WO2000037630A1

WO2000037630A1 - Secreted proteins

Info

Publication number: WO2000037630A1
Application number: PCT/US1999/031005
Authority: WO
Inventors: Kenneth Jacobs; John M. Mccoy; Edward R. Lavallie; Lisa A. Collins-Racie; Cheryl Evans; David Merberg; Maurice Treacy; Michael R. Bowman
Original assignee: Genetics Institute, Inc.
Priority date: 1998-12-23
Filing date: 1999-12-22
Publication date: 2000-06-29
Also published as: EP1141267A4; EP1141267A1; AU2390800A

Abstract

Novel proteins are disclosed.

Description

SECRETED PROTEINS

This application is a continuation-in-part of the following applications:

(1) Ser. No. 08/634,325, filed April 18, 1996;

(2) Ser. No. 08/783,520, filed January 13, 1997, which is a continuation-in-part of application Ser. No. 08/634,325, filed April 18, 1996;

(3) Ser. No. 08/885,610, filed June 30, 1997, which is a continuation-in-part of application Ser. No. 08/634,325, filed April 18, 1996;

(4) Ser. No. 08/943,861, filed October 3, 1997, which is a continuation of application Ser. No. 60/080,227 (converted to a provisional application from non-provisional application 08/725,885), filed October 4, 1996;

(5) Ser. No. 08/943,862, filed October 3, 1997, which is a continuation of application Ser. No. 60/093,043 (converted to a provisional application from non-provisional application 08/726,257), filed October 4, 1996;

(6) Ser. No. 08/960,024, filed October 29, 1997, which is a continuation-in-part of application Ser. No. 60/077,176 (converted to a provisional application from non-provisional application 08/742,973), filed November 1, 1996; and

(7) Ser. No. 09/137,226, filed August 20, 1998, which is a continuation-in-part of application Ser. No. 60/092,114 (converted to a provisional application from non-provisional application 08/916,041), filed August 21, 1997;

all of which are incorporated by reference herein. FIELD OF THE INVENTION The present invention provides novel proteins , along with therapeutic, diagnostic and research utilities for these proteins.

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

SUMMARY OF THE INVENTION In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ

ID NOJ;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NOJ from nucleotide 19 to nucleotide 561;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AK296_li deposited under accession number ATCC 98026;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AK296_li deposited under accession number ATCC 98026; (e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AK296_li deposited under accession number ATCC 98026;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AK296_li deposited under accession number ATCC 98026; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:2;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:2; (i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; and

(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above.

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO.J from nucleotide 19 to nucleotide 561; the nucleotide sequence of the full-length protein coding sequence of clone AK296_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AK296_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AK296_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:2 from amino acid 3 to amino acid 181. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:2, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2 having biological activity, the fragment comprising the amino acid sequence from amino acid 85 to amino acid 94 of SEQ ID NO:2.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:2; (b) the amino acid sequence of SEQ ID NO:2 from amino acid

3 to amino acid 181;

(c) fragments of the amino acid sequence of SEQ ID NO:2, each fragment comprising eight consecutive amino acids of SEQ ID NO:2; and

(d) the amino acid sequence encoded by the cDNA insert of clone AK296_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:2 or the amino acid sequence of SEQ ID NO:2 from amino acid 3 to amino acid 181. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:2, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2, the fragment comprising the amino acid sequence from amino acid 85 to amino acid 94 of SEQ ID NO:2. In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:3; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:3 from nucleotide 123 to nucleotide 1457;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AK533_li deposited under accession number ATCC 98026;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AK533_li deposited under accession number ATCC 98026;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AK533_li deposited under accession number ATCC 98026;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AK533_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:4;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ;

(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; and

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:3 from nucleotide 123 to nucleotide 1457; the nucleotide sequence of the full-length protein coding sequence of clone AK533_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AK533_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AK533_li deposited under accession number ATCC 98026. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NOJ;

(b) fragments of the amino acid sequence of SEQ ID NOJ, each fragment comprising eight consecutive amino acids of SEQ ID NOJ; and

(c) the amino acid sequence encoded by the cDNA insert of clone AK533_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ, the fragment comprising the amino acid sequence from amino acid 217 to amino acid 226 of SEQ ID NOJ.

In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ

ID NO:5;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:5 from nucleotide 258 to nucleotide 392;

(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:5 from nucleotide 330 to nucleotide 392;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AK583_li deposited under accession number ATCC 98026;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AK583_li deposited under accession number ATCC

98026;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AK583_li deposited under accession number ATCC 98026; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AK583_li deposited under accession number ATCC 98026;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:6;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:6 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:6;

(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above; and (k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above.

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:5 from nucleotide 258 to nucleotide 392; the nucleotide sequence of SEQ ID NO:5 from nucleotide 330 to nucleotide 392; the nucleotide sequence of the full-length protein coding sequence of clone AK583_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AK583_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AK583_li deposited under accession number ATCC 98026. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:6;

(b) fragments of the amino acid sequence of SEQ ID NO:6, each fragment comprising eight consecutive amino acids of SEQ ID NO:6; and

(c) the amino acid sequence encoded by the cDNA insert of clone AK583_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:6. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:6 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:6, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:6, the fragment comprising the amino acid sequence from amino acid 17 to amino acid 26 of SEQ ID NO:6.

In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:7;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:7 from nucleotide 6 to nucleotide 1424;

(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:7 from nucleotide 78 to nucleotide 1424;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AM282_li deposited under accession number ATCC 98026;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AM282_li deposited under accession number ATCC

98026;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone A-VI282_li deposited under accession number ATCC 98026; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AM282_li deposited under accession number ATCC 98026; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:8;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:8 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:8;

(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above; and

(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above.

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:7 from nucleotide 6 to nucleotide 1424; the nucleotide sequence of SEQ ID NO:7 from nucleotide 78 to nucleotide 1424; the nucleotide sequence of the full-length protein coding sequence of clone AM282_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AM282_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AM282_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:8 from amino acid 1 to amino acid 91. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:8 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:8, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:8 having biological activity, the fragment comprising the amino acid sequence from amino acid 231 to amino acid 240 of SEQ ID NO:8.

(a) the amino acid sequence of SEQ ID NO:8;

(b) the amino acid sequence of SEQ ID NO:8 from amino acid 1 to amino acid 91; (c) fragments of the amino acid sequence of SEQ ID NO:8, each fragment comprising eight consecutive amino acids of SEQ ID NO:8; and

(d) the amino acid sequence encoded by the cDNA insert of clone AM282_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:8 or the amino acid sequence of SEQ ID NO:8 from amino acid 1 to amino acid 91. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:8 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:8, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:8, the fragment comprising the amino acid sequence from amino acid 231 to amino acid 240 of

SEQ ID NO:8.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:9;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:9 from nucleotide 87 to nucleotide 458; (c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:9 from nucleotide 378 to nucleotide 458;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AM340_li deposited under accession number ATCC 98026;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AM340_li deposited under accession number ATCC 98026;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AM340_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AM340_li deposited under accession number ATCC 98026;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NOrlO;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ0 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:10;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:9 from nucleotide 87 to nucleotide 458; the nucleotide sequence of SEQ ID NO:9 from nucleotide 378 to nucleotide 458; the nucleotide sequence of the full-length protein coding sequence of clone AM340_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AM340_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AM340_li deposited under accession number ATCC 98026.

(a) the amino acid sequence of SEQ ID NOJ0; (b) fragments of the amino acid sequence of SEQ ID NOJ0, each fragment comprising eight consecutive amino acids of SEQ ID NOJ0; and

(c) the amino acid sequence encoded by the cDNA insert of clone AM340_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ0. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 10 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO: 10, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ0, the fragment comprising the amino acid sequence from amino acid 57 to amino acid 66 of SEQ ID NOJ0.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:ll;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NOJ1 from nucleotide 17 to nucleotide 685; (c) a polynucleotide comprising the nucleotide sequence of SEQ

ID NO:ll from nucleotide 86 to nucleotide 685;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AM610_li deposited under accession number ATCC 98026; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AM610_li deposited under accession number ATCC 98026;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AM610_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AM610_li deposited under accession number ATCC 98026;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 12; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ2 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:12;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ1 from nucleotide 17 to nucleotide 685; the nucleotide sequence of SEQ ID NO:ll from nucleotide 86 to nucleotide 685; the nucleotide sequence of the full-length protein coding sequence of clone AM610_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AM610_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AM610_li deposited under accession number ATCC 98026.

(a) the amino acid sequence of SEQ ID NO: 12; (b) fragments of the amino acid sequence of SEQ ID NO.J2, each fragment comprising eight consecutive amino acids of SEQ ID NO:12; and (c) the amino acid sequence encoded by the cDNA insert of clone AM610_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ2. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO.J2 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:12, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:12, the fragment comprising the amino acid sequence from amino acid 106 to amino acid 115 of SEQ ID NOJ2.

In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 13;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NOJ3 from nucleotide 70 to nucleotide 504; (c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AP162_li deposited under accession number ATCC 98026;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AP162_li deposited under accession number ATCC 98026;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AP162_li deposited under accession number ATCC 98026;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AP162_li deposited under accession number ATCC 98026;

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

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 14 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:14;

(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ

ID NO:13 from nucleotide 70 to nucleotide 504; the nucleotide sequence of the full-length protein coding sequence of clone AP162_li deposited under accession number ATCC

98026; or the nucleotide sequence of a mature protein coding sequence of clone AP162_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AP162_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:14 from amino acid 42 to amino acid 61. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ4 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ4, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 14 having biological activity, the fragment comprising the amino acid sequence from amino acid 67 to amino acid 76 of SEQ ID NO.14.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NOJ4;

(b) the amino acid sequence of SEQ ID NO: 14 from amino acid 42 to amino acid 61;

(c) fragments of the amino acid sequence of SEQ ID NOJ4, each fragment comprising eight consecutive amino acids of SEQ ID NO: 14; and (d) the amino acid sequence encoded by the cDNA insert of clone AP162_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 14 or the amino acid sequence of SEQ ID NO:14 from amino acid 42 to amino acid 61. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 14 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ4, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:14, the fragment comprising the amino acid sequence from amino acid 67 to amino acid 76 of SEQ ID NO:14.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:16;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:16 from nucleotide 77 to nucleotide 694;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AR260_li deposited under accession number ATCC 98026;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AR260_li deposited under accession number ATCC 98026; (e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AR260_li deposited under accession number ATCC 98026;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AR260_li deposited under accession number ATCC 98026; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 17;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:17 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO: 17; (i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; and

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO: 16 from nucleotide 77 to nucleotide 694; the nucleotide sequence of the full-length protein coding sequence of clone AR260_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AR260_li deposited under accession number ATCC 98026. In other preferred embodiments, t e polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AR260_li deposited under accession number ATCC 98026.

(a) the amino acid sequence of SEQ ID NO: 17; (b) fragments of the amino acid sequence of SEQ ID NO: 17, each fragment comprising eight consecutive amino acids of SEQ ID NO: 17; and (c) the amino acid sequence encoded by the cDNA insert of clone AR260_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 17. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ7 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO: 17, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ7, the fragment comprising the amino acid sequence from amino acid 98 to amino acid 107 of SEQ ID NOJ7.

In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of :

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO-18;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:18 from nucleotide 23 to nucleotide 676; (c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AS32_li deposited under accession number ATCC 98026;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AS32_li deposited under accession number ATCC 98026;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AS32_li deposited under accession number ATCC 98026;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AS32_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.19;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ9 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO: 19;

(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO: 18 from nucleotide 23 to nucleotide 676; the nucleotide sequence of the full-length protein coding sequence of clone AS32_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AS32_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AS32_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NOJ9 from amino acid 78 to amino acid 97. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ9 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ9, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ9 having biological activity, the fragment comprising the amino acid sequence from amino acid 102 to amino acid 111 of SEQ ID NO:19.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 19;

(b) the amino acid sequence of SEQ ID NO:19 from amino acid 78 to amino acid 97;

(c) fragments of the amino acid sequence of SEQ ID NO: 19, each fragment comprising eight consecutive amino acids of SEQ ID NO:19; and (d) the amino acid sequence encoded by the cDNA insert of clone AS32_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:19 or the amino acid sequence of SEQ ID NO:19 from amino acid 78 to amino acid 97. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 19 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ9, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:19, the fragment comprising the amino acid sequence from amino acid 102 to amino acid 111 of SEQ ID NO:19.

ID NO:21;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:21 from nucleotide 65 to nucleotide 490;

(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:21 from nucleotide 137 to nucleotide 490;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AS34_li deposited under accession number ATCC 98026;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AS34_li deposited under accession number ATCC

98026;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AS34_li deposited under accession number ATCC 98026; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AS34_li deposited under accession number ATCC 98026; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:22;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:22 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:22;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:21 from nucleotide 65 to nucleotide 490; the nucleotide sequence of SEQ ID NO:21 from nucleotide 137 to nucleotide 490; the nucleotide sequence of the full-length protein coding sequence of clone AS34_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AS34_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AS34_li deposited under accession number ATCC 98026. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:22;

(b) fragments of the amino acid sequence of SEQ ID NO:22, each fragment comprising eight consecutive amino acids of SEQ ID NO:22; and

(c) the amino acid sequence encoded by the cDNA insert of clone AS34_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:22. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:22 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:22, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:22, the fragment comprising the amino acid sequence from amino acid 66 to amino acid 75 of SEQ ID NO:22.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:23;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:23 from nucleotide 225 to nucleotide 677;

(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:23 from nucleotide 387 to nucleotide 677; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AT205_li deposited under accession number ATCC 98026;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AT205_li deposited under accession number ATCC 98026;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AT205_li deposited under accession number ATCC 98026; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AT205_li deposited under accession number ATCC 98026; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:24;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:24 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:24;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:23 from nucleotide 225 to nucleotide 677; the nucleotide sequence of SEQ ID NO:23 from nucleotide 387 to nucleotide 677; the nucleotide sequence of the full-length protein coding sequence of clone AT205_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AT205_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AT205_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:24 from amino acid 6 to amino acid 25. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:24 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:24, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:24 having biological activity, the fragment comprising the amino acid sequence from amino acid 70 to amino acid 79 of SEQ ID NO:24.

(a) the amino acid sequence of SEQ ID NO:24;

(b) the amino acid sequence of SEQ ID NO:24 from amino acid 6 to amino acid 25; (c) fragments of the amino acid sequence of SEQ ID NO:24, each fragment comprising eight consecutive amino acids of SEQ ID NO:24; and (d) the amino acid sequence encoded by the cDNA insert of clone AT205_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:24 or the amino acid sequence of SEQ ID NO:24 from amino acid 6 to amino acid 25. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:24 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:24, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:24, the fragment comprising the amino acid sequence from amino acid 70 to amino acid 79 of SEQ ID NO:24.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:25;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:25 from nucleotide 38 to nucleotide 832; (c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AT211_li deposited under accession number ATCC 98026;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AT211_li deposited under accession number ATCC 98026;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AT211_li deposited under accession number ATCC 98026;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AT211_li deposited under accession number ATCC 98026; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:26;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:26 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:26;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:25 from nucleotide 38 to nucleotide 832; the nucleotide sequence of the full-length protein coding sequence of clone AT211_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AT211_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AT211_li deposited under accession number ATCC 98026.

(a) the amino acid sequence of SEQ ID NO:26;

(b) fragments of the amino acid sequence of SEQ ID NO:26, each fragment comprising eight consecutive amino acids of SEQ ID NO:26; and

(c) the amino acid sequence encoded by the cDNA insert of clone AT211_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:26. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:26 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:26, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:26, the fragment comprising the amino acid sequence from amino acid 127 to amino acid 136 of SEQ ID NO:26.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:27; (b) a polynucleotide comprising the nucleotide sequence of SEQ

ID NO:27 from nucleotide 194 to nucleotide 423;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AT319_li deposited under accession number ATCC 98026; (d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AT319_li deposited under accession number ATCC 98026;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AT319_li deposited under accession number ATCC 98026;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AT319_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:28; (h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:28 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:28;

(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; and (j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above.

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:27 from nucleotide 194 to nucleotide 423; the nucleotide sequence of the full-length protein coding sequence of clone AT319_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AT319_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AT319_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:28 from amino add 2 to amino add 21. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:28 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:28, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:28 having biological activity, the fragment comprising the amino acid sequence from amino acid 30 to amino acid 39 of SEQ ID NO:28.

(a) the amino acid sequence of SEQ ID NO:28;

(b) the amino acid sequence of SEQ ID NO:28 from amino acid 2 to amino acid 21; (c) fragments of the amino acid sequence of SEQ ID NO:28, each fragment comprising eight consecutive amino acids of SEQ ID NO:28; and (d) the amino acid sequence encoded by the cDNA insert of clone AT319_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino add sequence of SEQ ID NO:28 or the amino acid sequence of SEQ ID NO:28 from amino acid 2 to amino acid 21. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:28 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:28, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:28, the fragment comprising the amino acid sequence from amino acid 30 to amino acid 39 of SEQ ID NO:28.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:30;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:30 from nucleotide 61 to nucleotide 514; (c) a polynudeotide comprising the nucleotide sequence of SEQ ID NO:30 from nucleotide 112 to nucleotide 514;

(d) a polynudeotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AW191_li deposited under accession number ATCC 98026;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AW191_li deposited under accession number ATCC 98026;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AW191_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AW191_li deposited under accession number ATCC 98026;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:31;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:31 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:31;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:30 from nucleotide 61 to nucleotide 514; the nucleotide sequence of SEQ ID NO:30 from nucleotide 112 to nucleotide 514; the nucleotide sequence of the full-length protein coding sequence of clone AW191_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone AW191_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AW191_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:31 from amino acid 24 to amino acid 43. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:31 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:31, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:31 having biological activity, the fragment comprising the amino acid sequence from amino acid 70 to amino acid 79 of SEQ ID NO:31.

(a) the amino acid sequence of SEQ ID NO:31; (b) the amino acid sequence of SEQ ID NO:31 from amino acid

24 to amino acid 43;

(c) fragments of the amino acid sequence of SEQ ID NO:31, each fragment comprising eight consecutive amino acids of SEQ ID NO:31; and

(d) the amino acid sequence encoded by the cDNA insert of clone AW191_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino add sequence of SEQ ID NO:31 or the amino acid sequence of SEQ ID NO:31 from amino acid 24 to amino acid 43. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:31 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:31, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:31, the fragment comprising the amino acid sequence from amino acid 70 to amino acid 79 of SEQ ID NO:31. In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynudeotide comprising the nucleotide sequence of SEQ ID NO:33; (b) a polynucleotide comprising the nucleotide sequence of SEQ

ID NO:33 from nucleotide 14 to nucleotide 391;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone BB9_li deposited under accession number ATCC 98026; (d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone BB9_Ji deposited under accession number ATCC 98026;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone BB9_li deposited under accession number ATCC 98026;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone BB9_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:34;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:34;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:33 from nucleotide 14 to nucleotide 391; the nucleotide sequence of the full-length protein coding sequence of clone BB9_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone BB9_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone BB9_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino add sequence of SEQ ID NO:34 from amino add 75 to amino acid 94. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:34, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34 having biological activity, the fragment comprising the amino acid sequence from amino acid 55 to amino acid 64 of SEQ ID NO:34.

