQ ID NO: 61
A nucleotide sequence extending continuously from 19 to nucleotide 757 to a nucleotide sequence corresponding to the nucleotide sequence corresponding to the 3 'end of said sequence.

In another aspect, the invention provides a composition comprising a protein, wherein the protein is (a) the amino acid sequence of SEQ ID NO: 62; (b) a fragment of the amino acid sequence of SEQ ID NO: 62. And SE
A fragment comprising the eight contiguous amino acids of Q ID NO: 62; and (c) c of clone vp8_1 deposited with the ATCC under accession number 98886.
The protein comprises an amino acid sequence selected from the group consisting of: an amino acid sequence encoded by a DNA insert; and the protein is substantially free of other mammalian proteins. Preferably,
Such a protein comprises the amino acid sequence of SEQ ID NO: 62. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 6
A fragment of the amino acid sequence of 2, preferably 8 (more preferably 20
, Most preferably 30) a protein comprising a fragment comprising the amino acids of adjacent SEQ ID NO: 62, or SEQ ID NO having biological activity:
A protein comprising a fragment of the amino acid sequence of SEQ ID NO: 62 comprising the amino acid sequence of amino acids 117 to 126 of SEQ ID NO: 62.

In one aspect, the present invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 63; (b) from nucleotide 1048 to nucleotide 37 of SEQ ID NO: 63
(C) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vp22_1 deposited at the ATCC under accession number 98933; A polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vp22_1; (e) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone vp22_1 deposited at the ATCC under accession number 98933; A) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone vp22_1 deposited at the ATCC under accession number 98933; (g) the polynucleotide of SEQ ID NO: 64; A polynucleotide encoding a protein comprising a amino acid sequence; (h) a protein comprising a biologically active fragment of the amino acid sequence of SEQ ID NO: 64, comprising a fragment comprising 8 contiguous amino acids of SEQ ID NO: 64 (I) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (f); and (j) encodes a species homolog of the protein of (g) or (h). (K) a polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(h); and (1) a polynucleotide specified in (a)-(h). Hybridized under stringent conditions with any one of the polynucleotides of SEQ ID NO: 63 Providing a composition comprising at least 25% of the isolated polynucleotide selected from the group consisting of a polynucleotide having a length.

Preferably, such a polynucleotide is the nucleotide sequence from nucleotide 1048 to nucleotide 3726 of SEQ ID NO: 63; the nucleotide sequence of the full length protein coding sequence of clone vp22_1 deposited at the ATCC under accession number 98933; Or the nucleotide sequence of the mature protein coding sequence of clone vp22_1 deposited at the ATCC under accession number 98933. In another preferred embodiment, the polynucleotide comprises ATC
C encodes the full-length or mature protein encoded by the cDNA insert of clone vp22_1 deposited under accession number 98933. In a further preferred embodiment, the present invention is a fragment of the amino acid sequence of SEQ ID NO: 64 having biological activity, preferably flanking 8 (more preferably 20, most preferably 30) of SEQ ID NO: 64. A polynucleotide encoding a protein comprising a fragment comprising an amino acid, or a fragment of the amino acid sequence of SEQ ID NO: 64 having biological activity, wherein the fragment comprises
Provided is a polynucleotide encoding a protein comprising a fragment comprising the amino acid sequence from amino acid 441 to amino acid 450 of ID NO: 64.

[0184] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 63. Further aspects of the invention include: (a) (i) at 65 ° C. in 6 × SSC: (aa) SEQ ID NO: 63, where 3 ′ of SEQ ID NO: 63
(Ab) clone vp22_1 deposited at the ATCC under accession number 98933
Preparing one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of a cDNA insert of: (ii) at least 4X SSC at as stringent conditions as 50 ° C. (B) (i) at 65 ° C. in 6 × SSC at 65 ° C., and (ba) SEQ ID. NO: 63, but 3 'of SEQ ID NO: 63
(Bb) clone vp22_1 deposited at the ATCC under accession number 98933
Preparing one or more polynucleotide primers that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of a cDNA insert of: (ii) at least 4X SSC at as stringent conditions as 50 ° C. (Iii) amplifying the human DNA sequence; (iv) a process comprising the steps of: (iv) isolating the polynucleotide product of step (b) (iii). An isolated polynucleotide produced by the process is provided.

Preferably, the polynucleotide isolated according to the above process is SE
This corresponds to the cDNA sequence of Q ID NO: 63, and corresponds to SEQ ID NO: 63-5.
A nucleotide sequence that extends continuously from the nucleotide sequence corresponding to the 'end to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 63, but does not include a poly (A) tail at the 3 'end of SEQ ID NO: 63 including. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
SEQ ID NO: 63 corresponds to the cDNA from nucleotide 1048 to nucleotide 3726 of SEQ ID NO: 63.
SEQ ID NO: 26 from the nucleotide sequence corresponding to the 5 'end of the sequence
NO: 3 'of the sequence from nucleotide 1048 to nucleotide 3726 of 63
Includes nucleotide sequences that extend continuously to the nucleotide sequence corresponding to the terminus.

In another aspect, the invention provides a composition comprising a protein, wherein the protein is: (a) a fragment of the amino acid sequence of SEQ ID NO: 64; (b) a fragment of the amino acid sequence of SEQ ID NO: 64 Ah, SE
A fragment comprising the eight contiguous amino acids of Q ID NO: 64; and (c) an amino acid sequence selected from the group consisting of: the amino acid sequence encoded by the cDNA insert of clone vp22_1 deposited at the ATCC under accession number 98933. Wherein the protein is substantially free of other mammalian proteins. Preferably,
Such a protein comprises the amino acid sequence of SEQ ID NO: 64. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 6
A fragment of the amino acid sequence of 4, preferably 8 (more preferably 20
, Most preferably 30) a fragment comprising a contiguous SEQ ID NO: 64 amino acid fragment, or a biologically active SEQ ID NO:
A protein comprising a fragment of the amino acid sequence of SEQ ID NO: 64, comprising a fragment of the amino acid sequence from amino acid 441 to amino acid 450.

In one aspect, the invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 65; (b) nucleotide 134 to nucleotide 667 of SEQ ID NO: 65
(C) nucleotides 191 to 667 of SEQ ID NO: 65.
A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vp48_1 deposited with the ATCC under accession number 98933; (e) a clone deposited under the accession number 98933 at the ATCC. a polynucleotide encoding the full length protein encoded by the cDNA insert of vp48_1; (f) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone vp48_1 deposited at the ATCC under accession number 98933; (g) ATCC A polynucleotide encoding the mature protein encoded by the cDNA of clone vp48_1 deposited under accession number 98933 at (h) the amino acid sequence of SEQ ID NO: 66. A polynucleotide encoding a protein; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 66 having biological activity, the fragment comprising the eight contiguous amino acids of SEQ ID NO: 66 (J) a polynucleotide that is an allelic variant of the polynucleotide of (a) to (g); (k) a polynucleotide that encodes a species homolog of the protein of (h) or (i); ) A polynucleotide that hybridizes under stringent conditions to any one of the polynucleotides specified in (a)-(i); and (m) a polynucleotide of any of the polynucleotides specified in (a)-(i). Hybridizes under stringent conditions with any one of them and has at least 2 of a length of SEQ ID NO: 65 % Of selected from the group consisting of a polynucleotide having a length to provide a composition comprising an isolated polynucleotide.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 134 to nucleotide 667 of SEQ ID NO: 65; SEQ ID NO: 65.
NO: nucleotide sequence from nucleotide 191 to nucleotide 667 of 65;
Nucleotide sequence of the full length protein coding sequence of clone vp48_1 deposited at the ATCC under accession number 98933; or accession number 9 at the ATCC
8933 contains the nucleotide sequence of the mature protein coding sequence of clone vp48_1 deposited at 8933. In another preferred embodiment, the polynucleotide is the c of clone vp48_1 deposited with the ATCC under accession number 98933.
Encodes the full-length or mature protein encoded by the DNA insert.
In a further preferred embodiment, the present invention provides a biologically active SEQ ID N
O: a fragment of the amino acid sequence of 66, preferably SEQ ID N
A polynucleotide encoding a protein comprising a fragment comprising 8 (more preferably 20, most preferably 30) contiguous amino acids of O: 66, or a fragment of the amino acid sequence of SEQ ID NO: 66 having biological activity. , SEQ ID NO: 66, comprising a fragment comprising the amino acid sequence from amino acid 84 to amino acid 93.

[0189] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 65. Further aspects of the invention include: (a) (i) at 65 ° C. in 6 × SSC: (aa) SEQ ID NO: 65, where 3 ′ of SEQ ID NO: 65
(Ab) clone vp48_1 deposited at the ATCC under accession number 98933
Preparing one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of a cDNA insert of: (ii) at least 4X SSC at as stringent conditions as 50 ° C. Hybridizing the probe with human genomic DNA; (iii) a process comprising isolating the DNA polynucleotide detected with the probe; and (b) (i) at 65 ° C. in 6 × SSC, (ba) SEQ ID NO: 65, but 3 'of SEQ ID NO: 65
(Bb) clone vp48_1 deposited at the ATCC under accession number 98933
Preparing one or more polynucleotide primers that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of a cDNA insert of: (ii) at least 4X SSC at as stringent conditions as 50 ° C. (Iii) amplifying the human DNA sequence; (iv) a process comprising the steps of: (iv) isolating the polynucleotide product of step (b) (iii). An isolated polynucleotide produced by the process is provided.

Preferably, the polynucleotide isolated according to the above process is SE
This corresponds to the cDNA sequence of Q ID NO: 65, and corresponds to the sequence of SEQ ID NO: 65-5.
A nucleotide sequence that extends continuously from the nucleotide sequence corresponding to the 'end to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 65, but does not include a poly (A) tail at the 3 'end of SEQ ID NO: 65 including. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
SEQ ID NO: 65 corresponds to the cDNA sequence from nucleotide 134 to nucleotide 667 of SEQ ID NO: 65.
From the nucleotide sequence corresponding to the 5 'end of the sequence of SEQ ID NO:
A nucleotide sequence extending continuously from nucleotide 134 at 65 to the nucleotide sequence corresponding to the 3 'end of the sequence at nucleotide 667. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
SEQ ID NO: 65 corresponds to the nucleotide sequence from nucleotide 191 to nucleotide 667 of SEQ ID NO: 65.
From the nucleotide sequence corresponding to the 5 'end of the sequence of SEQ ID NO:
A nucleotide sequence extending continuously from nucleotide 191 at 65 to the nucleotide sequence corresponding to the 3 'end of the sequence at nucleotide 667.

In another aspect, the invention provides a composition comprising a protein, wherein the protein is: (a) an amino acid sequence of SEQ ID NO: 66; (b) a fragment of the amino acid sequence of SEQ ID NO: 66 Oh, SE
A fragment comprising the eight contiguous amino acids of Q ID NO: 66; and (c) an amino acid sequence selected from the group consisting of: the amino acid sequence encoded by the cDNA insert of clone vp48_1 deposited at the ATCC under accession number 98933. Wherein the protein is substantially free of other mammalian proteins. Preferably,
Such a protein comprises the amino acid sequence of SEQ ID NO: 66. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 6
A fragment of the amino acid sequence of 6, preferably 8 (more preferably 20
, Most preferably 30) a protein comprising a fragment comprising the amino acids of adjacent SEQ ID NO: 66, or SEQ ID NO having biological activity:
A protein comprising a fragment of the amino acid sequence of SEQ ID NO: 66 comprising the amino acid sequence of amino acids 84 to 93 of SEQ ID NO: 66.

In one aspect, the invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 67; (b) a polynucleotide comprising the nucleotide sequence of nucleotide 65 to nucleotide 457 of SEQ ID NO: 67; c) nucleotides 158 to 457 of SEQ ID NO: 67
(D) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone vp3_1 deposited with the ATCC under accession number 98933; C of clone vp3_1
A polynucleotide encoding the full length protein encoded by the DNA insert; (f) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone vp3_1 deposited at the ATCC under accession number 98933; (g) a deposit at the ATCC C of clone vp3_1 deposited under number 98933
A polynucleotide encoding a mature protein encoded by the DNA insert; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 68; (i) an amino acid sequence of SEQ ID NO: 68 having biological activity A polynucleotide encoding a protein comprising a fragment comprising the eight contiguous amino acids of SEQ ID NO: 68; (j) an allelic variant of the polynucleotide of (a) to (g) above. (K) a polynucleotide encoding a species homolog of the protein of (h) or (i); (l) any one of the polynucleotides specified in (a) to (i) and strictly Polynucleotides that hybridize under mild conditions; and (m) (a)-(i) An isolated polynucleotide selected from the group consisting of: a polynucleotide that hybridizes under stringent conditions to any one of the specified polynucleotides and has a length of at least 25% of the length of SEQ ID NO: 67. A composition comprising a nucleotide is provided.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 65 to nucleotide 457 of SEQ ID NO: 67; SEQ ID N
O: nucleotide sequence from nucleotide 158 to nucleotide 457 of 67;
Nucleotide sequence of the full length protein coding sequence of clone vp3_1 deposited at the TCC under accession number 98933; or accession number 989 at the ATCC
33 contains the nucleotide sequence of the mature protein coding sequence of the clone vp3_1 deposited. In another preferred embodiment, the polynucleotide comprises A
It encodes the full-length or mature protein encoded by the cDNA insert of clone vp3_1 deposited at the TCC under accession number 98933. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 68
A fragment of the amino acid sequence of SEQ ID NO: 68,
A polynucleotide encoding a protein comprising a fragment comprising 8 (more preferably 20, most preferably 30) contiguous amino acids, or a fragment of the amino acid sequence of SEQ ID NO: 68 having biological activity, comprising:
Provided is a polynucleotide encoding a protein comprising a fragment comprising the amino acid sequence from amino acid 60 to amino acid 69 of Q ID NO: 68.

[0194] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 67. Further aspects of the invention include: (a) (i) at 65 ° C. in 6 × SSC: (aa) SEQ ID NO: 67, where 3 ′ of SEQ ID NO: 67
(Ab) one or more of the nucleotide sequences that hybridize with a nucleotide sequence selected from the group consisting of: a nucleotide sequence of a cDNA insert of clone vp3-1 deposited with the ATCC under accession number 98933. Preparing a polynucleotide probe; (ii) hybridizing said probe with human genomic DNA under as stringent conditions as at least 4X SSC, 50 ° C .; (iii) isolating a DNA polynucleotide detected by said probe And (b) (i) at 65 ° C. in 6XSSC, (ba) SEQ ID NO: 67, where 3 ′ of SEQ ID NO: 67.
(Bb) one or more nucleotide sequences that hybridize with a nucleotide sequence selected from the group consisting of: a nucleotide sequence of the cDNA insert of clone vp3-1 deposited with the ATCC under accession number 98933. Preparing polynucleotide primers; (ii) hybridizing said primers to human genomic DNA under as stringent conditions as at least 4X SSC, 50 ° C .; (iii) amplifying human DNA sequences; (iv) step (iv). b) A process comprising the step of isolating the polynucleotide product of (iii). An isolated polynucleotide produced by a process selected from the group consisting of:

Preferably, the polynucleotide isolated according to the above process is SE
This corresponds to the cDNA sequence of Q ID NO: 67, and corresponds to SEQ ID NO: 67-5.
A nucleotide sequence that extends continuously from the nucleotide sequence corresponding to the 'end to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 67, but does not include a poly (A) tail at the 3 'end of SEQ ID NO: 67 including. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
SEQ ID NO: 67 corresponds to the nucleotide sequence from nucleotide 65 to nucleotide 457 of SEQ ID NO: 67.
From the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 67 to the nucleotide sequence corresponding to the 3' end of nucleotide 457. Furthermore, the polynucleotide preferably isolated according to the above process corresponds to the cDNA from nucleotide 158 to nucleotide 457 of SEQ ID NO: 67,
And SEQ ID NO: 67. It comprises a nucleotide sequence extending continuously from the nucleotide sequence corresponding to the 5 ′ end of nucleotide 157 to nucleotide 457 of SEQ ID NO: 67 to the nucleotide sequence corresponding to the 3 ′ end of nucleotide 457 of SEQ ID NO: 67.

In another embodiment, the present invention provides a composition comprising a protein, wherein the protein is: (a) an amino acid sequence of SEQ ID NO: 68; (b) a fragment of the amino acid sequence of SEQ ID NO: 68 Oh, SE
A fragment comprising the eight contiguous amino acids of Q ID NO: 68; and (c) c of clone vp3_1 deposited with the ATCC under accession number 98933.
The protein comprises an amino acid sequence selected from the group consisting of: an amino acid sequence encoded by a DNA insert; and the protein is substantially free of other mammalian proteins. Preferably,
Such a protein comprises the amino acid sequence of SEQ ID NO: 68. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 6
A fragment of the amino acid sequence of 8, preferably 8 (more preferably 20
, Most preferably 30) a protein comprising a fragment comprising the amino acids of adjacent SEQ ID NO: 68, or SEQ ID NO having biological activity:
68. A protein comprising a fragment of the amino acid sequence of SEQ ID NO: 68 comprising the amino acid sequence of amino acids 60 to 69 of SEQ ID NO: 68.

In one aspect, the invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 69; (b) nucleotide 29 to nucleotide 1387 of SEQ ID NO: 69
A polynucleotide comprising the nucleotide sequence of SEQ ID NO: 69 from nucleotide 113 to nucleotide 138.
A polynucleotide comprising the nucleotide sequence of SEQ ID NO: 7; (d) clone vc61_1 deposited with the ATCC under accession number 2007012
A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of (c) vc61_1 deposited with the ATCC under accession number 2007012
A polynucleotide encoding the full-length protein encoded by the cDNA insert of SEQ ID NO: (f) clone vc61_1 deposited at the ATCC under accession number 2007012
A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of: (g) clone vc61_1 deposited with the ATCC under accession number 202012
(H) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 70; (i) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 70; A polynucleotide encoding a protein comprising a fragment comprising the eight contiguous amino acids of SEQ ID NO: 70; (j) a polynucleotide that is an allelic variant of the polynucleotide of (a)-(g) above. (K) a polynucleotide encoding a species homolog of the protein of (h) or (i); (l) a strictly similar to any one of the polynucleotides specified in (a) to (i); A polynucleotide that hybridizes under conditions; and (m) (a)-(i) Wherein the polynucleotide hybridizes under stringent conditions to any one of the polynucleotides specified in SEQ ID NO: 69 and has a length at least 25% of the length of SEQ ID NO: 69. A composition comprising the polynucleotide is provided.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 29 to nucleotide 1387 of SEQ ID NO: 69; SEQ ID NO: 69.
NO: nucleotide sequence from nucleotide 113 to nucleotide 1387 of 69; nucleotide sequence of the full-length protein coding sequence of clone vc61_1 deposited at the ATCC under accession number 2007012; or maturation of clone vc61_1 deposited at the ATCC under accession number 2007012 Contains the nucleotide sequence of the protein coding sequence. In another preferred embodiment, the polynucleotide comprises the clone vc61 deposited at the ATCC under accession number 2007012.
-1 encodes the full-length or mature protein encoded by the cDNA insert. In a further preferred embodiment, the present invention provides a biologically active SEQ
A fragment of the amino acid sequence of ID NO: 70, preferably SEQ.
A polynucleotide encoding a protein comprising a fragment comprising the 8 (more preferably 20, most preferably 30) contiguous amino acids of ID NO: 70;
Alternatively, there is provided a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 70 having biological activity, the fragment comprising the amino acid sequence of amino acids 221 to 230 of SEQ ID NO: 70.

Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 69. Further aspects of the invention include: (a) (i) at 65 ° C. in 6 × SSC: (aa) SEQ ID NO: 69, where 3 ′ of SEQ ID NO: 69
(Ab) Clone vc61_ deposited at the ATCC under accession number 2007012
Preparing one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of one cDNA insert; (ii) at least 4X SSC, as stringent conditions as 50 ° C. (B) (i) at 65 ° C. in 6 × SSC at a temperature of 65 ° C., wherein (ba) SEQ. ID NO: 69, but 3 'of SEQ ID NO: 69
(Bb) Clone vc61_ deposited at the ATCC under accession number 2007012
Preparing one or more polynucleotide primers that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of one of the cDNA inserts; (ii) at least 4X SSC, as stringent conditions as 50 ° C. (Iii) amplifying the human DNA sequence; (iv) step (b) isolating the polynucleotide product of step (iii). Provided by the process.

Preferably, the polynucleotide isolated according to said process is SE
This corresponds to the cDNA sequence of Q ID NO: 69, and corresponds to SEQ ID NO: 69-5.
A nucleotide sequence that extends continuously from the nucleotide sequence corresponding to the 'end to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 69, but does not include a poly (A) tail at the 3 'end of SEQ ID NO: 69 including. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
From the nucleotide sequence corresponding to the cDNA sequence of SEQ ID NO: 69 and corresponding to the 5 'end of the sequence from nucleotide 29 to nucleotide 1387 of SEQ ID NO: 69, from nucleotide 29 to nucleotide 13 of SEQ ID NO: 69
87 nucleotide sequences which extend continuously to the nucleotide sequence corresponding to the 3 'end of said sequence. Further, preferably, the polynucleotide isolated according to the above process corresponds to the cDNA sequence from nucleotide 113 to nucleotide 1387 of SEQ ID NO: 69 and 5 ′ of said sequence from nucleotide 113 to nucleotide 1387 of SEQ ID NO: 69. It includes a nucleotide sequence extending continuously from the nucleotide sequence corresponding to the terminus to the nucleotide sequence corresponding to the 3 'terminus of said sequence at nucleotide 1387 from nucleotide 113 of SEQ ID NO: 69.

In another embodiment, the present invention provides a composition comprising a protein, wherein the protein is: (a) an amino acid sequence of SEQ ID NO: 70; (b) a fragment of the amino acid sequence of SEQ ID NO: 70 Ah, SE
A fragment comprising the eight contiguous amino acids of Q ID NO: 70; and (c) clone vc61_1 deposited at the ATCC under accession number 2007012.
Wherein the protein is substantially free of other mammalian proteins. Preferably,
Such a protein comprises the amino acid sequence of SEQ ID NO: 70. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 7
0, preferably 8 (more preferably 20
, Most preferably 30) a protein comprising a fragment comprising the amino acids of contiguous SEQ ID NO: 70, or a SEQ ID NO having biological activity:
A fragment of the amino acid sequence of SEQ ID NO: 70, wherein the protein comprises the amino acid sequence of amino acids 221 to 230 of SEQ ID NO: 70.

In one embodiment, the present invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 71; (b) from nucleotide 44 to nucleotide 1513 of SEQ ID NO: 71
(C) nucleotides from nucleotide 92 to nucleotide 1513 of SEQ ID NO: 71.
(D) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 71 from nucleotide 1 to nucleotide 458; (e) a clone vp15_1 deposited with the ATCC under accession number 2070212
A polynucleotide comprising the nucleotides of the full-length protein coding sequence of the following: (f) clone vp15_1 deposited with the ATCC under accession number 202012
A polynucleotide encoding the full-length protein encoded by the cDNA insert of (c) clone vp15_1 deposited with the ATCC under accession number 2007012
A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of: (h) clone vp15_1 deposited with the ATCC under accession number 2007012
A polynucleotide encoding a mature protein encoded by the cDNA insert of SEQ ID NO: 72; (i) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 72; (j) an amino acid of SEQ ID NO: 72 having biological activity A polynucleotide encoding a protein comprising a fragment of the sequence, the fragment comprising eight contiguous amino acids of SEQ ID NO: 72; (k) an allelic variant of the polynucleotide of (a) to (h) above. (1) a polynucleotide encoding a species homolog of the protein of (i) or (j); (m) any one of the polynucleotides specified in (a) to (j); A polynucleotide that hybridizes under stringent conditions; and (n) (a (J) hybridizing under stringent conditions to any one of the polynucleotides specified in (j), selected from the group consisting of polynucleotides having a length of at least 25% of the length of SEQ ID NO: 71 Compositions comprising the isolated polynucleotides provided.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 44 to nucleotide 1513 of SEQ ID NO: 71; SEQ ID NO: 71.
NO: nucleotide sequence from nucleotide 92 to nucleotide 1513 of 71;
SEQ ID NO: 71 nucleotide sequence from nucleotide 1 to nucleotide 458; clone vp15 deposited at the ATCC under accession number 202012
_1 nucleotide sequence of the full-length protein coding sequence; or ATCC
Contains the nucleotide sequence of the mature protein coding sequence of clone vp15_1 deposited under accession number 2007012. In another preferred embodiment, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone vp15_1 deposited at the ATCC under accession number 2007012. In yet another preferred embodiment, the invention relates to SEQ ID NO.
The present invention provides a polynucleotide encoding a protein comprising the amino acid sequence from amino acid 1 to amino acid 139 of 72. In a further preferred embodiment, the invention is a fragment of the amino acid sequence of SEQ ID NO: 72 having biological activity, preferably flanking 8 (more preferably 20, most preferably 30) of SEQ ID NO: 72. A polynucleotide encoding a protein comprising a fragment comprising an amino acid, or SEQ ID NO: 72 having biological activity
A polynucleotide comprising a fragment of the amino acid sequence of SEQ ID NO: 72 comprising the amino acid sequence of amino acids 240 to 249.

[0204] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 71. Further aspects of the invention include: (a) (i) at 65 ° C. in 6 × SSC: (aa) SEQ ID NO: 71, where 3 ′ of SEQ ID NO: 71
(Ab) Clone vp15_ deposited at the ATCC under accession number 2007012
Preparing one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of one of the cDNA inserts; (ii) at least 4X SSC, as stringent conditions as 50 ° C. (Iii) a process comprising the steps of: (iii) isolating the DNA polynucleotides detected by the probe; and (b) (i) at 65 ° C. in 6 × SSC at (ba) SEQ. ID NO: 71, but 3 'of SEQ ID NO: 71
(Bb) Clone vp15_ deposited at the ATCC under accession number 2007012
Preparing one or more polynucleotide primers that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of one of the cDNA inserts: (ii) at least 4X SSC, as stringent conditions as 50 ° C. (Iii) amplifying the human DNA sequence; (iv) step (b) isolating the polynucleotide product of (iii). Provided by the process.

[0205] Preferably, the polynucleotide isolated according to the process is SE
This corresponds to the cDNA sequence of Q ID NO: 71, and corresponds to the sequence of SEQ ID NO: 71-5.
A nucleotide sequence that extends continuously from the nucleotide sequence corresponding to the 'end to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 71, but does not include a poly (A) tail at the 3 'end of SEQ ID NO: 71 including. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
SEQ ID NO: 71 corresponds to the cDNA sequence from nucleotide 44 to nucleotide 1513 of SEQ ID NO: 71.
SEQ ID NO: 7 from the nucleotide sequence corresponding to the 5 'end of the above sequence
A nucleotide sequence that extends continuously from one nucleotide 44 to the nucleotide sequence corresponding to the 3 'end of the sequence at nucleotide 1513. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
SEQ ID NO: 71 corresponds to the cDNA sequence from nucleotide 92 to nucleotide 1513 of SEQ ID NO: 71.
3 from the nucleotide sequence corresponding to the 5 'end of SEQ ID NO: 71 to the nucleotide sequence corresponding to the 3' end of nucleotide 1513. Furthermore, the polynucleotide preferably isolated according to the above process corresponds to the cDNA sequence from nucleotide 1 to nucleotide 458 of SEQ ID NO: 71,
SEQ ID NO: 71 extends continuously from the nucleotide sequence corresponding to the 5 'end of the sequence from nucleotide 1 to nucleotide 458 from SEQ ID NO: 71 to the nucleotide sequence corresponding to the 3' end of the sequence from nucleotide 458 Includes nucleotide sequence.

In another aspect, the invention provides a composition comprising a protein, wherein the protein comprises: (a) the amino acid sequence of SEQ ID NO: 72; (b) the amino acid 1 of the amino acid sequence of SEQ ID NO: 72 From amino acid 13
(C) a fragment of the amino acid sequence of SEQ ID NO: 72, wherein
A fragment comprising the eight contiguous amino acids of Q ID NO: 72; and (d) clone vp15_1 deposited with the ATCC under accession number 202012.
Wherein the protein is substantially free of other mammalian proteins. Preferably, such a protein is the amino acid sequence of SEQ ID NO: 72 or SEQ ID NO: 72.
It contains the amino acid sequence of amino acids 1 to 139 of ID NO: 72. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO:
72 amino acid sequences, preferably 8 (more preferably 2
0, most preferably 30) a protein comprising a fragment comprising the contiguous SEQ ID NO: 72 amino acids, or a biologically active SEQ ID NO:
No .: 72, comprising a fragment comprising the amino acid sequence of amino acids 240 to 249 of SEQ ID NO: 72.

In one embodiment, the present invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 73; (b) nucleotide 348 to nucleotide 743 of SEQ ID NO: 73
(C) nucleotides 414 to 743 of SEQ ID NO: 73.
(D) clone vp17_1 deposited with the ATCC under accession number 2007012
A polynucleotide comprising the nucleotides of the full-length protein coding sequence of (c) clone vp17_1 deposited with the ATCC under accession number 202012
A polynucleotide encoding the full-length protein encoded by the cDNA insert of (c) vp17_1 deposited with the ATCC under accession number 2007012
A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of the following: (g) clone vp17_1 deposited with the ATCC under accession number 202012
(H) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 74; (i) an amino acid of SEQ ID NO: 74 having biological activity A polynucleotide encoding a protein comprising a fragment of the sequence, the fragment comprising eight contiguous amino acids of SEQ ID NO: 74; (j) an allelic variant of the polynucleotide of (a)-(g) above. (K) a polynucleotide encoding a species homolog of the protein of the above (h) or (i); (1) any one of the polynucleotides specified in (a) to (i); A polynucleotide that hybridizes under stringent conditions; and (m) (a Selected from the group consisting of polynucleotides that hybridize under stringent conditions to any one of the polynucleotides specified in (i) and have a length of at least 25% of the length of SEQ ID NO: 73 Compositions comprising the isolated polynucleotides provided.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 348 to nucleotide 743 of SEQ ID NO: 73; SEQ ID NO: 73.
NO: nucleotide sequence from nucleotide 414 to nucleotide 743 of 73;
The nucleotide sequence of the full length protein coding sequence of clone vp17_1 deposited at the ATCC under accession number 2007012; or the mature protein coding sequence of clone vp17_1 deposited at the ATCC under accession number 2007012. In another preferred embodiment, the polynucleotide is the clone vp17_ deposited with the ATCC under accession number 2007012.
Encodes a full-length or mature protein encoded by one cDNA insert. In a further preferred embodiment, the present invention provides a biologically active SEQ I
A fragment of the amino acid sequence of D NO: 74, preferably SEQ ID NO:
A polynucleotide encoding a protein comprising a fragment comprising 8 (more preferably 20, most preferably 30) contiguous amino acids of D NO: 74, or a fragment of the amino acid sequence of SEQ ID NO: 74 having biological activity. Thus, there is provided a polynucleotide encoding a protein comprising a fragment comprising the amino acid sequence of amino acid 61 to amino acid 70 of SEQ ID NO: 74.