(a) the amino acid sequence of SEQ ID NO:34;

(b) the amino acid sequence of SEQ ID NO:34 from ammo acid 75 to amino acid 94;

(c) fragments of the amino acid sequence of SEQ ID NO:34, each fragment comprising eight consecutive amino acids of SEQ ID NO:34; and

(d) the amino acid sequence encoded by the cDNA insert of clone BB9_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:34 or the amino acid sequence of SEQ ID NO:34 from amino acid 75 to amino acid 94. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:34, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:34, the fragment comprising the amino acid sequence from amino acid 55 to amino acid 64 of SEQ ID NO:34.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:36;

(b) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:36 from nucleotide 58 to nucleotide 655;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone H617_li deposited under accession number ATCC 98026;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone H617_li deposited under accession number ATCC

98026;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone H617_li deposited under accession number ATCC 98026; (f) a polynucleotide encoding a mature protein encoded by the cDNA insert of done H617_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:37; (h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:37 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:37;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:36 from nucleotide 58 to nucleotide 655; the nucleotide sequence of the full-length protein coding sequence of clone H617_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone H617_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone H617_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:37 from amino acid 65 to amino acid 84. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:37 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:37, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:37 having biological activity, the fragment comprising the amino acid sequence from amino acid 95 to amino acid 104 of SEQ ID NO:37.

(a) the amino acid sequence of SEQ ID NO:37;

(b) the amino acid sequence of SEQ ID NO:37 from amino acid 65 to amino acid 84;

(c) fragments of the amino acid sequence of SEQ ID NO:37, each fragment comprising eight consecutive amino acids of SEQ ID NO:37; and (d) the amino acid sequence encoded by the cDNA insert of clone H617_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:37 or the amino acid sequence of SEQ ID NO:37 from amino acid 65 to amino acid 84. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:37 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:37, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:37, the fragment comprising the amino acid sequence from amino acid 95 to amino acid 104 of SEQ ID NO:37.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:39;

(b) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:39 from nucleotide 71 to nucleotide 377; (c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone K39_li deposited under accession number ATCC 98026;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone K39_li deposited under accession number ATCC 98026;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone K39_li deposited under accession number ATCC 98026;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone K39_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:40;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:40 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:40;

(j) a polynucleotide which encodes a spedes homologue of the protein of (g) or (h) above.

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:39 from nucleotide 71 to nucleotide 377; the nucleotide sequence of the full-length protein coding sequence of clone K39_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone K39_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone K39_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino add sequence of SEQ ID NO:40 from amino acid 62 to amino acid 81. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:40;

(b) the amino acid sequence of SEQ ID NO:40 from amino acid 62 to amino acid 81;

(c) fragments of the amino acid sequence of SEQ ID NO:40, each fragment comprising eight consecutive amino acids of SEQ ID NO:40; and

(d) the amino acid sequence encoded by the cDNA insert of clone K39_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:40. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:40 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:40, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:40, the fragment comprising the amino acid sequence from amino acid 46 to amino acid 55 of SEQ ID NO.40.

(a) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:42;

(b) a polynudeotide comprising the nucleotide sequence of SEQ ID NO:42 from nucleotide 1 to nucleotide 332;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone K640_li deposited under accession number ATCC 98026;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone K640_li deposited under accession number ATCC

98026;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone K640_li deposited under accession number ATCC 98026; (f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone K640_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:43;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:43 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:43;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:42 from nucleotide 1 to nucleotide 332; the nucleotide sequence of the full-length protein coding sequence of clone K640_li deposited under accession number ATCC 98026; or the nucleotide sequence of a mature protein coding sequence of clone K640_li deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone K640_li deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:43 from amino add 11 to amino acid 30. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the ammo acid sequence of SEQ ID NOJ3 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:43, or a polynucleotide encoding a protem comprising a fragment of the ammo acid sequence of SEQ ID NO:43 having biological activity, the fragment comprising the ammo acid sequence from ammo acid 50 to amino acid 59 of SEQ ID NO:43.

In other embodiments, the present invention provides a composition comprising a protein, wherem said protein comprises an ammo acid sequence selected from the group consisting of:

(a) the ammo acid sequence of SEQ ID NO:43,

(b) the ammo acid sequence of SEQ ID NO:43 from ammo acid

(c) fragments of the ammo acid sequence of SEQ ID NO:43, each fragment comprising eight consecutive amino acids of SEQ ID NO:43; and

(d) the ammo acid sequence encoded by the cDNA insert of clone K640_lι deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:43 or the ammo acid sequence of SEQ ID NO:43 from ammo acid 11 to amino acid 30. In further preferred embodiments, the present invention provides a protein comprising a fragment of the ammo acid sequence of SEQ ID NO:43 having biological activity, the fragment preferably compnsmg eight (more preferably twenty, most preferably thirty) consecutive ammo acids of SEQ ID NO:43, or a protem compnsmg a fragment of the ammo acid sequence of SEQ ID NO:43, the fragment compnsmg the ammo acid sequence from amino acid 50 to amino acid 59 of SEQ ID NO:43.

In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of: (a) a polynucleotide compnsmg the nucleotide sequence of SEQ

ID NO:45;

(b) a polynucleotide compnsmg the nudeotide sequence of SEQ ID NO:45 from nucleotide 12 to nucleotide 539;

(c) a polynucleotide compnsmg the nucleotide sequence of the full- length protein coding sequence of clone AE402_li deposited under accession number ATCC 98190;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AE402_li deposited under accession number ATCC 98190;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AE402_li deposited under accession number ATCC 98190;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AE402_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:46;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:46 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:46;

ID NO:45 from nucleotide 12 to nucleotide 539; the nucleotide sequence of the full-length protein coding sequence of clone AE402_li deposited under accession number ATCC

98190; or the nucleotide sequence of a mature protein coding sequence of clone AE402_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AE402_li deposited under accession number ATCC 98190.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO:46;

(b) fragments of the amino acid sequence of SEQ ID NO:46, each fragment comprising eight consecutive amino acids of SEQ ID NO:46; and

(c) the amino acid sequence encoded by the cDNA insert of clone AE402_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO.J6. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:46 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:46, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:46, the fragment comprising the amino acid sequence from amino acid 83 to amino acid 92 of SEQ ID NO:46.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:47;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:47 from nucleotide 61 to nucleotide 513;

(c) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:47 from nucleotide 322 to nucleotide 513;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AE610_li deposited under accession number ATCC 98190;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AE610_li deposited under accession number ATCC 98190;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AE610_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AE610_li deposited under accession number ATCC 98190;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:48;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:48 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:48;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:47 from nucleotide 61 to nucleotide 513; the nucleotide sequence of SEQ ID NO:47 from nucleotide 322 to nucleotide 513; the nucleotide sequence of the full-length protein coding sequence of clone AE610_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AE610_li deposited under accession number ATCC 98190. In other prefened embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AE610_li deposited under accession number ATCC 98190.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO:48;

(b) fragments of the amino acid sequence of SEQ ID NO:48, each fragment comprising eight consecutive amino acids of SEQ ID NO:48; and

(c) the amino acid sequence encoded by the cDNA insert of clone AE610_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:48. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:48 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:48, or a protein comprising a fragment of the amino add sequence of SEQ ID NO:48, the fragment comprising the amino acid sequence from amino acid 70 to amino acid 79 of SEQ ID NO:48.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:50;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:50 from nucleotide 20 to nucleotide 523; (c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AH106_li deposited under accession number ATCC 98190;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AH106_li deposited under accession number ATCC

98190;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AH106_li deposited under accession number ATCC 98190; (f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AH106_li deposited under accession number ATCC 98190; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:51;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:51 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:51;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:50 from nucleotide 20 to nucleotide 523; the nucleotide sequence of the full-length protein coding sequence of clone AH106_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AH106_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AH106_li deposited under accession number ATCC 98190.

(a) the amino acid sequence of SEQ ID NO:51;

(b) fragments of the amino acid sequence of SEQ ID NO:51, each fragment comprising eight consecutive amino acids of SEQ ID NO:51; and

(c) the amino acid sequence encoded by the cDNA insert of clone AH106_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:51. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:51 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:51, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:51, the fragment comprising the amino acid sequence from amino acid 79 to amino acid 88 of SEQ ID NO:51. In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:52; (b) a polynucleotide comprising the nucleotide sequence of SEQ

ID NO:52 from nucleotide 130 to nucleotide 309;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AH196_li deposited under accession number ATCC 98190; (d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AH196_li deposited under accession number ATCC 98190;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AH196_li deposited under accession number ATCC 98190;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AH196_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:53; (h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:53 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:53;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:52 from nucleotide 130 to nucleotide 309; the nucleotide sequence of the full-length protein coding sequence of clone AH196_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AH196_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AH196_li deposited under accession number ATCC 98190. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:53;

(b) fragments of the amino acid sequence of SEQ ID NO:53, each fragment comprising eight consecutive amino acids of SEQ ID NO:53; and

(c) the amino acid sequence encoded by the cDNA insert of clone AH196_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:53. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:53 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:53, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:53, the fragment comprising the amino acid sequence from amino acid 25 to amino acid 34 of SEQ ID NO:53.

(a) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:55;

(b) a polynudeotide comprising the nudeotide sequence of SEQ ID NO:55 from nucleotide 69 to nucleotide 467;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AI6_li deposited under accession number ATCC 98190;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AI6_li deposited under accession number ATCC 98190; (e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AI6_li deposited under accession number ATCC 98190;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AI6_li deposited under accession number ATCC 98190; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:56;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:56 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:56; (i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; and

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:55 from nucleotide 69 to nucleotide 467; the nucleotide sequence of the full-length protein coding sequence of clone AI6_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AI6_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AI6_li deposited under accession number ATCC 98190. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:56 from amino acid 69 to amino acid 133. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino a id sequence of SEQ ID NO:56 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:56, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:56 having biological activity, the fragment comprising the amino acid sequence from amino acid 61 to amino acid 70 of SEQ ID NO:56. In other embodiments, the present invention provides a composition comprising a protein, wherem said protem comprises an amino acid sequence selected from the group consisting of

(a) the ammo acid sequence of SEQ ID NO 56, (b) the ammo acid sequence of SEQ ID NO 56 from ammo acid

(c) fragments of the ammo acid sequence of SEQ ID NO.56, each fragment compnsmg eight consecutive ammo acids of SEQ ID NO.56; and

(d) the ammo acid sequence encoded by the cDNA insert of clone AI6_lι deposited under accession number ATCC 98190, the protem bemg substantially free from other mammalian protems Preferably such protem compnses the ammo acid sequence of SEQ ID NO 56 or the ammo acid sequence of SEQ ID NO.56 from ammo acid 69 to ammo acid 133 In further preferred embodiments, the present invention provides a protem comprising a fragment of the ammo acid sequence of SEQ ID NO 56 havmg biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:56, or a protem compnsmg a fragment of the am o acid sequence of SEQ ID NO.56, the fragment compnsmg the ammo acid sequence from ammo acid 61 to ammo acid 70 of SEQ ID NO:56. In one embodiment, the present invention provides a composition compnsmg an isolated protem encoded by a polynucleotide selected from the group consistmg of:

(a) a polynudeotide compnsmg the nudeotide sequence of SEQ ID NO:58; (b) a polynucleotide compnsmg the nucleotide sequence of SEQ

ID NO:58 from nucleotide 55 to nucleotide 363;

(c) a polynucleotide compnsmg the nucleotide sequence of the full- length protem coding sequence of clone AJ13_lι deposited under accession number ATCC 98190; (d) a polynucleotide encodmg the full-length protem encoded by the cDNA insert of clone AJ13_lι deposited under accession number ATCC 98190;

(e) a polynucleotide comprising the nucleotide sequence of a mature protem coding sequence of clone ATJ3_lι deposited under accession number ATCC 98190;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AJ13_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:59;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:59 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:59;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:58 from nucleotide 55 to nucleotide 363; the nucleotide sequence of the full-length protein coding sequence of clone AJ13_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AJ13_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AJ13_li deposited under accession number ATCC 98190. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:59;

(b) fragments of the amino acid sequence of SEQ ID NO:59, each fragment comprising eight consecutive amino acids of SEQ ID NO:59; and

(c) the amino acid sequence encoded by the cDNA insert of clone AJ13_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:59. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:59 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:59, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:59, the fragment comprising the amino acid sequence from amino acid 46 to amino acid 55 of SEQ ID NO:59.

In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nudeotide sequence of SEQ

ID NO:60;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:60 from nucleotide 33 to nucleotide 422;

(c) a polynudeotide comprising the nudeotide sequence of SEQ ID NO:60 from nucleotide 114 to nucleotide 422;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protem coding sequence of clone AJ27_li deposited under accession number ATCC 98190;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AJ27_li deposited under accession number ATCC

98190;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AJ27_li deposited under accession number ATCC 98190; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AJ27_li deposited under accession number ATCC 98190;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:61;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:61 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:61;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:60 from nucleotide 33 to nucleotide 422; the nucleotide sequence of SEQ ID NO:60 from nucleotide 114 to nucleotide 422; the nucleotide sequence of the full-length protein coding sequence of clone AJ27_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AJ27_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AJ27_li deposited under accession number ATCC 98190. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:61;

(b) fragments of the amino acid sequence of SEQ ID NO:61, each fragment comprising eight consecutive amino acids of SEQ ID NO:61; and

(c) the amino acid sequence encoded by the cDNA insert of clone AJ27_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:61. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:61 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:61, or a protein comprising a fragment of the amino add sequence of SEQ ID NO:61, the fragment comprising the amino acid sequence from amino acid 60 to amino acid 69 of SEQ ID NO:61.

(a) a polynudeotide comprising the nudeotide sequence of SEQ ID NO:63;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:63 from nucleotide 47 to nucleotide 517;

(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:63 from nucleotide 116 to nucleotide 517; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AJ142_li deposited under accession number ATCC 98190;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AJ142_li deposited under accession number ATCC 98190;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AJ142_li deposited under accession number ATCC 98190; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AJ142_li deposited under accession number ATCC 98190; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:64;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:64 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:64;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:63 from nucleotide 47 to nucleotide 517; the nucleotide sequence of SEQ ID NO:63 from nucleotide 116 to nucleotide 517; the nucleotide sequence of the full-length protein coding sequence of clone AJ142_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AJ142_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AJ142_li deposited under accession number ATCC 98190.

(a) the amino acid sequence of SEQ ID NO:64;

(b) fragments of the amino acid sequence of SEQ ID NO:64, each fragment comprising eight consecutive amino acids of SEQ ID NO:64; and (c) the amino acid sequence encoded by the cDNA insert of clone AJ142_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:64. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:64 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:64, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:64, the fragment comprising the amino acid sequence from amino acid 73 to amino acid 82 of SEQ ID NO:64.

(a) a polynudeotide comprising the nucleotide sequence of SEQ ID NO:65;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:65 from nucleotide 312 to nucleotide 417;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AK604_li deposited under accession number ATCC 98190;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AK604_li deposited under accession number ATCC 98190;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AK604_li deposited under accession number ATCC 98190;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AK604_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:66;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 66 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:66;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:65 from nucleotide 312 to nucleotide 417; the nucleotide sequence of the full-length protein coding sequence of clone AK604_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AK604_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AK604_li deposited under accession number ATCC 98190.

(a) the amino acid sequence of SEQ ID NO:66; (b) fragments of the amino acid sequence of SEQ ID NO:66, each fragment comprising eight consecutive amino acids of SEQ ID NO:66; and (c) the amino acid sequence encoded by the cDNA insert of clone AK604_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:66. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:66 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:66, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:66, the fragment comprising the amino acid sequence from amino acid 12 to amino acid 21 of SEQ ID NO:66.

ID NO:68;

(b) a polynudeotide comprising the nucleotide sequence of SEQ ID NO:68 from nucleotide 57 to nucleotide 353;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AK620_li deposited under accession number ATCC 98190;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AK620_li deposited under accession number ATCC 98190; (e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AK620_li deposited under accession number ATCC 98190;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AK620_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:69;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:69 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:69;

ID NO:68 from nucleotide 57 to nucleotide 353; the nucleotide sequence of the full-length protein coding sequence of clone AK620_li deposited under accession number ATCC

98190; or the nucleotide sequence of a mature protein coding sequence of clone AK620_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AK620_li deposited under accession number ATCC 98190.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO:69;

(b) fragments of the amino acid sequence of SEQ ID NO:69, each fragment comprising eight consecutive amino acids of SEQ ID NO:69; and

(c) the amino acid sequence encoded by the cDNA insert of clone AK620_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:69. In further prefereed embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:69 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:69, or a protein comprising a fragment of the amino add sequence of SEQ ID NO:69, the fragment comprising the amino acid sequence from amino acid 44 to amino acid 53 of SEQ ID NO:69.

(a) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:70;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:70 from nucleotide 464 to nucleotide 751;

(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:70 from nucleotide 542 to nucleotide 751;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AK650_li deposited under accession number ATCC 98190;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AK650_li deposited under accession number ATCC 98190;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AK650_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AK650_li deposited under accession number ATCC 98190;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:71;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:71 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:71;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:70 from nucleotide 464 to nucleotide 751; the nucleotide sequence of SEQ ID NO:70 from nucleotide 542 to nucleotide 751; the nucleotide sequence of the full-length protein coding sequence of clone AK650_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AK650_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AK650_li deposited under accession number ATCC 98190.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO:71;

(b) fragments of the amino acid sequence of SEQ ID NO:71, each fragment comprising eight consecutive amino acids of SEQ ID NO:71; and

(c) the amino acid sequence encoded by the cDNA insert of clone AK650_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:71. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:71 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:71, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:71, the fragment comprising the amino acid sequence from amino acid 43 to amino acid 52 of SEQ ID NO:71.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:72;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:72 from nucleotide 116 to nucleotide 310; (c) a polynucleotide comprising the nucleotide sequence of SEQ

ID NO:72 from nucleotide 173 to nucleotide 310;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AM226_li deposited under accession number ATCC 98190; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AM226_li deposited under accession number ATCC 98190;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AM226_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AM226_li deposited under accession number ATCC 98190;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:73;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:73 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:73;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:72 from nucleotide 116 to nucleotide 310; the nucleotide sequence of SEQ ID NO:72 from nucleotide 173 to nucleotide 310; the nucleotide sequence of the full-length protein coding sequence of clone AM226_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AM226_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AM226_li deposited under accession number ATCC 98190.

(a) the amino acid sequence of SEQ ID NO: 73; (b) fragments of the amino acid sequence of SEQ ID NO:73, each fragment comprising eight consecutive amino acids of SEQ ID NO:73; and (c) the amino acid sequence encoded by the cDNA insert of clone AM226_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:73. In further prefened embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:73 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:73, or a protein comprising a fragment of the amino add sequence of SEQ ID NO:73, the fragment comprising the amino acid sequence from amino acid 27 to amino acid 36 of SEQ ID NO:73.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:75;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:75 from nucleotide 220 to nucleotide 453; (c) a polynucleotide comprising the nucleotide sequence of SEQ

ID NO:75 from nucleotide 352 to nucleotide 453;

(d) a polynucleotide comprising the nudeotide sequence of the full- length protein coding sequence of clone AR417_li deposited under accession number ATCC 98190; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AR417_li deposited under accession number ATCC

98190;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AR417_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AR417_li deposited under accession number ATCC 98190;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:76; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:76 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:76;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:75 from nucleotide 220 to nucleotide 453; the nucleotide sequence of SEQ ID NO:75 from nucleotide 352 to nucleotide 453; the nucleotide sequence of the full-length protein coding sequence of clone AR417_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AR417_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AR417_li deposited under accession number ATCC 98190.

(a) the amino acid sequence of SEQ ID NO:76; (b) fragments of the amino acid sequence of SEQ ID NO:76, each fragment comprising eight consecutive amino acids of SEQ ID NO:76; and (c) the amino acid sequence encoded by the cDNA insert of clone AR417_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:76. In further preferred embodiments, the present invention provides a protem comprising a fragment of the amino acid sequence of SEQ ID NO:76 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:76, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:76, the fragment comprising the amino acid sequence from amino acid 34 to amino acid 43 of SEQ ID NO:76.

ID NO:77;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:77 from nucleotide 496 to nucleotide 583;

(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:77 from nucleotide 565 to nucleotide 583;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AU43_li deposited under accession number ATCC 98190; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AU43_li deposited under accession number ATCC 98190;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AU43_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AU43_li deposited under accession number ATCC 98190;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:78; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:78 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:78;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:77 from nucleotide 496 to nucleotide 583; the nucleotide sequence of SEQ ID NO:77 from nucleotide 565 to nucleotide 583; the nucleotide sequence of the full-length protein coding sequence of clone AU43_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AU43_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AU43_li deposited under accession number ATCC 98190. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:78;

(b) fragments of the amino acid sequence of SEQ ID NO:78, each fragment comprising eight consecutive amino acids of SEQ ID NO:78; and (c) the amino acid sequence encoded by the cDNA insert of clone AU43_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:78. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:78 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:78, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:78, the fragment comprising the amino a id sequence from amino acid 9 to amino acid 18 of SEQ ID NO:78.

ID NO:80;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:80 from nucleotide 55 to nucleotide 405;

(c) a polynudeotide comprising the nudeotide sequence of SEQ ID NO:80 from nucleotide 148 to nucleotide 405;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AW60_li deposited under accession number ATCC 98190;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AW60_li deposited under accession number ATCC

98190;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AW60_li deposited under accession number ATCC 98190; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AW60_li deposited under accession number ATCC 98190;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.81;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:81 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:81;

(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above; and (k) a polynucleotide which encodes a spedes homologue of the protein of (h) or (i) above.

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:80 from nucleotide 55 to nucleotide 405; the nucleotide sequence of SEQ ID NO:80 from nucleotide 148 to nucleotide 405; the nucleotide sequence of the full-length protein coding sequence of clone AW60_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone AW60_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AW60_li deposited under accession number ATCC 98190. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:81;

(b) fragments of the amino acid sequence of SEQ ID NO:81, each fragment comprising eight consecutive amino acids of SEQ ID NO:81; and

(c) the amino acid sequence encoded by the cDNA insert of clone AW60_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:81. In further preferred embodiments, the present invention provides a protem comprising a fragment of the amino acid sequence of SEQ ID NO:81 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:81, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:81, the fragment comprising the amino acid sequence from amino acid 53 to amino acid 62 of SEQ ID NO:81.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:83;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:83 from nucleotide 256 to nucleotide 1338;

(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:83 from nucleotide 1120 to nucleotide 1338;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone BA176_li deposited under accession number ATCC 98190;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone BA176_li deposited under accession number ATCC

98190;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone BA176_li deposited under accession number ATCC 98190; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone BA176_li deposited under accession number ATCC 98190; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:84;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:84 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:84;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:83 from nucleotide 256 to nucleotide 1338; the nucleotide sequence of SEQ ID NO:83 from nucleotide 1120 to nucleotide 1338; the nucleotide sequence of the full-length protein coding sequence of clone BA176_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone BA176_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone BA176_li deposited under accession number ATCC 98190.

(a) the amino acid sequence of SEQ ID NO:84;

(b) fragments of the amino acid sequence of SEQ ID NO:84, each fragment comprising eight consecutive amino acids of SEQ ID NO:84; and

(c) the amino acid sequence encoded by the cDNA insert of clone BA176_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:84. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:84 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:84, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:84, the fragment comprising the amino acid sequence from amino acid 175 to amino acid 184 of SEQ ID NO:84.

(a) a polynudeotide comprising the nucleotide sequence of SEQ ID NO:85;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:85 from nucleotide 199 to nucleotide 396;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone BD140_li deposited under accession number ATCC 98190;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone BD140_li deposited under accession number ATCC 98190;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone BD140_li deposited under accession number ATCC 98190;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone BD140_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:86;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:86 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:86; (i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; and

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:85 from nucleotide 199 to nucleotide 396; the nucleotide sequence of the full-length protein coding sequence of clone BD140_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone BD140_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone BD140_li deposited under accession number ATCC 98190.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino add sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:86; (b) fragments of the amino acid sequence of SEQ ID NO:86, each fragment comprising eight consecutive amino acids of SEQ ID NO:86; and (c) the amino acid sequence encoded by the cDNA insert of clone BD140_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:86. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:86 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NO:86, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:86, the fragment comprising the amino acid sequence from amino acid 28 to amino acid 37 of SEQ ID NO:86.

In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of: (a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:87;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:87 from nucleotide 303 to nucleotide 617; (c) a polynucleotide comprising the nucleotide sequence of SEQ

ID NO:87 from nucleotide 345 to nucleotide 617;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone BD407_li deposited under accession number ATCC 98190; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone BD407_li deposited under accession number ATCC 98190;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone BD407_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone BD407_li deposited under accession number ATCC 98190;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:88; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 88 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:88;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:87 from nucleotide 303 to nucleotide 617; the nucleotide sequence of SEQ ID NO:87 from nucleotide 345 to nucleotide 617; the nucleotide sequence of the full-length protein coding sequence of clone BD407_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone BD407_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone BD407_li deposited under accession number ATCC 98190. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:88 from amino acid 1 to amino acid 32. In further prefened embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:88 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:88, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:88 having biological activity, the fragment comprising the amino acid sequence from amino acid 47 to amino acid 56 of SEQ ID NO:88. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:88;

(b) the amino add sequence of SEQ ID NO:88 from amino acid 1 to amino acid 32;

(c) fragments of the amino acid sequence of SEQ ID NO:88, each fragment comprising eight consecutive amino acids of SEQ ID NO:88; and

(d) the amino add sequence encoded by the cDNA insert of clone BD407_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino add sequence of SEQ ID NO:88 or the amino acid sequence of SEQ ID NO:88 from amino acid 1 to amino acid 32. In further prefened embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:88 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:88, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:88, the fragment comprising the amino acid sequence from amino acid 47 to amino acid 56 of SEQ ID NO:88.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:89;

(b) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:89 from nucleotide 152 to nucleotide 535;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone BF290_li deposited under accession number ATCC 98190; (d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone BF290_li deposited under accession number ATCC 98190;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone BF290_li deposited under accession number ATCC 98190;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone BF290_li deposited under accession number ATCC 98190;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:90; (h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:90 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:90;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:89 from nucleotide 152 to nucleotide 535; the nucleotide sequence of the full-length protein coding sequence of clone BF290_li deposited under accession number ATCC 98190; or the nucleotide sequence of a mature protein coding sequence of clone BF290_li deposited under accession number ATCC 98190. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone BF290_li deposited under accession number ATCC 98190.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protem comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:90;

(b) fragments of the amino acid sequence of SEQ ID NO:90, each fragment comprising eight consecutive amino acids of SEQ ID NO:90; and (c) the amino acid sequence encoded by the cDNA insert of clone BF290_li deposited under accession number ATCC 98190; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:90. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NO:90 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:90, or a protein comprising a fragment of the amino acid sequence of

SEQ ID NO:90, the fragment comprising the amino acid sequence from amino acid 59 to amino acid 68 of SEQ ID NO:90.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:91;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:91 from nucleotide 160 to nucleotide 474;

(c) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:91 from nucleotide 331 to nucleotide 474; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone BG236_li deposited under accession number ATCC 98191;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone BG236_li deposited under accession number ATCC 98191;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone BG236_li deposited under accession number ATCC 98191;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone BG236_li deposited under accession number ATCC 98191;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:92;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:92 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:92;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:91 from nucleotide 160 to nucleotide 474; the nucleotide sequence of SEQ ID NO:91 from nucleotide 331 to nucleotide 474; the nucleotide sequence of the full-length protein coding sequence of clone BG236_li deposited under accession number ATCC 98191; or the nucleotide sequence of a mature protein coding sequence of clone BG236_li deposited under accession number ATCC 98191. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone BG236_li deposited under accession number ATCC 98191.

(a) the amino acid sequence of SEQ ID NO:92;

(b) fragments of the amino acid sequence of SEQ ID NO:92, each fragment comprising eight consecutive amino acids of SEQ ID NO:92; and (c) the amino acid sequence encoded by the cDNA insert of clone BG236_li deposited under accession number ATCC 98191; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:92. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:92 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:92, or a protein comprising a fragment of the amino add sequence of SEQ ID NO:92, the fragment comprising the amino acid sequence from amino acid 47 to amino acid 56 of SEQ ID NO:92. In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:93; (b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:93 from nucleotide 139 to nucleotide 419;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone BG237_li deposited under accession number ATCC 98191;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone BG237_li deposited under accession number ATCC 98191;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone BG237_li deposited under accession number ATCC 98191;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone BG237_li deposited under accession number ATCC 98191;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:94;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:94 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:94;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:93 from nucleotide 139 to nucleotide 419; the nucleotide sequence of the full-length protein coding sequence of clone BG237_li deposited under accession number ATCC 98191; or the nucleotide sequence of a mature protein coding sequence of clone BG237_li deposited under accession number ATCC 98191. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone BG237_li deposited under accession number ATCC 98191. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:94 from amino acid 9 to amino acid 93. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:94 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:94, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:94 having biological activity, the fragment comprising the amino acid sequence from amino acid 41 to amino acid 50 of SEQ ID NO:94. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:94;

(b) the amino acid sequence of SEQ ID NO:94 from amino acid 9 to amino acid 93;

(c) fragments of the amino acid sequence of SEQ ID NO:94, each fragment comprising eight consecutive amino acids of SEQ ID NO:94; and

(d) the amino acid sequence encoded by the cDNA insert of clone BG237_li deposited under accession number ATCC 98191; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:94 or the amino acid sequence of SEQ ID NO:94 from amino acid 9 to amino acid 93. In further prefened embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:94 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NO:94, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:94, the fragment comprising the amino acid sequence from amino acid 41 to amino acid 50 of SEQ ID NO:94.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:96;

(b) a polynudeotide comprising the nucleotide sequence of SEQ ID NO:96 from nucleotide 294 to nucleotide 431;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of done BG255_li deposited under accession number ATCC 98191;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone BG255_li deposited under accession number ATCC 98191;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone BG255_li deposited under accession number ATCC 98191;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone BG255_li deposited under accession number ATCC 98191;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:97; (h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:97 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:97;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:96 from nucleotide 294 to nucleotide 431; the nucleotide sequence of the full-length protein coding sequence of clone BG255_li deposited under accession number ATCC 98191; or the nucleotide sequence of a mature protein coding sequence of clone BG255_li deposited under accession number ATCC 98191. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone BG255_li deposited under accession number ATCC 98191.

(a) the amino acid sequence of SEQ ID NO:97;

(b) fragments of the amino acid sequence of SEQ ID NO:97, each fragment comprising eight consecutive amino acids of SEQ ID NO:97; and (c) the amino acid sequence encoded by the cDNA insert of clone BG255_li deposited under accession number ATCC 98191; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:97. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO:97 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO:97, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO:97, the fragment comprising the amino acid sequence from amino acid 18 to amino acid 27 of SEQ ID NO:97.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:99;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:99 from nucleotide 57 to nucleotide 968;

(c) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:99 from nucleotide 105 to nucleotide 968; (d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone H541_3i deposited under accession number ATCC 98191;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone H541_3i deposited under accession number ATCC 98191;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone H541_3i deposited under accession number ATCC 98191;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone H541_3i deposited under accession number ATCC 98191;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NOJOO;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJOO having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJOO;

(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:99 from nucleotide 57 to nucleotide 968; the nucleotide sequence of SEQ ID NO:99 from nucleotide 105 to nucleotide 968; the nucleotide sequence of the full-length protein coding sequence of clone H541_3i deposited under accession number ATCC 98191; or the nucleotide sequence of a mature protein coding sequence of clone H541_3i deposited under accession number ATCC 98191. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone H541_3i deposited under accession number ATCC 98191.

(a) the amino acid sequence of SEQ ID NOJOO;

(b) fragments of the amino acid sequence of SEQ ID NOJOO, each fragment comprising eight consecutive amino acids of SEQ ID NOJOO; and (c) the amino acid sequence encoded by the cDNA insert of clone H541_3i deposited under accession number ATCC 98191; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJOO. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NOJOO having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NOJOO, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJOO, the fragment comprising the amino acid sequence from amino acid 147 to amino acid 156 of SEQ ID NOJOO. In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynudeotide comprising the nucleotide sequence of SEQ ID NO.101; (b) a polynucleotide comprising the nudeotide sequence of SEQ

ID NO: 101 from nucleotide 37 to nucleotide 220;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone H978_li deposited under accession number ATCC 98191; (d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone H978_li deposited under accession number ATCC 98191;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone H978_li deposited under accession number ATCC 98191;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone H978_li deposited under accession number ATCC 98191;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.102;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 102 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ02;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ01 from nucleotide 37 to nucleotide 220; the nucleotide sequence of the full-length protein coding sequence of clone H978_li deposited under accession number ATCC 98191; or the nudeotide sequence of a mature protein coding sequence of clone H978_li deposited under accession number ATCC 98191. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone H978_li deposited under accession number ATCC 98191. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino add sequence of SEQ ID NOJ02 from amino acid 1 to amino acid 31. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ02 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ02, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 102 having biological activity, the fragment comprising the amino acid sequence from amino acid 25 to amino acid 34 of SEQ ID NO.102.

(a) the amino acid sequence of SEQ ID NO: 102;

(b) the amino add sequence of SEQ ID NOJ02 from amino add 1 to amino acid 31;

(c) fragments of the amino acid sequence of SEQ ID NOJ02, each fragment comprising eight consecutive amino acids of SEQ ID NOJ02; and

(d) the amino acid sequence encoded by the cDNA insert of clone H978_li deposited under accession number ATCC 98191; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 102 or the amino acid sequence of SEQ ID NOJ02 from amino acid 1 to amino acid 31. In further prefened embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ02 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NOJ02, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 102, the fragment comprising the amino acid sequence from amino acid 25 to amino acid 34 of SEQ ID NO.102.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.104;

(b) a polynudeotide comprising the nudeotide sequence of SEQ ID NOJ04 from nucleotide 2 to nucleotide 422;

(c) a polynudeotide comprising the nucleotide sequence of the full- length protein coding sequence of clone L161_li deposited under accession number ATCC 98191;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone L161_li deposited under accession number ATCC

98191;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone IJ61_Ji deposited under accession number ATCC 98191; (f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone L161_li deposited under accession number ATCC 98191;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.105; (h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ05 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ05;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ04 from nucleotide 2 to nucleotide 422; the nucleotide sequence of the full-length protein coding sequence of clone L161_li deposited under accession number ATCC 98191; or the nucleotide sequence of a mature protein coding sequence of clone L161_li deposited under accession number ATCC 98191. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone L161_li deposited under accession number ATCC 98191. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO: 105 from amino acid 72 to amino acid 91. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ05 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ05, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ05 having biological activity, the fragment comprising the amino acid sequence from amino acid 65 to amino acid 74 of SEQ ID NOJ05.

In other embodiments, the present invention provides a composition comprising a protem, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NOJ05;

(b) the amino add sequence of SEQ ID NO: 105 from amino add 72 to amino acid 91;

(c) fragments of the amino acid sequence of SEQ ID NOJ05, each fragment comprising eight consecutive amino acids of SEQ ID NOJ05; and

(d) the amino acid sequence encoded by the cDNA insert of clone L161_li deposited under accession number ATCC 98191; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino add sequence of SEQ ID NOJ05 or the amino acid sequence of SEQ ID NO: 105 from amino acid 72 to amino acid 91. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ05 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NOJ05, or a protem comprising a fragment of the amino acid sequence of SEQ ID NOJ05, the fragment comprising the amino acid sequence from amino acid 65 to amino acid 74 of SEQ ID NOJ05.