[0209] Another embodiment provides a gene corresponding to the cDNA of SEQ ID NO: 73. Further aspects of the invention include: (a) (i) at 65 ° C. in 6 × SSC: (aa) SEQ ID NO: 73, where 3 ′ of SEQ ID NO: 73
(Ab) Clone vp17_ deposited with ATCC under accession number 2007012
Preparing one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of one of the cDNA inserts; (ii) at least 4X SSC, as stringent conditions as 50 ° C. (B) (i) at 65 ° C. in 6XSSC at 65 ° C., wherein (ba) SEQ. ID NO: 73, but 3 'of SEQ ID NO: 73
(Bb) Clone vp17_ deposited with the ATCC under accession number 2007012
Preparing one or more polynucleotide primers that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of one of the cDNA inserts: (ii) at least 4X SSC, as stringent conditions as 50 ° C. (Iii) amplifying the human DNA sequence; (iv) step (b) isolating the polynucleotide product of (iii). Provided by the process.

[0210] Preferably, the polynucleotide isolated according to the above process is SE
This corresponds to the cDNA sequence of Q ID NO: 73, and corresponds to SEQ ID NO: 73-5.
A nucleotide sequence that extends continuously from the nucleotide sequence corresponding to the 'end to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 73, but does not include a poly (A) tail at the 3 'end of SEQ ID NO: 73 including. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
SEQ ID NO: 73 corresponds to the nucleotide sequence from nucleotide 348 to nucleotide 743 of SEQ ID NO: 73.
From the nucleotide sequence corresponding to the 5 'end of the sequence of SEQ ID NO:
A nucleotide sequence extending continuously from nucleotide 348 at 73 to the nucleotide sequence corresponding to the 3 'end of the sequence at nucleotide 743. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
SEQ ID NO: 73 corresponds to the cDNA sequence from nucleotide 414 to nucleotide 743 of SEQ ID NO: 73.
SEQ ID NO: 7 from the nucleotide sequence corresponding to the 5 'end of the above sequence
A nucleotide sequence extending continuously from nucleotide 414 at 3 to the nucleotide sequence corresponding to the 3 'end of said sequence at nucleotide 743.

In another aspect, the invention provides a composition comprising a protein, wherein the protein is a fragment of (a) the amino acid sequence of SEQ ID NO: 74; (b) a fragment of the amino acid sequence of SEQ ID NO: 74. And SE
A fragment comprising the eight contiguous amino acids of Q ID NO: 74; and (c) clone vp17_1 deposited with the ATCC under accession number 202012.
Wherein the protein is substantially free of other mammalian proteins. Preferably, such a protein comprises the amino acid sequence of SEQ ID NO: 74. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 7
A fragment of the amino acid sequence of 4, preferably 8 (more preferably 20
, Most preferably 30) a protein comprising a fragment comprising the contiguous SEQ ID NO: 74 amino acids, or a biologically active SEQ ID NO:
Provided is a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 74, wherein the fragment comprises the amino acid sequence of amino acids 61 to 70 of SEQ ID NO: 74.

In one aspect, the invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 75; (b) nucleotide 144 to nucleotide 461 of SEQ ID NO: 75
(C) a clone vp19_1 which has been deposited with the ATCC under accession number 2007012
A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of (d) clone vp19_1 deposited with the ATCC under accession number 2007012
A polynucleotide encoding the full-length protein encoded by the cDNA insert of SEQ ID NO: (e) clone vp19_1 deposited with the ATCC under accession number 2007012
A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of the following: (f) clone vp19_1 deposited with the ATCC under accession number 2070212
A polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 76; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 76; (h) an amino acid of SEQ ID NO: 76 having biological activity A polynucleotide encoding a protein comprising a fragment of the sequence, the fragment comprising eight contiguous amino acids of SEQ ID NO: 76; (i) an allelic variant of the polynucleotide of (a)-(f) above (J) a polynucleotide encoding a species homolog of the protein of (g) or (h); (k) any one of the polynucleotides specified in (a) to (h); A polynucleotide that hybridizes under stringent conditions; and (l) (a (J) hybridizing under stringent conditions with any one of the polynucleotides specified in (j), selected from the group consisting of polynucleotides having a length of at least 25% of the length of SEQ ID NO: 75 Compositions comprising the isolated polynucleotides provided.

Preferably, such a polynucleotide is the nucleotide sequence from nucleotide 144 to nucleotide 461 of SEQ ID NO: 75; the nucleotide sequence of the full-length protein coding sequence of clone vp19_1 deposited at the ATCC under accession number 2007012; Or the nucleotide sequence of the mature protein coding sequence of clone vp19_1 deposited at the ATCC under accession number 2007012. In another preferred embodiment, the polynucleotide comprises ATC
C, encodes the full-length or mature protein encoded by the cDNA insert of clone vp19_1 deposited under accession number 2007012. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 76
A fragment of the amino acid sequence of SEQ ID NO: 76,
A polynucleotide encoding a protein comprising a fragment comprising 8 (more preferably 20, most preferably 30) contiguous amino acids, or a fragment of the amino acid sequence of SEQ ID NO: 76 having biological activity, comprising:
Provided is a polynucleotide encoding a protein comprising a fragment comprising the amino acid sequence from amino acid 48 to amino acid 57 of Q ID NO: 76.

[0214] Another embodiment provides a gene corresponding to the cDNA sequence of SEQ ID NO: 75. Further aspects of the invention include: (a) (i) at 65 ° C. in 6 × SSC: (aa) SEQ ID NO: 75, where 3 ′ of SEQ ID NO: 75
(Ab) Clone vp19_ deposited with the ATCC under accession number 2007012
Preparing one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of a cDNA insert of (1); (B) (i) at 65 ° C. in 6 × SSC at a temperature of 65 ° C., wherein (a) SEQ. ID NO: 75, except for the poly (A) tail at the 3 'end of SEQ ID NO: 75; (bb) clone vp19_ deposited with the ATCC under accession number 2070212
Preparing one or more polynucleotide primers that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of one of the cDNA inserts; (Iii) amplifying the human DNA sequence; (iv) step (b) isolating the polynucleotide product of (iii). Provided in accordance with the process.

[0215] Preferably, the polynucleotide isolated by the process is SEQ.
It corresponds to the cDNA sequence of D NO: 75 and extends continuously from the nucleotide sequence corresponding to the 5 ′ end of SEQ ID NO: 75 to the nucleotide sequence corresponding to the 3 ′ end of SEQ ID NO: 75. : 75 including the nucleotide sequence without the poly (A) tail at the 3 'end. Further, preferably, the polynucleotide isolated according to the above process has SEQ ID NO:
SEQ ID NO: 75, corresponding to the cDNA sequence of SEQ ID NO: 75.
From the nucleotide sequence corresponding to the 5 'end of the sequence from 4 to nucleotide 461, from nucleotide 144 to nucleotide 46 of SEQ ID NO: 75
A nucleotide sequence that extends continuously to the nucleotide sequence corresponding to the 3 'end of one of the above sequences.

In another aspect, the invention provides a composition comprising a protein, wherein the protein is: (a) an amino acid sequence of SEQ ID NO: 76; (b) a fragment of the amino acid sequence of SEQ ID NO: 76 Ah, SE
A fragment comprising the eight contiguous amino acids of Q ID NO: 76; and (c) clone vp19_1 deposited with the ATCC under accession number 202012.
Wherein the protein is substantially free of other mammalian proteins. Preferably, such a protein comprises the amino acid sequence of SEQ ID NO: 76. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 7
A fragment of the amino acid sequence of 6, preferably 8 (more preferably 20
, Most preferably 30) a protein comprising a fragment comprising the amino acids of adjacent SEQ ID NO: 76, or a SEQ ID NO having biological activity:
76. A protein comprising a fragment of the amino acid sequence of SEQ ID NO: 76, wherein the fragment comprises the amino acid sequence of amino acids 48 to 57 of SEQ ID NO: 76.

In one aspect, the invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 77; (b) a polynucleotide comprising the nucleotide sequence of nucleotide 54 to nucleotide 368 of SEQ ID NO: 77; c) nucleotides 141 to 368 of SEQ ID NO: 77
(D) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 77 from nucleotide 51 to nucleotide 332; (e) the full-length protein coding of clone vq1_1 deposited at the ATCC under accession number 207012 (F) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone vq1_1 deposited at the ATCC under accession number 2007012; (g) a depository number at the ATCC under accession number 2007012 A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone vq1_1 that has been cloned; (h) cDN of clone vq1_1 deposited with the ATCC under accession number 2007012 A polynucleotide encoding a mature protein encoded by the insert; (i) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 78; (j) an amino acid sequence of SEQ ID NO: 78 having biological activity. A polynucleotide encoding a protein comprising a fragment comprising the eight contiguous amino acids of SEQ ID NO: 78; (k) a polynucleotide which is an allelic variant of the polynucleotide of (a) to (h) above. Nucleotides; (l) a polynucleotide encoding a species homolog of the protein of (i) or (j); (m) strictly corresponding to any one of the polynucleotides specified in (a)-(j). A polynucleotide that hybridizes under conditions; and (n) (a)-(j) Wherein the polynucleotide hybridizes under stringent conditions to any one of the polynucleotides specified in SEQ ID NO: 77 and has a length at least 25% of the length of SEQ ID NO: 77. A composition comprising the polynucleotide is provided.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 54 to nucleotide 368 of SEQ ID NO: 77; SEQ ID N
O: nucleotide sequence from nucleotide 141 to nucleotide 368 at 77; S
SEQ ID NO: 77 nucleotide sequence from nucleotide 51 to nucleotide 332 of clone 77; clone vq1_ deposited at the ATCC under accession number 202012
1 the full length protein coding sequence; or the nucleotide sequence of the mature protein coding sequence of clone vq1_1 deposited at the ATCC under accession number 2007012. In another preferred embodiment, the polynucleotide comprises the clone vq deposited at the ATCC under accession number 2007012.
It encodes the full-length or mature protein encoded by the 1-1 cDNA insert. In yet another preferred embodiment, the polynucleotide has SEQ ID
Provided is a polynucleotide encoding a protein comprising the amino acid sequence of amino acids 1 to 93 of NO: 78. In a further preferred embodiment, the invention is a fragment of the amino acid sequence of SEQ ID NO: 78 having biological activity, preferably flanking 8 (more preferably 20, most preferably 30) of SEQ ID NO: 78. A polynucleotide encoding a protein comprising a fragment comprising an amino acid, or SEQ ID NO: 7 having biological activity
A polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 78 comprising the amino acid sequence of amino acids 47 to 56 is provided.

[0219] Another embodiment provides a gene corresponding to the cDNA sequence of SEQ ID NO: 77. Further aspects of the invention include: (a) (i) at 65 ° C. in 6 × SSC: (aa) SEQ ID NO: 77, where 3 ′ of SEQ ID NO: 77
(Ab) Clone vq1_1 deposited at the ATCC under accession number 2007012
Preparing one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of a cDNA insert of: (ii) at least 4X SSC at as stringent conditions as 50 ° C. (B) (i) at 65 ° C. in 6 × SSC at 65 ° C., and (ba) SEQ ID. NO: 77, but 3 'of SEQ ID NO: 77
(Bb) Clone vq1_1 deposited at ATCC under accession number 2007012
Preparing one or more polynucleotide primers that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of a cDNA insert of: (ii) at least 4X SSC at as stringent conditions as 50 ° C. (Iii) amplifying the human DNA sequence; (iv) a process comprising the steps of: (iv) isolating the polynucleotide product of step (b) (iii). An isolated polynucleotide produced according to the process is provided.

Preferably, the polynucleotide isolated according to said process is SE
This corresponds to the cDNA sequence of Q ID NO: 77, and corresponds to the sequence of SEQ ID NO: 77-5.
A nucleotide sequence that extends continuously from the nucleotide sequence corresponding to the 'end to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 77, but does not include a poly (A) tail at the 3 'end of SEQ ID NO: 77 including. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
From the nucleotide sequence corresponding to the cDNA sequence from nucleotide 54 to nucleotide 368m of SEQ ID NO: 77 and corresponding to the 5 'end of nucleotide 54 to nucleotide 368 of SEQ ID NO: 77, from nucleotide 54 to nucleotide 368 of SEQ ID NO: 77 A nucleotide sequence that extends continuously to the nucleotide sequence corresponding to the 3 'end of Further, preferably, the polynucleotide isolated according to the above process is the cDN of SEQ ID NO: 77.
A from the nucleotide sequence corresponding to the A sequence and corresponding to the 5 'end of the sequence from nucleotide 141 to nucleotide 368 of SEQ ID NO: 77,
It includes a nucleotide sequence that extends continuously from nucleotide 141 of ID NO: 77 to the nucleotide sequence corresponding to the 3 ′ end of the sequence at nucleotide 368. More preferably, the polynucleotide isolated according to the above process comprises a cD from nucleotide 51 to nucleotide 332 of SEQ ID NO: 77.
From the nucleotide sequence corresponding to the NA sequence and corresponding to the 5 ′ end of the sequence from nucleotide 51 to nucleotide 332 of SEQ ID NO: 77, SEQ ID NO:
D NO: 77 comprises a nucleotide sequence extending continuously from nucleotide 51 at 77 to the nucleotide sequence corresponding to the 3 'end of the sequence at nucleotide 332.

In another embodiment, the present invention provides a composition comprising a protein, wherein the protein comprises: (a) the amino acid sequence of SEQ ID NO: 78; (b) the amino acid sequence of SEQ ID NO: 78; Amino acid 93
(C) a fragment of the amino acid sequence of SEQ ID NO: 78, wherein the fragment is
A fragment comprising the eight contiguous amino acids of Q ID NO: 78; and (d) an amino acid sequence selected from the group consisting of: (a) the amino acid sequence encoded by the cDNA insert of clone vq1_1 deposited with the ATCC under accession number 2007012; Wherein the protein is substantially free of other mammalian proteins. Preferably, such a protein comprises the amino acid sequence of SEQ ID NO: 78. In a further preferred embodiment, the present invention provides a biologically active SEQ ID NO: 7
A fragment of the amino acid sequence of 8, preferably 8 (more preferably 20
, Most preferably 30) a protein comprising a fragment comprising the amino acids of contiguous SEQ ID NO: 78, or SEQ ID NO: having biological activity:
78. A protein comprising a fragment of the amino acid sequence of SEQ ID NO: 78, comprising the amino acid sequence of amino acids 47 to 56 of SEQ ID NO: 78.

In one aspect, the present invention provides: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 79; (b) a polynucleotide comprising the nucleotide sequence of nucleotide 2 to nucleotide 1018 of SEQ ID NO: 79; c) nucleotides 53 to 1018 of SEQ ID NO: 79
(D) clone vp14_1 deposited with the ATCC under accession number 207011
A polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence encoded by the cDNA of (e) clone vp14_1 deposited with the ATCC under accession number 207011
(F) clone vp14_1 deposited with the ATCC under accession number 207011
A polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of: g) clone vp14_1 deposited at the ATCC under accession number 207011
(H) a polynucleotide that encodes a protein comprising the amino acid sequence of SEQ ID NO: 80; (i) a amino acid of SEQ ID NO: 80 that has biological activity A polynucleotide encoding a protein comprising a fragment of the sequence, the fragment comprising eight contiguous amino acids of SEQ ID NO: 80; (j) an allelic variant of the polynucleotide of (a)-(g) above. (K) a polynucleotide encoding a species homolog of the protein of the above (h) or (i); (1) any one of the polynucleotides specified in (a) to (i); A polynucleotide that hybridizes under stringent conditions; and (m) (a (I) hybridizing under stringent conditions with any one of the polynucleotides specified in (i), selected from the group consisting of polynucleotides having a length of at least 25% of the length of SEQ ID NO: 79 Compositions comprising the isolated polynucleotides provided.

Preferably, such a polynucleotide is a nucleotide sequence from nucleotide 2 to nucleotide 1018 of SEQ ID NO: 79; SEQ ID N
O: nucleotide sequence from nucleotide 53 to nucleotide 1018 at 79;
Nucleotide sequence of the full-length protein coding sequence of clone vp14_1 deposited at the TCC under accession number 207011; or accession number 2 at the ATCC
07011 contains the nucleotide sequence of the mature protein coding sequence of the clone vp14_1 deposited. In another preferred embodiment, the polynucleotide comprises the clone vp14_1 deposited with the ATCC under accession number 207011.
Encodes the full-length or mature protein encoded by the cDNA insert. In a further preferred embodiment, the present invention provides a biologically active SEQ ID
NO: 80 is a fragment of the amino acid sequence, preferably SEQ ID NO.
A polynucleotide encoding a protein comprising a fragment comprising eight (more preferably 20, most preferably 30) contiguous amino acids of NO: 80, or a fragment of the amino acid sequence of SEQ ID NO: 80 having biological activity. , SEQ ID NO: 80, comprising a fragment comprising the amino acid sequence of amino acids 164 to 173.

[0224] Another aspect provides a gene corresponding to the cDNA sequence of SEQ ID NO: 79. Further aspects of the invention include: (a) (i) at 65 ° C. in 6 × SSC: (aa) SEQ ID NO: 79, where 3 ′ of SEQ ID NO: 79
(Ab) clone vp14_ deposited at the ATCC under accession number 207011
Preparing one or more polynucleotide probes that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of one of the cDNA inserts; (ii) at least 4X SSC, as stringent conditions as 50 ° C. (B) (i) at 65 ° C. in 6XSSC at 65 ° C., wherein (ba) SEQ. ID NO: 79, but 3 'of SEQ ID NO: 79
(Bb) clone vp14_ deposited at the ATCC under accession number 207011
Preparing one or more polynucleotide primers that hybridize to a nucleotide sequence selected from the group consisting of: a nucleotide sequence of one of the cDNA inserts; (Iii) amplifying the human DNA sequence; (iv) step (b) isolating the polynucleotide product of (iii). Provided in accordance with the process.

[0225] Preferably, the polynucleotide isolated according to the above process is SE
This corresponds to the cDNA sequence of Q ID NO: 79, and corresponds to the sequence of SEQ ID NO: 79
A nucleotide sequence extending continuously from the nucleotide sequence corresponding to the 'end to the nucleotide sequence corresponding to the 3' end of SEQ ID NO: 79, but without the poly (A) tail at the 3 'end of SEQ ID NO: 79 including. Further, preferably, the polynucleotide isolated according to the above process has the SEQ ID
From the nucleotide sequence corresponding to the cDNA sequence from nucleotide 2 to nucleotide 1018 of SEQ ID NO: 79 and corresponding to the 5 'end of the sequence from nucleotide 2 to nucleotide 1018 of SEQ ID NO: 79, SEQ ID NO: 79
From nucleotide 2 to the nucleotide sequence corresponding to the 3 'end of said sequence at nucleotide 1018. Further, preferably, the polynucleotide isolated according to the above process has SEQ ID NO:
: Corresponding to the cDNA sequence from nucleotide 53 to nucleotide 1018 of 79,
5 ′ from nucleotide 53 to nucleotide 1018 of SEQ ID NO: 79
It comprises a nucleotide sequence extending continuously from the nucleotide sequence corresponding to said terminal sequence to the nucleotide sequence corresponding to the 3 'end of said sequence at nucleotide 1018 from nucleotide 53 of SEQ ID NO: 79.

In another aspect, the invention provides a composition comprising a protein, wherein the protein is: (a) an amino acid sequence of SEQ ID NO: 80; (b) a fragment of the amino acid sequence of SEQ ID NO: 80. Oh, SE
A fragment comprising the eight contiguous amino acids of Q ID NO: 80; and (c) clone vp14_1 deposited with the ATCC under accession number 207011.
Wherein said protein is substantially free of other mammalian proteins. Preferably such a protein is SEQ.
Contains the amino acid sequence of ID NO: 80. In a further preferred embodiment, the present invention relates to a fragment of the amino acid sequence of SEQ ID NO: 80 having biological activity, preferably of 8 (more preferably 20, most preferably 30) of the contiguous SEQ ID NO: 80. A protein comprising a fragment comprising an amino acid, or a fragment of the amino acid sequence of SEQ ID NO: 80 having biological activity, wherein the fragment is a fragment having the amino acid sequence of SEQ ID NO: 80.
A protein comprising a fragment comprising the amino acid sequence of

In one preferred embodiment, the polynucleotide is operably linked to an expression control sequence. The present invention further provides host cells, including bacteria, yeast, insect and mammalian cells, transformed with such polynucleotide compositions. Further, the present invention also provides an organism having improved, reduced or modified expression of a gene corresponding to the polynucleotide sequence disclosed herein.

(A) growing a culture of such host cells transformed with the napolynucleotide composition in a suitable medium; (b) a method for producing a protein, comprising purifying the protein from the medium. Is also provided. A protein produced according to such a method is also provided by the present invention.

[0229] The protein compositions of the present invention can further include a pharmaceutically acceptable carrier. Compositions comprising antibodies that specifically react with such proteins are also provided by the present invention. Also provided is a method of preventing, treating or ameliorating a medical condition comprising administering to a mammalian patient a therapeutically effective amount of a composition comprising a protein of the present invention and a pharmaceutically acceptable carrier.

BRIEF DESCRIPTION OF THE DRAWINGS FIGS. 1A and 1B are schematic diagrams showing the pED6 and pNOTs vectors, respectively, used for depositing the clones disclosed herein.

Isolated Proteins and Polynucleotides The nucleotide and amino acid sequences as currently determined are set forth below for each clone and protein disclosed in this application. The nucleotide sequence of each clone can be readily determined by sequencing the deposited clones according to known methods. The predicted amino acid sequence (both full-length and mature forms) can then be determined from such nucleotide sequence.
The amino acid sequence of a protein encoded by a particular clone can also be determined by expressing the clone in a suitable host cell, collecting the protein, and determining the sequence. For each protein disclosed, Applicants identified what they determined to be the best discriminating reading frame by the 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 across a membrane and as a result of a signal sequence in its amino acid sequence. Including transportation. "Secreted" proteins include, but are not limited to, proteins that are completely (eg, soluble proteins) or partially (eg, receptors) secreted from the cells in which they are expressed. "Secreted" proteins also include, without limitation, proteins that are transported across the endoplasmic reticulum membrane.

Clone "vb11_1" The polynucleotide of the present invention has been identified as clone "vb11_1".
vb11_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vb11_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vb11_1 protein).

The currently determined nucleotide sequence of vb11_1 is SEQ ID NO:
: 1 and contains a poly (A) tail. What applicants believe is the current valid reading frame and the predicted amino acid sequence of the vb11_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 2. Other potential vb11_1 reading frames and predicted amino acid sequences that can be encoded by base pairs 84 to 236 of SEQ ID NO: 1 are reported in SEQ ID NO: 121. SEQ ID N
Amino acids 13 to 25 of O: 121 are the predicted leader / signal sequence, and the predicted mature amino acid sequence starts at amino acid 26 of SEQ ID NO: 121. Due to the hydrophobic nature of the predicted leader / signal sequence, if it does not separate from the rest of the protein of SEQ ID NO: 121, it probably serves as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vb11_1 should be approximately 1751 bp.

The nucleotide sequences disclosed herein for vb11_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vb11_1
Corresponds to N94870 (yy63b05.r1 homosapiens cDNA clone 278)
It showed at least some similarity with the sequence identified as 193 5 '). Based on sequence similarity, the vb11_1 proteins and respective similar proteins or peptides will share at least some activity. TopPr
edII computer program identifies potential transmembrane domains with SEQ ID
Predicted within the vb11_1 protein sequence centered around amino acid 27 of NO: 2.

Clone "vb12_1" The polynucleotide of the present invention has been identified as clone "vb12_1".
vb12_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vb12_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as vb12_1 protein).

The nucleotide sequence of vb12_1 that has been determined is SEQ ID NO:
: 3, containing a poly (A) tail. What applicants believe is the current valid reading frame and the predicted amino acid sequence of the vb12_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 4. Amino acids 34 to 46 of SEQ ID NO: 4 are the predicted leader / signal sequence, with the predicted mature amino acid sequence beginning at amino acid 47. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vb12_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vb12_1 should be approximately 2289 bp.

The nucleotide sequences disclosed herein for vb12_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vb12_1
Means AA42609 (zw49e11.s1 Soares whole fetus Nb2HF8
9w Homo sapiens cDNA clone 773420 3 ', mRNA sequence). Based on sequence similarity, the vb12_1 proteins and respective similar proteins or peptides will share at least some activity. The TopPredII computer program is based on amino acids 11, 60, and 10 of SEQ ID NO: 4.
3 additional potential transmembrane domains, each centered around 4,
Predict inside the 2_1 protein sequence. The nucleotide sequence of vb12_1 suggests that it will contain a THE1B repeat sequence.

The vb12_1 protein was expressed in the COS cell expression system, and a band of the expressed protein of approximately 17 kDa was detected in the membrane fraction using SDS polyacrylamide gel electrophoresis.

Clone "vb14_1" The polynucleotide of the present invention has been identified as clone "vb14_1".
vb14_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vb14_1 is a full-length clone and contains the entire coding sequence of a secreted protein (also referred to herein as vb14_1 protein).

The nucleotide sequence of vb14_1 that is currently determined has the SEQ ID NO:
: 5, containing a poly (A) tail. What applicant believes to be the current valid reading frame and the predicted amino acid sequence of the vb14_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 6. Amino acids 79 to 91 of SEQ ID NO: 6 are the predicted leader / signal sequence, with the predicted mature amino acid sequence beginning at amino acid 92. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vb14_1 protein, it probably acts as a transmembrane domain. SEQ ID NO:
Other potential vb14_ that can be encoded by 5 base pairs 182 to 484
1 Reading frame and predicted amino acid sequence are as shown in SEQ ID NO:
122.

The EcoRI / NotI restriction fragment from the deposit containing clone vb14_1 should be approximately 2377 bp.

The nucleotide sequences disclosed herein for vb14_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vb14_1
Is at least AF007149 (Homo sapiens clone 23568, 2362)
1, 23795, 23873 and 23874 mRNA sequences), AF07061
2 (Homo sapiens clone 24771 mRNA sequence), T23635 (human gene signature HUMGS05495; standard; from cDNA to mRNA), and W
02197 (za57e04.r1 Soares fetal liver spleen 1NFLS homosapiens cDNA clone 296670 5 ', mRNA sequence) showed some similarity to the sequence identified. Based on sequence similarity, the vb14_1 proteins and respective similar proteins or peptides will share at least some activity.

Clone "ve11_1" The polynucleotide of the present invention has been identified as clone "ve11_1".
vb11_1 is isolated from a human adult brain (Alzheimer's hippocampus level 7) cDNA library and encodes a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. Identified. ve11_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as ve11_1 protein).

The currently determined nucleotide sequence of ve11_1 is as shown in SEQ ID NO:
: 7, containing a poly (A) tail. What applicants believe is currently the valid reading frame and the predicted amino acid sequence of the ve11_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 8. Amino acids 1-9 of SEQ ID NO: 8 are the predicted leader / signal sequences, with the predicted mature amino acid sequence beginning at amino acid 10. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the ve11_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone ve11_1 should be approximately 984 bp.

The nucleotide sequences disclosed herein for ve11_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. ve11_1
Is F22745 (Homo sapiens EST sequence from skeletal muscle (LL45 / C09);
mRNA sequence) and Q60824 (Human Brain Expressed Sequence)
e Tag (expressed sequence tag) EST00928; standard; DNA) showed at least some similarity to the identified sequence. Based on sequence similarity, ve11
The —1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program predicts a potential transmembrane domain within the ve11_1 protein sequence centered around amino acid 35 of SEQ ID NO: 8.

Clone "vf2_1" The polynucleotide of the present invention has been identified as clone "vf2_1". v
f2_1 was isolated from a human adult cardiac cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vf2_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as vf2_1 protein).

The nucleotide sequence of vf2_1 that has been determined is SEQ ID NO:
9 and contains a poly (A) tail. What applicants believe is the current valid reading frame and the predicted amino acid sequence of the vf2_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 10. Amino acids 20 to 32 of SEQ ID NO: 10 are the predicted leader / signal sequence, with the predicted mature amino acid sequence beginning at amino acid 33. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vf2_1 protein, it probably serves as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vf2_1 should be approximately 1162 bp.

The nucleotide sequences disclosed herein for vf2_1 are BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. vf2_1 is A
A605037 (no68h10.s1 NCI_CGAP_AA1 Homo sapiens cDNA clone IMAGE: 1112035, similar to containing Alu repeat element; including element THR repeat element; mRNA sequence) showed at least some similarity to the sequence identified. Based on sequence similarity, vf
The 2_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program vf two potential transmembrane domains centered around amino acid 30 of SEQ ID NO: 10 and the other around amino acid 70.
Predict inside the 2_1 protein sequence. The nucleotide sequence of vf2_1 suggests that it will contain an Alu repeat element.

Clone "vg2_1" The polynucleotide of the present invention has been identified as clone "vg2_1". v
g2_1 was isolated from a human adult brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vg2_1 is a full-length clone and contains the entire coding sequence of a secreted protein (also referred to herein as the vg2_1 protein).

The nucleotide sequence of vg2_1 that has been determined is SEQ ID NO:
11 and contains a poly (A) tail. What applicants believe is the current valid reading frame and the predicted amino acid sequence of the vg2_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 12. Amino acids 34 to 46 of SEQ ID NO: 12 are the predicted leader / signal sequence, with the predicted mature amino acid sequence beginning at amino acid 47. Due to the hydrophobic nature of the predicted leader / signal sequence, if it does not separate from the rest of the vg2_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vg2_1 should be approximately 1993 bp.

The nucleotide sequence disclosed herein for vg2_1 is BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. vg2_1 is A
A830272 (oc similar to TR Q92953 Q92253 HU-K4
45g11. It showed at least some similarity with the sequences identified as s1 NCI_CGAP_GCB1 homosapiens cDNA clones IMAGE1352708 3 ′; mRNA sequence) and D31740 (homosapiens DNA, CpG island). The predicted amino acid sequence disclosed herein for vg2_1 is GenP
ept and GeneSeq amino acid sequence databases were searched using the BLASTX search protocol. The predicted vg2_1 protein is AF0
26124 (Schwannoma-related protein [Mus musculus]) and U60644 (
HU-K4 [Homo sapiens]) showed at least some similarity to the sequence identified. Based on sequence similarity, the vg2_1 protein and each similar protein or peptide will share at least some activity. Predicted vg2_1 protein profile hiding Markov model analysis (Ed
dy, SR, 1996, Curr. Opin. Struct. Biol. 6 (3): 361-365; incorporated herein by reference) has two phospholipase D active sites (SEQ ID
NO: 12 amino acid residues 209 to 236 and 423 to 449) were revealed. The phospholipase D (PLD) gene is a member of the superfamily defined by several highly conserved motifs. In mammals, phospholipase D has been proposed to play a role in membrane vesicle trafficking and signaling. Using site-directed mutagenesis, 25 position mutants were created in human PLD1 (hPLD1) and then characterized (S
ung et al., 1997, EMBO J. 16 (15): 4519-4530: incorporated herein by reference). Describe certain motifs (HxKxxxxD; see, for example, amino acids 214 to 221 of SEQ ID NO: 12) and serine / threonine that are conserved in all members of the PLD superfamily and are critical for the biological activity of PLD. We found this and proposed a possible catalytic mechanism. vg2
The —1 clone appears to encode a membrane protein that may be a phospholipase related to the phospholipase D family. The TopPredII computer program comprises amino acids 40, 305, 330 of SEQ ID NO: 12,
And four potential transmembrane domains, each centered around 455 and v
Predicted inside g2_1 protein sequence.

Clone "vj1_1" The polynucleotide of the present invention has been identified as clone "vj1_1". v
j1_1 is isolated from a human fetal brain cDNA library (enriched for G protein-coupled receptors) and secreted or transmembrane based on computer analysis of the amino acid sequence of the protein it encodes. Was encoded. vj1_1 is a full-length clone and contains the entire coding sequence of a secreted protein (also referred to herein as vj1_1 protein).

The currently determined nucleotide sequence of vj1_1 is SEQ ID NO:
13 What applicants believe is the current valid reading frame and the predicted amino acid sequence of the vj1_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 14.
Amino acids 1 to 12 of SEQ ID NO: 14 are the predicted leader / signal sequences, with the predicted mature amino acid sequence beginning at amino acid 13.
Due to the hydrophobic nature of the predicted leader / signal sequence, if the predicted leader / signal sequence is not separated from the rest of the vj1_1 protein,
It probably acts as a transmembrane domain. Base pair 17 at SEQ ID NO: 13
Other potential vj1_1 reading frames and predicted amino acid sequences that can be encoded by 95-2064 are reported in SEQ ID NO: 123.

The EcoRI / NotI restriction fragment from the deposit containing clone vj1_1 should be approximately 2895 bp.

The nucleotide sequences disclosed herein for vj1_1 are BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. vj1_1 is A
It showed at least some similarity to the sequence identified as A410352 (zv11f01.r1 Soares NhHMPU S1 homosapiens cDNA clone 7553337 5 ′, mRNA sequence). Based on sequence similarity, vj
The 1_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program predicts one potential transmembrane domain within the vj1_1 protein sequence centered around amino acid 70 of SEQ ID NO: 14.
The nucleotide sequence of vj1_1 suggests that it will contain repetitive elements.

Clone "v11_1" The polynucleotide of the present invention has been identified as clone "v11_1". v
11_1 has been isolated from a human fetal cartilage cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. v11_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as v11_1 protein).

The nucleotide sequence of v11_1 currently determined is SEQ ID NO:
15 and contains a poly (A) tail. What applicants believe is the current valid reading frame and the predicted amino acid sequence of the v11_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 16. Amino acids 187 to 199 of SEQ ID NO: 16 are the predicted leader / signal sequences, and the predicted mature amino acid sequence is amino acid 2
It starts from 00. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the v11_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment obtained from the deposit containing clone v11_1 should be approximately 1936 bp.

The nucleotide sequences disclosed herein for v11_1 have BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. v11_1 is A
A463362 (zx81b12.r1 Sales Ovarian tumor NbHOT homosapiens cDNA clone 810143 5 ', mRNA sequence), M90089 (
Mouse inositol 1,4,5-triphosphate receptor mRNA sequence), and T2
1689 (human gene signature HUMGS03131; standard; cDNA to mRN
At least some similarity with the sequence identified as A). vl1_1
The predicted amino acid sequences disclosed herein against GenPept and GenPent
The eSeq amino acid sequence database was searched using the BLASTX search protocol. The predicted v11_1 protein is U80846 (partial CD
S [C. Elegance]) showed at least some similarity to the sequence identified as Based on sequence similarity, the v11_1 protein and each similar protein or peptide will share at least some activity. To
The pPredII computer program has one, SEQ ID NO: 16
Predicts two additional potential transmembrane domains centered around amino acid 192 and the other around amino acid 234 within the v11_1 protein sequence.

The v11_1 protein is expressed in the COS cell expression system and is approximately 37 kD
The band of the expressed protein in a was detected in the membrane fraction using SDS polyacrylamide gel electrophoresis.

Clone "vk2_1" The polynucleotide of the present invention has been identified as clone "vk2_1". v
k2_1 is isolated from a human adult brain cDNA library (enriched for G protein-coupled receptors) and secreted or transmembrane proteins based on computer analysis of the amino acid sequence of the protein it encodes. Was encoded. vk2_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vk2_1 protein).

The currently determined nucleotide sequence of vk2_1 is SEQ ID NO:
17 and contains a poly (A) tail. What applicants believe is the current valid reading frame and the predicted amino acid sequence of the vk2_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 18. Amino acids 10 to 22 of SEQ ID NO: 18 are the predicted leader / signal sequences, with the predicted mature amino acid sequence beginning at amino acid 23. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vk2_1 protein, it probably serves as a transmembrane domain. SEQ ID NO:
Seventeen base pairs 416 to 418 would represent a site of an alternatively spliced exon that is not present in clone vk2_1.

The EcoRI / NotI restriction fragment from the deposit containing clone vk2_1 should be approximately 1284 bp.

The nucleotide sequences disclosed herein for vk2_1 are BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. vk2_1 is A
A152101 (zl49f09.s1 Soares pregnant uterine NbHPU homosapiens cDNA clone 505289 3 ', mRNA sequence) and Q786
It showed at least some similarity to the sequence identified as 96 (sequence encoding a therapeutic polypeptide from a neuroglioblastoma cell line; standard; from cDNA to mRNA). The predicted amino acid sequences disclosed herein for vk2_1 are BLA against the GenPept and GeneSeq amino acid sequence databases.
Searched using the STX search protocol. The predicted vk2_1 protein showed at least some similarity to the sequence identified as R66278 (therapeutic polypeptide from a glioblastoma cell line). Based on sequence similarity,
The 2_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program predicts two additional potential transmembrane domains centered around amino acid 61 of SEQ ID NO: 18 and the other around amino acid 97 within the vk2_1 protein sequence, one around amino acid 97. .

Clone "vb21_1" The polynucleotide of the present invention has been identified as clone "vb21_1".
vb21_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vb21_1 is a full-length clone that contains the entire coding sequence of a secreted protein (also referred to herein as the vb21_1 protein).

The currently determined nucleotide sequence of vb21_1 is SEQ ID NO:
: 19, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vb21_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 20.
Has been reported to. Amino acids 296-308 of SEQ ID NO: 20 are the predicted leader / signal sequences, with the predicted mature amino acid sequence beginning at amino acid 309. Due to the hydrophobic nature of the predicted leader / signal sequence, if it does not separate from the rest of the vb21_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vb21_1 should be approximately 4159 bp.

The nucleotide sequences disclosed herein for vb21_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vb21_1
Is AA026150 (zj99c10.s1 Soares pregnant uterus NbHPU
Homo sapiens cDNA clone 469170 3 ', mRNA sequence), T721
08 (human semaphorin Z gene; standard; from cDNA to mRNA), U5284
0 (human semaphorin F homolog), X97817 (house mouse mRNA for semaphorin F) and X97818 (house mouse mRNA for semaphorin G)
Showed at least some similarity to the sequence identified as The predicted amino acid sequences disclosed herein for vb21_1 are GenPept and GeneSe
The q amino acid sequence database was searched using the BLASTX search protocol. The predicted vb21_1 protein showed at least some similarity to the sequences identified as W19857 (human semaphorin Z) and X97818 (semaphorin G [house mouse]). Semaphorin is an important membrane protein involved in embryonic axonal guidance and may also play a role in nerve regeneration after injury. Based on sequence similarity, the vb21_1 proteins and respective similar proteins or peptides will share at least some activity. The TopPredII computer program has SEQ ID NO: 20
Four additional potential transmembrane domains, centered around amino acids 237, 523, 769, and 895, respectively, are predicted within the vb21_1 protein sequence.

Clone "vc35_1" The polynucleotide of the present invention has been identified as clone "vc35_1". vc35_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc35_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as vc35_1 protein).

The nucleotide sequence of vc35_1 currently determined is SEQ ID NO:
: 21, containing a poly (A) tail. What applicants believe is currently the valid reading frame and the predicted amino acid sequence of the vc35_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 22.
Has been reported to. Amino acids 38-50 of SEQ ID NO: 22 are the predicted leader / signal sequences, and the predicted mature amino acid sequence is amino acid 5
Starting from 1. Because of the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vc35_1 protein, it will likely act as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc35_1 should be approximately 3042 bp.

The nucleotide sequence disclosed herein for vc35_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc35_1
Is AA532364 (nj12a08.s1 NCI_CGAP_Pr22 homosapiens cDNA clone IMAGE: 986102, mRNA sequence), AF
0293343 (human protocadherin 68) and T22263 (human gene signature HUMGS03835; standard; from cDNA to mRNA) showed at least some similarity. The predicted amino acid sequence disclosed herein for vc35_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc35_1 protein showed at least some similarity with the sequence identified as Y08715 (protocadherin-4 [house mouse]). Based on sequence similarity, the vc35_1 protein and each similar protein or peptide will share at least some activity.

Clone "vc36_1" The polynucleotide of the present invention has been identified as clone "vc36_1". vc36_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc36_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc36_1 protein).

The nucleotide sequence of vc36_1 that is currently determined has the SEQ ID NO:
: 23, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vc36_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 24.
Has been reported to. Amino acids 24-36 of SEQ ID NO: 24 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 3
Starting from 7. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vc36_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc36_1 should be approximately 1395 bp.

The nucleotide sequence disclosed herein for vc36_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc36_1
Are AA259070 (zs33c04.r1 NCI_CGAP_GCB1 homosapiens cDNA clone IMAGE686982, mRNA sequence) and W
67508 (zd40f11.sl Soares fetal heart NbHH19W homosapiens cDNA clone 343149 3 ', mRNA sequence) showed at least some similarity to the sequence identified. Based on sequence similarity, vc3
The 6_1 protein and each similar protein or peptide will share at least some activity. The nucleotide sequence of vc36_1 will contain repetitive elements.

Clone "vc38_1" The polynucleotide of the present invention has been identified as clone "vc38_1". vc38_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc38_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc38_1 protein).

The nucleotide sequence of vc38_1 that is currently determined is as shown in SEQ ID NO:
: 25, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vc38_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 26.
Has been reported to.

The EcoRI / NotI restriction fragment from the deposit containing clone vc38_1 should be approximately 2468 bp.

The nucleotide sequence disclosed herein for vc38_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc38_1
Is AF037400 (neuropeptide Y / peptide YY receptor Ya [Danio rer
io]) showed at least some similarity to the sequence identified as Predicted v
Both the motif analysis of the c38_1 protein and the analysis of the profile-hidden Markov model revealed the presence of the G protein-coupled receptor signature. G protein-coupled receptors (also called R7G) are a broad group of hormones, neurotransmitters,
An odorant, a receptor for light, that transmits extracellular signals by interacting with guanine nucleotide binding (G) proteins. Most G protein-coupled receptors are
Like the predicted vc38_1, lacks the signal peptide. Based on sequence similarity, the vc38_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program comprises amino acids 60, 90, 1 of SEQ ID NO: 26.
Seven potential transmembrane domains centered around 30, 170, 225, 280, and 318 are predicted within the vc38_1 protein sequence.

The vc38_1 protein is expressed in the COS cell expression system and
The band of the expressed protein of Da was detected in the conditioned medium using SDS polyacrylamide gel electrophoresis.

Clone "vc39_1" The polynucleotide of the present invention has been identified as clone "vc39_1". vc39_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc39_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc39_1 protein).

The nucleotide sequence of vc39_1 currently determined is SEQ ID NO:
: 27, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vc39_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 28.
Has been reported to. Amino acids 2 to 14 of SEQ ID NO: 28 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 15
Starting from. Due to the predicted hydrophobic nature of the leader / signal sequence,
If its predicted leader / signal sequence is not separated from the rest of the vc39_1 protein, it will likely act as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc39_1 should be approximately 2048 bp.

The nucleotide sequence disclosed herein for vc39_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc39_1
Is AA631722 (gb: M21121 T-CELL SPECIFIC)
Np similar to RANTES PROTEIN PRECURSOR (HUMAN)
79d04. sl NCI_CGAP_Pr2 homo sapiens cDNA clone IMAGE: 1132519; containing Alu repeat elements; mRNA sequence). Based on sequence similarity, the vc39_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program predicts a potential transmembrane domain within the vc39_1 protein sequence centered around amino acid 40 of SEQ ID NO: 28. The nucleotide sequence of vc39_1 suggests that it will contain an Alu / SVA repeat element.

Clone "vc40_1" The polynucleotide of the present invention has been identified as clone "vc40_1". vc40_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc40_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc40_1 protein).

The currently determined nucleotide sequence of vc40_1 is SEQ ID NO:
: 29, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vc40_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 30.
Has been reported to. Amino acids 19 to 31 of SEQ ID NO: 30 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 3
Starting from 2. Because of the hydrophobic nature of the predicted leader / signal sequence, if it does not separate from the rest of the vc40_1 protein, it will likely act as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc40_1 should be approximately 2297 bp.

The nucleotide sequences disclosed herein for vc40_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc40_1
Is AA143014 (zl48g04.rl Soares pregnant uterus NbHPU
Homo sapiens cDNA clone 505206 5 ', mRNA) and T20
006 (human gene signature HUMGS01143; standard; mRNA from cDNA
And at least some similarity to the sequence identified as Based on sequence similarity, the vc40_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program is based on amino acids 101, 136 of SEQ ID NO: 30.
, And three additional potential transmembrane domains, each centered around 182, are predicted within the vc40_1 protein sequence.

Clone "vc46_1" The polynucleotide of the present invention has been identified as clone "vc46_1". vc46_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc46_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc46_1 protein).

The nucleotide sequence of vc46_1 that has been determined is SEQ ID NO:
: 31, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vc46_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 32.
Has been reported to. Amino acids 10 to 22 of SEQ ID NO: 32 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 2
Starting from 3. Due to the hydrophobic nature of the predicted leader / signal sequence, if it does not separate from the rest of the vc46_1 protein, it will likely act as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc46_1 should be approximately 2938 bp.

The nucleotide sequence disclosed herein for vc46_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc46_1
Is AA029404 (ze94e06.rl Soares fetal heart NbHH1
9W Homo sapiens cDNA clone 366658 5 ', mRNA) and A
It showed at least some similarity to the sequence identified as Q071029 (human genomic fragment). Based on sequence similarity, the vc46_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program has one of SEQ ID N
O: predicts two additional potential transmembrane domains centered around amino acid 70 of 32 and the other around amino acid 130, respectively, within the vc46_1 protein sequence.

The vc46_1 protein is expressed in the COS cell expression system and
The band of the expressed protein of Da was detected in the conditioned medium and in the membrane fraction using SDS polyacrylamide gel electrophoresis.

Clone "vc49_1" The polynucleotide of the present invention has been identified as clone "vc49_1". vc49_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc49_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc49_1 protein).

[0302] The nucleotide sequence of vc49_1 currently determined is SEQ ID NO:
: 33, containing a poly (A) tail. What applicant believes to be the current valid reading frame and the predicted amino acid sequence of the vc49_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 34.
Has been reported to. Amino acids 14 to 26 of SEQ ID NO: 34 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 2
Starting from 7. Because of the hydrophobic nature of the predicted leader / signal sequence, if it does not separate from the rest of the vc49_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc49_1 should be approximately 3471 bp.

The nucleotide sequences disclosed herein for vc49_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc49_1
Is AI07929 (TR Q63418 Q63418 PROTOCADH
Ov46h11 similar to ERIN-3. x1 Soares_testis_NHT homosapiens cDNA clone IMAGE1640421 3 ′; mRNA sequence)
, I79964 (sequence 109 from US Pat. No. 5,708,143), and T03.
572 (human protocadherin pc3 coding sequence; standard; cDNA) showed at least some similarity to the sequence identified. The predicted amino acid sequence disclosed herein for vc49_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol.
The predicted vc49_1 protein is L43592 (protocadherin-3 [Ratt
us norvegicus] and R86865 (human protocadherin pc3) showed at least some similarity. Based on sequence similarity, vc
The 49_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program has two potentials, one potential transmembrane domain centered around amino acid 700 of SEQ ID NO: 34 and another potential transmembrane domain centered at amino acid 260. Transmembrane domain is vc49_
Predicts within one protein sequence. Profile concealed Markov model and motif analysis of the predicted vc49_1 protein is shown in SEQ ID NO: 34.
Amino acids 142 to 242, 251 to 347, 356 to 451, 460 to 561, and 576 to 671 contain five cadherin extracellular repeat domain signatures. Cadherins are a family of animal glycoproteins responsible for calcium-dependent cell-cell adhesion. Cadherin interacts with itself in a predominantly homophilic manner in cell attachment; thus, it behaves as both a receptor and a ligand. Structurally, cadherin is composed of the following domains: a signal sequence, followed by a propeptide of approximately 130 residues, then an extracellular domain of about 600 residues, then a transmembrane domain, and finally approximately 150 residue C-terminal cytoplasmic domain. The sequence of the predicted vc49_1 protein almost strictly follows this structure (its cytoplasmic domain is nearly 100
Amino acids). Apparently, the vc49_1 protein appears to represent a new member of the cadherin superfamily.

Clone "vc50_1" The polynucleotide of the present invention has been identified as clone "vc50_1". vc50_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc50_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc50_1 protein).

The nucleotide sequence of vc50_1 currently determined is SEQ ID NO:
: 35, containing a poly (A) tail. What applicant believes to be the current valid reading frame and the predicted amino acid sequence of the vc50_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 36.
Has been reported to. Amino acids 20-32 of SEQ ID NO: 36 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 3
Starting from 3. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vc50_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc50_1 should be approximately 3819 bp.

The nucleotide sequence disclosed herein for vc50_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc50_1
Is AA193122 (zr39d05.r1 SoaresNhHMPU S1
Homo sapiens cDNA clone 665768 5 ', mRNA sequence), T26
031 (human gene signature HUMGS08267; standard; mRNA from cDNA
), Z31718 (Homo sapiens gene against myelin protein zero)
, And Z99943 (human DNA from PAC313L4 on chromosome 1q24)
Sequence)). The predicted amino acid sequence disclosed herein for vc50_1 is GenPept and Gene.
The Seq amino acid sequence database was searched using the BLASTX search protocol. The predicted vc50_1 protein was K03242 (rat P0
Myelin pre-peptide), L24893 (myelin protein zero [Homo sapiens]), and M62860 (mouse peripheral myelin protein). Based on sequence similarity, vc50_
One protein and each similar protein or peptide will share at least some activity. The TopPredII computer program further predicts one potential transmembrane domain within the vc50_1 protein sequence centered around amino acid 181 of SEQ ID NO: 36.

The vc50_1 protein is expressed in the COS cell expression system and is approximately 26k
The band of the expressed protein of Da was detected in the membrane fraction using SDS polyacrylamide gel electrophoresis.

Clone "vc51_1" The polynucleotide of the present invention has been identified as clone "vc51_1". vc51_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc51_1 is a full-length clone and contains the entire coding sequence of a secreted protein (also referred to herein as the vc51_1 protein).

The nucleotide sequence of vc51_1 that has been determined is SEQ ID NO:
: 37, containing a poly (A) tail. What applicant believes to be the currently relevant reading frame and the predicted amino acid sequence of the vc51_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 38.
Has been reported to. Amino acids 12 to 24 of SEQ ID NO: 38 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 2
Starting from 5. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vc51_1 protein, it probably acts as a transmembrane domain. If SEQ ID
If the "G" residue at position 388 of NO: 37 was deleted, two alternative potential reading frames and base pairs 333 to 1310 of SEQ ID NO: 37 and SEQ ID NO: 37 The predicted amino acid sequence as encoded by base pairs 139-522 of SEQ ID NO:
: 124 and SEQ ID NO: 125.

The EcoRI / NotI restriction fragment from the deposit containing clone vc51_1 should be approximately 1992 bp.

The nucleotide sequence disclosed herein for vc51_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc51_1
Are T21514 (human gene signature HUMGS02887; standard; from cDNA to mRNA) and W52782 (zd13h06.r1 Soares fetal heart NbHH19W homosapiens cDNA clone 340571 5 ', mRN
A sequence) and at least some similarity. vc51_1
The predicted amino acid sequences disclosed herein against GenPept and GenPent
The eSeq amino acid sequence database was searched using the BLASTX search protocol. The predicted vc51_1 proteins are U90716 (human cell surface protein HCAR), Y07593 (Coxsackie and adenovirus receptor proteins [Homo sapiens]), Y10320 (mouse Coxsackie and adenovirus receptor homologs), and W14146 (human A33 antigen). ) Showed at least some similarity to the sequence identified as Based on sequence similarity,
The c51_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program comprises amino acids 17, 216, 260 of SEQ ID NO: 38,
And four additional potential transmembrane domains, each centered around 373, are predicted within the vc51_1 protein sequence.

Clone "vc52_1" The polynucleotide of the present invention has been identified as clone "vc52_1". vc52_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc52_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc52_1 protein).

The nucleotide sequence of vc52_1 that has been determined is SEQ ID NO:
: 39, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vc52_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 40.
Has been reported to. Amino acids 19 to 31 of SEQ ID NO: 40 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 3
Starting from 2. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vc52_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc52_1 should be approximately 2018 bp.

The nucleotide sequences disclosed herein for vc52_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc52_1
Is AA075627 (zm89a01.s1 Stratagene ovarian tumor (
# 937219) Homo sapiens cDNA clone 545064 3 ', mRN
A sequence) and T24879 (human gene signature HUMGS06985; standard; c
(From DNA to mRNA). The predicted amino acid sequence disclosed herein for vc52_1 is GenP
ept and GeneSeq amino acid sequence databases were searched using the BLASTX search protocol. The predicted vc52_1 protein is AL
021890 (A putative protein [Arabidopsis thaliana]), L47993 (ORF
YJR072c [Saccharomyces cerevisiae]), and U10402 (Caenorhabditis elegans) and at least some similarity with the sequences identified. Based on sequence similarity, the vc52_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program predicts one potential transmembrane domain within the vc52_1 protein centered around amino acid 145 of SEQ ID NO: 40.

The vc52_1 protein is expressed in the COS cell expression system and
The band of the expressed protein of Da was detected in the conditioned medium and the membrane fraction using SDS polyacrylamide gel electrophoresis.

Clone "vc33_1" The polynucleotide of the present invention has been identified as clone "vc33_1". vc33_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc33_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc33_1 protein).

The nucleotide sequence of vc33_1 currently determined is SEQ ID NO:
: 41, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vc33_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 42.
Has been reported to. Amino acids 99-111 of SEQ ID NO: 42 are the predicted leader / signal sequence, with the predicted mature amino acid sequence beginning at amino acid 112. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vc33_1 protein, it will likely act as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc33_1 should be approximately 2877 bp.

The nucleotide sequences disclosed herein for vc33_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc33_1
Is AA846599 (gb: M95549 SODIUM / GLUCOSE C)
Aj97g similar to OTRANSPORTER-LIKE (HUMAN) 02.
Soares parathyroid tumor NbHPA homosapiens cDNA clone IMAG
E: 1404434 3 ', mRNA sequence), M95549 (sodium homosapiens / glucose cotransporter-like protein mRNA, complete cds), and Q8
It showed at least some similarity with the sequence identified as 9779 (cotransporter protein SNST1 cDNA; standard; cDNA). The predicted amino acid sequence disclosed herein for vc33_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc33_1 protein showed at least some similarity to the sequences identified as M95549 (sodium / glucose cotransporter-like protein [Homo sapiens]) and R73593 (cotransporter protein SNST1). Based on sequence similarity, the vc33_1 protein and each similar protein or peptide will share at least some activity. Top
The PredII computer program predicts three additional potential transmembrane domains, centered around amino acids 186, 260, and 324 of SEQ ID NO: 42, respectively, within the vc33_1 protein.

The vc33_1 protein is expressed in the COS cell expression system and
The band of the expressed protein of Da was detected in the membrane fraction using SDS polyacrylamide gel electrophoresis.

Clone "vc34_1" The polynucleotide of the present invention has been identified as clone "vc34_1". vc34_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc34_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as vc34_1 protein).

[0325] The nucleotide sequence of vc34_1 that is currently determined is SEQ ID NO:
: 43, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vc34_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 44.
Has been reported to. Amino acids 4 to 16 of SEQ ID NO: 44 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 17
Starting from. Due to the predicted hydrophobic nature of the leader / signal sequence,
If the predicted leader / signal sequence is not separated from the rest of the vc34_1 protein, it will likely act as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc34_1 should be approximately 3062 bp.

The nucleotide sequence disclosed herein for vc34_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc34_1
Showed at least some similarity to the sequences identified as AA927558 (om71e04.s1 NCI_CGAP_GC4 homosapiens cDNA clone IMAGE15552638 3 ', mRNA sequence) and U79281 (human clone 23588 mRNA sequence). Based on sequence similarity, the vc34_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program reports two additional potential transmembrane domains, one centered around amino acid 251 of SEQ ID NO: 44 and the other around amino acid 283, respectively.
Predicted inside the c34_1 protein sequence.

The vc34_1 protein is expressed in the COS cell expression system and
The band of the expressed protein of Da was detected using SDS polyacrylamide gel electrophoresis in the conditioned medium.

Clone "vc47_1" The polynucleotide of the present invention has been identified as clone "vc47_1". vc47_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc47_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc47_1 protein).

[0330] The nucleotide sequence of vc47_1 currently determined is SEQ ID NO:
: 45, containing a poly (A) tail. What applicants believe is currently the valid reading frame and the predicted amino acid sequence of the vc47_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 46.
Has been reported to. Amino acids 93 to 105 of SEQ ID NO: 46 are the predicted leader / signal sequence, with the predicted mature amino acid sequence beginning at amino acid 106. Due to the hydrophobic nature of the predicted leader / signal sequence, if it does not separate from the rest of the vc47_1 protein, it probably acts as a transmembrane domain. SEQ ID
NO: 45. Another potential vc47_1 reading frame and predicted amino acid sequence that could be encoded by base pairs 1047 through 1322 at SEQ ID NO:
ID NO: 126. Amino acids 11 to 23 of SEQ ID NO: 126 are the 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, if the predicted leader / signal sequence
If not separated from the rest of the protein of ID NO: 126, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc47_1 should be approximately 3676 bp.

The nucleotide sequence disclosed herein for vc47_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc47_1
Is AA339320 (EST44392 fetal brain I homosapiens cDNA 5 ′)
End, mRNA sequence) and at least some similarity to the sequence identified as R02462 (ye82h04.r1 homosapiens cDNA clone 124279 5 '). Based on sequence similarity, the vc47_1 proteins and each similar protein or peptide will share at least some activity. The nucleotide sequence of vc47_1 has been suggested to include one or more of the following repeating elements: Alu, L1MB7.

Clone "vc54_1" The polynucleotide of the present invention has been identified as clone "vc54_1". v54_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc54_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc54_1 protein).

The currently determined nucleotide sequence of vc54_1 is SEQ ID NO:
: 47, containing a poly (A) tail. What applicant believes to be the current valid reading frame and the predicted amino acid sequence of the vc54_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 48.
Has been reported to. Amino acids 33 to 45 of SEQ ID NO: 48 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 4
Starting from 6. Due to the hydrophobic nature of the predicted leader / signal sequence, if it does not separate from the rest of the vc54_1 protein, it will likely act as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc54_1 should be approximately 2083 bp.

The nucleotide sequence disclosed herein for vc54_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc54_1
AF007152 (Homo sapiens clones 23649 and 23755 unknown mRNA, partial cds), Q76901 (human genomic fragment (preferred); standard; D
NA), and T46905 (EST014BL29 Burkitt's lymphoma, Pascal
is Sideras Homo sapiens cDNA clone BL29-14 5 ', mRNA
Sequence)). The predicted amino acid sequence disclosed herein for vc54_1 is GenPept and Gene.
The Seq amino acid sequence database was searched using the BLASTX search protocol. The predicted vc54_1 protein showed at least some similarity to the sequence identified as AF007152 (unknown [Homo sapiens]). Based on sequence similarity, the vc54_1 protein and each similar protein or peptide will share at least some activity. TopP
The redII computer program predicts two additional potential transmembrane domains centered around amino acid 220 of SEQ ID NO: 48 and around 247 on the one inside the vc54_1 protein sequence.