(a) a polynucleotide comprising the nudeotide sequence of SEQ ID NO.107;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.107 from nucleotide 73 to nucleotide 702; (c) a polynudeotide comprising the nudeotide sequence of SEQ

ID NOJ07 from nucleotide 118 to nucleotide 702;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AE648_li deposited under accession number ATCC 98237; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AE648_li deposited under accession number ATCC

98237;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AE648_li deposited under accession number ATCC 98237;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AE648_li deposited under accession number ATCC 98237;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.108; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 108 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ08;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ

ID NO: 107 from nucleotide 73 to nucleotide 702; the nucleotide sequence of SEQ ID NOJ07 from nucleotide 118 to nucleotide 702; the nucleotide sequence of the full-length protein coding sequence of clone AE648_li deposited under accession number ATCC

98237; or the nucleotide sequence of a mature protein coding sequence of clone AE648_li deposited under accession number ATCC 98237. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AE648_li deposited under accession number ATCC 98237. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NOJ08 from amino add 1 to amino acid 34. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 108 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ08, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ08 having biological activity, the fragment comprising the amino acid sequence from amino acid 100 to amino acid 109 of SEQ ID NO.108. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NOJ08;

(b) the amino add sequence of SEQ ID NOJ08 from amino add 1 to amino acid 34;

(c) fragments of the amino acid sequence of SEQ ID NO: 108, each fragment comprising eight consecutive amino acids of SEQ ID NO: 108; and

(d) the amino acid sequence encoded by the cDNA insert of clone AE648_li deposited under accession number ATCC 98237; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 108 or the amino acid sequence of SEQ ID NO: 108 from amino acid 1 to amino acid 34. In further prefened embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ08 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ08, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ08, the fragment comprising the amino acid sequence from amino acid 100 to amino acid 109 of SEQ ID NO.108. In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.109; (b) a polynudeotide comprising the nucleotide sequence of SEQ

ID NO: 109 from nucleotide 92 to nucleotide 268;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AE693_li deposited under accession number ATCC 98237; (d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AE693_li deposited under accession number ATCC 98237;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AE693_li deposited under accession number ATCC 98237;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AE693_li deposited under accession number ATCC 98237;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 110; (h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ 10 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ 10;

(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; and (_]) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO 109 from nucleotide 92 to nucleotide 268; the nucleotide sequence of the full-length protem coding sequence of clone AE693_lι deposited under accession number ATCC 98237, or the nucleotide sequence of a mature protem coding sequence of clone AE693_lι deposited under accession number ATCC 98237. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA msert of clone AE693_lι deposited under accession number ATCC 98237 In other embodiments, the present mvention provides a composition comprising a protem, wherein said protem comprises an ammo acid sequence selected from the group consisting of:

(a) the ammo acid sequence of SEQ ID NOJ 10,

(b) fragments of the amino acid sequence of SEQ ID NOJ10, each fragment compnsmg eight consecutive ammo acids of SEQ ID NOJ 10; and

(c) the ammo acid sequence encoded by the cDNA msert of clone AE693_lι deposited under accession number ATCC 98237; the protem being substantially free from other mammalian protems Preferably such protein comprises the ammo acid sequence of SEQ ID NOJ 10 In further preferred embodiments, the present mvention provides a protem compnsmg a fragment of the amino acid sequence of SEQ ID NOJ 10 havmg biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive ammo acids of SEQ ID NOJ10, or a protem compnsmg a fragment of the amino acid sequence of SEQ ID NOJ10, the fragment compnsmg the ammo acid sequence from ammo acid 24 to ammo acid 33 of SEQ ID NOJ 10.

In one embodiment, the present mvention provides a composition compnsmg an isolated protem encoded by a polynucleotide selected from the group consisting of:

(a) a polynucleotide compnsmg the nucleotide sequence of SEQ ID NO:112;

(b) a polynucleotide compnsmg the nucleotide sequence of SEQ ID NO.112 from nucleotide 137 to nucleotide 412;

(c) a polynucleotide compnsmg the nucleotide sequence of the full- length protem codmg sequence of clone AK438_lι deposited under accession number ATCC 98237;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AK438_li deposited under accession number ATCC 98237; (e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AK438_li deposited under accession number ATCC 98237;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AK438_li deposited under accession number ATCC 98237; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.113;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 113 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ13; (i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; and

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ 12 from nucleotide 137 to nucleotide 412; the nucleotide sequence of the full-length protein coding sequence of clone AK438_li deposited under accession number ATCC 98237; or the nucleotide sequence of a mature protein coding sequence of clone AK438_li deposited under accession number ATCC 98237. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AK438_li deposited under accession number ATCC 98237.

(a) the amino acid sequence of SEQ ID NO: 113; (b) fragments of the amino acid sequence of SEQ ID NOJ 13, each fragment comprising eight consecutive amino acids of SEQ ID NOJ 13; and

(c) the amino acid sequence encoded by the cDNA insert of clone AK438_li deposited under accession number ATCC 98237; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ 13. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ 13 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ13, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ13, the fragment comprising the amino acid sequence from amino acid 41 to amino acid 50 of SEQ ID NOJ 13.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.115;

(b) a polynudeotide comprising the nucleotide sequence of SEQ ID NOJ15 from nucleotide 1 to nucleotide 285; (c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AK609_li deposited under accession number ATCC 98237;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AK609_li deposited under accession number ATCC 98237;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AK609_li deposited under accession number ATCC 98237;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AK609_li deposited under accession number ATCC 98237;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 116;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ16 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ16;

(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ 15 from nucleotide 1 to nucleotide 285; the nucleotide sequence of the full-length protein coding sequence of clone AK609_li deposited under accession number ATCC 98237; or the nucleotide sequence of a mature protein coding sequence of clone AK609_li deposited under accession number ATCC 98237. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AK609_li deposited under accession number ATCC 98237.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of :

(a) the amino acid sequence of SEQ ID NO: 116;

(b) fragments of the amino acid sequence of SEQ ID NOJ16, each fragment comprising eight consecutive amino acids of SEQ ID NO: 116; and

(c) the amino acid sequence encoded by the cDNA insert of clone AK609_li deposited under accession number ATCC 98237; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ16. In further prefened embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ 16 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO: 116, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 116, the fragment comprising the amino acid sequence from amino acid 42 to amino acid 51 of SEQ ID NO:116.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.118;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:118 from nucleotide 43 to nucleotide 282;

(c) a polynudeotide comprising the nucleotide sequence of SEQ ID NOJ18 from nucleotide 118 to nucleotide 282;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AM1060_li deposited under accession number ATCC 98237;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AM1060_li deposited under accession number ATCC 98237; (f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AM1060_li deposited under accession number ATCC 98237;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AM1060_li deposited under accession number ATCC 98237; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.119;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ19 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ 19; (j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above; and

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ18 from nucleotide 43 to nucleotide 282; the nucleotide sequence of SEQ ID NOJ18 from nucleotide 118 to nucleotide 282; the nucleotide sequence of the full-length protein coding sequence of clone AM1060_li deposited under accession number ATCC 98237; or the nucleotide sequence of a mature protein coding sequence of clone AM1060_li deposited under accession number ATCC 98237. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AM1060_li deposited under accession number ATCC 98237.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selerted from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 119;

(b) fragments of the amino acid sequence of SEQ ID NOJ19, each fragment comprising eight consecutive amino acids of SEQ ID NO:l 19; and

(c) the amino acid sequence encoded by the cDNA insert of clone AM1060_li deposited under accession number ATCC 98237; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ19. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ 19 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ 19, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ 19, the fragment comprising the amino add sequence from amino acid 35 to amino acid 44 of SEQ ID NO.119.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO: 121;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NOJ21 from nucleotide 316 to nucleotide 438;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AQ2_li deposited under accession number ATCC 98237;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AQ2_li deposited under accession number ATCC

98237;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AQ2_li deposited under accession number ATCC 98237; (f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AQ2_li deposited under accession number ATCC 98237;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NOJ22;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ22 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ22;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ21 from nucleotide 316 to nucleotide 438; the nucleotide sequence of the full-length protein coding sequence of clone AQ2_li deposited under accession number ATCC 98237; or the nucleotide sequence of a mature protein coding sequence of clone AQ2_li deposited under accession number ATCC 98237. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AQ2_li deposited under accession number ATCC 98237. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NOJ22 from amino acid 1 to amino acid 25. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ22 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ22, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 122 having biological activity, the fragment comprising the amino acid sequence from amino acid 15 to amino acid 24 of SEQ ID NOJ22.

(a) the amino acid sequence of SEQ ID NO: 122;

(b) the amino add sequence of SEQ ID NOJ22 from amino add 1 to amino acid 25;

(c) fragments of the amino acid sequence of SEQ ID NOJ22, each fragment comprising eight consecutive amino acids of SEQ ID NOJ22; and

(d) the amino acid sequence encoded by the cDNA insert of clone AQ2_li deposited under accession number ATCC 98237; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 122 or the amino acid sequence of SEQ ID NOJ22 from amino acid 1 to amino acid 25. In further prefened embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 122 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO: 122, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 122, the fragment comprising the amino acid sequence from amino acid 15 to amino acid 24 of SEQ ID NO.122.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.J24;

(b) a polynudeotide comprising the nudeotide sequence of SEQ ID NOJ24 from nucleotide 142 to nucleotide 285; (c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone K433_li deposited under accession number ATCC 98237;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone K433_li deposited under accession number ATCC 98237;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone K433_li deposited under accession number ATCC 98237;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone K433_li deposited under accession number ATCC 98237;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 125;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 125 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ25;

(j) a polynucleotide which encodes a spedes homologue of the protein of (g) or (h) above. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ

ID NOJ24 from nucleotide 142 to nucleotide 285; the nucleotide sequence of the full-length protein coding sequence of clone K433_li deposited under accession number ATCC 98237; or the nucleotide sequence of a mature protein coding sequence of clone K433_li deposited under accession number ATCC 98237. In other prefened embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of done K433_li deposited under accession number ATCC 98237. In yet other prefened embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NOJ25 from amino acid 1 to amino acid 30. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 125 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ25, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 125 having biological activity, the fragment comprising the amino acid sequence from amino acid 19 to amino acid 28 of SEQ ID NO:125.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 125;

(b) the amino add sequence of SEQ ID NOJ25 from amino add 1 to amino acid 30;

(c) fragments of the amino acid sequence of SEQ ID NO: 125, each fragment comprising eight consecutive amino acids of SEQ ID NOJ25; and (d) the amino acid sequence encoded by the cDNA insert of clone K433_li deposited under accession number ATCC 98237; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ25 or the amino acid sequence of SEQ ID NOJ25 from amino acid 1 to amino acid 30. In further prefened embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ25 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO: 125, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ25, the fragment comprising the amino acid sequence from amino acid 19 to amino acid 28 of SEQ ID NO:125.

(a) a polynudeotide comprising the nucleotide sequence of SEQ ID NO:127;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.J27 from nucleotide 47 to nucleotide 517;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone L256_li deposited under accession number ATCC 98237;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone L256_li deposited under accession number ATCC 98237; (e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone L256_li deposited under accession number ATCC 98237;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone L256_li deposited under accession number ATCC 98237; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.128;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 128 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO: 128; (i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; and

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ27 from nucleotide 47 to nucleotide 517; the nucleotide sequence of the full-length protein coding sequence of clone L256_li deposited under accession number ATCC 98237; or the nucleotide sequence of a mature protein coding sequence of clone L256_li deposited under accession number ATCC 98237. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone L256_li deposited under accession number ATCC 98237. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NOJ28 from amino acid 8 to amino acid 157. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ28 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ28, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 128 having biological activity, the fragment comprising the amino acid sequence from amino acid 73 to amino acid 82 of SEQ ID NO:128.

(a) the amino acid sequence of SEQ ID NOJ28; (b) the amino add sequence of SEQ ID NOJ28 from amino add

8 to amino acid 157;

(c) fragments of the amino acid sequence of SEQ ID NO: 128, each fragment comprising eight consecutive amino acids of SEQ ID NOJ28; and

(d) the amino acid sequence encoded by the cDNA insert of clone L256_li deposited under accession number ATCC 98237; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ28 or the amino add sequence of SEQ ID NOJ28 from amino acid 8 to amino acid 157. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NOJ28 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NO: 128, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ28, the fragment comprising the amino acid sequence from amino acid 73 to amino acid 82 of SEQ ID NO:128. In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynudeotide comprising the nucleotide sequence of SEQ ID NO.130; (b) a polynudeotide comprising the nudeotide sequence of SEQ

ID NOJ30 from nucleotide 389 to nucleotide 694;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AM207_li deposited under accession number ATCC 98510; (d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AM207_li deposited under accession number ATCC 98510;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AM207_li deposited under accession number ATCC 98510;

(f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AM207_li deposited under accession number ATCC 98510;

(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:131;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 131 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ31;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ30 from nucleotide 389 to nucleotide 694; the nucleotide sequence of the full-length protein coding sequence of clone AM207_li deposited under accession number ATCC 98510; or the nucleotide sequence of a mature protein coding sequence of clone AM207_li deposited under accession number ATCC 98510. In other preferred embodiments, the polynudeotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AM207_li deposited under accession number ATCC 98510. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NOJ31;

(b) fragments of the amino acid sequence of SEQ ID NOJ31, each fragment comprising eight consecutive amino acids of SEQ ID NOJ31; and

(c) the amino acid sequence encoded by the cDNA insert of clone AM207_li deposited under accession number ATCC 98510; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ31. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ31 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO: 131, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ31, the fragment comprising the amino acid sequence from amino acid 46 to amino acid 55 of SEQ ID NO.131.

ID NO:133;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NOJ33 from nucleotide 122 to nucleotide 685;

(c) a polynudeotide comprising the nudeotide sequence of SEQ ID NOJ33 from nucleotide 179 to nucleotide 685;

(d) a polynucleotide comprising the nudeotide sequence of the full- length protein coding sequence of clone AM910_li deposited under accession number ATCC 98510;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AM910_li deposited under accession number ATCC

98510;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AM910_li deposited under accession number ATCC 98510; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AM910_li deposited under accession number ATCC 98510; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NOJ34;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ34 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ34;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ33 from nucleotide 122 to nucleotide 685; the nucleotide sequence of SEQ ID NOJ33 from nucleotide 179 to nucleotide 685; the nucleotide sequence of the full-length protein coding sequence of clone AM910_li deposited under accession number ATCC 98510; or the nucleotide sequence of a mature protein coding sequence of clone AM910_li deposited under accession number ATCC 98510. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AM910_li deposited under accession number ATCC 98510. In yet other prefened embodiments, such polynucleotide encodes a protein comprising the amino add sequence of SEQ ID NOJ34 from amino acid 85 to amino acid 139. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO.J34 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ34, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 134 having biological activity, the fragment comprising the amino acid sequence from amino acid 89 to amino acid 98 of SEQ ID NOJ34.

(a) the amino acid sequence of SEQ ID NOJ34;

(b) the amino add sequence of SEQ ID NOJ34 from amino add 85 to amino acid 139; (c) fragments of the amino acid sequence of SEQ ID NOJ34, each fragment comprising eight consecutive amino acids of SEQ ID NOJ34; and

(d) the amino acid sequence encoded by the cDNA insert of clone AM910_li deposited under accession number ATCC 98510; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino add sequence of SEQ ID NOJ34 or the amino acid sequence of SEQ ID NO: 134 from amino acid 85 to amino acid 139. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NOJ34 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ34, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 134, the fragment comprising the amino add sequence from amino acid 89 to amino acid 98 of SEQ ID NOJ34.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.135;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.J35 from nucleotide 84 to nucleotide 269;

(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NOJ35 from nucleotide 144 to nucleotide 269;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AR54_li deposited under accession number ATCC 98510;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AR54_li deposited under accession number ATCC 98510;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AR54_li deposited under accession number ATCC 98510;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AR54_li deposited under accession number ATCC 98510;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NOJ36;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ36 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ36;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ35 from nucleotide 84 to nucleotide 269; the nucleotide sequence of SEQ ID NOJ35 from nucleotide 144 to nucleotide 269; the nucleotide sequence of the full-length protein coding sequence of clone AR54_li deposited under accession number ATCC 98510; or the nucleotide sequence of a mature protein coding sequence of clone AR54_li deposited under accession number ATCC 98510. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AR54_li deposited under accession number ATCC 98510.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 136;

(b) fragments of the amino acid sequence of SEQ ID NO: 136, each fragment comprising eight consecutive amino acids of SEQ ID NOJ36; and

(c) the amino acid sequence encoded by the cDNA insert of clone AR54_li deposited under accession number ATCC 98510; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ36. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ36 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NO: 136, or a protein comprising a fragment of the ammo acid sequence of SEQ ID NO: 136, the fragment comprising the amino acid sequence from amino acid 26 to amino acid 35 of SEQ ID NOJ36.

(a) a polynudeotide comprising the nucleotide sequence of SEQ ID NO:137;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:137 from nucleotide 32 to nucleotide 1300; (c) a polynucleotide comprising the nucleotide sequence of SEQ

ID NO:137 from nucleotide 884 to nucleotide 1300;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone L200_li deposited under accession number ATCC 98510; (e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone L200_li deposited under accession number ATCC 98510;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone L200_li deposited under accession number ATCC 98510;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone L200_li deposited under accession number ATCC 98510;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.138;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ38 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO: 138;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO: 137 from nucleotide 32 to nucleotide 1300; the nucleotide sequence of SEQ ID NOJ37 from nucleotide 884 to nucleotide 1300; the nucleotide sequence of the full-length protein coding sequence of clone L200_li deposited under accession number ATCC 98510; or the nucleotide sequence of a mature protein coding sequence of clone L200_li deposited under accession number ATCC 98510. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone L200_li deposited under accession number ATCC 98510. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino add sequence of SEQ ID NOJ38 from amino acid 1 to amino acid 144. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ38 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ38, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ38 having biological activity, the fragment comprising the amino acid sequence from amino acid 206 to amino acid 215 of SEQ ID NO:138. In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NOJ38; (b) the amino add sequence of SEQ ID NOJ38 from amino add

1 to amino acid 144;

(c) fragments of the amino acid sequence of SEQ ID NOJ38, each fragment comprising eight consecutive amino acids of SEQ ID NOJ38; and

(d) the amino acid sequence encoded by the cDNA insert of clone L200_li deposited under accession number ATCC 98510; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 138 or the amino acid sequence of SEQ ID NOJ38 from amino acid 1 to amino acid 144. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 138 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ38, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ38, the fragment comprising the amino acid sequence from amino acid 206 to amino acid 215 of SEQ ID NO:138. In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynucleotide comprising the nudeotide sequence of SEQ ID NO.139; (b) a polynucleotide comprising the nucleotide sequence of

SEQ ID NOJ39 from nucleotide 85 to nucleotide 1059;

(c) a polynudeotide comprising the nudeotide sequence of SEQ ID NO.139 from nucleotide 151 to nucleotide 1059;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone WA129_2i deposited under accession number ATCC 98510;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone WA129_2i deposited under accession number ATCC 98510; (f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone WA129_2i deposited under accession number ATCC 98510;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of done WA129_2i deposited under accession number ATCC 98510;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.14.0;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ40 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO: 140;

(k) a polynucleotide which encodes a species homologue of the protein of (h) or (i) above. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ

ID NOJ39 from nucleotide 85 to nucleotide 1059; the nucleotide sequence of SEQ ID

NOJ39 from nucleotide 151 to nucleotide 1059; the nucleotide sequence of the full-length protein coding sequence of clone WA129_2i deposited under accession number ATCC

98510; or the nucleotide sequence of a mature protein coding sequence of clone WA129_2i deposited under accession number ATCC 98510. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone WA129_2i deposited under accession number ATCC 98510.