The vc54_1 protein is expressed in the COS cell expression system and
The band of the expressed protein of Da was detected in the membrane fraction using SDS polyacrylamide gel electrophoresis.

Clone "vc57_1" The polynucleotide of the present invention has been identified as clone "vc57_1". v57_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc57_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc57_1 protein).

The currently determined nucleotide sequence of vc57_1 is SEQ ID NO:
: 49, containing a poly (A) tail. What applicant believes to be the current valid reading frame and the predicted amino acid sequence of the vc57_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 50.
Has been reported to. Amino acids 15 to 27 of SEQ ID NO: 50 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 2
Starting from 8. Due to the hydrophobic nature of the predicted leader / signal sequence, if it does not separate from the rest of the vc57_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc57_1 should be approximately 2564 bp.

The nucleotide sequences disclosed herein for vc57_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc57_1
Is AA156231 (z150a11.s1 Soares pregnant uterus NbHPU
Homo sapiens cDNA clone 505340 3 ', mRNA sequence). The predicted amino acid sequence disclosed herein for vc57_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc57_1 protein showed at least some similarity to the sequence identified as U41635 (OS-9 precursor [Homo sapiens]). Based on sequence similarity, the vc57_1 protein and each similar protein or peptide will share at least some activity.

The vc57_1 protein is expressed in the COS cell expression system and is approximately 51k
The band of the expressed protein of Da was detected using SDS polyacrylamide gel electrophoresis in the conditioned medium.

Clone "ve13_1" The polynucleotide of the present invention has been identified as clone "ve13_1". ve13_1 is isolated from a human adult brain (Alzheimer's hippocampus level 7) cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. Was done. ve13_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as ve13_1 protein).

The nucleotide sequence of ve13_1 that is currently determined is shown in SEQ ID NO:
: 51, containing a poly (A) tail. What applicant believes to be the current valid reading frame and the predicted amino acid sequence of the ve13_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 52.
Has been reported to. Amino acids 551 to 563 of SEQ ID NO: 52 are the predicted leader / signal sequences, with the predicted mature amino acid sequence beginning at amino acid 564. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the ve13_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone ve13_1 should be approximately 3046 bp.

The nucleotide sequences disclosed herein for ve13_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. ve13_1
Are AA587395 (nn82h06.s1 NCI_CGAP_Co9 homosapiens cDNA clone IMAGE: 10904427, an mRNA sequence similar to the one containing the THR repeat element) and Q76778 (a human genomic fragment).
(Preferred); standard; DNA) showed at least some similarity to the sequence identified. The predicted amino acid sequence disclosed herein for ve13_1 is GenGen
BLASTX against Pept and GeneSeq amino acid sequence databases
Searched using the search protocol. The predicted ve13_1 protein is U
It showed at least some similarity with the sequence identified as 50828 (the sel-1 gene product [Caenorhabditis elegans]). Based on sequence similarity, ve13
The —1 protein and each similar protein or peptide will share at least some activity.

Clone "ve16_1" The polynucleotide of the present invention has been identified as clone "ve16_1". ve16_1 is isolated from a human adult brain (Alzheimer's hippocampus level 7) cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. Was done. ve16_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as ve16_1 protein).

[0348] The nucleotide sequence of ve16_1 that is currently determined is SEQ ID NO:
: 53, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the ve16_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 54.
Has been reported to. Amino acids 14 to 26 of SEQ ID NO: 54 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 2
Starting from 7. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the ve16_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone ve16_1 should be approximately 2033 bp.

The nucleotide sequences disclosed herein for ve16_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. There were no hits in the database. The nucleotide sequence of ve16_1 suggests that it will contain one or more of the following repeating elements: Alu, MER
.

Clone "vf3_1" The polynucleotide of the present invention has been identified as clone "vf3_1".
vf3_1 was isolated from a human adult cardiac cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vf3_1 is a full-length clone and contains the entire coding sequence of a secreted protein (also referred to herein as vf3_1 protein).

The currently determined nucleotide sequence of vf3_1 is SEQ ID NO:
55 and contains a poly (A) tail. What applicants believe is the current valid reading frame and the predicted amino acid sequence of the vf3_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 56. Amino acids 8 to 20 of SEQ ID NO: 56 are the predicted leader / signal sequences, with the predicted mature amino acid sequence beginning at amino acid 21. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vf3_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vf3_1 should be approximately 2987 bp.

The nucleotide sequences disclosed herein for vf3_1 are BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. vf3_1 is z
78394 (Homo sapiens mRNA, expressed sequence
tag (expression sequence tag) ICRFp507K11187 (5 '), mRNA sequence
) Showed at least some similarity to the sequence identified. The predicted amino acid sequences disclosed herein for vf3_1 are GenPept and GeneSeq
The amino acid sequence database was searched using the BLASTX search protocol. The predicted vf3_1 protein showed at least some similarity with the sequence identified as U41558 (K02B2.3 gene product [Caenorhabditis elegans]). Based on sequence similarity, vf3_1 proteins and respective similar proteins or peptides will share at least some activity. The TopPredII computer program has one, SEQ ID
NO: predicts two additional potential transmembrane domains centered around amino acid 242 at 56 and the other around amino acid 275 within the vf3_1 protein sequence.

The vf3_1 protein is expressed in the COS cell expression system and has an approximate 39 kD
The band of the expressed protein in a was detected in the membrane fraction using SDS polyacrylamide gel electrophoresis.

Clone "vj2_1" The polynucleotide of the present invention has been identified as clone "vj2_1".
vj2_1 is the human fetal brain (whole brain, enriched for G protein-coupled receptors) c
It was isolated from a DNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encoded. vj2_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as vj2_1 protein).

The currently determined nucleotide sequence of vj2_1 is SEQ ID NO:
57 and contains a poly (A) tail. What applicants believe is the current valid reading frame and the predicted amino acid sequence of the vj2_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 58. Amino acids 59-71 of SEQ ID NO: 58 are the predicted leader / signal sequences, with the predicted mature amino acid sequence beginning at amino acid 72. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vj2_1 protein, it probably acts as a transmembrane domain.

Other potential vj2_1 reading frames and predicted amino acid sequences that can be encoded by base pairs 146 to 400 of SEQ ID NO: 57 are reported in SEQ ID NO: 127. The TopPredII computer program combines two potential transmembrane domains with SEQ ID NO: 1.
Predicted within the amino acid sequence of 27.

The EcoRI / NotI restriction fragment from the deposit containing clone vj2_1 should be approximately 1762 bp.

The nucleotide sequences disclosed herein for vj2_1 are BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. vj2_1 is N
36445 (yx83c04.r1 Homo sapiens cDNA clone 26832
It showed at least some similarity with the sequence identified as 65 '). Based on sequence similarity, the vj2_1 proteins and respective similar proteins or peptides will share at least some activity. TopPred
The II computer program comprises amino acids 30, SEQ ID NO: 58,
Three potential transmembrane domains, each centered around 67 and 90, are predicted within the vj2_1 protein sequence. The nucleotide sequence of vj2_1 indicates that it will contain one or more repetitive elements.

Clone "vp7_1" The polynucleotide of the present invention has been identified as clone "vp7_1".
vp7_1 was isolated from a human adult prostate cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vp7_1 is a full-length clone and contains the entire coding sequence of a secreted protein (also referred to herein as vp7_1 protein).

The nucleotide sequence of vp7_1 that has been determined is SEQ ID NO:
59 and contains a poly (A) tail. What applicants believe is currently the valid reading frame and the predicted amino acid sequence of the vp7_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 60. Amino acids 6 to 18 of SEQ ID NO: 60 are the predicted leader / signal sequences, with the predicted mature amino acid sequence beginning at amino acid 19. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vp7_1 protein, it probably acts as a transmembrane domain. SEQ ID NO: 5
Other potential vp7 that can be encoded by 9 base pairs 2071 to 2430
_ 1 reading frame and predicted amino acid sequence are as defined in SEQ ID NO.
: 128.

The EcoRI / NotI restriction fragment from the deposit containing clone vp7_1 should be approximately 2638 bp.

The nucleotide sequences disclosed herein for vp7_1 are BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. vp7_1 is N
49433 (yv21e12.r1 homosapiens cDNA clone 24340
65 ') and Q63882 (AP obtained by PCR against tumor-specific DNA
2 sequence; standard; cDNA) and showed at least some similarity to the sequence identified. Based on sequence similarity, the vp7_1 proteins and each similar protein or peptide will share at least some activity.
The TopPredII computer program also added one potential transmembrane domain to vp7 centered around amino acid 75 of SEQ ID NO: 60.
Predict inside the _1 protein sequence. The nucleotide sequence of vp7_1 suggests that it will contain one or more Alu repeats.

Clone "vp8_1" The polynucleotide of the present invention has been identified as clone "vp8_1".
vp8_1 was isolated from a human adult prostate cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vp8_1 is a full-length clone and contains the entire coding sequence of a secreted protein (also referred to herein as vp8_1 protein).

The nucleotide sequence of vp8_1 that has been determined is SEQ ID NO:
61 and contains a poly (A) tail. What applicants believe is the current valid reading frame and the predicted amino acid sequence of the vp8_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 62. Amino acids 20 to 32 of SEQ ID NO: 62 are the predicted leader / signal sequence, with the predicted mature amino acid sequence beginning at amino acid 33. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vp8_1 protein, it probably acts as a transmembrane domain. If two "C" residue insertions are made in the nucleotide sequence of SEQ ID NO: 61, one after the "A" at position 380 and the other after the "G" at position 382, the resulting nucleotide sequence is It is predicted to encode the amino acid reported in SEQ ID NO: 129.

The EcoRI / NotI restriction fragment from the deposit containing clone vp8_1 should be approximately 1513 bp.

The nucleotide sequences disclosed herein for vp8_1 are BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. vp8_1 is A
A284421 (ss59c10.r1 similar to NCI_CGAP_GCB1 homosapiens cDNA clone IMAGE701778 containing 5 'Alu repeat element; mRNA sequence) and AC002086 (human PAC from Xq23)
(Clone DJ525N14, full sequence). Based on sequence similarity, the vp8_1 proteins and each similar protein or peptide will share at least some activity. Profile hiding Markov model analysis reveals the presence of the SH2 domain in the predicted vp8_1 protein (SEQ ID NO: 62).
The SH2 domain functions as a regulatory modulator of the intracellular signal cascade by interacting with a target peptide containing phosphorylated tyrosine with high affinity in a sequence-specific and strictly phosphorylation-dependent manner. The nucleotide sequence of vp8_1 suggests that it will contain one or more Alu repeats.

The vp8_1 protein is expressed in the COS cell expression system and has an approximate 34 kD
The band of the expressed protein in a was detected in the membrane fraction using SDS polyacrylamide gel electrophoresis.

Clone "vb22_1" The polynucleotide of the present invention has been identified as clone "vb22_1". vb22_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vb22_1 is a full-length clone that contains the entire coding sequence of a secreted protein (also referred to herein as the vb22_1 protein).

The nucleotide sequence of vb22_1 that has been determined is SEQ ID NO:
: 63, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vb22_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 64.
Has been reported to. Other potential vb22_1 reading frames and predicted amino acid sequences that can be encoded by base pairs 152 to 1006 of SEQ ID NO: 63 are reported in SEQ ID NO: 130.

The EcoRI / NotI restriction fragment from the deposit containing clone vb22_1 should be approximately 4176 bp.

The nucleotide sequences disclosed herein for vb22_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vb22_1
Is L10335 (Homo sapiens neuroendocrine-specific protein C (NSP) mR
NA, all cds), N21304 (SP: A60021 A60021 TROP)
Yx53f07. Similar to OMYOSIN-RELATED PROTEIN. s
1 Homo sapiens cDNA clone 265467 3 ', NEURONAL),
And at least some similarity to the sequence identified as V23695 (human NSLP protein A coding sequence; standard; cDNA). The predicted amino acid sequences disclosed herein for vb22_1 are GenPept and GeneSeq
The amino acid sequence database was searched using the BLASTX search protocol. The predicted vb22_1 protein showed at least some similarity to the sequences identified as L10333 (neuroendocrine-specific protein A [Homo sapiens]) and W53947 (human NSLP protein A). Based on sequence similarity, the vb22_1 proteins and respective similar proteins or peptides will share at least some activity. TopPredII
The computer program has one amino acid 73 of SEQ ID NO: 64
Around 0, the other predicts two potential transmembrane domains centered around amino acid 846 within the vb22_1 protein sequence. The nucleotide sequence of vb22_1 appears to contain a short, simple nucleotide repeat ("GGA") region.

Clone "vc48_1" The polynucleotide of the present invention has been identified as clone "vc48_1". vc48_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc48_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as the vc48_1 protein).

The nucleotide sequence of vc48_1 currently determined is SEQ ID NO:
: 65, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vc48_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 66.
Has been reported to. Amino acids 7 to 19 of SEQ ID NO: 66 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 20
Starting from. Due to the predicted hydrophobic nature of the leader / signal sequence,
If its predicted leader / signal sequence is not separated from the rest of the vc48_1 protein, it will likely act as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc48_1 should be approximately 3096 bp.

The nucleotide sequence disclosed herein for vc48_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc48_1
Is AA292779 (zt56c06.s1 Soares ovarian tumor NbHOT
Homo sapiens cDNA clone 726346 3 '; mRNA sequence). The predicted amino acid sequence disclosed herein for vc48_1 was searched against the GenPept and GeneSeq amino acid sequence databases using the BLASTX search protocol. The predicted vc48_1 proteins are AL031765 (Drosophila genomic product 22E5.z) and Z81058 (F11E6.e [Caenorhabditis elegans]).
Showed at least some similarity to the sequence identified as Based on sequence similarity, the vc48_1 proteins and each similar protein or peptide will share at least some activity. The TopPredII computer program shows that one is centered around amino acid 39 of SEQ ID NO: 66 and the other is centered around amino acids 69, 107 and 134, respectively.
Are predicted within the vc48_1 protein sequence. The nucleotide sequence of vc48_1 appears to contain simple nucleotide repeats ("AC") and one or more of the following repeat elements: Alu and M
IR.

Clone "vp3_1" The polynucleotide of the present invention has been identified as clone "vp3_1".
vp3_1 was isolated from a human adult prostate cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vp3_1 is a full-length clone, containing the entire coding sequence of a secreted protein (also referred to herein as vp3_1 protein).

The nucleotide sequence of vp3_1 that has been determined is SEQ ID NO:
67 and contains a poly (A) tail. What applicants believe is the current valid reading frame and the predicted amino acid sequence of the vp3_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 68. Amino acids 19 to 31 of SEQ ID NO: 68 are the 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, if it is not separated from the rest of the vp3_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vp3_1 should be approximately 552 bp.

The nucleotide sequences disclosed herein for vp3_1 are BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. vp3_1 is A
A225045 (nc34c06.r1 NCI_CGAP_Pr2 homosapiens cDNA clone IMAGE1010026, mRNA sequence), M1815
7 (human gland kallikrein gene, complete cds), and at least some similarity to sequences identified as T35868 (prostate specific antigen gene subsequence; standard; DNA). Based on sequence similarity, the vp3_1 proteins and respective similar proteins or peptides will share at least some activity.

Clone "vc61_1" The polynucleotide of the present invention has been identified as clone "vc61_1". vc61_1 was isolated from a human fetal brain cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vc61_1 is a full-length clone that contains the entire coding sequence of a secreted protein (also referred to herein as the vc61_1 protein).

The nucleotide sequence of vc61_1 currently determined is SEQ ID NO:
: 69, containing a poly (A) tail. What applicant believes to be the current valid reading frame and the predicted amino acid sequence of the vc61_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 70.
Has been reported to. Amino acids 16 to 28 of SEQ ID NO: 70 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 2
Starting from 9. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vc61_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vc61_1 should be approximately 3199 bp.

The nucleotide sequence disclosed herein for vc61_1 is BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vc61_1
Is AI028115 (gb S67859 TRANSCRIPTION IN
ITIATION FACTOR IIE-ALPHA CHAIN (HUMA
Ow51d09.N). x1 Soares_parathyroid_tumor_NbHP
A homosapiens cDNA clone IMAGE1650353 3 '; mRNA
), V20913 (Human derived oncoprotein cDNA), and Z99129 (Human DNA sequence from clone 425C on chromosome 6q22) are unknown similar to heat shock factor 2 (heat shock transcription factor 2, HSF2 gene) and placental protein DIFF33 gene. Including genes; including ESTs, STSs, and GSSs;
(Complete sequence). vc61
The predicted amino acid sequence disclosed herein for G_1 is GenPept and G
The eneSeq amino acid sequence database was searched using the BLASTX search protocol. The predicted vc61_1 protein showed at least some similarity to the sequences identified as W52812 (human derived oncoprotein) and Z99129 (dj425C14.2 (placental protein DIFF33LIKE) [Homo sapiens]). The derived vc61_1 protein has amino acid similarity to human and mouse diff33 proteins. diff33 is a transmembrane protein that is overexpressed in testicular tumors in polyomavirus large T-antigen transgenic mice. Based on sequence similarity, the vc61_1 protein and each similar protein or peptide will share at least some activity. The TopPredII computer program is based on SEQ I
D NO: 70 amino acids 50, 100, 150, 210, 240, 270, 3
Nine additional potential transmembrane domains, centered around 20, 390, and 430, respectively, are predicted within the vc61_1 protein. vc array 61
The nucleotide sequence of _ 1 suggests that it will contain an Alu repeat element.

Clone "vp15_1" The polynucleotide of the present invention has been identified as clone "vp15_1". vp15_1 was isolated from a human adult prostate cDNA library,
It was identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the encoded protein. vp15_1
Is a full-length clone that contains the entire coding sequence of a secreted protein (also referred to herein as the vp15_1 protein).

The nucleotide sequence of vp15_1 that is currently determined has SEQ ID NO:
: 71, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vp15_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 72.
Has been reported to. Amino acids 4 to 16 of SEQ ID NO: 72 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 17
Starting from. Due to the predicted hydrophobic nature of the leader / signal sequence,
If the predicted leader / signal sequence is not separated from the rest of the vp15_1 protein, it will likely act as a transmembrane domain. If one "C" residue was inserted between nucleotides 458 and 459 of SEQ ID NO: 71, nucleotides 44 to 568 of the resulting nucleotide sequence would be SEQ ID NO: 71.
Would encode a protein having the amino acid sequence reported as NO: 131.

The EcoRI / NotI restriction fragment from the deposit containing clone vp15_1 should be approximately 2033 bp.

The nucleotide sequences disclosed herein for vp15_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vp15_1
Is AI033082 (ow97g04.s1 Soares_fetal_liver_spleen_1NFLS_S1 homosapiens cDNA clone IMAGE1654806
3 ′; mRNA sequence) and T21877 (human gene signature HUMGS034)
18) showed at least some similarity to the sequence identified as 18). The predicted amino acid sequence disclosed herein for vp15_1 is GenPept and Gene.
The Seq amino acid sequence database was searched using the BLASTX search protocol. The predicted vp15_1 protein showed at least some similarity with the sequences identified as R45335 (thrombomodulin analogs Q336N, Q365E) and U94333 (C1qR (p) [Homo sapiens]). The predicted vp15_1 protein has numerous thrombomodulin analogs (eg, Gene
Seq access number R445335), and shows "... a human C1q / MBL / that regulates enhanced phagocytosis in vitro.
SPA receptor "(Nepomuceno et al., 1997, Immunity 6 (2): 119-129, which is incorporated herein by reference) and a slightly end-to-end GenPept access number U94333. Based on sequence similarity, the vp15_1 protein and each similar protein or peptide will share at least some activity.

The vp15_1 protein is expressed in the COS cell expression system and is approximately 24k
The band of the expressed protein of Da was detected in the conditioned medium and the membrane fraction using SDS polyacrylamide gel electrophoresis.

Clone "vp17_1" The polynucleotide of the present invention has been identified as clone "vp17_1". vp17_1 has been isolated from a human adult prostate cDNA library,
It was identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the encoded protein. vp17_1
Is a full-length clone containing the entire coding sequence of a secreted protein (also referred to herein as the vp17_1 protein).

The nucleotide sequence of vp17_1 that has been determined is SEQ ID NO:
: 73, containing a poly (A) tail. What applicant believes to be the current valid reading frame and the predicted amino acid sequence of the vp17_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 74.
Has been reported to. Amino acids 10 to 22 of SEQ ID NO: 74 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 2
Starting from 3. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vp17_1 protein, it probably acts as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vp17_1 should be approximately 3150 bp.

The nucleotide sequences disclosed herein for vp17_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vp17_1
Is AI056890 (oz03g07.x1 Soares_fetal_liver_spleen_1NFLS_S1 homosapiens cDNA clone IMAGE16774300
3 ', mRNA sequence) and T64815 (tumor suppressor activation pathway gene TSAP6). Based on sequence similarity, the vp17_1 protein and each similar protein or peptide will share at least some activity. TopPr
The edII computer program predicts two additional potential transmembrane domains, centered around amino acid 50 of SEQ ID NO: 74 and the other around amino acid 80, within the vp17_1 protein sequence.

Clone "vp19_1" The polynucleotide of the present invention has been identified as clone "vp19_1". vp19_1 was isolated from a human adult prostate cDNA library,
It was identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the encoded protein. vp19_1
Is a full-length clone that contains the entire coding sequence of a secreted protein (also referred to herein as the vp19_1 protein).

The nucleotide sequence of vp19_1 currently determined is SEQ ID NO:
: 75, containing a poly (A) tail. What applicant believes to be the current valid reading frame and the predicted amino acid sequence of the vp19_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 76.
Has been reported to.

The EcoRI / NotI restriction fragment obtained from the deposit containing clone vp19_1 should be approximately 971 bp.

The nucleotide sequences disclosed herein for vp19_1 are BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vp19_1
Is AA716408 (zg64b02.s1 Soares fetal heart NbHH1
It showed at least some similarity with the sequences identified as 9W Homo sapiens cDNA clone 398091 3 ', mRNA sequence) and T20711 (human gene signature HUMGS01928). Based on sequence similarity, the vp19_1 proteins and each similar protein or peptide will share at least some activity. The TopPredII computer program assigns one potential transmembrane domain to amino acid 23 of SEQ ID NO: 76.
Predicted within the vp19_1 protein sequence centered around; due to its hydrophobic nature this region (amino acids 20 to 32) can also be a leader / signal sequence and the mature protein has SEQ ID NO: 76 amino acids 3
Start with 3.

Clone "vq1_1" The polynucleotide of the present invention has been identified as clone "vq1_1".
vq1_1 was isolated from a human adult liver cDNA library and identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the protein it encodes. vq1_1 is a full-length clone, which contains the entire coding sequence of a secreted protein (also referred to herein as vq1_1 protein).

The currently determined nucleotide sequence of vq1_1 has SEQ ID NO:
77 and includes a poly (A) tail. What Applicants believe is the current valid reading frame and the predicted amino acid sequence of the vq1_1 protein corresponding to the aforementioned nucleotide sequence is reported in SEQ ID NO: 78. Amino acids 17 to 29 of SEQ ID NO: 78 are the predicted leader / signal sequences, with the predicted mature amino acid sequence beginning at amino acid 30. Due to the hydrophobic nature of the predicted leader / signal sequence, if it is not separated from the rest of the vq1_1 protein, it probably acts as a transmembrane domain. If one "T" residue was inserted between nucleotides 332 and 333 of SEQ ID NO: 77, nucleotides 54 through 496 of the resulting nucleotide sequence would be SEQ ID NO: 77.
Would encode a protein having the amino acid sequence reported as NO: 132.

The EcoRI / NotI restriction fragment from the deposit containing clone vq1_1 should be approximately 873 bp.

The nucleotide sequences disclosed herein for vq1 — 1 are BLASTN / BLA against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using STX and FASTA search protocols. vq1_1 showed at least some similarity to the identified sequence as there were no hits in the database. The TopPredII computer program has the SEQ ID
An additional potential transmembrane domain extending from about amino acid 23 to about amino acid 76 of NO: 78 is predicted within the vq1_1 protein sequence. The nucleotide sequence of vq1_1 suggests that it will contain an Alu repeat element.

Clone "vp14_1" The polynucleotide of the present invention has been identified as clone "vp14_1". vp14_1 has been isolated from a human adult prostate cDNA library,
It was identified as encoding a secreted or transmembrane protein based on computer analysis of the amino acid sequence of the encoded protein. vp14_1
Is a full-length clone that contains the entire coding sequence of a secreted protein (also referred to herein as the vp14_1 protein).

The nucleotide sequence of vp14_1 currently determined is SEQ ID NO:
: 79, containing a poly (A) tail. What applicant believes to be the currently valid reading frame and the predicted amino acid sequence of the vp14_1 protein corresponding to the aforementioned nucleotide sequence is shown in SEQ ID NO: 80.
Has been reported to. Amino acids 5 to 17 of SEQ ID NO: 80 are the predicted leader / signal sequence, and the predicted mature amino acid sequence is amino acid 18
Starting from. Due to the predicted hydrophobic nature of the leader / signal sequence,
If the predicted leader / signal sequence is not separated from the rest of the vp15_1 protein, it will likely act as a transmembrane domain.

The EcoRI / NotI restriction fragment from the deposit containing clone vp14_1 should be approximately 1355 bp.

The nucleotide sequences disclosed herein for vp — 141 have BLASTN / BL against the GenBank and GeneSeq nucleotide sequence databases.
Searches were made using ASTX and FASTA search protocols. vp14_1
Is AI052724 (SW: YQJQ_BACSU P54554HYPOTH
ETICAL OXIDOREDUCTASE IN GLNQ-ANSR I
Oz27a12 similar to NTERGENIC REGION. x1 Soares
_All_Fetal Nb2HF8_9w Homo sapiens cDNA clone IMAGE:
1676542 3 ′; mRNA sequence) and T20001 (human gene signature H)
UMGS01138) was at least somewhat similar. The predicted amino acid sequence disclosed herein for vp14_1 is GenPep
The t and GeneSeq amino acid sequence databases were searched using the BLASTX search protocol. The predicted vp14_1 protein is R614
It showed at least some similarity to sequences identified as 77 (clavulanate dehydrogenase sequence) and Z99116 (similar to ketoacyl reductase [Bacillus subtilis]). The predicted vp14_1 protein was identified at amino acid 5 in SEQ ID NO: 80 as detected by motif and hidden Markov model analysis.
The presence of the family signature of short-chain alcohol dehydrogenases from 1 to 240 indicates some amino acid similarity to the various dehydrogenases. Based on sequence similarity, the vp14_1 proteins and each similar protein or peptide will share at least some activity. TopP
The redII computer program predicts four additional potential transmembrane domains centered around amino acids 55, 195, 230, and 300 of SEQ ID NO: 80 within the vp14_1 protein sequence.

Deposit of clones Clone vb11_1, vb12_1, vb14_1, ve11_1, vf2_1
, Vg2_1, vj1_1, and v11_1 are registered on August 20, 1998 with the ATTC (
American Type Culture Collection, 10801 University Boulevard, Manassas,
Virginia 20110-2209 USA), deposited as an original deposit under the Budapest Treaty, and given accession number 98846, whereby each clone consisting of a particular nucleotide can be obtained.

[0408] vk2_1 was released on August 20, 1998 by ATTC (American Type Culture Collec).
tion, 10801 University Boulevard, Manassas, Virginia 20110-2209 USA)
Was deposited as an original deposit under the Budapest Treaty, and was assigned accession number 98838, thereby comprising a vk2 consisting of a particular nucleotide.
_1 clone can be obtained.

Clone vb21_1, vc35_1, vc36_1, vc38_1, vc39_
1, vc40_1, vc46_1, vc49_1, vc50_1, vc51_1, and vc52_1 were released on September 2, 1998 by ATTC (American Type Culture Collec).
tion, 10801 University Boulevard, Manassas, Virginia 20110-2209 USA)
Has been deposited as an original deposit under the Budapest Treaty and has been assigned accession number 98862, whereby each clone consisting of a particular nucleotide can be obtained.

Clone vc33_1, vc34_1, vc47_1, vc54_1, vc57_
1, ve13_1, ve16_1, vf3_1, vj2_1, vp7_1, and vp
8_1 was released on September 22, 1998 by ATTC (American Type Culture Collection,
10801 University Boulevard, Manassas, Virginia 20110-2209 USA) as an original deposit under the Budapest Treaty, access number 9
8886, whereby each clone consisting of a specific nucleotide can be obtained.

Clone vb22_1, vc48_1, and vp3_1 were cloned on October 1, 1998.
ATTC (American Type Culture Collection, 10801 University Boulev
ard, Manassas, Virginia 20110-2209 USA), deposited as an original deposit under the Budapest Treaty and given accession number 98933, whereby each clone consisting of a particular nucleotide can be obtained.

Clone vc61_1, vp15_1, vp17_1, vp19_1, and vq
1_1 was published on December 23, 1998 by the ATTC (American Type Culture Collection).
, 10801 University Boulevard, Manassas, Virginia 20110-2209 USA), deposited as an original deposit under the Budapest Treaty and given accession number 2007012, whereby each clone consisting of a particular nucleotide can be obtained. .

The clone vp14_1 was obtained on December 23, 1998 by ATTC (American Type Cu
lture Collection, 10801 University Boulevard, Manassas, Virginia 20110-2
209 USA) as an original deposit under the Budapest Treaty,
An accession number 207011 is given, whereby each clone consisting of a specific nucleotide can be obtained.

All restrictions on the use of the deposited material for the general public are set forth in 37 CFR. F. R.
Except for the requirements set forth in § 1.808 (b), they are irrevocably removed upon the issuance of a patent, and the term of deposit is 37 C.E. F. R. § 1.806.

Each clone has been transformed into a separate bacterial cell (E. coli) in this composite deposit. Each clone was designated Ec from the vector with which it was deposited.
An oRI / NotI digestion (5 ′ site, EcoRI; 3 ′ site, NotI) can be removed to produce the appropriate fragment for such a clone. Each clone was deposited in either the pED6 or pNOTs vector depicted in FIGS. 1A 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 Aci.
ds Res. 19: 4485-4490); the pNOTs vector is pMT2 (Kaufman et al., 1989,
Mol. Cell. Biol. 9: 946-958), which was derived by deletion of the DHFR sequence, insertion of a new polylinker, and insertion of the M13 origin of replication at the ClaI site. In certain instances, the deposited clone may be “inverted” (ie, in the opposite direction) in the deposited isolate. In such an example, the cDNA insert would still be Eco-friendly.
It can be isolated by RI / NotI digestion. However, to place the cDNA in a reasonable orientation for expression in some suitable vector, NotI was then 5
A 'site will be created and EcoRI will create a 3' site. The cDNA may also be expressed from a vector deposited therein.

Bacterial cells containing a particular clone can be obtained from a composite deposit as follows.

[0417] One or more oligonucleotide probes should be designed against a sequence that is known for that particular clone. This sequence can be derived from the sequences provided herein, or a combination thereof. The sequences of the oligonucleotide probes used to isolate or sequence each full-length clone are identified below and should be the most reliable in isolating the clone of interest.

[0418]

[Table 1]

[Table 2] (Continued) For sequences containing an N at position 2 as indicated above, that position may be a biotinylated phosphoramidite residue (eg, biotin phosphoramidite (1-dimethoxytrityloxy- 2
-(N-biotinyl-4-aminobutyl) -propyl-3-O- (2-cyanoethyl)-(N, N-diisopropyl) -phosphoramadite) (Glen Research, cat.no. 10-1953) As produced by the use of

The design of the oligonucleotide probes should preferably follow these parameters. (a) It should be designed for regions of the sequence that have few, if any, ambiguous bases (N's). (b) It should be designed to have a T _{m of} approximately 80 ° C. (assuming 2 ° for each A or T and 4 degrees for each G or C). The oligonucleotide is preferably γ- ³² P ATP (specific activity 6000 Ci / mmo) using techniques commonly used to label oligonucleotides.
l) and T4 polynucleotide kinase. Other labeling techniques may also be used. Uninserted label should preferably be removed by gel filtration chromatography or other established methods. The amount of radioactivity inserted into the probe should be quantified by measurement with a scintillation counter. Preferably, the specific activity of the resulting probe should be approximately 4e + 6 dpm / pmole.

Bacterial cultures containing a pool of full-length clones are preferably thawed,
100 μl of the stock solution should be used to incubate a sterile culture flask containing 25 ml of sterile L-broth containing 100 μg / ml ampicillin. The culture is preferably grown to saturation at 37 ° C., and the saturated culture should preferably be diluted in fresh L-broth. Aliquots of these dilutions are preferably plated and plated on solid bacterial medium containing L-broth containing 100 μg / ml ampicillin and 1.5% agar in 150 mm Petri dishes.
C. When growing overnight at .degree. C., the dilution and amount that should give rise to approximately 5000 distinct and well-separated colonies should be determined. Known methods for obtaining clear and well-separated colonies may also be used.

[0421] The colonies are then transferred to nitrocellulose filters using standard colony hybridization techniques, and they are lysed, denatured, and fired.

The filters are then preferably filtered at 65 ° C. for 1 hour, 0.5% SDS, 100%
6 × SSC (175.3 g of 20 × stock solution) containing μg / ml yeast RNA and 10 mM EDTA (approximately 10 mL per 150 mm filter)
NaCl / liter, 88.2 g Na citrate / liter, p with NaOH
(Adjusted to H7.0) with gentle agitation.
Preferably, the probe is then added to the hybridization mixture at a concentration greater than or equal to 1e + 6 / mL. The filters are then incubated overnight, preferably at 65 ° C. with gentle agitation. The filter is then preferably washed in 500 mL of 2 × SSC / 0.5% SDS at room temperature without stirring, preferably then in 500 mL of 2 × SSC / 0.1% SDS for 15 minutes at room temperature with gentle shaking. . A third wash in 0.1X SSC / 0.5% SDS with gentle agitation at 65 ° C for 30 minutes to 1 hour is optional.
The filters are then preferably dried and autoradiographed for a time sufficient to visualize positives on X-ray film. Other known hybridization methods may also be employed.

[0437] Positive colonies are picked, grown in culture, and plasmid DNA is isolated using standard techniques. Clones can then be identified by restriction analysis, hybridization analysis, or DNA sequencing.

A protein fragment of the invention that can exhibit biological activity is also encompassed by the invention. Protein fragments may be linear or, for example, HU Saragovi et al., Bio / Technology 10, both of which are incorporated herein by reference.
773-778 (1992) and RS McDowell et al., J. Amer. Chem. Soc. 114, 9245-9253.
(1992), cyclization may be performed using known methods. Such fragments may be fused to carrier molecules such as immunoglobulins for many purposes, including increasing the valency of the protein binding site. For example, a protein fragment may be fused to the Fc portion of an immunoglobulin through a "linker" sequence. To make the protein a bivalent form, such a fusion would be to the Fc portion of an IgG molecule. Other immunoglobulin isotypes may also be used to generate such a fusion. For example, a protein-IgM fusion will produce a decavalent form of the invented protein.

The present invention also provides for both full-length and mature forms of the disclosed proteins. Full-length forms of such proteins are identified by sequence listing by translation of the nucleotide sequence of each disclosed clone. The mature form (s) of such proteins may comprise the disclosed full-length polynucleotides (preferably ATT
(Deposited by C) in appropriate mammalian cells or other host cells. The sequence (s) of the mature form (s) of the protein will also be determined from the amino acid sequence of the full-length form.

[0426] The present invention also provides genes corresponding to the polynucleotide sequences disclosed herein. A “corresponding gene” is a region of the genome that is transcribed to produce mRNA from which a cDNA polynucleotide sequence is derived and that may include flanking regions of the genome necessary for controlled expression of such a gene. It is. The corresponding gene will therefore include, but is not limited to, coding sequences, 5 'and 3' untranslated regions, alternatively spliced exons, introns, promoters, enhancers, and silencer or suppressor elements. . The corresponding gene can be isolated according to known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for gene identification and / or amplification in a suitable genomic library or other source of genomic material. An "isolated gene" is a gene that has been separated from any adjacent coding sequences, if at all, in the genome of the organism from which it was isolated.

A chromosomal location corresponding to a polynucleotide sequence disclosed herein will also be determined, for example, by hybridizing an appropriately labeled polynucleotide of the present invention to the chromosome in situ. The expressed sequence tag already mapped to a specific chromosomal location
Corresponding chromosomal locations for the disclosed polynucleotides can also be determined by identifying significantly similar nucleotide sequences in public databases, such as (expressed sequence tags) (ESTs). For at least some of the polynucleotides disclosed herein, public database sequences having at least some similarity to the polynucleotides of the present invention are designated by their database access number. A search using the GenBank access number of these public database sequences is then performed to identify the "UniGene cluster" of overlapping sequences at http: // www. ncbi. nlm. nih. gov / Uni
National Center for Bi with Gene / address
It can be implemented on an Internet site provided by technology Information. Many of the "UniGene clusters" so identified will have already been mapped to specific chromosomal sites.

[0428] Organisms having enhanced, reduced, or modified expression of a gene corresponding to a polynucleotide disclosed herein are provided. Desired changes in gene expression can be achieved through the use of antisense polynucleotides or ribozymes that bind and / or cleave mRNA transcribed from the gene (Albert and
Morris, 1994, Trends Pharmacol.Sci. 15 (7): 250-254; Lavarosky et al., 1997,
Biochem. Mol. Med. 621 (1) 11-33; and Hampel, 1998, Prog. Nucleic Acid
Res. Mol. Biol. 58: 1-39; all of which are incorporated herein by reference). The desired change in gene expression may also include the mR transcribed from the gene.
Double-stranded ribonucleotide molecules that have some complementarity to NA and that interfere with the transcription, stability, or expression of mRNA ("RNA interference" or "RNAi"; Fire et al., 1998, Nature 391 (6669): 806). -811; Montgomery et al., 1998, Proc. Natl. Ac
ad. Sci. USA 95 (26): 15502-15507; and Sharp, 1999, Genes Dev. 13 (2):
139-141; all of which are hereby incorporated by reference). Transgenic animals having multiple copies of the gene (s) corresponding to the polynucleotides disclosed herein are preferably obtained by transformation of the transformed cells and cells having a genetic structure that is stably conserved in progeny thereof. Produced and provided. Also provided are transgenic animals that have modified gene regulatory regions that increase or decrease gene expression levels or that alter the temporal or spatial pattern of gene expression (European patents incorporated herein by reference. No. 0644964B1). In addition, the gene (s) corresponding to the polynucleotide sequence disclosed herein may include a corresponding gene (
Also provided are organisms that have been partially or completely inactivated by insertion of a foreign sequence into (s) or by deletion of all or part of the corresponding gene (s). Partial or complete gene inactivation can be achieved by using interchangeable elements (Plasterk, 1992, Bi
oassays 14 (9): 629-633; Zwaal et al., 1993, Proc. Natl. Acad. Sci. USA 90 (16
): 7431-7435; Clark et al., 1994, Proc. Natl. Acad. Sci. USA 91 (2): 719-722;
All of which are incorporated herein by reference) and then preferably by ambiguous excision, or preferably by a positive / negative gene selection method (M
ansour et al., 1988, Nature 336: 348-352; U.S. Patent Nos. 5,464,764; 5.
487,992; 5,627,059; 5,631,153; 5,614,39.
6; 5,616,491; 5,679,523; all of which are incorporated herein by reference). Organisms with altered gene expression are preferably eukaryotes and more preferably animals. Such organisms are useful for developing non-human models for studying disorders involving the corresponding gene and for developing assay systems for identifying molecules that interact with the protein product (s) of the corresponding gene (s). .

Where a protein of the invention is membrane-bound (eg, is a receptor), the invention also provides a soluble form of such protein. In such forms, some or all of the intracellular and transmembrane domains of the protein are deleted so that the protein is secreted from cells in which it is fully expressed. The intracellular and transmembrane domains of the proteins of the invention can be identified according to known techniques for determining such domains from sequence information. For example, the TopPredII computer program locates the transmembrane domain in an amino acid sequence, i.e., the domain described by the central position of the transmembrane domain, at least 10 positions on each side of the reported central residue (s). Can be used to make predictions with a single transmembrane amino acid.

The proteins and protein fragments of the present invention include proteins having an amino acid sequence length of at least 25% (more preferably at least 50%, and most preferably at least 75%) of the disclosed protein length, And at least 60% sequence identity (more preferably at least 7
5% identity; most preferably at least 90% or 95% identity), wherein sequence identity is such that when aligned to maximize overlap and identity, while minimizing sequence gaps. Determined by comparing the amino acid sequences of the proteins. Also included in the invention is at least 75% sequence identity (more preferably at least 85%) to all such segments of each of the disclosed proteins.
Preferably 8 or more (more preferably at least 20 or more, most preferably at least 30 or more) contiguous amino acids sharing a% identity; and most preferably at least 95% identity). Proteins and protein fragments comprising segments consisting of

In particular, sequence identity was determined using WU-BLAST (Washington University).
site BLAST) version 2.0 software, which is an extension of WU-BLAST version 1.4, which in turn is the public domain NCBI-BLAST version 1.4 (Altschul and Gi
sh, 1996, Local alignment statistics, Doolittle ed., Methods in Enzymology 2
66: 460-480; Altschul et al., 1990, Basic local alignment search tool, Journa
l of Molecular Biology 215, 403-410; Gish and States, 1993, Recognition of protein coding regions by database equivalence search, Nature Genetics 3: 266-272
Karlin and Altschul, 1993, Applications and Statistics for Multiple High-Score Segments in Molecular Sequences, Proc. Natl. Acad. Sci. USA 90: 5873-5877; all of which are incorporated herein by reference). It is based on. Some UNI
The executable program WU-BLAST version 2.0 for the X® platform is available at ftp: // blast. wustl. It can be downloaded from edu / blast / executables. A complete set of search programs (BLASTP, BLASTN, BLASTX, TBLASTN, and TBLASTX) are provided on that site, along with several support programs. WU-BLAST 2.0 is copyrighted and will not be sold or redistributed in any form or manner without the express written consent of the authors; however, the published executable is not a commercial, non-profit It may be used freely for research or academic purposes. In all of its suites--BLASTP, BLASTN, BLASTX, TBLASTN, and TBLASTX--the gapped alignment routines are integral to the database search itself, and It produces much easier sensitivity and selectivity while producing output that is easily interpreted. If desired, gapping can be arbitrarily stopped in all of these programs. The default penalty (Q) for gaps of length 1 is Q = 9 for protein and BLASTP, and Q = 10 for BLASTN, but from 0,1 to 8,9,10,11. , 12 to 20, 21 to 50, 51 to 100, and so on. The default penalty per residue (R) to extend the gap is R = 2 for proteins and BLASTP and R = 10 for BLASTN, but 0, 1, 2, 3, It can be changed to any integer value including 4,5,6,7,8,9,10,11,12 to 20,21 to 50,51 to 100, etc. Any combination of values for Q and R can be used to align the sequences to maximize overlap and identity while minimizing sequence gaps. The default amino acid comparison matrix is BLOSUM62, but other amino acid comparison matrices such as PAM can be used.

Species homologs of the disclosed polynucleotides and proteins are also provided by the invention. As used herein, a "species homolog" is a protein or polynucleotide for a species of a different origin than that of a given protein or polynucleotide, but with significant sequence similarity to the given protein or polynucleotide. With Preferably, the polynucleotide homolog has at least 60% sequence identity (more preferably at least 75% identity; most preferably at least 90% identity) with a given polynucleotide;
And the protein homolog has at least 30% sequence identity with the given protein
(More preferably at least 45% identity; most preferably at least 60%
Where the sequence identity is determined by comparing the nucleotide sequence of a polynucleotide or the amino acid sequence of a protein when aligned to maximize overlap and identity while minimizing sequence gaps. Is done. Species homologues will be isolated and identified by making appropriate probes or primers from the sequences provided herein and screening for an appropriate source of nucleic acid from the desired species. Preferably, the species homolog is one that is isolated from a mammalian species.
Most preferably, the species homolog is, for example, Pan troglodytes, Gorilla gorilla, Po
ngo pygmaeus, Hydrobates concolor, Macaca mullatta, Papio papio, Papio h
amadryas, Cercopithecus aethiops, Cebus capucinus, Aotus trivirgatus, Sa
nguinus oedipus, Microcebus murinus, Mus musculus, Rattus norvegicus, Cr
icetulus griseus, Felis catus, Mustera vison, Canis familiaris, Oryctola
gus cuniculus, Bos taurus, Ovis aries, Sus scrofa, or Equus cavallu
s, but for which a genetic map has been created to enable the identification of homology between the genomic organization of the gene of one species and the genomic organization of the related gene of another species (O ' Brien and Seuanez, 1988, Ann. Rev. Genet. 22: 323-351; O'Brien
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, Tr
ends in Genetics 13 (10): 393-399; Carver and Stubbs, 1997, Genome Resear
ch 7: 1123-1137; all of which are incorporated herein by reference).

The invention also encompasses allelic variants of the disclosed polynucleotides or proteins; that is, proteins that have sequences identical or significantly similar to those encoded by the disclosed polynucleotides. Is an alternative form of the naturally occurring isolated polynucleotide to be converted. Preferably, the allelic variant has at least 60% sequence identity (more preferably at least 75% identity; most preferably at least 90% identity to the given protein).
% Identity), where sequence identity is determined by comparing the nucleotide sequences of the polynucleotides as they are aligned to maximize overlap and identity while minimizing sequence gaps. Allelic variants will be isolated and identified by making appropriate probes or primers from the sequences provided herein and screening for an appropriate source of nucleic acid from an individual of the appropriate species.

The invention also includes polynucleotides that have a sequence complementary to that of the polynucleotides disclosed herein.

The present invention also includes polynucleotides that hybridize to polynucleotides described herein under conditions of low stringency, more preferably, conditions of stringency, and most preferably, conditions of high stringency. Examples of stringency conditions are shown in the following table:
Highly stringent conditions are at least as stringent as, for example, conditions AF; stringent conditions are at least as stringent as, for example, conditions GF; and low. The stringency conditions are at least as stringent as, for example, conditions MR.

[0436]

[Table 3]

[Table 4] (Continued) ^‡ : Hybrid length is expected for the hybridized region (s) of the hybridizing polynucleotide. When hybridizing a polynucleotide to a target polynucleotide of unknown sequence, the hybrid length is expected to be that of the hybridizing polynucleotide. When hybridizing polynucleotides of known sequence, the hybrid length is determined by juxtaposing the sequences of the polynucleotides and recognizing one or more regions of any sequence complementarity. ⁺ : SSPE (1 × SSPE is 0.15 M NaCl, 10 mM Na ₂ PO ₄ and 1.25 mM EDTA, pH 7.4) is SSC (1 × SSSC is 0.15 M NaCl and 1 × SSC is 0.15 M NaCl and Fifteen
(mM sodium citrate); washing is performed for 15 minutes after the end of hybridization. ^{* _T} B _{~T R:} The hybridization temperature for hybrids anticipated to 50 base pairs or less in length, but must no 5-10 ° C. lower than the hybrid of the melting point (T _m), where T _m Is determined by the following equation. For hybrids of 18 base pairs or less in length, T _m (° C.) = 2 (A + T base #) + 4 (G + C base #)
. For hybrids between 18 and 49 base pairs in length, T _m (° C.) = 81
. 5 + 16.6 (log ₁₀ [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 ⁺ ] to 1 × SSC)
= 0.165M).

Additional examples of stringency conditions for polynucleotide hybridization include:
Here incorporated by reference: Sambrook, J., EF Fritsch, and T.
Maniatis, 1989, Molecular Cloning: A Laboratory Manual, Cold Spring Harb
or Laboratory Press, Cold Spring Harbor, NY, Chapters 9 and 11 and C
urrent Protocols in Molecular biology, 1995, FM Ausubel, etc., edited by John W
iley & Sons, Inc., Sections 2.10 and 6.3-6.4.

Preferably, each such hybridizing polynucleotide is at least 25% (more preferably at least 50%, most preferably at least 75%) of the length of the polynucleotide of the invention to which it hybridizes. At least 60% sequence identity (more preferably at least 75% identity; most preferably at least 90% or 95% identity) to a polynucleotide of the invention having a length and to which it hybridizes. However, when sequenced is arranged to maximize overlap and identity while minimizing sequence gaps,
It is determined by comparing the sequences of the hybridizing polynucleotides.

The isolated polynucleotide that encodes the protein of the invention can be obtained using the methods described in Kaufman et al., Nucleic Acids Res. 19, 4485-4490 to produce the protein recombinantly.
(1991) may be operably linked to an expression control sequence such as the pMT2 or pED expression vector. Many suitable expression control sequences are known in the art. General methods for expressing recombinant proteins are also known and are described in R. Kaufman,
Methods in Enzymology 185, 537-566 (1996). "Operably linked," as defined herein, means that the isolated polynucleotide and expression control sequence of the invention are transformed with the linked polynucleotide / expression control sequence.
(Transfected) means that the protein is expressed in the vector or cell so that the protein is expressed by the host cell.

[0440] Many types of cells can serve as suitable host cells for expression of the protein. Examples of mammalian host cells include monkey COS cells, Chinese hamster ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human Colo205 cells, 3T3 cells, CV-1 cells, and other traits. Converted primate cell line, normal diploid cell, cell line derived from in vitro culture of primary tissue, primary graft, HeLa cell, mouse L cell, BHK, HL-6
0, U937, HaK or Jurkat cells.

Alternatively, it is 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 strain, Ca
ndida or yeast strains capable of expressing a heterologous protein. Potentially suitable bacterial strains include Escherichia coli, Bacillus subtilis, Sal
monella typhimurium or each bacterial strain capable of expressing a heterologous protein. If the protein is made in yeast or bacteria, it may be necessary to modify the protein produced there to obtain a functional protein, for example, by phosphorylation or glycosylation at appropriate positions. . Such a covalent linkage can be achieved using known chemical or enzymatic methods.

The protein can also be produced in one or more insect expression vectors by operably linking the isolated polynucleotide of the present invention to appropriate control sequences and using an insect expression system. obtain. Materials and methods for baculovirus / insect cell expression systems are described, for example, in Invitrogen, San Diego, California, USA.
(MaxBac® kit) is commercially available in kit form, and such methods are described in Summers and Smith, Texas, hereby incorporated by reference.
It is well known in the art, as described in Agricultural Experiment Station Bulletin No. 1555 (1987). As used herein, insect cells capable of expressing the polynucleotides of the present invention are "transformed."

The proteins of the present invention can be made by culturing the transformed host cells under culture conditions suitable for expressing the recombinant protein. The resulting expressed protein can then be purified from such culture (ie, medium or cell extract) using known purification methods, such as gel filtration or ion exchange chromatography. Purification of the protein may also be achieved by affinity columns containing an agent that will bind to the protein; an affinity column on an affinity resin such as Concanavalin A-agarose, Heparin-Toyo Pearl® or Cibachrome Blue 3GA Sepharose®. It may include one or more column steps; one or more steps involving hydrophobic interaction chromatography using a resin such as phenyl ether, butyl ether, or propyl ether; or immunoaffinity chromatography.

Alternatively, the proteins of the invention may be expressed in a form that will facilitate purification. For example, maltose binding protein (MBP), glutathione-S-
It may be expressed as a fusion protein such as transferase (GST) or thioredoxin (TRX). Kits for expression and purification of such fusion proteins are commercially available from New England BioLabs (Beverly, MA), Pharmacia (Piscataway, NJ) and Invitrogen Corporation (Carlsbad, CA), respectively. Proteins can also be tagged with epitopes and subsequently purified using specific antibodies directed against such epitopes. One such epitope ("flag") is commercially available from Eastman Kodak Company (New Haven, CT).

Finally, one or more reversed-phase high-performance liquid chromatographs (RP
-HPLC) step can be used to further purify the protein using, for example, hydrophobic RP-HPLC, such as silica gel with methyl or other alkyl groups attached. Some or all of the foregoing purification steps, in various combinations, can also be used to provide a substantially homogeneous isolated recombinant protein. The protein thus purified is substantially free of other mammalian proteins and is defined according to the invention as an "isolated protein".

The protein of the present invention may also be transformed, for example, as a component of transformed bovine, goat, pig, or sheep milk characterized by somatic or germ cells containing a nucleotide sequence encoding the protein. It may be expressed as a product of an animal.

The protein may also be produced by known conventional chemical synthesis. Methods for constructing the proteins of the invention by synthetic means are known to those skilled in the art. Synthetically constructed protein sequences possess common biological properties, including the activity of the protein, thanks to the sharing of primary, secondary or tertiary structural and / or conformational characteristics with the protein. I have. Thus, they can be used as immunological substitutes for naturally occurring purified proteins in the screening of therapeutic compounds and in the immunization process for the development of antibodies.

The proteins provided herein also include proteins that are similar in sequence to the purified protein, but are characterized by amino acid sequences within which modifications are naturally conferred or manipulated. For example, modifications in the peptide or DNA sequence can be made by those skilled in the art using known techniques. Modifications of interest in the protein sequence may include alterations, substitutions, exchanges, insertions or deletions of selected amino acid residues in the coding sequence. For example, one or more cysteine residues can be deleted or replaced with another amino acid to change the conformation of the molecule. Techniques for such modifications, substitutions, exchanges, insertions or deletions are well known to those skilled in the art (see, for example, US Pat. No. 4,518,584). Such modifications, substitutions, exchanges, insertions or deletions preferably retain the desired properties of the protein.

Other fragments and derivatives of the protein sequence, which are expected to retain, in whole or in part, the activity of the protein, and thus may be useful in screening and other immunological techniques, are also described herein. Given the disclosure in the above, those skilled in the art can easily make it.

Uses and Biological Activities The polynucleotides and proteins of the present invention exhibit one or more of the uses and biological activities identified below, including those associated with the assays described herein. Is expected. The uses and biological activities described for the proteins of the present invention are suitable for the administration or use of such proteins or for the administration or use of polynucleotides encoding such proteins (e.g., in gene therapy or for the introduction of DNA). Vector).

Research Uses and Utility The polynucleotides provided herein can be used for various purposes by the research community. The polynucleotide is to express the recombinant protein for analysis, characterization or therapeutic use; where the corresponding protein is preferentially expressed (constitutively or at a particular stage of tissue differentiation or development or in a disease state). As a marker for tissue; as a molecular weight marker on Southern gels; as a chromosomal marker or tag (when labeled) for recognizing chromosomes or mapping relevant gene locations; potential genetic disorders Comparing to an endogenous DNA sequence in a patient to recognize a DNA sequence; as a probe to hybridize and thereby discover novel related DNA sequences;
As a source of information for deriving PCR primers for gene fingerprinting; as a probe to "remove" a known sequence in the process of discovering other novel polynucleotides; To select or create oligomers for attachment to "gene chips" or other carriers;
To raise anti-protein antibodies using DNA immunization techniques; and anti-D
NA antibodies can be raised or used as an antigen to elicit other immune responses. If the polynucleotide encodes a protein that binds or potentially binds to another protein (e.g., as in a receptor-ligand interaction), the polynucleotide may also be a protein that binds to another protein. Interaction trap assays to recognize polynucleotides encoding or recognize inhibitors of binding interactions (e.g., Gyuris et al., 1993, Cell 75: 791--all of which are incorporated herein by reference). 803 and Rossi et al., 1997, Proc. Natl.
Acad. Sci. USA 94: 8405-8410).

The proteins provided by the present invention can also be used in assays to measure biological activity, including in multiplex protein panels for high-throughput screening; to raise antibodies or elicit an immune response; Reagents (including labeled reagents) in assays designed to quantitatively measure the level of protein (or its receptor) in biological fluids; where the corresponding protein is preferentially expressed ( It can be used as a marker for tissue, either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate correlated receptors or ligands. If the protein binds or potentially binds to another protein (e.g., as in a receptor-ligand interaction), the protein also recognizes or binds to another protein where binding is taking place. It can be used to recognize inhibitors of action. Proteins involved in these binding interactions can also be used to screen for peptides or small molecule inhibitors or agonists of the binding interaction.

Each or all of these research utilities can be developed into reagent grade or kit formats that are marketed as research products.

[0464] Methods of performing the uses listed above are well known to those skilled in the art. A literature disclosing such a method is: "Molecular Cloning: A Laboratory Manual" 2d ed., Cold Spri.
ng Harbor Laboratory Press, Sambrook, J., EF Fritsch, and T. Maniatis
Ed., Eds., 1989, and "Methods in Enzymology: Guide to Molecular Cloning
Techniques ", Academic Press, Berger, SL and AR Kimmel, Editing, 1987
, Including without limitation.

Nutritional Uses The polynucleotides and proteins of the present invention can also be used as a nutritional source or supplement. Such uses include, but are not limited to, the use of protein or amino acids as a food supplement, as a carbon source, as a nitrogen source, and as a hydrocarbon source. In such cases, the protein or polynucleotide of the present invention may be added to the diet of the particular organism or may be added to another solid or liquid, such as in the form of a powder, pill, solution, suspension or capsule. It can be administered as a formulation. In the case of microorganisms, the proteins or polynucleotides of the invention can be added to the medium in which or on which the microorganism is cultured.

Cytokines and Cell Proliferation / Differentiation Activity The proteins of the present invention may exhibit cytokine, cell proliferation (either induction or inhibition) or cell differentiation (either induction or inhibition) activity, or some cell population. May induce the production of other cytokines. Many protein factors discovered to date, including all known cytokines, show activity in one or more factor-dependent cell proliferation assays, and therefore, the assay is a convenient method of cytokine activity. Useful for confirmation. The activity of the protein of the present invention is 32D, DA2, DA1G, T10, B9, B9 / 11, BaF3, MC
9 / G, M + (preB M +), 2E8, RB5, DA1, 123, T1165
, HT2, CTLL2, TF-1, Mo7e and CMK, as demonstrated by any one of a number of routine factor-dependent cell proliferation assays in cell lines, including but not limited to.

The activity of a protein of the invention is measured, among other means, by the following method:

Assays for the proliferation of T-cells or thymocytes are: Current Protocols in Imm
unology, Ed by JE Coligan, AM Kruisbeek, DH Margulies, EM Sh
evach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscien
ce (Chapter 3, In Vitro Assay of Mouse Lymphocyte Function 3.1-3.1
9; Chapter 7, immunological studies in humans); Takai et al., J. Immunol. 137: 3494-3500.
J. Immunol. 145: 1706-1712, 1990; Bertagnolli et al., Cellular Immunology 133: 327-341, 1991; Bertagnolli et al., J. Immunol. 149.
Including, but not limited to, those described in Bowman et al., J. Immunol. 152: 1756-1761, 1994.

Assays for cytokine production and / or proliferation of spleen cells, lymph nodes or thymocytes include: Polyclonal T cell stimulation, Kruisbeek, AM and Shevach
, EM In Current Protocols in Immunology. JE ea Coligan eds. Vol
1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto, 1994; and measurement of mouse and human interferon gamma, Schreiber, RD In Current Pr
otocols in Immunology. JE ea Coligan eds. Vol 1 pp. 6.8.1-6.8.8, J
including, but not limited to, those described in Ohn Wiley and Sons, Toronto, 1994.

Assays for proliferation and differentiation of hematopoietic and lymphocyte-producing cells include: Measurement of human and murine interleukin 2 and interleukin 4, Bottomly, K., Da
vis, LS and Lipsky, PE In Current Protocols in Immunology. JE 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. USA 80: 2931-2.
938, 1983; Measurement of mouse and human interleukin-6-Nordan, R. In Cur
rent Protocols in Immunology. JE ea Coligan eds. Vol 1 pp. 6.6.1-6
.6.5, John Wiley and Sons, Toronto, 1991; Smith et al., Proc. Natl. Acad. Sci.
USA 83: 1857-1861, 1986; Measurement of human interleukin-11-Bennett,
F., Giannotti, J., Clark, SC and Turner, KJ In Current Protocols
in Immunology. JE ea Coligan eds. Vol 1 pp. 6.15.1, John Wiley and
Sons, Toronto, 1991; Measurement of mouse and human interleukin 9-Ciarle
tta, A., Giannotti, J., Clark, SC and Turner, KJ In Current Protoc
ols in Immunology. JE ea Coligan eds. Vol 1 pp. 6.13.1, John Wiley
and Sons, Toronto, 1991, including, but not limited to.