(a) the amino acid sequence of SEQ ID NO: 140;

(b) fragments of the amino acid sequence of SEQ ID NOJ40, each fragment comprising eight consecutive amino acids of SEQ ID NOJ40; and

(c) the amino acid sequence encoded by the cDNA insert of clone WA129_2i deposited under accession number ATCC 98510; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 140. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ40 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO: 140, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 140, the fragment comprising the amino add sequence from amino acid 157 to amino acid 166 of SEQ ID NO.140. In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynucleotide comprising the nudeotide sequence of SEQ ID NO:141; (b) a polynucleotide comprising the nucleotide sequence of

SEQ ID NOJ41 from nucleotide 128 to nucleotide 643;

(c) a polynucleotide comprising the nudeotide sequence of SEQ ID NOJ41 from nucleotide 197 to nucleotide 643;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone WA154_3i deposited under accession number ATCC 98510;

(e) a polynucleotide encoding the full-length protem encoded by the cDNA insert of clone WA154_3i deposited under accession number ATCC 98510; (f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone WA154_3i deposited under accession number ATCC 98510;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone WA154_3i deposited under accession number ATCC 98510; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:142;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ42 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ42; (j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above; and

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ41 from nucleotide 128 to nucleotide 643; the nucleotide sequence of SEQ ID NOJ41 from nucleotide 197 to nucleotide 643; the nucleotide sequence of the full-length protein coding sequence of clone WA154_3i deposited under accession number ATCC 98510; or the nucleotide sequence of a mature protein coding sequence of clone WA154_3i deposited under accession number ATCC 98510. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone WA154_3i deposited under accession number ATCC 98510. In yet other prefened embodiments, such polynucleotide encodes a protein comprising the amino add sequence of SEQ ID NO: 142 from amino acid 37 to amino acid 77. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 142 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ42, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 142 having biological activity, the fragment comprising the amino acid sequence from amino acid 81 to amino acid 90 of SEQ ID NO.142.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NOJ42;

(b) the amino add sequence of SEQ ID NOJ42 from amino add 37 to amino acid 77;

(c) fragments of the amino acid sequence of SEQ ID NOJ42, each fragment comprising eight consecutive amino acids of SEQ ID NOJ42; and (d) the amino acid sequence encoded by the cDNA insert of clone WA154_3i deposited under accession number ATCC 98510; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ42 or the amino add sequence of SEQ ID NOJ42 from amino acid 37 to amino acid 77. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ42 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ42, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ42, the fragment comprising the amino acid sequence from amino acid 81 to amino acid 90 of SEQ ID NOJ42.

ID NO.143;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.143 from nucleotide 51 to nucleotide 815;

(c) a polynucleotide comprising the nucleotide sequence of SEQ ID NOJ43 from nucleotide 96 to nucleotide 815;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AA36_li deposited under accession number ATCC XXXXX;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AA36_Ji deposited under accession number ATCC

XXXXX;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AA36.Ji deposited under accession number ATCC XXXXX; (g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AA36_li deposited under accession number ATCC XXXXX; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 144;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 144 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO: 144;

(k) a polynucleotide which encodes a spedes homologue of the protein of (h) or (i) above.

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ43 from nucleotide 51 to nucleotide 815; the nucleotide sequence of SEQ ID NO: 143 from nucleotide 96 to nucleotide 815; the nucleotide sequence of the full-length protein coding sequence of clone AA36_li deposited under accession number ATCC XXXXX; or the nucleotide sequence of a mature protein coding sequence of clone AA36_li deposited under accession number ATCC XXXXX. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AA36_li deposited under accession number ATCC XXXXX. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NOJ44 from amino acid 1 to amino acid 136. In further preferred embodiments, the present invention provides a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 144 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NO: 144, or a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 144 having biological activity, the fragment comprising the amino acid sequence from amino acid 122 to amino acid 131 of SEQ ID NOJ44.

(a) the amino acid sequence of SEQ ID NO: 144;

(b) the -3-mino add sequence of SEQ ID NOJ44 from amino add 1 to amino acid 136; (c) fragments of the amino acid sequence of SEQ ID NO: 144, each fragment comprising eight consecutive amino acids of SEQ ID NOJ44; and

(d) the amino acid sequence encoded by the cDNA insert of clone AA36_li deposited under accession number ATCC XXXXX; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 144 or the amino acid sequence of SEQ ID NOJ44 from amino acid 1 to amino acid 136. In further prefened embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NOJ44 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NOJ44, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ44, the fragment comprising the amino acid sequence from amino add 122 to amino acid 131 of SEQ ID NOJ44.

(a) a polynudeotide comprising the nudeotide sequence of SEQ ID NO.145;

(b) a polynudeotide comprising the nudeotide sequence of SEQ ID NO: 145 from nucleotide 76 to nucleotide 594;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AC175_2i deposited under accession number ATCC XXXXX;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AC175_2i deposited under accession number ATCC

XXXXX;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AC175_2i deposited under accession number ATCC XXXXX; (f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AC175_2i deposited under accession number ATCC XXXXX; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NOJ46;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ46 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ46;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:145 from nucleotide 76 to nucleotide 594; the nucleotide sequence of the full-length protein coding sequence of clone AC175_2i deposited under accession number ATCC XXXXX; or the nucleotide sequence of a mature protein coding sequence of clone AC175_2i deposited under accession number ATCC XXXXX. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AC175_2i deposited under accession number ATCC XXXXX.

(a) the amino acid sequence of SEQ ID NO: 146;

(b) fragments of the amino acid sequence of SEQ ID NO: 146, each fragment comprising eight consecutive amino acids of SEQ ID NOJ46; and (c) the amino acid sequence encoded by the cDNA insert of clone AC175_2i deposited under accession number ATCC XXXXX; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ46. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ46 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NOJ46, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ46, the fragment comprising the amino acid sequence from amino acid 81 to amino acid 90 of SEQ ID NO: 146. In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO.147; (b) a polynucleotide comprising the nucleotide sequence of

SEQ ID NO: 147 from nucleotide 387 to nucleotide 734;

(c) a polynudeotide comprising the nudeotide sequence of SEQ ID NO: 147 from nucleotide 639 to nucleotide 734;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone AV189_li deposited under accession number ATCC XXXXX;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AV189_li deposited under accession number ATCC XXXXX; (f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AV189_li deposited under accession number ATCC XXXXX;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of done AV189_li deposited under accession number ATCC XXXXX; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO: 148;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ48 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO: 148;

(k) a polynucleotide which encodes a spedes homologue of the protein of (h) or (i) above. Preferably, such polynucleotide comprises the nucleotide sequence of SEQ

ID NO: 147 from nucleotide 387 to nucleotide 734; the nucleotide sequence of SEQ ID

NOJ47 from nucleotide 639 to nucleotide 734; the nucleotide sequence of the full-length protein coding sequence of clone AV189_li deposited under accession number ATCC

XXXXX; or the nucleotide sequence of a mature protein coding sequence of clone AV189_li deposited under accession number ATCC XXXXX. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone AV189_li deposited under accession number ATCC XXXXX.

(a) the amino acid sequence of SEQ ID NO: 148;

(b) fragments of the amino acid sequence of SEQ ID NOJ48, each fragment comprising eight consecutive amino acids of SEQ ID NOJ48; and

(c) the amino acid sequence encoded by the cDNA insert of clone AV189_li deposited under accession number ATCC XXXXX; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO: 148. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino add sequence of SEQ ID NOJ48 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NOJ48, or a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 148, the fragment comprising the amino acid sequence from amino acid 53 to amino acid 62 of SEQ ID NO.148.

(a) a polynucleotide comprising the nudeotide sequence of SEQ ID NO.149; (b) a polynucleotide comprising the nucleotide sequence of

SEQ ID NO:149 from nucleotide 66 to nucleotide 827;

(c) a polynudeotide comprising the nucleotide sequence of SEQ ID NOJ49 from nucleotide 366 to nucleotide 827;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone K368_li deposited under accession number ATCC XXXXX;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone K368_li deposited under accession number ATCC XXXXX; (f) a polynucleotide comprising the nudeotide sequence of a mature protein coding sequence of clone K368_li deposited under accession number ATCC XXXXX;

(g) a polynudeotide encoding a mature protein encoded by the cDNA insert of clone K368_Ji deposited under accession number ATCC XXXXX; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.150;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 150 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO: 150; (j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above; and

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO: 149 from nucleotide 66 to nucleotide 827; the nucleotide sequence of SEQ ID NO: 149 from nudeotide 366 to nucleotide 827; the nucleotide sequence of the full-length protein coding sequence of clone K368_li deposited under accession number ATCC XXXXX; or the nucleotide sequence of a mature protein coding sequence of clone K368_li deposited under accession number ATCC XXXXX. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone K368_li deposited under accession number ATCC XXXXX.

(a) the amino acid sequence of SEQ ID NOJ50;

(b) fragments of the amino acid sequence of SEQ ID NOJ50, each fragment comprising eight consecutive amino acids of SEQ ID NOJ50; and

(c) the amino acid sequence encoded by the cDNA insert of clone K368_li deposited under accession number ATCC XXXXX; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ50. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 150 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino adds of SEQ ID NO: 150, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ50, the fragment comprising the amino acid sequence from amino acid 122 to amino acid 131 of SEQ ID NOJ50.

(a) a polynudeotide comprising the nucleotide sequence of SEQ ID NO.151;

(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:151 from nucleotide 219 to nucleotide 668;

(c) a polynucleotide comprising the nudeotide sequence of SEQ ID NOJ51 from nucleotide 426 to nucleotide 668;

(d) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone K568_li deposited under accession number ATCC XXXXX;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone K568_li deposited under accession number ATCC XXXXX;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone K568_li deposited under accession number ATCC XXXXX;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone K568_li deposited under accession number ATCC XXXXX; (h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.152;

(i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 152 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ52; (j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above; and

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NOJ51 from nucleotide 219 to nucleotide 668; the nucleotide sequence of SEQ ID NOJ51 from nucleotide 426 to nucleotide 668; the nucleotide sequence of the full-length protein coding sequence of clone K568_li deposited under accession number ATCC XXXXX; or the nucleotide sequence of a mature protein coding sequence of clone K568_li deposited under accession number ATCC XXXXX. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone K568_Ji deposited under accession number ATCC XXXXX.

In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of: (a) the amino acid sequence of SEQ ID NO: 152;

(b) fragments of the amino acid sequence of SEQ ID NO: 152, each fragment comprising eight consecutive amino acids of SEQ ID NOJ52; and

(c) the amino acid sequence encoded by the cDNA insert of clone K568_li deposited under accession number ATCC XXXXX; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NOJ52. In further prefened embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 152 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ52, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ52, the fragment comprising the amino acid sequence from amino acid 70 to amino acid 79 of SEQ ID NO.152.

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:153;

(b) a polynudeotide comprising the nucleotide sequence of SEQ ID NO: 153 from nucleotide 14 to nucleotide 1438;

(c) a polynucleotide comprising the nucleotide sequence of the full- length protein coding sequence of clone T85_li deposited under accession number ATCC XXXXX;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone T85.Ji deposited under accession number ATCC

XXXXX;

(e) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone T85_li deposited under accession number ATCC XXXXX; (f) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone T85_Ji deposited under accession number ATCC XXXXX; (g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO.154;

(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO: 154 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NOJ54;

Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO: 153 from nucleotide 14 to nucleotide 1438; the nucleotide sequence of the full-length protem coding sequence of clone T85_li deposited under accession number ATCC XXXXX; or the nucleotide sequence of a mature protein coding sequence of clone T85_li deposited under accession number ATCC XXXXX. In other preferred embodiments, the polynucleotide encodes the full-length or a mature protein encoded by the cDNA insert of clone T85_li deposited under accession number ATCC XXXXX.

(a) the amino acid sequence of SEQ ID NOJ54;

(b) fragments of the amino acid sequence of SEQ ID NOJ54, each fragment comprising eight consecutive amino acids of SEQ ID NOJ54; and (c) the amino acid sequence encoded by the cDNA insert of clone T85_li deposited under accession number ATCC XXXXX; the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:154. In further preferred embodiments, the present invention provides a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ54 having biological activity, the fragment preferably comprising eight (more preferably twenty, most preferably thirty) consecutive amino acids of SEQ ID NOJ54, or a protein comprising a fragment of the amino acid sequence of SEQ ID NOJ54, the fragment comprising the amino acid sequence from ammo add 232 to amino acid 241 of SEQ ID NO:154. Protein compositions of the present invention may further comprise a pharmaceutically acceptable carrier. Compositions comprising an antibody which specifically reacts with such protein are also provided by the present invention.

Methods are also provided for preventing, treating or ameliorating a medical condition which comprises administering to a mammalian subject a therapeutically effective amount of a composition comprising a protein of the present invention and a pharmaceutically acceptable carrier.

BRIEF DESCRIPTION OF THE DRAWINGS Figures 1A and IB are schematic representations of the pED6 and pNOTs vectors, respectively, used for deposit of clones disclosed herein.

DETAILED DESCRIPTION ISOLATED PROTEINS

Nucleotide and amino acid sequences, as presently determined, are reported below for each clone and protein disclosed in the present application. The nucleotide sequence of each clone can readily be determined by sequencing of the deposited clone in accordance with known methods. The predided amino acid sequence oth full-length and mature forms) can then be determined from such nucleotide sequence. The amino acid sequence of the protein encoded by a particular clone can also be determined by expression of the clone in a suitable host cell, collecting the protein and determining its sequence. For each disclosed protein applicants have identified what they have determined to be the reading frame best identifiable with sequence information available at the time of filing. As used herein a "secreted" protein is one which, when expressed in a suitable host cell, is transported across or through a membrane, including transport as a result of signal sequences in its amino add sequence. "Secreted" proteins include without limitation proteins secreted wholly (e.g., soluble proteins) or partially (e.g. , receptors) from the cell in which they are expressed. "Secreted" proteins also include without limitation proteins which are transported across the membrane of the endoplasmic reticulum.

Protein 'AK296 li"

One protein of the present invention has been identified as protem "AK296_li". A partial cDNA clone encoding AK296_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AK296_li". Applicants' methods identified clone AK296_li as encoding a secreted protein.

The nucleotide sequence of AK296_li as presently determined is reported in SEQ ID NOJ, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AK296_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:2.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AK296_li should be approximately 1264 bp.

AK296_li protein was expressed in a Baculovirus expression system, and an expressed protein band of approximately 20 kDa detected in a membrane fraction using SDS polyacrylamide gel electrophoresis.

Protein "AK533 li"

One protein of the present invention has been identified as protein "AK533_li". A partial cDNA clone encoding AK533_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and detennined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AK533_li". Applicants' methods identified clone AK533_li as encoding a secreted protein.

The nucleotide sequence of AK533_li as presently determined is reported in SEQ ID NO:3, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AK533_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone AK533_li should be approximately 1751 bp.

AK533_li protein was expressed in a COS cell expression system, and an expressed protein band of approximately 47 kDa detected in conditioned medium and membrane fractions using SDS polyacrylamide gel electrophoresis.

Protein "AK583 li"

One protein of the present invention has been identified as protein "AK583_li". A partial cDNA clone encoding AK583_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AK583_li". Applicants' methods identified clone AK583_li as encoding a secreted protein.

The nucleotide sequence of AK583_li as presently determined is reported in SEQ ID NO:5, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AK583_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:6. Amino acids 12 to 24 of SEQ ID NO:6 are a predided leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 25. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AK583_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AK583_li should be approximately 870 bp.

Protein "AM282 li" One protein of the present invention has been identified as protein

"AM282_li". A partial cDNA clone encoding AM282_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AM282_li". Applicants' methods identified clone AM282_li as encoding a secreted protein.

The nucleotide sequence of AM282_li as presently determined is reported in SEQ ID NO:7, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AM282_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:8. Amino acids 12 to 24 of SEQ ID NO:8 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beg^i-nning at amino acid 25. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AM282_Ji protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AM282_li should be approximately 1750 bp. AM282_li protein was expressed in a Baculovirus expression system, and an expressed protein band of approximately 54 kDa detected m a conditioned medium fraction using SDS polyacrylamide gel electrophoresis.

Protein "AM340 li" One protein of the present invention has been identified as protein

"AM340_li". A partial cDNA clone encoding AM340_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AM340_li". Applicants' methods identified clone AM340_li as encoding a secreted protein.

The nucleotide sequence of AM340_li as presently determined is reported in SEQ ID NO:9, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AM340_li protein conesponding to the foregoing nudeotide sequence is reported in SEQ ID NOJ0. Amino acids 85 to 97 of SEQ ID NOJ0 are a predicted leader/signal sequence, with the predicted mature amino add sequence beginning at amino acid 98. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/ signal sequence not be separated from the remainder of the AM340_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AM340_li should be approximately 650 bp. AM340_li protein was expressed in a Baculovirus expression system, and an expressed protein band of approximately 27 kDa detected in a membrane fraction using SDS polyacrylamide gel electrophoresis.

Protein "AM610 li" One protein of the present invention has been identified as protein

"AM610_li". A partial cDNA clone encoding AM610_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AM610_li". Applicants' methods identified clone AM610_li as encoding a secreted protein.

The nucleotide sequence of AM610_li as presently determined is reported in SEQ ID NOJ1, and includes the poly (A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AM610_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ2. Amino acids 11 to 23 of SEQ ID NOJ2 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature of the predicted leader /signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AM610_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AM610_li should be approximately 1900 bp. AM610_li protein was expressed in a COS cell expression system, and an expressed protein band of approximately 23 kDa detected in conditioned medium and membrane fractions using SDS polyacrylamide gel electrophoresis.

Protein "AP162 li" One protein of the present invention has been identified as protein

"AP162_li". A partial cDNA clone encoding AP162_li was first isolated from a human fetal placenta cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5-536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AP162_li". Applicants' methods identified clone AP162_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AP162_li as presently determined is reported in SEQ ID NO.J 3. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AP162_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ4. Additional nucleotide sequence from the 3' portion of AP162_li, including a poly(A) tail, is reported in SEQ ID NOJ5.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AP162_li should be approximately 1200 bp.