To antigens (proteins that affect APC-T cell interactions and that direct T cell effects will be recognized, among other things, by measuring proliferation and cytokine production) T cell clone assay: Current P
rotocols in Immunology, Ed by JE Coligan, AM Kruisbeek, DH Marg
ulies, EM Shevach, W Strober, Pub.Green Publishing Associates and W
iley-Interscience (Chapter 3, In Vitro Assay of Mouse Lymphocyte Function; Chapter 6, Cytokines and Their Cell Receptors; Chapter 7, Immunological Studies in Humans); Weinberger et al., Proc. Natl. Acad. Sci. USA 77: 6091-6095, 1980; W
Einberger et al., Eur. J. Immun. 11: 405-411, 1981; Takai et al., J. Immunol. 137:
3494-3500, 1986; including, but not limited to those described in Takai et al., J. Immunol. 140: 508-512, 1988.

Immunostimulatory or Suppressive Activity The proteins of the invention may also exhibit immunostimulatory or immunosuppressive activity, including without limitation those assays described herein. The protein is useful in the treatment of various immunodeficiencies and abnormalities, including severe combined immunodeficiency (SCID), for example, in regulating the (up or down) growth and proliferation of T and / or B lymphocytes and in NK cells and other Would be useful in eliciting cytolytic activity in a cell population of These immunodeficiencies may be genetic or caused by viral (eg, HIV) and bacterial or fungal infections, or may be due to autoimmune abnormalities. More specifically, infectious diseases caused by viral, bacterial, fungal as well as other infections may be treatable using the proteins of the present invention, wherein HIV, hepatitis virus, herpes virus,
Includes various fungal infections such as infections with mycobacteria, Leishmania species, malaria species and candidiasis. Of course, in this regard, the proteins of the invention may also be useful where boosting the immune system is generally desired, for example, in the treatment of cancer.

Autoimmune disorders that can be treated using the proteins of the invention include, for example, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barré Syndrome, autoimmune thyroiditis, insulin-dependent diabetes, myasthenia gravis, graft-versus-host disease and autoimmune inflammatory eye disease. Such proteins of the invention may also be useful in treating allergic reactions or conditions, such as asthma (particularly allergic asthma) or other respiratory problems. Thus, other conditions in which immunosuppression is desired (including, for example, organ transplantation) may also be treated using the proteins of the present invention.

The proteins of the present invention could also be used to modulate an immune response in a number of ways. Downregulation may be in the form of suppressing or blocking an immune response that is already in progress or inhibiting the induction of an immune response. Activated T cell function may be suppressed by suppressing T cell responses, inducing specific tolerance in T cells, or both. Immunosuppression of T cell responses is generally
An active, non-antigen-specific process that requires continuous exposure of cells to the inhibitor. Tolerance involved in inducing unresponsiveness or inapparentness in T cells is distinguished from immunosuppression in that it is generally antigen-specific and persists after tolerance drug exposure has ceased I can do it. Operationally, tolerance is
Demonstrated by the lack of a T cell response when re-exposed to a specific antigen in the absence of a tolerant.

One or more antigen functions (B lymphocyte antigen functions (eg, such as B7)
), Including, but not limited to) down-regulation or prevention, e.g., prevention of high-level lymphokine synthesis by activated T cells is useful in the context of tissue, skin and organ transplantation and in graft-versus-host disease (GVHD) Will. For example, blockage of T cells should result in reduced tissue destruction in tissue transplantation. Typically, in tissue grafts, graft rejection is initiated by an immune response that destroys the graft following recognition of foreign matter by T cells. Prior to transplantation, molecules that inhibit or block the interaction of B7 lymphocyte antigen with natural ligand on immune cells (alone or with other B lymphocyte antigens (eg, B7-1, B7-3) Administration (such as a soluble monomeric form of a peptide having B7-2 activity) in conjunction with a monomeric form of the peptide having the activity of a blocking antibody) can produce the native form on immune cells without transmitting the corresponding costimulatory signal. Can lead to the binding of the molecule to the ligand. B in this matter
Lymphocyte antigen function prevents cytokine synthesis by immune cells such as T cells, and thus acts as an immunosuppressant. Furthermore, the lack of costimulation may also be sufficient to render T cells antigenic insensitive, thereby inducing tolerance in the subject. Induction of long-term tolerance by B lymphocyte antigen-blocking agents may obviate the need for frequent administration of these blocking agents. It may also be necessary to block B lymphocyte antigen binding function in order for the subject to achieve adequate immunosuppression and tolerance.

The efficacy of a specific blocking agent in preventing organ graft rejection or GVHD can be evaluated using animal models that predict efficacy in humans. Examples of suitable systems that can be used include allogeneic heart grafts in rats and xenogeneic islet transplants in mice, while Lenschow et al., Science 257: 789-792 (
1992) and Turka et al., Proc. Natl. Acad. Sci. USA 89: 11102-11105 (1992),
, Both have been used to test the immunosuppressive effects of CTLA4Ig fusion proteins in vivo. In addition, a rat model of GVHD (Paul ed., Fundamental Immunology, Raven Press, New York, 1989)
pp. 846-847) show that the effect of B lymphocyte antigen function on the development of the disease is i.
It can be used to measure in vivo.

Blocking antigen function may also be therapeutically useful for treating autoimmune diseases. Many autoimmune abnormalities are the result of inappropriate activation of T cells that are reactive with self tissues and promote the production of cytokines and autoantibodies involved in disease pathology. Preventing the activation of autoreactive T cells will reduce or eliminate the symptoms of the disease. Administration of an agent that blocks the costimulatory effects of T cells by disrupting the receptor: ligand interaction of the B lymphocyte antigen may result in the inhibition of T cell activation and autoantibodies or It can be used to prevent the production of T cell-induced cytokines. In addition, blocking agents can induce antibody-specific tolerance of autoreactive T cells, which may lead to long-term relief from disease. The efficacy of blocking agents to prevent or reduce autoimmune abnormalities can be measured using a number of well-characterized animal models of human autoimmune disease. Examples include murine experimental autoimmune encephalitis, systemic lupus erythematosus in MRL / lpr / lpr or NZB hybrid mice, murine autoimmune collagen arthritis, diabetes in NOD mice and BB rats, and experimental murine myasthenia in rats. (Paul ed., Fundamental Immunology, Raven Press, New York
, 1989, pp. 840-856).

As a means of up-regulating the immune response, up-regulation of antigen function (preferably B lymphocyte antigen function) may also be therapeutically useful. Upregulation of the immune response will be in a form that enhances an existing immune response or induces an early immune response. For example, enhancing the immune response by stimulating B lymphocyte antigen function would be useful in the case of a viral infection. In addition, systemic viral diseases such as influenza, cold and encephalitis will be reduced systemically by administration of a stimulated form of B lymphocyte antigen.

Alternatively, an anti-viral immune response can be achieved by removing T cells from a patient and expressing a peptide of the invention or, together with a stimulated form of a soluble peptide of the invention,
The T cells can be enhanced in infected patients by co-stimulating the T cells in vitro with APCs pulsed with viral antigens and reintroducing the in vitro activated T cells into the patient. Another method of enhancing an anti-viral immune response is to isolate infected cells from a patient and, along with a nucleic acid encoding a peptide of the invention, cause the cells to remove all or a portion of the protein as described herein. The cells will be transfected to express on the surface and the transfected cells will be reintroduced into the patient. Infected cells now have a costimulatory signal T
It will transmit to the cells and thereby activate the T cells in vivo.

In another application, up-regulation or enhancement of antigen function (preferably B lymphocyte antigen function) may be useful for inducing tumor immunity. Tumor cells (e.g., sarcoma, melanoma, lymphoma, leukemia, neuroblastoma, carcinoma) transfected with a nucleic acid encoding at least one peptide of the invention can be administered to a subject to produce tumor-specific tolerance in the subject. Nature can be suppressed. If desired, the tumor cells can be transfected to express peptide binding. For example, tumor cells obtained from a patient may express a peptide having a B7-2-like activity alone or in combination with a peptide having a B7-1-like activity and / or a B7-3-like activity. It can be transfected ex vivo with the indicated expression vector. The transfected tumor cells are returned to the patient, causing expression of the peptide on the surface of the transfected cells. Alternatively, tumor cells can be targeted for transfection in vivo using gene therapy techniques.

The presence of a peptide of the invention having the activity of B lymphocyte antigen (s) on the surface of tumor cells provides the necessary costimulatory signal for T cells and T cell mediated immune response against transfected tumor cells Is induced. Also, tumor cells lacking MHC class I or MHC class II molecules or failing to re-express a sufficient amount of MHC class I or MHC class II molecules can be wholly or partially (eg,
Transfected with MHC class Iα chain protein and beta ₂ microglobulin protein or nucleic acid encoding the MHC class IIα chain protein and an MHC class IIβ protein cleavage removed portion of the cytoplasmic domain), whereby the MHC class I or MHC class II proteins can be expressed on the cell surface. B lymphocyte antigens (eg, B7-1, B7-2, B
Suitable class I or class II in cooperation with a peptide having the activity of 7-3)
MHC expression elicits a T cell-mediated immune response against transfected tumor cells. Optionally, a gene encoding an antisense construct that blocks expression of MHC class II-related proteins, such as the invariant chain, may also be co-transfected with DNA encoding a peptide having B lymphocyte antigen activity. To promote the provision of tumor-associated antigens and elicit tumor-specific immunity. Thus, eliciting a T cell-mediated immune response in a human subject would be sufficient to reduce tumor-specific tolerance in the subject.

The activity of the proteins of the invention is measured, among other means, by the following method:

An appropriate assay for thymocyte or splenocyte cytotoxicity is: Current Protocol
s in Immunology, Ed by JE Coligan, AM Kruisbeek, DH Margulies,
EM Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-In
terscience (Chapter 3, In Vitro Assay of Mouse Lymphocyte Function 3.1)
-3.19; Chapter 7, Immunological Studies in Humans); Herrmann et al., Proc. Natl. Aca
d. 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. 1
37: 3494-3500, 1986; Takai et al., J. Immunol. 140: 508-512, 1988; Herrmann et al., Proc. Natl. Acad. Sci. USA 78: 2488-2492, 1981; Herrmann et al., J. Immunol.
128: 1968-1974, 1982; Handa et al., J. Immunol. 135: 1564-1572, 1985; Takai.
J. Immunol. 137: 3494-3500, 1986; Bowmanet et al., J. Virology 61: 1992-1.
998; Takai et al., J. Immunol. 140: 508-512, 1988; Bertagnolli et al., Cellular Im.
munology 133: 327-341, 1991; Brown et al., J. Immunol. 153: 3079-3092, 1994,
Including but not limited to those described in

Assays for T cell-dependent immunoglobulin responses and isotype switching (recognize proteins that modulate T-cell dependent antibody responses and will affect Th1 / Th2 profiles, among others) Where) is: Malisze
wski, J. Immunol. 144: 3028-3033, 1990; and assays for B cell function: In vitro antibody production, Mond, JJ and Brunswick, M. In Current Protocol.
s in Immunology. JE ea Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John W
including, but not limited to, those described in iley and Sons, Toronto, 1994.

The mixed lymphocyte reaction (MLR) assay, which among other would recognize proteins that preferentially generate Th1 and CTL responses, is: Current Pro
tocols in Immunology, Ed by JE Coligan, AM Kruisbeek, DH Margul
ies, EM Shevach, W Strober, Pub.Green Publishing Associates and Wil
ey-Interscience (Chapter 3, In Vitro Assay for Mouse Lymphocyte Function 3)
. 1-3.19; Chapter 7, Immunological Studies in Humans); Takai et al., J. Immunol. 13
7: 3494-3500, 1986; Takai et al., J. Immunol. 140: 508-512, 1988; Bertagnolli
Including, but not limited to, those described in J. Immunol. 149: 3778-3783, 1992.

The dendritic cell-dependent assay (which, among others, would recognize proteins expressed by dendritic cells that activate naive T cells) is: Guery et al., J. Immunol. 134: 536-544, 1995; Inaba et al., Journal of Experimental Medic.
ine 173: 549-559, 1991; Macatonia et al., Journal of Immunology 154: 5071-507.
9, 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, 1
994; including but not limited to those described in Inaba et al., Journal of Experimental Medicine 172: 631-640, 1990.

Assays for lymphocyte survival / apoptosis (which, among others, would recognize proteins that prevent apoptosis and regulate lymphocyte homeostasis after superantigen induction) are: Darzynkiewicz et al., Cytometry 13 : 795-80
8, 1992; Gorczyca et al., Leukemia 7: 659-670, 1993; Gorrczyca et al., Cancer Resea
rch 53: 1945-1951, 1993; Itoh et al., Cell 66: 233-243, 1991; Zacharchuk, Jou.
rnal of Immunology 145: 4037-4095, 1990; Zamai et al., Cytometry 14: 891-897,
1993; Gorczyca et al., International Journal of Oncology 1: 639-648, 1992,
Including but not limited to those described in

Assays for proteins that affect T cell commitment and early stages of development are:
tica et al., Blood 84: 111-117, 1994; Fine et al., Cellular Immunology 155: 111-12.
2, 1994; Galy et al., Blood 85: 2770-2778, 1995; Tokai et al., Proc. Natl. Acad. S.
ci. USA 88: 7548-7551, 1991, including without limitation.

Hematopoietic modulatory activity [0479] The proteins of the present invention will be useful in hematopoietic modulation and, consequently, in the treatment of myeloid or lymphoid cell deficiencies. A biological activity that barely supports colony forming cells or factor-dependent cell lines may also be involved in hematopoietic regulation, including, by itself or in conjunction with other cytokines, the development and proliferation of erythroid progenitor cells. Support, thereby being useful, for example, in the treatment of various anemias, or in promoting erythroid progenitor cells and / or erythroid cells production in combination with irradiation / chemotherapy; Supports the growth and proliferation of myeloid cells such as granulocytes and monocytes / macrophages that are useful in preventing or treating the resulting myelosuppression (ie, conventional CSF activity); megakaryocytes and consequently platelet growth And proliferation, thereby preventing or treating various platelet disorders such as thrombocytopenia. And can generally be used instead of or in addition to platelet transfusions; and / or can mature into any and all hematopoietic cells described above, and therefore have various stem cell disorders (aplastic disorders) Supporting the growth and proliferation of hematopoietic stem cells, which show therapeutic benefit to those normally treated by transplantation (including but not limited to anemia and paroxysmal nocturnal hemoglobinuria), and radiation Genetic manipulations for normal cells or gene therapy in vivo or ex vivo after irradiation / chemotherapy (ie, in combination with bone marrow transplantation or in combination with peripheral progenitor cell transplantation (allogeneic or xenogeneic)) Regenerating the stem cell compartment by cells.

The activity of the protein of the invention is measured, among other means, by the following method:

Suitable methods for measuring the proliferation and differentiation of various hematopoietic cell lines are cited above.

Assays for embryonic stem cell differentiation (which, among others, will recognize proteins that affect embryonic hematopoiesis) include: Johansson et al., Cellular Biology 15: 141-151, 1
995; Keller et al., Molecular and Cellular Biology 13: 473-486, 1993; McClana
han et al., Blood 81: 2903-2915, 1993, including but not limited to.

Assays for stem cell survival and differentiation (among others that would recognize proteins that regulate lymphocyte production and hematopoiesis) include: Methylcellulose colony formation assay, Freshney, MG In Culture of Hematopoietic Cells. RI Fresh
ney et al., Vol pp. 265-268, Wiley-Liss, Inc., New York, NY. 1994; Hiray
Natl. Acad. Sci. USA 89: 5907-5911, 1992; Primitive hematopoietic colony forming cells with high growth potential, McNiece, IK and Briddell, RA In Cult.
ure of Hematopoietic Cells.Edited by RI Freshney et al., Vol pp. 23-39, Wiley-L
iss, Inc., New York, NY. 1994; Neben et al., Experimental Hematology 22: 353-
359, 1994; Granular area cell formation assay, Ploemacher, RE, In Culture of
Editing of Hematopoietic Cells.RI Freshney et al., Vol pp. 1-21, Wiley-Liss, In
c., New York, NY. 1994; Long-term bone marrow culture in the presence of stromal cells, Spooncer, E., De.
xter, M. and Allen, T. In Culture of Hematopoietic Cells.RI Freshney
Edited by Vol. Pp. 163-179, Wiley-Liss, Inc., New York, NY. 1994; Long-term culture initiation cell assay, Sutherland, HJ In Culture of Hematopoietic Cells.
Edited by RI Freshney et al., Vol pp. 136-162, Wiley-Liss, Inc., New York, NY.
Including, but not limited to, those described in 1994.

Tissue Growth Activity The proteins of the invention may also be used for the growth or regeneration of bone, cartilage, tendon, ligament and / or nerve tissue, and for wound healing, tissue repair and replacement,
It may also be useful as a composition for treating burns, cuts and ulcers.

A protein of the invention that induces cartilage and / or bone growth in an environment where bone is not normally produced has application in the healing of fractures and cartilage damage or defects in humans and other animals. . Such formulations using the proteins of the invention will have prophylactic utility in reducing closed as well as open fractures and also in improving fixation of artificial joints. De induced by osteogenic agents
Novo bone formation contributes to the repair of congenital, trauma-induced or oncological resection-induced craniofacial defects, and is also useful in cosmetic plastic surgery.

The proteins of the present invention may also be useful in the treatment of periodontal disease as well as in other tooth restoration processes. Such an agent would provide an environment for attracting osteogenic cells, promote the growth of osteogenic cells, or induce the differentiation of osteogenic cell precursors. The proteins of the present invention may also inhibit osteoporosis or osteoarthritis, such as by promoting bone and / or cartilage repair or by blocking inflammatory or inflammatory processes mediated tissue destruction processes (collagenase activity, osteoclast activity, etc.). Will be useful for treatment.

Another category of tissue regeneration activity that may be provided by the proteins of the present invention is tendon / ligament formation. Proteins of the invention that induce the formation of tendon / ligament-like or other tissues in an environment where they are not normally formed,
It has application in tendon or ligament rupture, deformation, and healing of other tendon or ligament defects in humans and other animals. Such agents that use tendon / ligament-like tissue-inducing proteins have prophylactic uses for damage to tendon or ligament tissue, as well as for improved fixation of tendon or ligament to bone or other tissue. And repair of tendon or ligament tissue defects. The de novo tendon / ligament-like tissue formation induced by the protein composition of the present invention contributes to the repair of congenital, wound-induced or other causes or other tendon ligament defects and Or it is also useful for cosmetic surgery for ligament attachment or repair. The compositions of the present invention provide an environment for attracting tendon or ligament forming cells, promote the growth of tendon or ligament forming cells, induce differentiation of tendon or ligament forming cell precursors, or effectively effect tissue repair. In vivo
Induces ex vivo proliferation of the tendon / ligament cells or progenitor cells returned to The compositions of the invention may also be useful in treating tendinitis, carpal tunnel compression syndrome and other tendon or ligament defects. The composition may also contain as carrier a suitable matrix and / or sequestering agent well known to those skilled in the art.

The proteins of the present invention also include in the growth of nerve cells and the regeneration of nerve and brain tissue, ie, central and peripheral nervous system diseases and disorders, and degeneration, death or trauma to nerve cells or nerve tissue. It may be useful in treating mechanical and traumatic disorders. More specifically, proteins are used for peripheral nerve damage, such as peripheral and localized neuropathy, and Alzheimer's disease, Parkinson's disease,
It could be used to treat central nervous system diseases such as Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome. Additional conditions that can be treated according to the present invention include mechanical and traumatic disorders such as spinal cord disorders, head trauma, and cerebrovascular diseases such as stroke. Peripheral neuropathy resulting from chemotherapy or other medical treatment could also be treated using the proteins of the present invention.

The proteins of the present invention are also useful in promoting better or faster closure of non-healing wounds, including but not limited to pressure ulcers, ulcers with vascular insufficiency, surgery and trauma, and the like. Will.

The proteins of the present invention also include organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal, or cardiac), and blood vessels (including vascular endothelium).
It is expected that they will exert their activity on the development or regeneration of other tissues, such as tissues, or on the promotion of the growth of cells forming such tissues.
Some of the desired effects may be due to the inhibition or modification of fibrotic scarring that regenerates normal tissue. The proteins of the present invention will also have angiogenic activity.

The proteins of the invention may also protect and regenerate the stomach, and lung or liver fibrosis,
It may also be useful in treating conditions caused by reperfusion injury and systemic cytokine damage in various tissues.

The proteins of the present invention may also be useful for promoting or inhibiting the above-described tissue differentiation from progenitor tissues or cells; or for inhibiting the growth of the above-described tissues.

The activity of a protein of the invention is measured, among other means, by the following method:

Assays for histogenetic activity include: WO 95/16035 (bones, cartilage, tendons); WO 95/05846 (nerves, neurons); WO 91/07471 ( Skin, endothelium).

The assay for wound healing activity is: Eaglstein and Mertz, J. Invest. Dermatol 7
1: 382-84 (1978), Winter, Epidermal Wound Healing, pps.
71-112 (Maibach, HI and Rovee, DT, eds.), Year Book Medical Publishers,
Inc., including but not limited to those described in Inc., Chicago.

Activin / Inhibin Activity The proteins of the present invention will also exert an activin or inhibin-related activity. Inhibin is characterized by its activity of inhibiting follicle stimulating hormone (FSH) release, whereas activin is characterized by its activity of promoting follicle stimulating hormone (FSH) release. Accordingly, the protein of the present invention, alone or as a heterodimer with a member of the inhibin α family, reduces fertility in female mammals,
It may be useful as a contraceptive based on the activity of inhibin, which reduces spermatogenesis in male mammals. Administration of sufficient amounts of other inhibins can induce infertility in these mammals. On the other hand, the protein of the present invention is useful alone or as a heterodimer with other protein subunits of the inhibin β group as an ovulation inducer based on the activity of an activin molecule that promotes FSH release from anterior pituitary cells. Would. See, for example, U.S. Patent No. 4,798,885. The proteins of the present invention may also be useful in sexually immature mammals to promote fertility initiation for the lifetime improvement of livestock such as cattle, sheep and pigs.

The activity of the protein of the invention is measured, among other means, by the following method:

Assays for activin / inhibin activity include: Vale et al., Endocrinology 91:56.
2-572, 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. Aca
d. Sci. USA 83: 3091-3095, 1986, including, but not limited to.

Chemotaxis / chemomotility activity The proteins of the invention include, for example, mammalian cells, including monocytes, fibroblasts, neutrophils, T cells, mast cells, eosinophils, epithelial and / or endothelial cells. Will have chemotactic or chemotactic activity against (eg, act as a chemokine). Chemotactic and chemotactic proteins can be used to recruit or attract a desired cell population to a desired site of action. Chemotactic or chemotactic proteins offer particular benefits in treating wounds and other trauma to tissues, as well as in treating localized infections. For example, attracting lymphocytes, monocytes or neutrophils to the tumor or site of infection will result in an improved immune response to the tumor or infectious agent.

A protein or peptide has chemotactic activity on a particular cell population if it can directly or indirectly promote the directing or movement of that cell population. Preferably, the protein or peptide has the activity of directly promoting the directed movement of cells. Whether a particular protein has chemotaxis for a cell population can be readily determined by any known cell chemotaxis assay using such a protein or peptide.

The activity of a protein of the invention is measured, among other means, by the following method:

Assays for chemotactic activity, which will recognize proteins that induce or block chemotaxis, are based on the activity of proteins that induce cell translocation across membranes, as well as another activity of certain cell populations. Measuring the activity of the protein to induce adhesion to a cell population. Appropriate assays to measure migration and adhesion are: Curr
ent Protocols in Immunology, Ed by JE Coligan, AM Kruisbeek, DH Ma
rgulies, EM 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, 199.
5; Lind et al., AMIS 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 I.
mmunol. 153: 1762-1768, 1994, including, but not limited to.

Hemostasis and thrombolytic activity The proteins of the present invention will also exert hemostatic or thrombolytic activity.
As a result, such proteins are useful in the treatment of various blood clotting disorders, including genetic disorders such as hemophilia, and in the treatment of wounds caused by trauma, surgery or other causes. And is expected to promote other hemostatic events. The proteins of the invention may also be useful for thrombolysis or inhibition of thrombus formation, and for the treatment and prevention of conditions resulting therefrom, such as, for example, infarction of blood vessels of the heart and central nervous system, such as stroke.

The activity of a protein of the invention is measured, among other means, by the following method:

Assays for hemostatic and thrombolytic activity are 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
, Including without limitation.

Receptor / Ligand Activity Proteins of the present invention will also exert activity as receptors, receptor ligands, or inhibitors or agonists of receptor / ligand interactions. Examples of such receptors and ligands include cytokine receptors and their ligands, receptor kinases and their ligands, receptor phosphatases and their ligands, receptors involved in cell-cell interactions and their ligands (cells Adhesion molecules (such as, but not limited to, selectins, integrins, and their ligands) and receptor / ligand pairs involved in antigen presentation, antigen recognition, and development of cells and humoral immune responses Included without limitation. Receptors and ligands are also useful in screening for potential peptidic or small molecule inhibitors of the involved receptor / ligand interaction. The proteins of the invention, including but not limited to receptor and ligand fragments, may themselves be useful as inhibitors of receptor / ligand interactions.

The activity of a protein of the invention is measured, among other means, by the following method:

Suitable assays for receptor-ligand activity include: Current Protocols in I
mmunology, Ed by JE Coligan, AM Kruisbeek, DH Margulies, EM S
hevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Intersci
ence (Chapter 7.28 Measurement of Cell Adhesion under Static Conditions 7.28.1 to 7.28)
. 22), Takai et al., Proc. Natl. Acad. Sci. USA 84: 6864-6868, 1987; Bierer
J. Exp. Med. 168: 1145-1156, 1988; Rosenstein et al., J. Exp. Med. 169: 1
49-160, 1989; Stoltenborg et al., J. Immunol.Methods 175: 59-68, 1994; Stitt
Et al., Cell 80: 661-670, 1995, including, but not limited to.

Anti-inflammatory activity The proteins of the present invention will also exert anti-inflammatory activity. Anti-inflammatory activity inhibits or promotes cell-cell interactions (such as cell adhesion) by stimulating cells involved in the inflammatory response, thereby inhibiting the chemotaxis of cells involved in the inflammatory process Or by promoting, by inhibiting or promoting cell extravasation, or by promoting or suppressing the production of other factors that more directly inhibit or promote the inflammatory process. Proteins that exert such activities include infections (such as septic shock, sepsis, or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection Inflammatory conditions associated with nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, or Crohn's disease, or inflammatory conditions that result from overproduction of cytokines such as TNF or IL-1. It can be used to treat inflammatory conditions (including chronic or acute conditions) including without. The proteins of the present invention will also be useful in the treatment of anaphylaxis and hypersensitivity to substances or materials having antigenicity.

Cadherin / Tumor Invasion Inhibitory Activity Cadherin is a calcium-dependent adhesion molecule that appears to play an important role during development, particularly in identifying specific cell types. Loss or modulation of normal cadherin expression can result in altered cell adhesion properties associated with tumor growth and metastasis. Cadherin dysfunction has also been linked to other human diseases such as pemphigus vulgaris and pemphigus foliaceus (autoimmune bullous dermatoses), Crohn's disease, and certain developmental abnormalities.

The cadherin superfamily contains well over 40 members, each with a unique expression pattern. While all members of this superfamily have a common extracellular repeat (the cadherin domain), structural differences have been found in other parts of the molecule. The cadherin domain associates with calcium to form a tertiary structure, and thus calcium is required to mediate its adhesion. Only a few amino acids in the first cadherin domain provide the basis for homophilic adhesion; modification of this recognition site alters the specificity of cadherin, and the mutant molecule now differs from recognizing only itself It can also bind to cadherin. In addition, some cadherins are involved in heterophilic adhesion to other cadherins.

E-cadherin is a member of the cadherin superfamily and is expressed on epithelial cell types. Pathologically, if E-cadherin expression is lost in the tumor, the malignant cells become invasive and the cancer can metastasize. Transfecting a cancer cell line with a polynucleotide that expresses E-cadherin returns the altered cell morphology to normal, restores cell-to-cell and substrate adherence, reduces cell growth rates, and The changes associated with cancer have been reversed, such as by dramatically reducing anchorage-dependent cell proliferation. Thus, reintroduction of E-cadherin expression returns the carcinoma to a less advanced stage. Other cadherins are likely to play a similar role in suppressing invasion in carcinomas from other tissue types. Therefore, the proteins of the present invention having cadherin activity, and the polynucleotides of the present invention encoding such proteins can be used for treating cancer. The introduction of such proteins or polynucleotides into cancer cells can reduce or eliminate the cancerous changes observed in these cells by producing normal cadherin expression.

[0513] Cancer cells have also been shown to express cadherins of different tissue types than those from which they originate, which allows these cells to invade and metastasize to different tissues in the body Become like The proteins of the invention having cadherin activity, and the polynucleotides of the invention encoding such proteins, restore normal cell adhesion by substituting cadherin that is inappropriately expressed in these cells. In addition, the tendency of cells to metastasize can be reduced or eliminated.

In addition, proteins of the invention having cadherin activity, and polynucleotides of the invention encoding such proteins, can be used to generate antibodies that recognize and bind to cadherin. Such antibodies can be used to block cadherin adhesion to improperly expressed tumor cells and prevent the cells from forming tumors elsewhere. Such anti-cadherin antibodies can be used as markers of cancer malignancy, pathological type and cancer prognosis, and therefore, the more advanced the cancer, the less likely the expression of cadherin, and the lower the cadherin expression. This decrease can be detected using a cadherin binding antibody.

Fragments of the proteins of the invention having cadherin activity, preferably polypeptides consisting of the decapeptide of the cadherin recognition site, and polynucleotides of the invention encoding such protein fragments also bind to cadherin and Can be used to block the function of cadherin by preventing it from binding in a way that produces undesirable effects. In addition, fragments of the proteins of the invention having cadherin activity, preferably truncated soluble cadherin fragments that have been found to be stable in the circulation of cancer patients, and encoding such protein fragments Polynucleotides can be used to prevent intrinsic cell-cell adhesion.

Assays for cadherin adhesion activity and invasion inhibitor activity can be found in: Hortsch et al., JB
iol Chem 270 (32): 18809-18817, 1995; Miyaki et al., Oncogene 11: 2547-2552,
1995; Ozawa et al., Cell 63: 1033-1038, 1990, including without limitation.

Tumor Inhibitory Activities In addition to the activities described above for immunological treatment or prevention of tumors, the proteins of the present invention may also exert other antitumor activities. The protein can directly or indirectly inhibit tumor growth (eg, such as antibody-dependent cellular cytotoxicity (ADCC)). By acting on tumor tissue or tumor precursor tissue, the protein
By inhibiting the formation of tissue necessary to support tumor growth (e.g., by inhibiting angiogenesis), causing the production of other factors, agents, or cell types that inhibit tumor growth, Alternatively, by suppressing or inhibiting a factor, an agent, or a cell type that promotes tumor growth, the tumor inhibitory activity can be exerted.

Other Activities The proteins of the present invention may also exert one or more of the following additional activities or effects: Without limitation, bacteria, viruses, molds and other parasites Inhibit or eliminate the growth, infection or function of infectious agents including; height, weight, hair color, eye color, skin, obesity, pigmentation of other tissues, or Effects on body characteristics (suppression or enhancement) including, but not limited to, size or shape (eg, breast enlargement or reduction, changes in bone shape, etc.); effects on biorhythms or circadian cycles or rhythms; men or women Effects on the fertility of the subject; fat, lipids, proteins, carbohydrates, vitamins, minerals, cofactors, or Trophic factors or components of metabolism (s), catabolic, anabolic, processing, use, storage, or effect on emissions; (including cognitive disorders) appetite, libido, stress, cognition, depression (
Effects on behavioral characteristics, including but not limited to depressive disorder) and violence; providing analgesic or other pain-relieving effects; promoting selective differentiation and proliferation of embryonic stem cells in non-hematopoietic lineages Hormonal or endocrine activity; in the case of enzymes, correction of enzyme deficiency and treatment of deficiency-related diseases; treatment of hyperproliferative disorders (eg, psoriasis); immunoglobulin-like activity (eg, binding to antigen or complement) And the like, which act as an antigen in a vaccine composition and elicit an immune response against such proteins or other substances or entities that cross-react with such proteins.

Usage and Volume The proteins of the present invention (from, but not limited to, from recombinant and non-recombinant sources, from any derived source) can be prepared when formulated with a pharmaceutically acceptable carrier. , Can be used in pharmaceutical compositions. Such compositions may also include (in addition to proteins and carriers) art-known additives, excipients, salts, buffers, stabilizers, solubilizers, and other materials known in the art. . The term “pharmaceutically acceptable”
A non-toxic material that does not interfere with the effect of the biological activity of the active ingredient (s). The nature of the carrier will depend on the route of administration. Pharmaceutical compositions of the invention also include cytokines, lymphokines or M-CSF, GM-CSF, TNF, IL-1, IL-
2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9
, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15
, IFN, TNF0, TNF1, TNF2, G-CSF, Meg-CSF, thrombopoietin, stem cell factor and hematopoietic factors such as erythropoietin. The pharmaceutical composition may further contain other agents that enhance the activity of the protein or aid in its activity or therapeutic use. Such additional factors and / or agents may be included in the pharmaceutical composition to produce a synergistic effect with the protein of the invention or to minimize side effects. Conversely, the proteins of the present invention may be included in formulations of certain cytokines, lymphokines, other hematopoietic factors, thrombolytic or antithrombolytic factors or anti-inflammatory agents to produce cytokines, lymphokines, other hematopoietic factors,
Side effects of thrombolytic or antithrombolytic factors or anti-inflammatory agents can be minimized.

The proteins of the present invention may be active in multimers (eg, heterodimers or homodimers) or in complexes with themselves or with other proteins. as a result,
The pharmaceutical composition of the present invention may consist of the protein of the present invention in such a high or complex form.

The pharmaceutical compositions of the invention may be in the form of a complex of the protein (s) of the invention and a protein or peptide antigen. Protein and / or peptide antigens will transmit a stimulatory signal to both B and T lymphocytes. B
Lymphocytes respond to antigens through their surface immunoglobulin receptors. T lymphocytes respond to antigen through the T cell receptor (TCR) following presentation of the antigen by MHC proteins. MHC and structure-related proteins, including those encoded by class I and class II MHC genes on host cells, are peptide antigens.
(Class) would serve to provide T lymphocytes. The antigen component may also be supplied alone or as a purified MHC-peptide complex with a costimulatory molecule capable of sending a signal directly to T cells. Instead, immunoglobulins and other molecules
Antigens that can bind on cells and antigens that can bind TCRs and other molecules on T cells may be combined with the pharmaceutical compositions of the present invention.

The pharmaceutical compositions of the present invention include those wherein the protein of the present invention comprises, in addition to other pharmaceutically acceptable carriers, a coagulant such as a micelle, insoluble monolayer, liquid crystal or layered layer in an aqueous solution. It may be in the form of a complex with a liposome that is combined with an amphiphilic drug, such as a lipid, which is present in the aggregate. Suitable lipids for the preparation of liposomes include, without limitation, monoglycerides, diglycerides, sulfatides, lysolectins, phospholipids, saponins, bile acids, and the like. The preparation of formulations of such liposomes is described, for example, in US Pat. No. 4,235,871; US Pat. No. 4,501,728; US Pat. No. 4,833, all of which are incorporated herein by reference.
7,028; and U.S. Pat. No. 4,737,323, which are within the state of the art.

As used herein, the term “therapeutically effective amount” means the total amount of each active ingredient of a pharmaceutical ingredient or method, and has significant patient benefit, ie, treatment, cure, or cure of an associated medical condition. That is sufficient to prevent or ameliorate, or to treat, cure, increase the speed of prevention or amelioration of such a condition. When applied to an individual active ingredient administered alone, the term refers to that ingredient alone. When applied to a formulation, the term refers to the amount of active ingredient that, when combined, whether sequentially or simultaneously, produces a therapeutic effect.

To practice the methods or uses of the invention, a therapeutically effective amount of a protein of the invention is administered to a mammal having the condition to be treated. The proteins of the invention may be administered either alone according to the methods of the invention or in combination with other therapies, such as treatment using cytokines, lymphokines or other hematopoietic factors. When co-administered with one or more cytokines, lymphokines or other hematopoietic factors, the proteins of the invention may include cytokines (s), lymphokines (s), other hematopoietic factors (s), thrombolytic or antithrombotic It may be administered either simultaneously with the lytic factor or sequentially. If administered sequentially, the attending physician should include cytokine (s), lymphokine (s), and other hematopoietic factor (s).
The appropriate sequence for administering the proteins of the present invention in combination with thrombolytic or antithrombolytic factors will be determined.

Administration of a protein of the invention for use in a pharmaceutical composition or for practicing a method of the invention may be by oral ingestion, inhalation, application or transdermal, subcutaneous, intraperitoneal, parenteral or intravenous injection. It is performed by various conventional methods. Intravenous administration to the patient is preferred.

When orally administering a therapeutically effective amount of a protein of the present invention, the protein of the present invention will be in the form of tablets, capsules, powders, solutions or elixirs. When administered in tablet form, the pharmaceutical composition of the invention may additionally contain a solid carrier such as gelatin or an adjuvant. Tablets, capsules and powders contain from about 5% to 95% of a protein of the invention, and preferably from about 25% to 90% of a protein of the invention. When administered in liquid form, a liquid carrier such as oil of animal or vegetable origin, such as water, petroleum, peanut oil, mineral oil, soybean oil or sesame oil, or a synthetic oil may be added. The liquid form of the pharmaceutical composition may further contain physiological saline, dextrose or other carbohydrate solution, or glycols such as ethylene glycol, propylene glycol or polyethylene glycol. When administered in liquid form, the pharmaceutical composition will comprise from about 0.5% to 90% by weight of the protein of the invention, and preferably from about 1%
From 50% of the protein of the invention.

When a therapeutically effective amount of a protein of the present invention is administered by intravenous, transdermal or subcutaneous injection, the 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, with due regard to pH, isotonicity, and stability, is within the skill of the art. Preferred pharmaceutical compositions of the present invention for intravenous, transdermal or subcutaneous injection include, in addition to the protein of the present invention, saline injection, Ringer's injection, dextrose injection, dextrose and saline injection, lactated Ringer's injection, Or it should contain an isotonic base such as another base known in the art. The pharmaceutical compositions of the present invention may also contain stabilizers, preservatives, buffers, antioxidants or other additives known to those skilled in the art.

The amount of a protein of the present invention in a pharmaceutical composition of the present invention will depend on the nature and severity of the condition being treated and on the nature of the previous treatment the patient has received, and will ultimately The attending physician will decide the amount of protein of the present invention to treat an individual patient. Initially, the attending physician will administer a low dose of a protein of the invention and observe the patient's response. Higher doses of the protein of the invention will be administered until the proper therapeutic effect is obtained in the patient, and at this point the dose is not further increased. The various pharmaceutical compositions of the present invention used to practice the methods of the present invention may contain from about 0.01 μg to about 100 mg (preferably from about 0.1 ng to about 10 mg, more preferably from about 0.1 ng to about 10 mg / kg body weight). 0.1 μg to about 1
(up to mg) of the protein of the invention.

The duration of intravenous therapy using the pharmaceutical compositions of the present invention will vary depending on the severity of the condition being treated and the condition and potential idiosyncratic response of the individual patient. It is contemplated that the duration of each application of the protein of the 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 therapy using the pharmaceutical composition of the present invention.

The proteins of the present invention can also be used to immunize animals to obtain polyclonal and monoclonal antibodies that specifically react with the protein. As used herein, the term “antibody” is not limited to polyclonal, monoclonal, chimeric, single chain, CDR-grafted, humanized, or fragments thereof that bind to the indicated proteins. Included. Such terms also include antibodies or any other species derived from antibody sequences that are capable of binding the indicated proteins.

[0531] Antibodies to specific proteins can be produced by methods well known to those skilled in the art. For example, monoclonal antibodies can be prepared by known methods (eg, Goding, 1983, Monoclonal Antibodies: Principles and Practice, Academic Press Inc., New York; and Yokoyama, 1992, "Production of Monoclonal Antibodies", Current Protocols in Imm.
(See unology, Unit 2.5, Greene Publishing Assoc. and John Wiley & Sons)
And can be produced by generation of an antibody-producing hybridoma. Polyclonal sera and antibodies can be produced by inoculating a mammalian subject with the relevant protein or fragment thereof according to known methods. Fragments of antibodies, receptors, or other reactive peptides can be prepared from the corresponding antibodies by known methods (eg, Goding, supra; and Andrew et al., 1992, "Fragmentation of immunoglobulins", Cu
rrent Protocols in Immunology, Unit 2.8, Greene Publishing Assoc. and Jo
hn Wiley & Sons) and the desired fragment can be cut and harvested. Chimeric and single chain antibodies can also be prepared by known recombinant methods (eg, 5,
169, 939, 5, 194, 594 and 5,576, 184). Humanized antibodies are also known from the corresponding murine antibodies by known methods.
(See, for example, US Pat. Nos. 5,530,101, 5,585,089 and 5,693,762). In addition, human antibodies include non-human animals such as mice that have been genetically altered to express human antibodies (eg, Fishwild et al., 1996, Nature Biotechnology 14, 845-851).
Et al., 1997, Nature Genetics 15: 146-156 (Nature Genetics 16: 410 is incorrect); and see U.S. Patent Nos. 5,877,397 and 5,625,126). . Such antibodies can be obtained using either the whole protein or a variant thereof as an immunogen. Peptide immunogens may additionally contain a cysteine group at the carboxyl terminus and are conjugated to a hapten such as keyhole limpet hemocyanin (KLH). Methods for synthesizing such peptides are described, for example, in RP Merrifield, J. Amer. Chem. Soc. 85, 2149-2.
154; JL Krstenansky et al., FEBS Lett. 211, 10 (1987).

A monoclonal antibody that binds to a protein of the invention may be a useful diagnostic agent for immunodetection of that protein. Neutralizing monoclonal antibodies that bind to this protein will also be useful therapeutic agents for both conditions associated with the protein and also in the treatment of some forms of cancer involving aberrant expression of the protein. In the case of cancerous or leukemia cells, neutralizing monoclonal antibodies to the protein will be useful in detecting and preventing metastatic spread of cancerous cells that will be mediated by the protein.

For compositions of the invention useful for the regeneration of bone, cartilage, tendon or ligament, the method of treatment may be topical, systematic, or partially as an implant or device. Administering to the subject. When administered, the therapeutic composition for use in the present invention is, of course, in a pyrogen-free, physiologically acceptable form. In addition, the composition will desirably be encapsulated or injected in a viscous form for delivery to the site of bone, cartilage, or tissue damage. The application may be suitable for wound healing and tissue repair. Therapeutically useful agents other than the protein of the invention, which may also optionally be included in the composition as described above, may be alternatively or additionally, simultaneously or sequentially with the composition of the method of the invention. It may be administered. Preferably, for the formation of bone and / or cartilage, the composition delivers the protein-containing composition to the site of the bone and / or cartilage, provides a structure for generating bone and cartilage, and optimally comprises the body. Will contain a matrix that can be absorbed into the matrix. Such matrices will be molded from materials currently used for other implantable medical applications.

The choice of matrix material is based on biocompatibility, biodegradability, mechanical properties, cosmetic appearance and interface properties. The particular application of the composition will dictate the appropriate formulation. Possible matrices of the composition will be biodegradable and chemically defined calcium sulfate, tricalcium phosphate, hydroxyapatite, polylactic acid, polyglycolic acid and polyanhydride. Other potential matrices, such as bone or skin collagen, are biodegradable and well defined biologically. Another matrix is composed of pure proteins or extracellular matrix components. Other possible matrices are non-biodegradable and chemically defined, such as sintered hydroxyapatite, bioglass, aluminates or other ceramics. The matrix may be composed of a blend of any of the above types, such as polylactic acid and hydroxyapatite or collagen and tricalcium phosphate. Bioceramics, like calcium-aluminate-phosphate, may be processed with varying compositions and varying pore size, particle size, particle shape and biodegradability.

Presently preferred is a 50:50 (molar weight) copolymer of lactic acid and glycolic acid in the form of porous particles having a diameter ranging from 150 to 800 microns.
In some applications, it may be useful to use a sequestering agent such as carboxymethylcellulose or an autoclot to prevent the protein composition from separating from the matrix.

A preferred family of sequestrants is cellulosic materials such as alkylcellulose (including hydroxyalkylcellulose), including methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl-methylcellulose and carboxymethylcellulose, and Preferred are cationic salts of carboxymethylcellulose (CMC). Other preferred sequestering agents include hyaluronic acid, sodium alginate, poly (ethylene glycol), polyoxyethylene oxide, carboxyvinyl polymers and poly (vinyl alcohol). The amount of sequestering agent useful herein is 0.5-20% by weight, preferably 1-1, based on the total formulation weight.
0% by weight, which prevents the desorption of proteins from the polymer matrix,
And the amount needed to provide proper handling of the composition, but still not large enough to prevent the progenitor cells from infiltrating the matrix, thus providing the protein with the opportunity to assist the progenitor's osteoblastic activity. provide.

In another composition, the protein of the present invention may be combined with other agents that are beneficial in treating bone and / or cartilage defects, wounds or tissue of interest. The agents include epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factors (TGF-α and TGF-β) and insulin-like growth factor (IGF)
Is mentioned.

Therapeutic compositions are also currently valuable for veterinary applications. In particular, in addition to humans, livestock and thoroughbred horses are desirable patients for such treatment with the proteins of the present invention.

The dosage regimen of the protein-containing pharmaceutical composition used for tissue regeneration will be determined by the attending physician, who will be aware of various factors that modify the action of the protein,
For example, the desired tissue weight to be formed, the site of damage, the condition of the damaged tissue, the size of the wound, the type of tissue damaged (e.g., bone), the age, gender and diet of the patient,
Consider the severity of each infection, time of administration, and other clinical factors. Dosages will vary with the type of matrix used in the reconstitution and with the inclusion of other proteins in the pharmaceutical composition. For example, IGFI (insulin-like growth factor I) to the final composition
The addition of known growth factors, such as, will also affect the dosage. Progress can be monitored by periodic assessment of tissue / bone growth and / or repair, eg, x-ray, histomorphometric measurements, and tetracycline labeling.

The polynucleotides of the present invention can also be used for gene therapy. Such polynucleotides can be expressed in mammalian cells in vivo in expression cells.
It can be introduced either in vivo or ex vivo. The polynucleotides of the present invention also include other known methods for introducing nucleic acids into cells or organs.
(Including but not limited to viral vectors or naked DNA forms).

The cells may also be cultured ex vivo in the presence of a protein of the invention in order to expand or produce the desired effect or activity on such cells. The treated cells can then be introduced in vivo for clinical purposes.

The patent and literature references cited herein are hereby incorporated by reference as if fully indicated.

[Sequence list]

[Brief description of the drawings]

FIG. 1A is a schematic diagram showing the pED6 and pNOTs vectors, respectively, used for depositing the clones disclosed herein.

FIG. 1B is a schematic diagram showing the pED6 and pNOTs vectors, respectively, used for depositing the clones disclosed herein.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI Theme coat ゛ (Reference) A61P 21/00 A61P 31/04 4H045 29/00 31/10 31/04 31/12 31/10 31/18 31/12 35/00 31/18 37/00 35/00 C07K 14/47 37/00 C12P 21/02 C C07K 14/47 G01N 33/15 Z C12N 5/10 33/50 Z C12P 21/02 C12N 15 / 00 ZNAA G01N 33/15 A61K 37/02 33/50 C12N 5/00 B (31) Priority claim number 60 / 099,618 (32) Priority date September 9, 1998 (September 9, 1998) (33) Priority claim country United States (US) (31) Priority claim number 60 / 102,092 (32) Priority date September 28, 1998 (September 28, 1998) (33) Priority claim country United States (US) (31) Priority claim number 60 / 109,978 (32) Priority date November 1998 25 (1998.11.25) (33) Priority claim country United States (US) (31) Priority claim number 60 / 113,645 (32) Priority date December 23, 1998 (December 23, 1998) (33) Priority claim country United States (US) (31) Priority claim number 60 / 113,646 (32) Priority date December 23, 1998 (1998.23.1998) (33) Priority claim country United States (US) (31) Priority claim number 09 / 379,246 (32) Priority date August 23, 1999 (August 23, 1999) (33) Priority claim country United States (US) (81) Designation Country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA (BF, BJ, CF, CG) , CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SL, SZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CU, CZ, DE, DK, EE, ES, FI, GB , GE, GH, GM, HR, HU, ID, IL, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, UA, UG, UZ, VN, YU, ZW (72) Inventor Heidi Hoffman, No. 260, West Cummings Park, Woburn, MA 01801, USA (72) Inventor Jeff Hall 260, West Cummings Park, Woburn, MA 01801, USA (72) Inventor Peter Lapisco, USA 01801 No. 260, West Cummings Park, Woburn, Mass., F No. 260 F-term (reference) GA11 HA01 4B064 AG01 CA02 CA10 CA19 CC24 DA01 DA13 4B065 AA90X AA90Y CA24 CA44 CA46 4C084 AA01 AA07 AA13 BA01 ZA02 ZA59 ZA94 ZA96 ZB11 ZB13 ZB15 ZC35 4H045 AA10 AA20 AA30 CA40 EA20

Claims (89)