AP162_li protein was expressed in a Baculovirus expression system, and an expressed protein band of approximately 20 kDa detected in a membrane fraction using SDS polyacrylamide gel electrophoresis. Protein "AR260 li"

One protein of the present invention has been identified as protein

"AR260_li". A partial cDNA clone encoding AR260_li was first isolated from a human adult retina cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "AR260_li".

Applicants' methods identified clone AR260_li as encoding a secreted protein. The nucleotide sequence of AR260_li as presently determined is reported in SEQ ID NOJ6, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AR260_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO.J7.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AR260_li should be approximately 1900 bp.

AR260_li protein was expressed in a COS cell expression system, and an expressed protein band of approximately 27 kDa detected in conditioned medium and membrane fractions using SDS polyacrylamide gel electrophoresis.

Protein "AS32 li"

One protein of the present invention has been identified as protein "AS32_li". A partial cDNA clone encoding AS32_li was first isolated from a human fetal brain cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "AS32_li".

Applicants' methods identified clone AS32_li as encoding a secreted protein. The nucleotide sequence of the 5' portion of AS32_li as presently determined is reported in SEQ ID NO: 18. What applicants believe is the proper reading frame and the predicted amino add sequence of the AS32_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ9. Additional nucleotide sequence from the 3' portion of AS32_li, including a poly(A) tail, is reported in SEQ ID NO.20.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AS32_li should be approximately 1100 bp.

Protein "AS34 li" One protein of the present invention has been identified as protein

"AS34_li". A partial cDNA clone encoding AS34_li was first isolated from a human fetal brain cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UT , including a poly(A) tail. This full-length clone is also referred to herein as "AS34_li".

Applicants' methods identified clone AS34_li as encoding a secreted protein.

The nucleotide sequence of AS34_li as presently determined is reported in SEQ ID NO:21, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AS34_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:22. Amino acids 12 to 24 of SEQ ID NO:22 are a predicted leader /signal sequence, with the predicted mature amino acid sequence beginning at amino acid 25. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AS34_li protein.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone AS34_li should be approximately 550 bp. AS34_li protein was expressed in a COS cell expression system, and an expressed protein band of approximately 8 kDa detected in conditioned medium and membrane fractions using SDS polyacrylamide gel electrophoresis.

Protein "AT205 li" One protein of the present invention has been identified as protein

"AT205_li". A partial cDNA clone encoding AT205_li was first isolated from a human adult blood (lymphocytes and dendritic cells, treated with mixed lymphocyte reaction) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR . This full-length clone is also refened to herein as "AT205_li".

Applicants' methods identified clone AT205_li as encoding a secreted protein.

The nucleotide sequence of AT205_li as presently determined is reported in SEQ ID NO:23. What appUcants believe is the proper reading frame and the predicted amino acid sequence of the AT205_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:24. Amino acids 42 to 54 of SEQ ID NO:24 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 55. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AT205_li protein.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone AT205_li should be approximately 825 bp. Protein "AT211 li"

One protein of the present invention has been identified as protein "AT211_li". A partial cDNA clone encoding AT211_li was first isolated from a human adult blood (lymphocytes and dendritic cells, treated with mixed lymphocyte reaction) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AT211_li".

Applicants' methods identified clone AT211_li as encoding a secreted protein.

The nucleotide sequence of AT211„li as presently determined is reported in SEQ ID NO:25, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AT211__.li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:26. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AT211_li should be approximately 1100 bp.

Protein "AT319 li"

One protein of the present invention has been identified as protein "AT319_li". A partial cDNA clone encoding AT319_li was first isolated from a human adult blood (lymphocytes and dendritic cells, treated with mixed lymphocyte reaction) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR . This full-length clone is also referred to herein as "AT319_li".

Applicants' methods identified clone AT319_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AT319_li as presently determined is reported in SEQ ID NO:27. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AT319_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:28. Additional nucleotide sequence from the 3' portion of AT319_li is reported in SEQ ID NO:29.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AT319_li should be approximately 1680 bp.

Protein "AW191 li"

One protein of the present invention has been identified as protein "AW191_li". A partial cDNA clone encoding AW191_li was first isolated from a human adult ovary (PA-1 teratocarcinoma line, pool of retinoic-acid-treated, activin-treated, and untreated tissue) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No.5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AW191_li". Applicants' methods identified clone AW191_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AW191_li as presently determined is reported in SEQ ID NO:30. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AW191_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:31. Amino acids 5 to 17 of SEQ ID NO:31 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 18. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/ signal sequence not be separated from the remainder of the AW191_li protein. Additional nucleotide sequence from the 3' portion of AW191_li, including a poly(A) tail, is reported in SEQ ID NO:32.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AW191_li should be approximately 1300 bp.

Protein "BB9 li"

One protein of the present invention has been identified as protein "BB9_li". A partial cDNA clone encoding BB9_li was first isolated from a human adult blood (peripheral blood mononuclear cells, TH1- or TH2-driven response) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "BB9_li".

AppUcants' methods identified clone BB9_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of BB9_li as presently determined is reported in SEQ ID NO:33. What appUcants beUeve is the proper reading frame and the predicted amino acid sequence of the BB9_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:34. Additional nucleotide sequence from the 3' portion of BB9_li, including a poly(A) tail, is reported in SEQ ID NO:35.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone BB9_li should be approximately 1080 bp.

Protem "H617 li" One protein of the present invention has been identified as protein

"H617_li". A partial cDNA clone encoding H617_li was first isolated from a human adult blood (peripheral blood mononuclear cells, treated with phytohemagglutinin, phorbol myristate acetate, and mixed ly cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length done, including a 5' end and 3' UTR , including a ρoly(A) tail. This full-length clone is also refened to herein as "H617_li".

Applicants' methods identified clone H617_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of H617_li as presently determined is reported in SEQ ID NO:36. What applicants believe is the proper reading frame and the predirted amino acid sequence of the H617_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:37. Additional nucleotide sequence from the 3' portion of H617_li, including a poly(A) tail, is reported in SEQ ID NO:38.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone H617_li should be approximately 1600 bp.

Protein "K39 li"

One protein of the present invention has been identified as protein "K39_li". A partial cDNA clone encoding K39_li was first isolated from a mouse adult bone marrow (stromal line FCM-4) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nudeotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "K39_li".

Applicants' methods identified clone K39_li as encoding a secreted protein. The nucleotide sequence of the 5' portion of K39_li as presently determined is reported in SEQ ID NO:39. What appUcants beUeve is the proper reading frame and the predicted amino acid sequence of the K39_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:40. Additional nucleotide sequence from the 3' portion of K39_li, including a poly(A) tail, is reported in SEQ ID NO:41.

Protein "K640 li"

One protein of the present invention has been identified as protein

"K640_li". A partial cDNA clone encoding K640_li was first isolated from a mouse adult bone marrow (stromal line FCM-4) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc.,

St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a fuU-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as

"K640_li". AppUcants' methods identified clone K640_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of K640_li as presently determined is reported in SEQ ID NO:42. What applicants believe is the proper reading frame and the predicted amino acid sequence of the K640_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:43. Additional nucleotide sequence from the 3' portion of K640_li, including a poly(A) tail, is reported in SEQ ID NO.-44.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone K640_li should be approximately 2400 bp.

Protein "AE402 li"

One protein of the present invention has been identified as protein "AE402_li". A partial cDNA clone encoding AE402_li was first isolated from a mouse adult spleen (stimulated with concanavalin A and mixed with dendritic cells) cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail This full-length clone is also referred to herein as "AE402_li". Applicants' methods identified clone AE402_li as encoding a secreted protein.

The nucleotide sequence of AE402_li as presently determined is reported in SEQ ID NO:45, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AE402_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:46.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AE402_li should be approximately 1200 bp.

Protein "AE610 li" One protein of the present invention has been identified as protein

"AE610_li". A partial cDNA clone encoding AE610_li was first isolated from a mouse adult spleen (stimulated with concanavalin A and mixed with dendritic cells) cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AE610_li".

Applicants' methods identified clone AE610_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AE610_li as presently determined is reported in SEQ ID NO:47. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AE610_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:48. Amino acids 75 to 87 of SEQ ID NO:48 are a predicted leader/signal sequence, with the predicted mature amino acid sequence begirining at amino acid 88. Due to the hydrophobic nature of the predided leader/signal sequence, it is likely to ad as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AE610_li protein. Additional nudeotide sequence from the 3' portion of AE610_li, including a poly(A) tail, is reported in SEQ ID NO:49. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AE610_li should be approximately 950 bp.

Protein "AH106 li"

One protein of the present invention has been identified as protein "AH106_li". A partial cDNA clone encoding AH106_li was first isolated from a mouse fetal thymus cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AH106_li". Applicants' methods identified clone AH106_li as encoding a secreted protein.

The nucleotide sequence of AH106_li as presently determined is reported in SEQ ID NO:50, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AH106_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:51.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone AH106_li should be approximately 500 bp.

Protein "AH196 li" One protein of the present invention has been identified as protein "AH196_li". A partial cDNA clone encoding AH196_li was first isolated from a mouse fetal thymus cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AH196_li". Applicants' methods identified clone AH196_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AH196_li as presently determined is reported in SEQ ID NO:52. What applicants believe is the proper reading frame and the predided amino acid sequence of the AH196_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:53. Additional nucleotide sequence from the 3' portion of AH196_li, including a poly(A) tail, is reported in SEQ ID NO:54. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AH196_li should be approximately 870 bp.

Protein "AI6 li"

One protein of the present invention has been identified as protein "AI6_li". A partial cDNA clone encoding AI6_li was first isolated from a human adult blood (peripheral blood mononuclear ceUs, TH1- or TH2-driven response) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AI6_li".

AppUcants' methods identified clone AI6_li as encoding a secreted protein.

The nudeotide sequence of the 5' portion of AI6_li as presently determined is reported in SEQ ID NO:55. What appUcants beUeve is the proper reading frame and the predicted amino acid sequence of the AI6_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:56. Additional nudeotide sequence from the 3' portion of AI6_li, including a poly(A) tail, is reported in SEQ ID NO:57.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AI6_li should be approximately 900 bp.

AI6_li protein was expressed in a Baculovirus expression system, and an expressed protein band of approximately 6 kDa detected in a membrane fraction using SDS polyacrylamide gel electrophoresis.

Protein "AT13 li"

One protein of the present invention has been identified as protein "AJ13_li". A partial cDNA clone encoding AJ13_li was first isolated from a human adult testes cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AJ13_li".

Applicants' methods identified clone AJ13_li as encoding a secreted protein.

The nucleotide sequence of AJ13_li as presently determined is reported in SEQ ID NO:58, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AJ13_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:59.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AJ13_li should be approximately 1200 bp. Protein "AΪ27 li"

One protein of the present invention has been identified as protein "AJ27_Ji". A partial cDNA clone encoding AJ27_li was first isolated from a human adult testes cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AJ27_li".

Applicants' methods identified clone AJ27_li as encoding a secreted protein. The nucleotide sequence of the 5' portion of AJ27_li as presently determined is reported in SEQ ID NO:60. What applicants believe is the proper reading frame and the predicted amino add sequence of the AJ27_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:61. Amino acids 15 to 27 of SEQ ID NO:61 are a predicted leader /signal sequence, with the predicted mature amino acid sequence beginning at amino acid 28. Due to the hydrophobic nature of the predicted leader/ signal sequence, it is likely to ad as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AJ27_li protein. Additional nucleotide sequence from the 3' portion of AT27_li, including a poly(A) tail, is reported in SEQ ID NO:62. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AJ27_li should be approximately 1500 bp.

Protein "AT142 li"

One protein of the present invention has been identified as protein "AJ142_li". A partial cDNA clone encoding AJ142_li was first isolated from a human adult testes cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "AJ142_li". Applicants' methods identified clone AJ142_li as encoding a secreted protein.

The nucleotide sequence of AJ142_li as presently determined is reported in SEQ ID NO:63, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AJ142_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:64. Amino acids 11 to 23 of SEQ ID NO:64 are a predicted leader /signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AJ142_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AJ142_li should be approximately 650 bp.

Protein "AK604 li"

One protein of the present invention has been identified as protein "AK604_li". A partial cDNA clone encoding AK604_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AK604_li". Applicants' methods identified clone AK604_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AK604_li as presently determined is reported in SEQ ID NO:65. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AK604_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:66. Additional nucleotide sequence from the 3' portion of AK604_li, including a poly(A) tail, is reported in SEQ ID NO:67.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AK604_li should be approximately 1350 bp.

Protein "AK620 li" One protein of the present invention has been identified as protein

"AK620_li". A partial cDNA clone encoding AK620_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. Ihe clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AK620_li". Applicants' methods identified clone AK620_li as encoding a secreted protein.

The nucleotide sequence of AK620_li as presently determined is reported in SEQ ID NO:68, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AK620_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:69.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AK620_li should be approximately 700 bp.

Protein "AK650 li"

One protein of the present invention has been identified as protein "AK650_li". A partial cDNA clone encoding AK650_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AK650_li". Applicants' methods identified clone AK650_li as encoding a secreted protein. The nucleotide sequence of AK650_li as presently determined is reported in SEQ ID NO:70, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AK650_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:71. Amino acids 14 to 26 of SEQ ID NO:71 are a predicted leader/signal sequence, with the predided mature amino acid sequence beginning at amino acid 27. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/ signal sequence not be separated from the remainder of the AK650_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AK650_li should be approximately 1000 bp.

Protein "AM226 li"

One protein of the present invention has been identified as protein "AM226_li". A partial cDNA clone encoding AM226_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "AM226_li".

Applicants' methods identified clone AM226_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AM226_li as presently determined is reported in SEQ ID NO:72. What applicants believe is the proper reading frame and the predicted amino add sequence of the AM226_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:73. Amino acids 7 to 19 of SEQ ID NO:73 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 20. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predided leader/signal sequence not be separated from the remainder of the AM226_li protein. Additional nucleotide sequence from the 3' portion of AM226_li, including a poly(A) tail, is reported in SEQ ID NO:74.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AM226_li should be approximately 1500 bp.

AM226_li protein was expressed in a Baculovirus expression system, and an expressed protein band of approximately 50 kDa detected in a conditioned medium fraction using SDS polyacrylamide gel electrophoresis.

Protein "AR417 li"

One protein of the present invention has been identified as protein "AR417_li". A partial cDNA clone encoding AR417_li was first isolated from a human adult retina cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "AR417_li". Applicants' methods identified clone AR417_li as encoding a secreted protein.

The nucleotide sequence of AR417_li as presently determined is reported in SEQ ID NO:75, and includes the poly(A) tail. What appUcants believe is the proper reading frame and the predicted amino acid sequence of the AR417_li protein conesponding to the foregoing nudeotide sequence is reported in SEQ ID NO:76. Amino acids 32 to 44 of SEQ ID NO:76 are a predicted leader/signal sequence, with the predided mature amino acid sequence beginning at amino add 45. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AR417_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AR417_li should be approximately 1500 bp.

Protein "AU43 li"

One protein of the present invention has been identified as protein "AU43_li". A partial cDNA clone encoding AU43_li was first isolated from a human adult testes cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AU43_li".

Applicants' methods identified clone AU43_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AU43_li as presently determined is reported in SEQ ID NO:77. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AU43_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:78. Amino adds 11 to 23 of SEQ ID NO:78 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AU43_li protein. Additional nucleotide sequence from the 3' portion of AU43_Ji, including a poly(A) tail, is reported in SEQ ID NO:79.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone AU43_li should be approximately 950 bp.

Protein "AW60 li"

One protein of the present invention has been identified as protein "AW60_li". A partial cDNA clone encoding AW60_li was first isolated from a human adult ovary (PA-1 teratocarcinoma line, pool of retinoic-acid-treated, activin-treated, and untreated tissue) cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "AW60_li".

Applicants' methods identified clone AW60_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AW60_li as presently determined is reported in SEQ ID NO:80. What applicants beUeve is the proper reading frame and the predicted amino acid sequence of the AW60_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:81. Amino acids 19 to 31 of SEQ ID NO:81 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 32. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AW60_li protein. Additional nucleotide sequence from the 3^' portion of AW60_li, induding a poly(A) tail, is reported in SEQ ID NO:82.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone AW60_li should be approximately 1800 bp.

Protein "BA176 li"

One protein of the present invention has been identified as protein "BA176_li". A partial cDNA clone encoding BA176_li was first isolated from a human fetal placenta cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "BA176_li". Applicants' methods identified clone BA176_1 i as encoding a secreted protein.

The nucleotide sequence of BA176_li as presently determined is reported in SEQ ID NO:83, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the BA176_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:84. Amino acids 276 to 288 of SEQ ID NO:84 are a predicted leader /signal sequence, with the predicted mature amino acid sequence beginning at amino acid 289. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the BA176_li protein. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone BA176_li should be approximately 2500 bp.

Protein "BD140 li"

One protein of the present invention has been identified as protein "BD140_li". A partial cDNA clone encoding BD140_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "BD140_li". Applicants' methods identified clone BD140_li as encoding a secreted protein.

The nucleotide sequence of BD140_li as presently determined is reported in SEQ ID NO:85, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the BD140_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:86.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone BD140_li should be approximately 2550 bp.

Protein "BD407 li"

One protein of the present invention has been identified as protein "BD407_li". A partial cDNA clone encoding BD407_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "BD407_li". Applicants' methods identified clone BD407_li as encoding a secreted protein.

The nudeotide sequence of BD407_li as presently determined is reported in SEQ ID NO:87, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the BD407_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:88. Amino acids 2 to 14 of SEQ ID NO:88 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 15. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the BD407_li protein.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone BD407_li should be approximately 1100 bp. Protein "BF290 li"

One protein of the present invention has been identified as protein "BF290_li". A partial cDNA clone encoding BF290_li was first isolated from a human fetal brain cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "BF290_li".

Applicants' methods identified clone BF290_li as encoding a secreted protein. The nucleotide sequence of BF290_li as presently determined is reported in SEQ ID NO:89, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the BF290_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:90.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone BF290_li should be approximately 1450 bp.

Protein "BG236 li"

One protein of the present invention has been identified as protein "BG236_li". A partial cDNA clone encoding BG236_li was first isolated from a human adult brain cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "BG236_li". Applicants' methods identified clone BG236_li as encoding a secreted protein.

The nucleotide sequence of BG236_li as presently determined is reported in SEQ ID NO:91, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the BG236_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:92. A ino acids 45 to 57 of SEQ ID NO:92 are a predicted leader/signal sequence, with the predided mature amino acid sequence beginning at amino acid 58. Due to the hydrophobic nature of the predicted leader /signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the BG236_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone BG236_li should be approximately 1350 bp.