[Claims] 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 nucleotides 638-934 of SEQ ID NO: 1. (C) the nucleotide sequence of the full-length protein coding sequence of clone vb11_1 of ATCC Deposit No. 98846; (d) the nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vb11_1 of ATCC Deposit No. 98846; ) A nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 2; (f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 2 (provided that the fragment is SEQ ID NO:
(G) at least 65 ° C with 4XSSC or 50% formamide at 42 ° C.
A) a nucleotide sequence that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(d); and (h) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridizes to any of the polynucleotides defined in (a)-(d) under stringent conditions of the order of 6XSSC and has SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of one. 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 according to claim 2. 4. The host cell according to claim 3, wherein the host cell is a mammalian cell. 5. A method for producing a protein encoded by the polynucleotide according to claim 2, comprising the following steps: (a) transformed in a suitable culture medium with the polynucleotide according to claim 2; Growing a culture of the host cells; and (b) purifying the protein from the culture. 6. A protein produced by the method according to 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 vb11_1 of ATCC Deposit No. 98846. 9. A protein, essentially free of other mammalian proteins, comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 2; (b) the amino acid sequence of SEQ ID NO: 2 (Provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 2)
And (c) the amino acid sequence encoded by the cDNA insert of clone vb11_1 of ATCC Deposit No. 98846. 10. The protein of claim 9, wherein the 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 nucleotides 63-482 of SEQ ID NO: 3. ;
(c) the nucleotide sequence of nucleotides 201-482 of SEQ ID NO: 3; (d) the nucleotide sequence of the full-length protein coding sequence of clone vb12_1 of ATCC deposit number 98846; (e) the cDNA insertion of clone vb12_1 of ATCC deposit number 98846. A nucleotide sequence encoding the full-length protein encoded by the body; (f) a nucleotide sequence of the mature protein coding sequence of clone vb12_1 of ATCC Deposit No. 98846; (g) a cDNA insert of clone vb12_1 of ATCC Deposit No. 98846. (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 4; (i) a fragment of the amino acid sequence of SEQ ID NO: 4; Nucleotide sequence encoding a protein comprising bets (provided that the fragment SEQ ID NO
(J) containing 8 consecutive amino acids of 4); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 3. 13. A protein, essentially free of other mammalian proteins, comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 4; (b) an amino acid sequence of SEQ ID NO: 4 (Provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 4)
And (c) the amino acid sequence encoded by the cDNA insert of clone vb12_1 of ATCC Deposit No. 98846. 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 nucleotides 1195 to 1527 of SEQ ID NO: 5 (C) the nucleotide sequence of nucleotides 1468 to 1527 of SEQ ID NO: 5; (d) the nucleotide sequence of the full-length protein coding sequence of clone vb14_1 of ATCC deposit number 98846; (e) the cDNA of clone vb14_1 of ATCC deposit number 98846; A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vb14_1 of ATCC deposit number 98846; (g) a cD of clone vb14_1 of ATCC deposit number 98846. A nucleotide sequence encoding the mature protein encoded by the NA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 6; (i) including a fragment of the amino acid sequence of SEQ ID NO: 6 A nucleotide sequence encoding a protein (provided that the fragment has SEQ ID NO:
(J) containing 8 contiguous amino acids of 6); (j) 42 ° C with 4XSSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 5. 15. A protein, essentially free of other mammalian proteins, comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 6; (b) an amino acid sequence of SEQ ID NO: 6. (Provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 4)
And (c) the amino acid sequence encoded by the cDNA insert of clone vb14_1 of ATCC Deposit No. 98846. 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 nucleotides 82-294 of SEQ ID NO: 7. ;
(c) the nucleotide sequence of nucleotides 109 to 294 of SEQ ID NO: 7; (d) the nucleotide sequence of the full-length protein coding sequence of clone ve11_1 of ATCC accession number 98846; (e) the cDNA insertion of clone ve11_1 of ATCC accession number 98846 A nucleotide sequence encoding the full-length protein encoded by the body; (f) a nucleotide sequence of the mature protein-encoding sequence of clone ve11_1 of ATCC accession number 98846; (g) a cDNA insert of clone ve11_1 of ATCC accession number 98846. (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 8; (i) a fragment of the amino acid sequence of SEQ ID NO: 8 Nucleotide sequence encoding a protein comprising bets (provided that the fragment SEQ ID NO
(J) containing 8 contiguous amino acids of 6); (j) 42 ° C with 4XSSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
7. A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 7. 17. A protein, essentially free of other mammalian proteins, comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 8; (b) the SEQ ID NO: 8 (Provided that the fragment contains eight consecutive amino acids of SEQ ID NO: 8)
And (c) the amino acid sequence encoded by the cDNA insert of clone ve11_1 of ATCC Deposit No. 98846. 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 nucleotides 22-468 of SEQ ID NO: 9. ;
(c) the nucleotide sequence of nucleotides 118-468 of SEQ ID NO: 9; (d) the nucleotide sequence of the full-length protein coding sequence of clone vf2_1 of ATCC deposit number 98846; (e) the cDNA insertion of clone vf2_1 of ATCC deposit number 98846 A nucleotide sequence encoding the full-length protein encoded by the body; (f) a nucleotide sequence of the mature protein coding sequence of clone vf2_1 of ATCC Deposit No. 98846; (g) a cDNA insert of clone vf2_1 of ATCC Deposit No. 98846. (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 10; (i) a fragment of the amino acid sequence of SEQ ID NO: 10 Nucleotide sequence encoding a protein comprising (provided that the fragment SEQ ID N
(J) 10 consecutive 8 amino acids); (j) at least 65 ° C with 4XSSC or 50% formamide at 42 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 9. 19. A protein, essentially free of other mammalian proteins, comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 10; (b) an amino acid sequence of SEQ ID NO: 10. (C) the amino acid sequence encoded by the cDNA insert of clone vf2_1 of ATCC Deposit No. 98846, wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 10. 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 nucleotides 124 to 1641 of SEQ ID NO: 11. (C) the nucleotide sequence of nucleotides 262 to 1641 of SEQ ID NO: 11; (d) the nucleotide sequence of the full-length protein coding sequence of clone vg2_1 of ATCC deposit number 98846; (e) the cDNA of clone vg2_1 of ATCC deposit number 98846; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vg2_1 of ATCC Deposit No. 98846; (g) cDNA insertion of clone vg2_1 of ATCC Deposit No. 98846 (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 12; (i) a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 12 (However, the fragment is SEQ ID N
O: contains 12 contiguous amino acids of 12); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 11. 21. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 12; (b) the SEQ ID NO: 12 (C) the amino acid sequence encoded by the cDNA insert of clone vg2_1 of ATCC Deposit No. 98846, wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 12. 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 nucleotides 380-892 of SEQ ID NO: 13. (C) the nucleotide sequence of nucleotides 416-892 of SEQ ID NO: 13; (d) the nucleotide sequence of the full length protein coding sequence of clone vj1_1 of ATCC Deposit No. 98846; (e) the cDNA of clone vj1_1 of ATCC Deposit No. 98846 A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vj1_1 of ATCC Deposit No. 98846; (g) a cDNA insert of clone vj1_1 of ATCC Deposit No. 98846 (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 14; (i) a protein encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 14 Nucleotide sequence (however, the fragment corresponds to SEQ ID N
O: contains eight consecutive amino acids of 14); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 13. 23. A protein, essentially free of other mammalian proteins, comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 14; (b) the SEQ ID NO: 14 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 14; and (c) the amino acid sequence encoded by the cDNA insert of clone vj1_1 of ATCC Deposit No. 98846. 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 nucleotides 62-1057 of SEQ ID NO: 15. (C) the nucleotide sequence of nucleotides 659-1057 of SEQ ID NO: 15; (d) the nucleotide sequence of the full-length protein coding sequence of clone v11_1 of ATCC deposit number 98846; (e) the cDNA of clone v11_1 of ATCC deposit number 98846; Nucleotide sequence encoding the full length protein encoded by the insert; (f) nucleotide sequence of the mature protein coding sequence of clone v11_1 of ATCC Deposit No. 98846; (g) cDNA insert of clone v11_1 of ATCC Deposit No. 98846 A nucleotide sequence encoding the mature protein encoded by the body; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 16; (i) a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 16; Encoding nucleotide sequence (provided that the fragment is SEQ ID N
O: contains 16 consecutive amino acids of 16); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 15. 25. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 16; (b) the SEQ ID NO: 16 (C) the amino acid sequence encoded by the cDNA insert of clone v11_1 of ATCC Deposit No. 98846, wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 16. 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 nucleotides 74-529 of SEQ ID NO: 17. (C) the nucleotide sequence of nucleotides 140-529 of SEQ ID NO: 17; (d) the nucleotide sequence of the full-length protein coding sequence of clone vk2_1 of ATCC deposit number 98838; (e) the cDNA of clone vk2_1 of ATCC deposit number 98838. A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vk2_1 of ATCC deposit no. 98838; (g) a cDNA insert of clone vk2_1 of ATCC deposit no. (H) nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 18; (i) encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 18 Nucleotide sequence (however, the fragment corresponds to SEQ ID N
O: contains 18 contiguous amino acids of 18); (j) 42 ° C with 4XSSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 17. 27. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 18; (b) the amino acid sequence of SEQ ID NO: 18 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 18; and (c) the amino acid sequence encoded by the cDNA insert of clone vk2_1 of ATCC Deposit No. 988838. 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 nucleotides 174-3170 of SEQ ID NO: 19 (C) the nucleotide sequence of nucleotides 1098-3170 of SEQ ID NO: 19; (d) the nucleotide sequence of the full-length protein coding sequence of clone vb21_1 of ATCC deposit no. 98862; (e) the cDNA of clone vb21_1 of ATCC deposit no. A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vb21_1 of ATCC deposit no. 98862; (g) a nucleotide sequence of clone vb21_1 of ATCC deposit no. a nucleotide sequence encoding the mature protein encoded by the cDNA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 20; (i) a fragment of the amino acid sequence of SEQ ID NO: 20 A nucleotide sequence encoding a protein (provided that the fragment has SEQ ID N
O: contains eight consecutive amino acids of 20); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having a length of at least 25% of the length of 19. 29. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 20; (b) an amino acid sequence of SEQ ID NO: 20 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 20; and (c) the amino acid sequence encoded by the cDNA insert of clone vb21_1 of ATCC Deposit No. 98862. 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 nucleotides 74-1453 of SEQ ID NO: 21. (C) the nucleotide sequence of nucleotides 224-1453 of SEQ ID NO: 21; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc35_1 of ATCC deposit number 98862; (e) the cDNA of clone vc35_1 of ATCC deposit number 98862; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc35_1 of ATCC deposit no. 98862; (g) a cD of clone vc35_1 of ATCC deposit no. A nucleotide sequence encoding the mature protein encoded by the NA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 22; (i) including a fragment of the amino acid sequence of SEQ ID NO: 22 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
O: contains 22 contiguous amino acids of 22); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having at least 25% of the length of 21. 31. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 22; (b) the amino acid sequence of SEQ ID NO: 22 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 22; and (c) the amino acid sequence encoded by the cDNA insert of clone vc35_1 of ATCC Deposit No. 98862. 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 nucleotides 135 to 368 of SEQ ID NO: 23. (C) the nucleotide sequence of nucleotides 243-368 of SEQ ID NO: 23; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc36_1 of ATCC deposit number 98862; (e) the cDNA of clone vc36_1 of ATCC deposit number 98862; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc36_1 of ATCC deposit no. 98862; (g) a cDN of clone vc36_1 of ATCC deposit no. A nucleotide sequence encoding the mature protein encoded by the A insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 24; (i) including a fragment of the amino acid sequence of SEQ ID NO: 24 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
O: contains 24 consecutive amino acids of 24); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 23. 33. A protein, essentially free of other mammalian proteins, comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 24; (b) the SEQ ID NO: 24 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 24; and (c) the amino acid sequence encoded by the cDNA insert of clone vc36_1 of ATCC Deposit No. 98862. 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 nucleotides 370-1662 of SEQ ID NO: 25. (C) the nucleotide sequence of the full length protein coding sequence of clone vc38_1 of ATCC Deposit No. 98862; (d) the nucleotide sequence encoding the full length protein encoded by the cDNA insert of clone vc38_1 of ATCC Deposit No. 98862; ) A nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 26; (f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 26 (provided that the fragment is SEQ ID N
O: contains 26 consecutive amino acids of 26); (g) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A) a nucleotide sequence that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(d); and (h) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridizes to any of the polynucleotides defined in (a)-(d) under stringent conditions of the order of 6XSSC and has SEQ ID NO:
A nucleotide sequence of the polynucleotide having at least 25% of the length of 25. 35. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 26; (b) the SEQ ID NO: 26 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 26; and (c) the amino acid sequence encoded by the cDNA insert of clone vc38_1 of ATCC Deposit No. 98862. 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 nucleotides 105-365 of SEQ ID NO: 27. (C) the nucleotide sequence of nucleotides 147-365 of SEQ ID NO: 27; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc39_1 of ATCC deposit number 98862; (e) the cDNA of clone vc39_1 of ATCC deposit number 98862; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc39_1 of ATCC Deposit No. 98862; (g) a cDN of clone vc39_1 of ATCC Deposit No. 98862. A nucleotide sequence encoding the mature protein encoded by the A insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 28; (i) including a fragment of the amino acid sequence of SEQ ID NO: 28 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
(J) containing 28 consecutive amino acids of 28); (j) 42 ° C with 4X SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 27. 37. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 28; (b) an amino acid sequence of SEQ ID NO: 28 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 28; and (c) the amino acid sequence encoded by the cDNA insert of clone vc39_1 of ATCC Deposit No. 98862. 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 nucleotides 35-1066 of SEQ ID NO: 29. (C) the nucleotide sequence of nucleotides 128 to 1066 of SEQ ID NO: 29; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc40_1 of ATCC deposit number 98862; (e) the cDNA of clone vc40_1 of ATCC deposit number 98862; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc40_1 of ATCC deposit no. 98862; (g) a cD of clone vc40_1 of ATCC deposit no. A nucleotide sequence encoding the mature protein encoded by the NA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 30; (i) including a fragment of the amino acid sequence of SEQ ID NO: 30. A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
(J) contains 8 contiguous amino acids of 30); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having a length of at least 25% of the length of 29. 39. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 30; (b) the amino acid sequence of SEQ ID NO: 30. (C) the amino acid sequence encoded by the cDNA insert of clone vc40_1 of ATCC Deposit No. 98862; and (c) the fragment comprising eight consecutive amino acids of SEQ ID NO: 30. 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 nucleotides 38-553 of SEQ ID NO: 31. (C) the nucleotide sequence of nucleotides 104-553 of SEQ ID NO: 31; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc46_1 of ATCC accession number 98862; (e) the cDNA of clone vc46_1 of ATCC accession number 98862; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc46_1 of ATCC deposit no. 98862; (g) a cDNA of clone vc46_1 of ATCC deposit no. A nucleotide sequence encoding the mature protein encoded by the insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 32; (i) a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 32 (Provided that the fragment has SEQ ID N
O: contains 32 consecutive amino acids of 32); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having a length of at least 25% of the length of 31. 41. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 32; (b) the SEQ ID NO: 32 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 32; and (c) the amino acid sequence encoded by the cDNA insert of clone vc46_1 of ATCC Deposit No. 98862. 42. An isolated polynucleotide comprising a nucleotide sequence selected from the following group: (a) the nucleotide sequence of SEQ ID NO: 33; (b) the nucleotide sequence of nucleotides 164-2548 of SEQ ID NO: 33 (C) the nucleotide sequence of nucleotides 242-2548 of SEQ ID NO: 33; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc49_1 of ATCC deposit number 98862; (e) the cDNA of clone vc49_1 of ATCC deposit number 98862; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc49_1 of ATCC deposit no. 98862; (g) a c of clone vc49_1 of ATCC deposit no. A nucleotide sequence encoding the mature protein encoded by the DNA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 34; (i) including a fragment of the amino acid sequence of SEQ ID NO: 34 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
(J) containing 8 consecutive amino acids of 34); (j) 42 ° C with 4XSSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 33. 43. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 34; (b) the SEQ ID NO: 34 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 34; and (c) the amino acid sequence encoded by the cDNA insert of clone vc49_1 of ATCC Deposit No. 98862. 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 nucleotides 150-776 of SEQ ID NO: 35. (C) the nucleotide sequence of nucleotides 246-776 of SEQ ID NO: 35; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc50_1 of ATCC deposit number 98862; (e) the cDNA of clone vc50_1 of ATCC deposit number 98862; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc50_1 of ATCC Deposit No. 98862; (g) a cDN of clone vc50_1 of ATCC Deposit No. 98862. A nucleotide sequence encoding the mature protein encoded by the A insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 36; (i) including a fragment of the amino acid sequence of SEQ ID NO: 36 A nucleotide sequence encoding a protein (provided that the fragment has SEQ ID N
O: contains 36 consecutive amino acids of 36); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having at least 25% of the length of 35. 45. A protein comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 36; and (b) SEQ ID NO: 36, essentially free of other mammalian proteins. Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 36; and (c) the amino acid sequence encoded by the cDNA insert of clone vc50_1 of ATCC Deposit No. 98862. 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 nucleotides 139 to 1308 of SEQ ID NO: 37 (C) the nucleotide sequence of nucleotides 211 to 1308 of SEQ ID NO: 37; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc51_1 of ATCC deposit number 98862; (e) the cDNA of clone vc51_1 of ATCC deposit number 98862; A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc51_1 of ATCC deposit no. 98862; (g) a c of clone vc51_1 of ATCC deposit no. A nucleotide sequence encoding a mature protein encoded by the DNA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 38; (i) a fragment of the amino acid sequence of SEQ ID NO: 38 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
(J) contains 8 contiguous amino acids of 38); (j) 42 ° C with 4XSSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having at least 25% of the length of 37. 47. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 38; (b) an amino acid sequence of SEQ ID NO: 38 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 38; and (c) the amino acid sequence encoded by the cDNA insert of clone vc51_1 of ATCC Deposit No. 98862. 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 nucleotides 21-1442 of SEQ ID NO: 39 (C) the nucleotide sequence of nucleotides 114 to 1142 of SEQ ID NO: 39; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc52_1 of ATCC deposit number 98862; (e) the cDNA of clone vc52_1 of ATCC deposit number 98862; A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc52_1 of ATCC deposit no. 98862; (g) a cD of clone vc52_1 of ATCC deposit no. A nucleotide sequence encoding a mature protein encoded by the NA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 40; (i) including a fragment of the amino acid sequence of SEQ ID NO: 40 A nucleotide sequence encoding a protein (provided that the fragment has SEQ ID N
O: 40 consecutive 8 amino acids); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having at least 25% of the length of 39. 49. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 40; (b) an amino acid sequence of SEQ ID NO: 40 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 40; and (c) the amino acid sequence encoded by the cDNA insert of clone vc52_1 of ATCC Deposit No. 98862. 50. An isolated polynucleotide comprising a nucleotide sequence selected from the following group: (a) the nucleotide sequence of SEQ ID NO: 41; (b) the nucleotide sequence of nucleotides 13-1416 of SEQ ID NO: 41 (C) the nucleotide sequence of nucleotides 346-1416 of SEQ ID NO: 41; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc33_1 of ATCC deposit number 98886; (e) the cDNA of clone vc33_1 of ATCC deposit number 98886; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc33_1 of ATCC deposit number 98886; (g) a cD of clone vc33_1 of ATCC deposit number 98886. A nucleotide sequence encoding the mature protein encoded by the NA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 42; (i) including a fragment of the amino acid sequence of SEQ ID NO: 42 A nucleotide sequence encoding a protein (provided that the fragment has SEQ ID N
(J) containing 8 consecutive amino acids of 42); (j) 42 ° C with 4XSSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
41. A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 41. 51. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 42; (b) the SEQ ID NO: 42 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 42; and (c) the amino acid sequence encoded by the cDNA insert of clone vc33_1 of ATCC Deposit No. 98886. 52. An isolated polynucleotide comprising a nucleotide sequence selected from the following group: (a) the nucleotide sequence of SEQ ID NO: 43; (b) the nucleotide sequence of nucleotides 232-1461 of SEQ ID NO: 43 (C) the nucleotide sequence of nucleotides 280-1461 of SEQ ID NO: 43; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc34_1 of ATCC deposit number 98886; (e) the cDNA of clone vc34_1 of ATCC deposit number 98886; A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc34_1 of ATCC deposit no. 98886; (g) a c of clone vc34_1 of ATCC deposit no. A nucleotide sequence encoding the mature protein encoded by the DNA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 44; (i) including a fragment of the amino acid sequence of SEQ ID NO: 44 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
(O: contains 8 consecutive amino acids of 44); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 43. 53. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 44; (b) the amino acid sequence of SEQ ID NO: 44 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 44; and (c) the amino acid sequence encoded by the cDNA insert of clone vc34_1 of ATCC Deposit No. 98886. 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 nucleotides 1922-2350 of SEQ ID NO: 45 (C) the nucleotide sequence of nucleotides 2237-2350 of SEQ ID NO: 45; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc47_1 of ATCC deposit number 98886; (e) the cDNA of clone vc47_1 of ATCC deposit number 98886; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc47_1 of ATCC deposit no. 98886; (g) a clone vc47_1 of ATCC deposit no. (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 46; (i) a fragment of the amino acid sequence of SEQ ID NO: 46; A nucleotide sequence encoding the protein containing the fragment (provided that the fragment is SEQ ID N
O: contains 8 consecutive amino acids of 46); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having at least 25% of the length of 45. 55. A protein essentially free of other mammalian proteins and 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 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 46; and (c) the amino acid sequence encoded by the cDNA insert of clone vc47_1 of ATCC Deposit No. 98886. 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 nucleotides 111 to 1337 of SEQ ID NO: 47 (C) the nucleotide sequence of nucleotides 246 to 1337 of SEQ ID NO: 47; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc54_1 of ATCC deposit number 98886; (e) the cDNA of clone vc54_1 of ATCC deposit number 98886; Nucleotide sequence encoding the full length protein encoded by the insert; (f) nucleotide sequence of the mature protein coding sequence of clone vc54_1 of ATCC deposit number 98886; (g) c of clone vc54_1 of ATCC deposit number 98886. A nucleotide sequence encoding a mature protein encoded by the DNA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 48; (i) including a fragment of the amino acid sequence of SEQ ID NO: 48 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
O: 48 consecutive 8 amino acids); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having a length of at least 25% of the length of 47. 57. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 48; (b) an amino acid sequence of SEQ ID NO: 48 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 48; and (c) the amino acid sequence encoded by the cDNA insert of clone vc54_1 of ATCC Deposit No. 98886. 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 nucleotides 189-1637 of SEQ ID NO: 49 (C) the nucleotide sequence of nucleotides 270-1637 of SEQ ID NO: 49; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc57_1 of ATCC deposit number 98886; (e) the cDNA of clone vc57_1 of ATCC deposit number 98886; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc57_1 of ATCC deposit number 98886; (g) a c of clone vc57_1 of ATCC deposit number 98886. A nucleotide sequence encoding the mature protein encoded by the DNA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 50; (i) including a fragment of the amino acid sequence of SEQ ID NO: 50 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
O: contains 50 consecutive 8 amino acids); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having at least 25% of the length of 49. 59. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 50; (b) an amino acid sequence of SEQ ID NO: 50 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 50; and (c) the amino acid sequence encoded by the cDNA insert of clone vc57_1 of ATCC Deposit No. 98886. 60. An isolated polynucleotide comprising a nucleotide sequence selected from the following group: (a) the nucleotide sequence of SEQ ID NO: 51; (b) the nucleotide sequence of nucleotides 15 to 1934 of SEQ ID NO: 51 (C) the nucleotide sequence of nucleotides 1704 to 1934 of SEQ ID NO: 51; (d) the nucleotide sequence of the full-length protein coding sequence of clone ve13_1 of ATCC accession number 98886; (e) the cDNA of clone ve13_1 of ATCC accession number 98886; A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone ve13_1 of ATCC deposit no. 98886; (g) a cD of clone ve13_1 of ATCC deposit no. A nucleotide sequence encoding the mature protein encoded by the A insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 52; (i) including a fragment of the amino acid sequence of SEQ ID NO: 52 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
O: contains 52 consecutive amino acids of 52); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having a length of at least 25% of the length of 51. 61. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 52; (b) the amino acid sequence of SEQ ID NO: 52 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 52; and (c) the amino acid sequence encoded by the cDNA insert of clone vel3_1 of ATCC Deposit No. 98886. 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 nucleotides 240-503 of SEQ ID NO: 53 (C) the nucleotide sequence of nucleotides 318-503 of SEQ ID NO: 53; (d) the nucleotide sequence of the full-length protein coding sequence of clone ve16_1 of ATCC accession number 98886; (e) the cDNA of clone ve16_1 of ATCC accession number 98886; A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone ve16_1 of ATCC accession number 98886; (g) a cDN of clone ve16_1 of ATCC accession number 98886. A nucleotide sequence encoding the mature protein encoded by the A insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 54; (i) including a fragment of the amino acid sequence of SEQ ID NO: 54 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
O: containing 54 consecutive amino acids of 54); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
53. A nucleotide sequence of a polynucleotide having a length of at least 25% of the length of 53. 63. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 54; (b) the amino acid sequence of SEQ ID NO: 54 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 54; and (c) the amino acid sequence encoded by the cDNA insert of clone ve16_1 of ATCC Deposit No. 98886. 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 nucleotides 11-1063 of SEQ ID NO: 55 (C) the nucleotide sequence of nucleotides 71-1063 of SEQ ID NO: 55; (d) the nucleotide sequence of the full-length protein coding sequence of clone vf3_1 of ATCC deposit number 98886; (e) the cDNA of clone vf3_1 of ATCC deposit number 98886; A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vf3_1 of ATCC deposit no. 98886; (g) a cDNA insert of clone vf3_1 of ATCC deposit no. (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 56; (i) a protein encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 56 Nucleotide sequence (however, the fragment corresponds to SEQ ID N
O: contains 56 consecutive amino acids of 56); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 55. 65. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 56; (b) the amino acid sequence of SEQ ID NO: 56 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 56; and (c) the amino acid sequence encoded by the cDNA insert of clone vf3_1 of ATCC Deposit No. 98886. 66. An isolated polynucleotide comprising a nucleotide sequence selected from the following group: (a) the nucleotide sequence of SEQ ID NO: 57; (b) the nucleotide sequence of nucleotides 542-886 of SEQ ID NO: 57 (C) the nucleotide sequence of nucleotides 755-886 of SEQ ID NO: 57; (d) the nucleotide sequence of the full-length protein coding sequence of clone vj2_1 of ATCC deposit number 98886; (e) the cDNA of clone vj2_1 of ATCC deposit number 98886; A nucleotide sequence encoding the full length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vj2_1 of ATCC Deposit No. 98886; (g) a cDNA insert of clone vj2_1 of ATCC Deposit No. 98886 (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 58; (i) a protein encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 58 Nucleotide sequence (however, the fragment corresponds to SEQ ID N
O: contains 58 contiguous amino acids of 58); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
57. A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 57. 67. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 58; (b) an amino acid sequence of SEQ ID NO: 58 (Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 58); and (c) the amino acid sequence encoded by the cDNA insert of clone vj2_1 of ATCC Deposit No. 98886. 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 nucleotides 30-344 of SEQ ID NO: 59 (C) the nucleotide sequence of nucleotides 84 to 344 of SEQ ID NO: 59; (d) the nucleotide sequence of the full-length protein coding sequence of clone vp7_1 of ATCC deposit number 98886; (e) the cDNA of clone vp7_1 of ATCC deposit number 98886; Nucleotide sequence encoding the full length protein encoded by the insert; (f) nucleotide sequence of the mature protein coding sequence of clone vp7_1 of ATCC Deposit No. 98886; (g) cDNA insert of clone vp7_1 of ATCC Deposit No. 98886. (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 60; (i) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 60; Encoding nucleotide sequence (provided that the fragment is SEQ ID N
O: contains 60 consecutive amino acids of 60); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 59. 69. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 60; (b) the amino acid sequence of SEQ ID NO: 60 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 60; and (c) the amino acid sequence encoded by the cDNA insert of clone vp7_1 of ATCC Deposit No. 98886. 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 nucleotides 23-757 of SEQ ID NO: 61. (C) the nucleotide sequence of nucleotides 119-757 of SEQ ID NO: 61; (d) the nucleotide sequence of the full-length protein coding sequence of clone vp8_1 of ATCC deposit number 98886; (e) the cDNA of clone vp8_1 of ATCC deposit number 98886; Nucleotide sequence encoding the full length protein encoded by the insert; (f) nucleotide sequence of the mature protein coding sequence of clone vp8_1 of ATCC deposit no. 98886; (g) cDNA insert of clone vp8_1 of ATCC deposit no. (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 62; (i) a protein encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 62 Nucleotide sequence (however, the fragment corresponds to SEQ ID N
O: contains 62 consecutive amino acids of 62); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having a length of at least 25% of the length of 61. 71. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 62; (b) the SEQ ID NO: 62 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 62; and (c) the amino acid sequence encoded by the cDNA insert of clone vp8_1 of ATCC Deposit No. 98886. 72. An isolated polynucleotide comprising a nucleotide sequence selected from the following group: (a) the nucleotide sequence of SEQ ID NO: 63; (b) the nucleotide sequence of nucleotides 1048-3726 of SEQ ID NO: 63 (C) the nucleotide sequence of the full length protein coding sequence of clone vb22_1 of ATCC Deposit No. 98933; (d) the nucleotide sequence encoding the full length protein encoded by the cDNA insert of clone vb22_1 of ATCC Deposit No. 98933; ) A nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 64; (f) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 64 (wherein the fragment is
(G) containing 8 consecutive amino acids of 64); (g) at least 65 ° C with 4XSSC or 50% formamide at 42 ° C.
A) a nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(d); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridizes to any of the polynucleotides defined in (a)-(d) under stringent conditions of the order of 6XSSC and has SEQ ID NO:
63. A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 63. 73. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 64; (b) an amino acid sequence of SEQ ID NO: 64 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 64; and (c) the amino acid sequence encoded by the cDNA insert of clone vb22_1 of ATCC Deposit No. 98933. 74. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence of SEQ ID NO: 65; (b) the nucleotide sequence of nucleotides 134-667 of SEQ ID NO: 65. (C) the nucleotide sequence of nucleotides 191-667 of SEQ ID NO: 65; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc48_1 of ATCC deposit number 98933; (e) the cDNA of clone vc48_1 of ATCC deposit number 98933; A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc48_1 of ATCC Deposit No. 98933; (g) a cDN of clone vc48_1 of ATCC Deposit No. 98933. A nucleotide sequence encoding the mature protein encoded by the A insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 66; (i) including a fragment of the amino acid sequence of SEQ ID NO: 66 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
O: contains 8 consecutive amino acids of 66); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 65. 75. A protein comprising an amino acid sequence selected from the group consisting of: (a) an amino acid sequence of SEQ ID NO: 66, essentially free of other mammalian proteins; (b) an amino acid sequence of SEQ ID NO: 66 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 66; and (c) the amino acid sequence encoded by the cDNA insert of clone vc48_1 of ATCC Deposit No. 98933. 76. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence of SEQ ID NO: 67; (b) the nucleotide sequence of nucleotides 65-457 of SEQ ID NO: 67 (C) the nucleotide sequence of nucleotides 158 to 457 of SEQ ID NO: 67; (d) the nucleotide sequence of the full-length protein coding sequence of clone vp3_1 of ATCC deposit number 98933; (e) the cDNA of clone vp3_1 of ATCC deposit number 98933; Nucleotide sequence encoding the full length protein encoded by the insert; (f) nucleotide sequence of the mature protein coding sequence of clone vp3_1 of ATCC Deposit No. 98933; (g) cDNA insert of clone vp3_1 of ATCC Deposit No. 98933. (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 68; (i) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 68 Nucleotide sequence (however, the fragment corresponds to SEQ ID N
O: contains 68 contiguous amino acids of 68); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having a length of at least 25% of the length of 67. 77. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 68; (b) the SEQ ID NO: 68 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 68; and (c) the amino acid sequence encoded by the cDNA insert of clone vp3_1 of ATCC Deposit No. 98933. 78. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence of SEQ ID NO: 69; (b) the nucleotide sequence of nucleotides 29-1387 of SEQ ID NO: 69 (C) the nucleotide sequence of nucleotides 113 to 1387 of SEQ ID NO: 69; (d) the nucleotide sequence of the full-length protein coding sequence of clone vc61_1 of ATCC deposit no. 2007012; (e) the cDNA of clone vc61_1 of ATCC deposit no. A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vc61_1 of ATCC accession number 2007012; (g) a clone vc61_ of ATCC accession number 2007012 A nucleotide sequence encoding a mature protein encoded by the cDNA insert of SEQ ID NO: 1; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 70; (i) a fragment of the amino acid sequence of SEQ ID NO: 70 (Provided that the fragment has SEQ ID N.
O: contains 70 consecutive amino acids of 70); (j) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having at least 25% of the length of 69. 79. A protein essentially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 70; (b) the amino acid sequence of SEQ ID NO: 70 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 70; and (c) the amino acid sequence encoded by the cDNA insert of clone vc61_1 of ATCC deposit no. 80. An isolated polynucleotide comprising a nucleotide sequence selected from the following group: (a) the nucleotide sequence of SEQ ID NO: 71; (b) the nucleotide sequence of nucleotides 44 to 1513 of SEQ ID NO: 71 (C) the nucleotide sequence of nucleotides 92 to 1513 of SEQ ID NO: 71; (d) the nucleotide sequence of nucleotides 1 to 458 of SEQ ID NO: 71;
(e) the nucleotide sequence of the full-length protein coding sequence of clone vp15_1 of ATCC Deposit No. 207012; (f) the nucleotide sequence encoding the full-length protein encoded by the cDNA insert of clone vp15_1 of ATCC Deposit No. 207012; (g) (H) nucleotide sequence encoding the mature protein encoded by the cDNA insert of clone vp15_1 of ATCC Deposit No. 207012; (i) SEQ ID NO: 72 (J) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 72; Fragment is SEQ ID N
O: contains 72 consecutive amino acids of 72); (k) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(h); and (1) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(h) under stringent conditions of the order of 6 × SSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 71. 81. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 72; (b) the SEQ ID NO: 72 (C) a fragment of the amino acid sequence of SEQ ID NO: 72 (provided that the fragment comprises eight consecutive amino acids of SEQ ID NO: 72); and (d) ATCC Amino acid sequence encoded by the cDNA insert of clone vp15_1 under accession number 2007012. 82. An isolated polynucleotide comprising a nucleotide sequence selected from the following group: (a) the nucleotide sequence of SEQ ID NO: 73; (b) the nucleotide sequence of nucleotides 348-743 of SEQ ID NO: 73 (C) the nucleotide sequence of nucleotides 414-743 of SEQ ID NO: 73; (d) the nucleotide sequence of the full-length protein coding sequence of clone vp17_1 of ATCC deposit no. 207012; (e) the cDNA of clone vp17_1 of ATCC deposit no. A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vp17_1 of ATCC Deposit No. 207012; (g) a clone vp17_1 of ATCC Deposit No. 207012 (H) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 74; (i) a fragment of the amino acid sequence of SEQ ID NO: 74; A nucleotide sequence encoding the protein containing the fragment (provided that the fragment is SEQ ID N
(J) containing 8 consecutive amino acids of 74); (j) 42 ° C with 4X SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
73. A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 73. 83. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 74; (b) the SEQ ID NO: 74 (C) the amino acid sequence encoded by the cDNA insert of clone vp17_1 of ATCC accession number 2007012, wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 74. 84. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence of SEQ ID NO: 75; (b) the nucleotide sequence of nucleotides 144-461 of SEQ ID NO: 75 (C) the nucleotide sequence of the full length protein coding sequence of clone vp19_1 of ATCC Deposit No. 207012; (d) the nucleotide sequence encoding the full length protein encoded by the cDNA insert of clone vp19_1 of ATCC Deposit No. 207012; ) Nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 76; (f) nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 76 (provided that the fragment is SEQ ID NO:
O: contains 76 contiguous amino acids of 76); (g) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A) a nucleotide sequence that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(d); and (h) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridizes to any of the polynucleotides defined in (a)-(d) under stringent conditions of the order of 6XSSC and has SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 75. 85. A protein substantially free of other mammalian proteins and comprising an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 76; (b) the amino acid sequence of SEQ ID NO: 76 Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 76; and (c) the amino acid sequence encoded by the cDNA insert of clone vp19_1 of ATCC deposit no. 86. An isolated polynucleotide comprising a nucleotide sequence selected from the following group: (a) the nucleotide sequence of SEQ ID NO: 77; (b) the nucleotide sequence of nucleotides 54 to 368 of SEQ ID NO: 77 (C) the nucleotide sequence of nucleotides 141-368 of SEQ ID NO: 77; (d) the nucleotide sequence of nucleotides 51-332 of SEQ ID NO: 77; (e) the full length protein code of clone vq1_1 of ATCC Deposit No. 207012 (F) a nucleotide sequence encoding the full length protein encoded by the cDNA insert of clone vq1_1 of ATCC Deposit No. 207012; (g) the nucleolog of the mature protein coding sequence of clone vq1_1 of ATCC Deposit No. 207012. (H) a nucleotide sequence encoding the mature protein encoded by the cDNA insert of clone vq1_1 of ATCC Deposit No. 207012; (i) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 78; j) a nucleotide sequence encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 78 (provided that the fragment is
O: contains 78 consecutive amino acids of 78); (k) 42 ° C. with 4 × SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(h); and (1) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(h) under stringent conditions of the order of 6 × SSC, and SEQ ID NO:
A nucleotide sequence of the polynucleotide having a length of at least 25% of the length of 77. 87. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 78; (b) the SEQ ID NO: 78 (C) a fragment of the amino acid sequence of SEQ ID NO: 78 (provided that the fragment comprises eight consecutive amino acids of SEQ ID NO: 78); and (d) ATCC Amino acid sequence encoded by the cDNA insert of clone vq1_1 under accession number 2007012. 88. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence of SEQ ID NO: 79; (b) the nucleotide sequence of nucleotides 2-1018 of SEQ ID NO: 79 (C) the nucleotide sequence of nucleotides 53 to 1018 of SEQ ID NO: 49; (d) the nucleotide sequence of the full-length protein coding sequence of clone vp14_1 of ATCC deposit number 2070011; (e) the cDNA of clone vp14_1 of ATCC deposit number 2070011 A nucleotide sequence encoding the full-length protein encoded by the insert; (f) a nucleotide sequence of the mature protein coding sequence of clone vp14_1 of ATCC Deposit No. 207011; (g) a nucleotide sequence of clone vp14_1 of ATCC Deposit No. 207011 a nucleotide sequence encoding the mature protein encoded by the cDNA insert; (h) a nucleotide sequence encoding a protein comprising the amino acid sequence of SEQ ID NO: 80; (i) a fragment of the amino acid sequence of SEQ ID NO: 80 A nucleotide sequence encoding a protein (provided that the fragment is SEQ ID N
(J) contains 8 consecutive amino acids of 80); (j) 42 ° C with 4X SSC or 50% formamide at least at 65 ° C.
A nucleotide sequence of a polynucleotide that hybridizes under stringent conditions of the order of 4XSSC to any of the polynucleotides defined in (a)-(g); and (k) 4XSSC or 50% at least at 50 ° C. 40 ° C with formamide
Hybridized to any of the polynucleotides defined in (a)-(g) under stringent conditions of the order of 6XSSC, and SEQ ID NO:
A nucleotide sequence of a polynucleotide having a length of at least 25% of the length of 79. 89. A protein comprising an amino acid sequence selected from the following group, essentially free of other mammalian proteins: (a) the amino acid sequence of SEQ ID NO: 80; (b) the amino acid sequence of SEQ ID NO: 80 (Wherein the fragment comprises eight consecutive amino acids of SEQ ID NO: 80); and (c) the amino acid sequence encoded by the cDNA insert of clone vp14_1 of ATCC accession number 207011.