Protein "BG237 li"

One protein of the present invention has been identified as protein "BG237_li". A partial cDNA clone encoding BG237_li was first isolated from a human adult brain cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a fuU-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "BG237_li". Applicants' methods identified clone BG237_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of BG237_li as presently determined is reported in SEQ ID NO:93. What applicants believe is the proper reading frame and the predicted amino acid sequence of the BG237_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:94. Additional nucleotide sequence from the 3' portion of BG237_li, including a poly(A) tail, is reported in SEQ ID NO:95. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone BG237_li should be approximately 1300 bp.

Protein "BG255 li" One protein of the present invention has been identified as protein

"BG255_li". A partial cDNA clone encoding BG255_li was first isolated from a human adult brain cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "BG255_li". Applicants' methods identified clone BG255_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of BG255_Ji as presently determined is reported in SEQ ID NO:96. What applicants believe is the proper reading frame and the predicted amino acid sequence of the BG255_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NO:97. Additional nucleotide sequence from the 3' portion of BG255_li, including a poly(A) tail, is reported in SEQ ID NO:98.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone BG255_li should be approximately 1450 bp.

Protein "H541 3i"

One protein of the present invention has been identified as protein "H541_3i". A partial cDNA clone encoding H541_3i was first isolated from a human adult blood (peripheral blood mononuclear cells treated with phytohemagglutinin and phorbol myristate acetate and mixed 1 cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St.

Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length done, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as

"H541_3i"-

Applicants' methods identified clone H541_3i as encoding a secreted protein.

The nucleotide sequence of H541_3i as presently determined is reported in SEQ ID NO:99, and includes the poly (A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the H541_3i protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJOO.

Amino acids 4 to 16 of SEQ ID NOJOO are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 17. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the H541_.3i protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone H541_3i should be approximately 1500 bp. H541_3i protein was expressed in a COS cell expression system, and an expressed protein band of approximately 41 kDa detected in a membrane fraction using

SDS polyacrylamide gel electrophoresis.

Protein "H978 li" One protein of the present invention has been identified as protein

"H978_li". A partial cDNA clone encoding H978_li was first isolated from a human adult blood (peripheral blood mononuclear cells treated with phytohemagglutinin and phorbol myristate acetate and mixed 1 cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "H978_li".

Applicants' methods identified clone H978_ li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of H978_li as presently determined is reported in SEQ ID NOJ01. What appUcants beUeve is the proper reading frame and the predicted amino acid sequence of the H978_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ02. Additional nucleotide sequence from the 3' portion of H978_li, including a poly(A) tail, is reported in SEQ ID NOJ03.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone H978_li should be approximately 1100 bp.

Protein "L161 li"

One protem of the present invention has been identified as protein "L161_li". A partial cDNA clone encoding L161_li was first isolated from a mouse adult thymus cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "L161_li".

Applicants' methods identified clone L161_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of L161_li as presently determined is reported in SEQ ID NOJ04. What appUcants beUeve is the proper reading frame and the predicted amino add sequence of the L161_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ05. Additional nucleotide sequence from the 3' portion of L161_li, including a poly(A) tail, is reported in SEQ ID NOJ06. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone L161_li should be approximately 1300 bp.

Protein "AE648 li" One protein of the present invention has been identified as protein

"AE648_li". A partial cDNA clone encoding AE648_li was first isolated from a mouse adult spleen (stimulated with concanavalin A and mixed with dendritic cells) cDNA

Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S.

Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E.

Consortium library. The clone received from the distributor was examined and determined to be a fuU-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AE648_li".

Applicants' methods identified clone AE648_li as encoding a secreted protein.

The nucleotide sequence of AE648_li as presently determined is reported in SEQ ID NOJ07, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AE648_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ08. Amino acids 3 to 15 of SEQ ID NOJ08 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 16. Due to the hydrophobic nature of the predicted leader /signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AE648_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AE648_li should be approximately 900 bp.

Protein "AE693 li"

One protein of the present invention has been identified as protein "AE693_li". A partial cDNA clone encoding AE693_li was first isolated from a mouse adult spleen (stimulated with concanavalin A and mixed with dendritic cells) cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "AE693_li". Applicants' methods identified clone AE693_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AE693_li as presently determined is reported in SEQ ID NOJ09. What appUcants beUeve is the proper reading frame and the predicted amino acid sequence of the AE693_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ10. Additional nucleotide sequence from the 3' portion of AE693_li, including a poly(A) tail, is reported in SEQ ID NOJ11.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AE693_li should be approximately 1200 bp.

Protein "AK438 li"

One protein of the present invention has been identified as protein "AK438_li". A partial cDNA clone encoding AK438_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "AK438_li". Applicants' methods identified clone AK438_li as encoding a secreted protein. The nucleotide sequence of the 5' portion of AK438_li as presently determined is reported in SEQ ID NOJ 12. What appUcants believe is the proper reading frame and the predicted amino acid sequence of the AK438_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ 13. Additional nucleotide sequence from the 3' portion of AK438_li, including a poly(A) tail, is reported in SEQ ID NO: 114.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AK438_li should be approximately 1000 bp.

Protein "AK609 li"

One protein of the present invention has been identified as protein "AK609_li". A partial cDNA clone encoding AK609_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR . This full-length clone is also referred to herein as "AK609_li".

Applicants' methods identified clone AK609_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AK609_li as presently determined is reported in SEQ ID NOJ 15. What appUcants beUeve is the proper reading frame and the predicted amino acid sequence of the AK609_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ16. Additional nucleotide sequence from the 3' portion of AK609_li is reported in SEQ ID NOJ17.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AK609_li should be approximately 750 bp.

Protein "AM1060 li"

One protein of the present invention has been identified as protein "AM1060_li". A partial cDNA clone encoding AM1060_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AM1060_li". Applicants' methods identified clone AM1060_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AM1060_li as presently determined is reported in SEQ ID NOJ18. What applicants beUeve is the proper reading frame and the predicted amino acid sequence of the AM1060_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ19. Amino acids 13 to 25 of SEQ ID NOJ19 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 26. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AM1060_li protein. Additional nucleotide sequence from the 3^' portion of AM1060_li, including a poly(A) tail, is reported in SEQ ID NOJ20.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AM1060_li should be approximately 1700 bp.

Protein "AQ2 li"

One protein of the present invention has been identified as protein "AQ2_li". A partial cDNA clone encoding AQ2_li was first isolated from a human adult ovary (PA-1 teratocarcinoma line, pool of retinoic-acid-treated, activin-treated, and untreated tissue) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AQ2_Ji".

Applicants' methods identified clone AQ2_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AQ2_li as presently determined is reported in SEQ ID NOJ21. What applicants beUeve is the proper reading frame and the predicted amino acid sequence of the AQ2_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO: 122. Additional nucleotide sequence from the 3' portion of AQ2_li, including a poly(A) tail, is reported in SEQ ID NOJ23.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AQ2_li should be approximately 1370 bp.

Protein "K433 li"

One protein of the present invention has been identified as protein "K433_li". A partial cDNA clone encoding K433_li was first isolated from a mouse adult bone marrow (stromal line FCM-4) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this done was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a fuU-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "K433_li".

Applicants' methods identified clone K433_li as encoding a secreted protein. The nucleotide sequence of the 5' portion of K433_li as presently determined is reported in SEQ ID NOJ24. What applicants beUeve is the proper reading frame and the predicted amino acid sequence of the K433_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO: 125. Additional nucleotide sequence from the 3' portion of K433_li, including a poly(A) tail, is reported in SEQ ID NO:126.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone K433_li should be approximately 1200 bp.

Protein "L256 li"

One protein of the present invention has been identified as protein "L256_li". A partial cDNA clone encoding L256_li was first isolated from a mouse adult thymus cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "L256_li".

Applicants' methods identified clone L256_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of L256_li as presently determined is reported in SEQ ID NOJ27. What appUcants beUeve is the proper reading frame and the predicted amino add sequence of the L256_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ28. Additional nucleotide sequence from the 3' portion of L256_li, including a poly(A) tail, is reported in SEQ ID NO:129. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone L256_li should be approximately 1400 bp.

Protein "AM207 li"

One protein of the present invention has been identified as protein "AM207_li". A partial cDNA clone encoding AM207_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly (A) tail. This full-length clone is also refened to herein as "AM207_li".

Applicants' methods identified clone AM207_li as encoding a secreted protein.

The nucleotide sequence of the 5' portion of AM207_li as presently determined is reported in SEQ ID NOJ30. What applicants beUeve is the proper reading frame and the predicted amino add sequence of the AM207_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ31. Additional nucleotide sequence from the 3' portion of AM207_li, including a poly(A) tail, is reported in SEQ ID NOJ32.

Protein "AM910 li"

One protein of the present invention has been identified as protein "AM910_li". A partial cDNA clone encoding AM910_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AM910_li". Applicants' methods identified clone AM910_li as encoding a secreted protein.

The nucleotide sequence of AM910_li as presently determined is reported in SEQ ID NOJ33, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AM910_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ34. Amino acids 7 to 19 of SEQ ID NOJ34 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 20. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AM910_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone AM910_li should be approximately 1200 bp.

Protein "AR54 li"

One protein of the present invention has been identified as protein "AR54_li". A partial cDNA clone encoding AR54_li was first isolated from a human adult retina cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M. A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AR54_li".

Applicants' methods identified clone AR54_ li as encoding a secreted protein.

The nucleotide sequence of AR54_li as presently determined is reported in SEQ ID NOJ35, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AR54_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ36. Amino acids 8 to 20 of SEQ ID NOJ36 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 21. Due to the hydrophobic nature of the predicted leader/signal sequence, it is Ukely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AR54_li protein. The EcoRI /Notl restriction fragment obtainable from the deposit containing clone AR54_li should be approximately 1300 bp.

Protein "L200 li"

One protein of the present invention has been identified as protein "L200_li". A partial cDNA clone encoding L200_li was first isolated from a mouse adult thymus cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "L200_Ji".

Applicants' methods identified clone L200_li as encoding a secreted protein.

The nucleotide sequence of L200_li as presently determined is reported in SEQ ID NOJ37, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the L200_Ji protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ38. Amino acids 272 to 284 of SEQ ID NOJ38 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 285. Due to the hydrophobic nature of the predicted leader/signal sequence, it is Ukely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the L200_li protem.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone L200_li should be approximately 1330 bp.

Protein "WA129 2i"

One protein of the present invention has been identified as protein "WA129_2i". A partial cDNA clone encoding WA129_2i was first isolated from a Xenopus embryo (dorsal mesoderm) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a fuE-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "WA129_2i".

Applicants' methods identified clone WA129_2i as encoding a secreted protein.

The nucleotide sequence of WA129_2i as presently determined is reported in SEQ ID NOJ39, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the WA129_2i protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ40. Amino acids 10 to 22 of SEQ ID NOJ40 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 23. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the WA129_2i protein. The EcoRI/Notl restriction fragment obtainable from the deposit containing clone WA129_2i should be approximately 1933 bp.

WA192_2i protein was expressed in a Baculovirus expression system, and an expressed protein band of approximately 39 kDa detected in a conditioned medium fraction using SDS polyacrylamide gel electrophoresis.

Protein "WA154 3i"

One protein of the present invention has been identified as protein "WA154_3i". A partial cDNA clone encoding WA154_3i was first isolated from a Xenopus embryo (dorsal mesoderm) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "WA154_3i".

Applicants' methods identified clone WA154_3i as encoding a secreted protein.

The nucleotide sequence of WA154_3i as presently determined is reported in SEQ ID NOJ41, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the WA154_3i protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ42. Amino acids 11 to 23 of SEQ ID NOJ42 are a predicted leader /signal sequence, with the predicted mature amino acid sequence beginning at amino acid 24. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the WA154_3i protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone WA154_3i should be approximately 1469 bp.

WA154_3i protein was expressed in a COS ceU expression system, and an expressed protein band of approximately 17 kDa detected in conditioned medium and membrane fractions using SDS polyacrylamide gel electrophoresis.

Protein "AA36 li"

One protein of the present invention has been identified as protein

"AA36_li". A partial cDNA clone encoding AA36_li was first isolated from a human fetal kidney cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AA36_li".

Applicants' methods identified clone AA36_li as encoding a secreted protein.

The nucleotide sequence of AA36_li as presently determined is reported in SEQ ID NOJ43, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AA36_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ44. Amino acids 3 to 15 of SEQ ID NOJ44 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 16. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader /signal sequence not be separated from the remainder of the AA36_li protein.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone AA36_li should be approximately 1450 bp.

Protein "AC175 2i" One protein of the present invention has been identified as protein

"AC175_2i". A partial cDNA clone encoding AC175_2i was first isolated from a human fetal placenta cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly (A) tail. This full-length clone is also referred to herein as "AC175_2i". Applicants' methods identified clone AC175_2i as encoding a secreted protein.

The nucleotide sequence of AC175_2i as presently determined is reported in SEQ ID NOJ45, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AC175_2i protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ46.

The EcoRI /Notl restriction fragment obtainable from the deposit containing clone AC175_2i should be approximately 842 bp.

Protein "AV189 li"

One protein of the present invention has been identified as protein "AV189_li". A partial cDNA clone encoding AV189_li was first isolated from a mouse adult spleen (concanavalin A stimulated and mixed with dendritic cells) cDNA Ubrary using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "AV189_li".

Applicants' methods identified clone AV189_li as encoding a secreted protein.

The nucleotide sequence of AV189_li as presently determined is reported in SEQ ID NO: 147, and includes the poly (A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the AV189_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ48. Amino acids 72 to 84 of SEQ ID NOJ48 are a predicted leader /signal sequence, with the predicted mature amino acid sequence beginning at amino acid 85. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the AV189_li protein.

Protein "K368 li"

One protein of the present invention has been identified as protein "K368_li". A partial cDNA clone encoding K368_li was first isolated from a mouse adult bone manow (stromal ceU line FCM-4) cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone conesponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium library. The clone received from the distributor was examined and determined to be a full-length done, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also refened to herein as "K368_li".

Applicants' methods identified clone K368_li as encoding a secreted protein.

The nucleotide sequence of K368_li as presently determined is reported in SEQ ID NOJ49, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the K368_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ50. Amino acids 88 to 100 of SEQ ID NOJ50 are a predided leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 101. Due to the hydrophobic nature of the predicted leader/signal sequence, it is Ukely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the K368_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone K368_li should be approximately 983 bp.

K368_li protein was expressed in a Baculovirus expression system, and an expressed protein band of approximately 28 kDa detected in conditioned medium and membrane fractions using SDS polyacrylamide gel electrophoresis.

Protein "K568 li"

One protein of the present invention has been identified as protein "K568_li". A partial cDNA clone encoding K568_li was first isolated from a mouse adult bone marrow (stromal cell Une FCM-4)cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino add sequence of the encoded protein. A human EST matching at least part of the nudeotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "K568_li". Applicants' methods identified clone K568_li as encoding a secreted protein.

The nucleotide sequence of K568_li as presently determined is reported in SEQ ID NOJ51, and includes the poly(A) tail. What applicants believe is the proper reading frame and the predicted amino acid sequence of the K568_li protein corresponding to the foregoing nucleotide sequence is reported in SEQ ID NOJ52. Amino acids 57 to 69 of SEQ ID NOJ52 are a predicted leader/signal sequence, with the predicted mature amino acid sequence beginning at amino acid 70. Due to the hydrophobic nature of the predicted leader/signal sequence, it is likely to act as a transmembrane domain should the predicted leader/signal sequence not be separated from the remainder of the K568_li protein.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone K568_li should be approximately 1254 bp.

Protein "T85 li"

One protein of the present invention has been identified as protein "T85_li". A partial cDNA clone encoding T85_li was first isolated from a mouse fetal brain cDNA library using methods which are selective for cDNAs encoding secreted proteins (see U.S. Pat. No. 5,536,637),or was identified as encoding a secreted or transmembrane protein on the basis of computer analysis of the amino acid sequence of the encoded protein. A human EST matching at least part of the nucleotide sequence of this clone was identified by database searches. The human cDNA clone corresponding to the EST database entry was ordered from Genome Systems, Inc., St. Louis, Mo, a distributor of the I.M.A.G.E. Consortium Ubrary. The clone received from the distributor was examined and determined to be a full-length clone, including a 5' end and 3' UTR , including a poly(A) tail. This full-length clone is also referred to herein as "T85_ϋ".

AppUcants' methods identified clone T85_li as encoding a secreted protein.

The nucleotide sequence of T85_li as presently determined is reported in SEQ ID NOJ53, and includes the poly(A) tail. What appUcants believe is the proper reading frame and the predicted amino acid sequence of the T85_li protein conesponding to the foregoing nucleotide sequence is reported in SEQ ID NO:154.

The EcoRI/Notl restriction fragment obtainable from the deposit containing clone T85_li should be approximately 1803 bp.

Deposit of Clones

Clones AK296_li, AK533_li, AK583_li, AM282_li, AM340_li, AM610_li, AP162_li, AR260_li, AS32_li, AS34_li, AT205_li, AT211_li, AT319_li, AW191_li, BB9_li, H617_li, K39_li and K640_li were deposited on April 17, 1996 with the American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC 98026, from which each clone comprising a particular polynucleotide is obtainable. Clones AE402_li, AE610_li, AH106_li, AH196_li, AI6_li, AJ13_li,

AT27_li, AJ142_li, AK604_li, AK620_li, AK650_li, AM226_li, AR417_li, AU43_li, AW60_li, BA176_li, BD140_li, BD407_li and BF290_li were deposited on October 2, 1996 with the American Type Culture Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC 98190, from which each clone comprising a particular polynucleotide is obtainable.

Clones BG236_li, BG237_li, BG255_li, H541_3i, H978_li and L161_li were deposited on October 2, 1996 with the American Type Culture Collection (10801

University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC 98191, from which each clone comprising a particular polynucleotide is obtainable.

Clones AE648_li, AE693_li, AK438_li, AK609_li, AM1060_li, AQ2_li,

K433_li and L256_li were deposited on October 31, 1996 with the American Type Culture

Collection (10801 University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC

98237, from which each clone comprising a particular polynucleotide is obtainable.

Clones AM207_li, AM910_li, AR54_li, L200_li, WA129_2i and WA154_3i were deposited on August 21, 1997 with the American Type Culture Collection (10801

University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC 98510, from which each clone comprising a particular polynucleotide is obtainable.

Clones AA36_li. AC175_2i, AV189_li, K368_li, K568_li and T85_li were deposited on December 18, 1998 with the American Type Culture Collection (10801

University Boulevard, Manassas, Virginia 20110-2209 U.S.A.) as an original deposit under the Budapest Treaty and were given the accession number ATCC XXXXX, from which each clone comprising a particular polynucleotide is obtainable.

All restrictions on the availability to the public of the deposited material will be irrevocably removed upon the granting of the patent, except for the requirements specified in 37 C.F.R. § 1.808(b), and the term of the deposit will comply with 37 C.F.R. § 1.806.

Each clone has been transfected into separate bacterial cells (E. coli) in this composite deposit. Each clone can be removed from the vector in which it was deposited by performing an EcoRI/Notl digestion (5' site, EcoRI; 3' site, Notl) to produce the appropriate fragment for such clone. Each clone was deposited in either the pED6 or pNOTs vector depicted in Figures 1A and IB, respectively. The pED6dpc2 vector

("pED6") was derived from pEDόdpcl by insertion of a new polylinker to facilitate cDNA cloning (Kaufman et al, 1991, Nucleic Acids Res. 19: 4485-4490); the pNOTs vector was derived from pMT2 (Kaufman et al, 1989, Mol. Cell. Biol. 9: 946-958) by deletion of the DHFR sequences, insertion of a new polylinker, and insertion of the M13 origin of replication m the Clal site. In some instances, the deposited clone can become "flipped"

(i.e., in the reverse orientation) in the deposited isolate. In such instances, the cDNA insert can still be isolated by digestion with EcoRI and Notl. However, Notl will then produce the 5' site and EcoRI will produce the 3' site for placement of the cDNA in proper orientation for expression in a suitable vector. The cDNA may also be expressed from the vectors in which they were deposited.

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

An oligonucleotide probe or probes should be designed to the sequence that is known for that particular clone. This sequence can be derived from the sequences provided herein, or from a combination of those sequences.

In the probe sequences derived from the sequences provided, position 2 is occupied in prefened probes/primers by a biotinylated phosphoaramidite residue rather than a nucleotide (such as, for example, that produced by use of biotin p h o s p h o r a m i d i t e (l-dimethoxytrityloxy-2-(N-biotinyl-4-aminobutyl)-propyl-3-0-(2-cyanoethyl)-(N,N-dii sopropyl)-phosphoramadite) (Glen Research, cat. no. 10-1953)).

The design of the oligonucleotide probe should preferably follow these parameters: (a) It should be designed to an area of the sequence which has the fewest ambiguous bases ("N's"), if any;

(b) It should be designed to have a T_m of approx. 80 ° C

(assuming 2° for each A or T and 4 degrees for each G or C). The oligonucleotide should preferably be labeled with -³²P ATP (specific activity 6000 Ci/mmole) and T4 polynucleotide kinase using commonly employed techniques for labeling oligonucleotides. Other labeling techniques can also be used. Unincorporated label should preferably be removed by gel filtration chromatography or other established methods. The amount of radioactivity incorporated into the probe should be quantitated by measurement in a scintillation counter. Preferably, specific activity of the resulting probe should be approximately 4e+6 dpm/pmole.

The bacterial culture containing the pool of full-length clones should preferably be thawed and 100 1 of the stock used to inoculate a sterile culture flask containing 25 ml of sterile L-broth containing ampidUin at 100 g/ml. The culture should preferably be grown to saturation at 37°C, and the saturated culture should preferably be diluted in fresh L-broth. Aliquots of these dilutions should preferably be plated to determine the dilution and volume which will yield approximately 5000 distinct and well-separated colonies on solid bacteriological media containing L-broth containing ampicillin at 100 g/ml and agar at 1.5% in a 150 mm petri dish when grown overnight at 37°C. Other known methods of obtaining distinct, well-separated colonies can also be employed.

Standard colony hybridization procedures should then be used to transfer the colonies to nitrocellulose filters and lyse, denature and bake them. The filter is then preferably incubated at 65°C for 1 hour with gentle agitation in 6X SSC (20X stock is 175.3 g NaCl/Uter, 88.2 g Na dtrate/Uter, adjusted to pH 7.0 with NaOH) containing 0.5% SDS, 100 g/ml of yeast RNA, and 10 mM EDTA (approximately 10 mL per 150 mm filter). Preferably, the probe is then added to the hybridization mix at a concentration greater than or equal to le+6 dpm/mL. The filter is then preferably incubated at 65°C with gentle agitation overnight. The filter is then preferably washed in 500 mL of 2X SSC/0.5% SDS at room temperature without agitation, preferably followed by 500 mL of 2X SSC/0J% SDS at room temperature with gentle shaking for 15 minutes. A third wash with 0JX SSC/0.5% SDS at 65°C for 30 minutes to 1 hour is optional. The filter is then preferably dried and subjected to autoradiography for sufficient time to visualize the positives on the X-ray film. Other known hybridization methods can also be employed.

The positive colonies are picked, grown in culture, and plasmid DNA isolated using standard procedures. The clones can then be verified by restriction analysis, hybridization analysis, or DNA sequencing. Fragments of the proteins of the present invention which are capable of exhibiting biological activity are also encompassed by the present invention. Fragments of the protein may be in linear form or they may be cyclized using known methods, for example, as described in H.U. Saragovi, et al, Bio/Technology 10, 773-778 (1992) and in R.S. McDowell, et al, J. Amer. Chem. Soc. 114, 9245-9253 (1992), both of which are incorporated herein by reference. Such fragments may be fused to carrier molecules such as immunoglobulins for many purposes, including increasing the valency of protein binding sites. For example, fragments of the protein may be fused through "linker" sequences to the Fc portion of an immunoglobulin. For a bivalent form of the protein, such a fusion could be to the Fc portion of an IgG molecule. Other immunoglobulin isotypes may also be used to generate such fusions. For example, a protein - IgM fusion would generate a decavalent form of the protein of the invention.

The present invention also provides both full-length and mature forms of the disclosed proteins. The full-length form of the such proteins is identified in the sequence listing by translation of the nucleotide sequence of each disclosed clone. The mature form(s) of such protein may be obtained by expression of the disclosed fuU-length polynucleotide (preferably those deposited with ATCC) in a suitable mammalian cell or other host cell. The sequence(s) of the mature form(s) of the protein may also be determinable from the amino acid sequence of the full-length form. Where the protein of the present invention is membrane-bound (e.g., is a receptor), the present invention also provides for soluble forms of such protein. In such forms, part or all of the intracellular and transmembrane domains of the protein are deleted such that the protein is fully secreted from the cell in which it is expressed. The intracellular and transmembrane domains of proteins of the invention can be identified in accordance with known techniques for determination of such domains from sequence information. For example, the TopPredll computer program can be used to predict the location of transmembrane domains in an amino acid sequence, domains which are described by the location of the center of the transmsmbrane domain, with at least ten transmembrane amino acids on each side of the reported central residue(s). Proteins and protein fragments of the present invention include proteins with amino add sequence lengths that are at least 25%(more preferably at least 50%, and most preferably at least 75%) of the length of a disclosed protein and have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90% or 95% identity) with that disclosed protein, where sequence identity is determined by comparing the amino acid sequences of the proteins when aligned so as to maximize overlap and identity while minimizing sequence gaps. Also included in the present invention are proteins and protein fragments that contain a segment preferably comprising 8 or more (more preferably 20 or more, most preferably 30 or more) contiguous amino acids that shares at least 75% sequence identity (more preferably, at least 85% identity; most preferably at least 95% identity) with any such segment of any of the disclosed proteins.

In particular, sequence identity may be determined using WU-BLAST (Washington University BLAST) version 2.0 software, which builds upon WU-BLAST version 1.4, which in turn is based on the public domain NCBI-BLAST version 1.4 (Altschul and Gish, 1996, Local alignment statistics, Doolittle ed., Methods in Enzymology 266: 460-480; Altschul et al, 1990, Basic local alignment search tool, Journal of Molecular Biology 215: 403-410; Gish and States, 1993, Identification of protein coding regions by database similarity search, Nature Genetics 3: 266-272; Karlin and Altschul, 1993, Applications and statistics for multiple high-scoring segments in molecular sequences, Proc. Natl. Acad. Sci. USA 90: 5873-5877; all of which are incorporated by reference herein). WU-BLAST version 2.0 executable programs for several UNIX platforms can be downloaded from ftp://blast.wustl.edu/blast/executables. The complete suite of search programs (BLASTP, BLASTN, BLASTX, TBLASTN, and TBLASTX) is provided at that site, in addition to several support programs. WU-BLAST 2.0 is copyrighted and may not be sold or redistributed in any form or manner without the express written consent of the author; but the posted executables may otherwise be freely used for commercial, nonprofit, or academic purposes. In all search programs in the suite ~ BLASTP, BLASTN, BLASTX, TBLASTN and TBLASTX - the gapped alignment routines are integral to the database search itself, and thus yield much better sensitivity and selectivity while producing the more easily interpreted output. Gapping can optionally be turned off in all of these programs, if desired. The default penalty (Q) for a gap of length one is Q=9 for proteins and BLASTP, and Q=10 for BLASTN, but may be changed to any integer value including zero, one through eight, nine, ten, eleven, twelve through twenty, twenty-one through fifty, fifty-one through one hundred, etc. The default per-residue penalty for extending a gap (R) is R=2 for proteins and BLASTP, and R=J0 for BLASTN, but may be changed to any integer value including zero, one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve through twenty, twenty-one through fifty, fifty-one through one hundred, etc. Any combination of values for Q and R can be used in order to align sequences so as to maximize overlap and identity while minimizing sequence gaps. The default amino acid comparison matrix is BLOSUM62, but other amino acid comparison matrices such as PAM can be utilized.

Species homologues of the disclosed proteins are also provided by the present invention. As used herein, a "species homologue" is a protein or polynucleotide with a different species of origin from that of a given protein or polynucleotide, but with significant sequence similarity to the given protein or polynucleotide. Preferably, polynucleotide species homologues have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90% identity) with the given polynucleotide, and protein species homologues have at least 30% sequence identity (more preferably, at least 45% identity; most preferably at least 60% identity) with the given protein, where sequence identity is determined by comparing the nucleotide sequences of the polynucleotides or the amino acid sequences of the proteins when aligned so as to maximize overlap and identity while minimizing sequence gaps. Species homologues may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from the desired species. Preferably, species homologues are those isolated from mammalian species. Most preferably, species homologues are those isolated from certain mammalian species such as, for example, Pan troglodytes, Gorilla gorilla, Pongo pygmaeus, Hylobates concolor, Macaca mulatta, Papio papio, Papio hamadryas, Cercopithecus aethiops, Cebus capucinus, Aotus trivirgatus, Sanguinus oedipus, Microcebus murinus, Mus musculus, Rattus norvegicus, Cricetulus griseus, Felis catus, Mustela vison, Canis familiaris, Oryctolagus cuniculus, Bos taurus, Ovis aries, Sus scrofa, and Equus caballus, for which genetic maps have been created aUowing the identification of syntenic relationships between the genomic organization of genes in one species and the genomic organization of the related genes in another species (O'Brien and Seuanez, 1988, Ann. Rev. Genet. 22: 323-351; O'Brien et al, 1993, Nature Genetics 3:103-112; Johansson et al, 1995, Genomics 25: 682-690; Lyons et al, 1997, Nature Genetics 15: 47-56; O'Brien et al, 1997, Trends in Genetics 13(10): 393-399; Carver and Stubbs, 1997, Genome Research 7:1123-1137; all of which are incorporated by reference herein).

The invention also encompasses allelic variants of the disclosed proteins; that is, naturaUy-occurring alternative forms of the isolated proteins which are identical or have significantly similar sequences to those encoded by the disclosed polynucleotides. Preferably, allelic variants have at least 60% sequence identity (more preferably, at least 75% identity; most preferably at least 90% identity) with the given polynucleotide, where sequence identity is determined by comparing the nucleotide sequences of the polynucleotides when aligned so as to maximize overlap and identity while mmimizing sequence gaps. Allelic variants may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from individuals of the appropriate species. The invention also includes polynucleotides with sequences complementary to those of the polynucleotides disclosed herein.

The isolated polynucleotide endcoing the protein of the invention may be operably linked to an expression control sequence such as the pMT2 or pED expression vectors disclosed in Kaufman et al, Nucleic Acids Res. 19, 4485-4490 (1991), in order to produce the protein recombinantly. Many suitable expression control sequences are known in the art. General methods of expressing recombinant proteins are also known and are exemplified in R. Kaufman, Methods in Enzymology 185, 537-566 (1990). As defined herein "operably linked" means that the isolated polynucleotide of the invention and an expression control sequence are situated within a vector or ceU in such a way that the proteir is expressed by a host cell which has been transformed (transfected) with the ligated polynucleotide/expression control sequence.

A number of types of cells may act as suitable host cells for expression of the protein. Mammalian host cells include, for example, monkey COS cells, Chinese Hamster Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 ceUs, human Colo205 cells, 3T3 cells, CV-1 cells, other transformed primate cell lines, normal diploid ceUs, ceU strains derived from in vitro culture of primary tissue, primary explants, HeLa cells, mouse L cells, BHK, HL-60, U937, HaK or Jurkat cells.

Alternatively, it may be possible to produce the protein in lower eukaryotes such as yeast or in prokaryotes such as bacteria. PotentiaUy suitable yeast strains include Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces strains, Candida, or any yeast strain capable of expressing heterologous proteins. Potentially suitable bacterial strains include Escherichia coli, Bacillus subtilis, Salmonella typhimurium, or any bacterial strain capable of expressing heterologous proteins. If the protein is made in yeast or bacteria, it may be necessary to modify the protein produced therein, for example by phosphorylation or glycosylation of the appropriate sites, in order to obtain the functional protein. Such covalent attachments may be accomplished using known chemical or enzymatic methods. The protein may also be produced by operably linking the isolated polynucleotide of the invention to suitable control sequences in one or more insect expression vectors, and employing an insect expression system. Materials and methods for baculovirus/insect ceU expression systems are commercially available in kit form from, e.g., Invitrogen, San Diego, California, U.S.A. (the MaxBac® kit), and such methods are weU known in the art, as described in Summers and Smith, Texas Agricultural Experiment Station Bulletin No. 1555 (1987), incorporated herein by reference. As used herein, an insect cell capable of expressing a polynucleotide of the present invention is "transformed."

The protein of the invention may be prepared by culturing transformed host cells under culture conditions suitable to express the recombinant protein. The resulting expressed protein may then be purified from such culture (i.e., from culture medium or ceU extracts) using known purification processes, such as gel filtration and ion exchange chromatography. The purification of the protein may also include an affinity column containing agents which will bind to the protein; one or more column steps over such affinity resins as concanavalin A-agarose. heparin-toyopearl® or Cibacrom blue 3GA Sepharose®; one or more steps involving hydrophobic interaction chromatography using such resins as phenyl ether, butyl ether, or propyl ether; or immunoaffinity chromatography.

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

Finally, one or more reverse-phase high performance liquid chromatography (RP-HPLC) steps employing hydrophobic RP-HPLC media, e.g., silica gel having pendant methyl or other aliphatic groups, can be employed to further purify the protein. Some or aU of the foregoing purification steps, in various combinations, can also be employed to provide a substantially homogeneous isolated recombinant protein. The protein thus purified is substantially free of other mammalian proteins and is defined in accordance with the present invention as an "isolated protein."

The protein of the invention may also be expressed as a product of transgenic animals, e.g., as a component of the milk of transgenic cows, goats, pigs, or sheep which are characterized by somatic or germ ceUs containing a nucleotide sequence encoding the protein. The protein may also be produced by known conventional chemical synthesis. Methods for constructing the proteins of the present invention by synthetic means are known to those skilled in the art. The synthetically-constructed protein sequences, by virtue of sharing primary, secondary or tertiary structural and/or conf ormational charaderistics with proteins may possess biological properties in common therewith, including protein activity. Thus, they may be employed as biologically active or immunological substitutes for natural, purified proteins in screening of therapeutic compounds and in immunological processes for the development of antibodies.

The proteins provided herein also include proteins characterized by amino acid sequences similar to those of purified proteins but into which modification are naturaUy provided or deUberately engineered. For example, modifications in the peptide or DNA sequences can be made by those skilled in the art using known techniques. Modifications of interest in the protein sequences may include the alteration, substitution, replacement, insertion or deletion of a selected amino acid residue in the coding sequence. For example, one or more of the cysteine residues may be deleted or replaced with another amino acid to alter the conformation of the molecule. Techniques for such alteration, substitution, replacement, insertion or deletion are weU known to those skilled in the art (see, e.g., U.S. Patent No. 4,518,584). Preferably, such alteration, substitution, replacement, insertion or deletion retains the desired activity of the protein.

Other fragments and derivatives of the sequences of proteins which would be expected to retain protein activity in whole or in part and may thus be useful for screening or other immunological methodologies may also be easily made by those skilled in the art given the disclosures herein. Such modifications are beUeved to be encompassed by the present invention. USES AND BIOLOGICAL ACTIVITY

The proteins of the present invention are expected to exhibit one or more of the uses or biological activities (including those associated with assays cited herein) identified below. Uses or activities described for proteins of the present invention may be provided by administration or use of such proteins or by administration or use of polynucleotides encoding such proteins (such as, for example, in gene therapies or vectors suitable for introduction of DNA).

Research Uses and Utilities The proteins provided by the present invention can similarly be used in assay to determine biological activity, including in a panel of multiple proteins for high-throughput screening; to raise antibodies or to elicit another immune response; as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels of the protein (or its receptor) in biological fluids; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate conelative receptors or Ugands. Where the protein binds or potentially binds to another protein (such as, for example, in a receptor-Ugand interaction), the protein can be used to identify the other protein with which binding occurs or to identify inhibitors of the binding interaction. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction.

Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products. Methods for performing the uses listed above are well known to those skiUed in the art. References disclosing such methods include without limitation "Molecular Cloning: A Laboratory Manual", 2d ed., Cold Spring Harbor Laboratory Press, Sambrook, J., E.F. Fritsch and T. Maniatis eds., 1989, and "Methods in Enzymology: Guide to Molecular Cloning Techniques", Academic Press, Berger, S.L. and A.R. Kimmel eds., 1987.

Nutritional Uses

Proteins of the present invention can also be used as nutritional sources or supplements. Such uses include without limitation use as a protein or amino acid supplement, use as a carbon source, use as a nitrogen source and use as a source of carbohydrate. In such cases the protein of the invention can be added to the feed of a particular organism or can be administered as a separate soUd or Uquid preparation, such as in the form of powder, pills, solutions, suspensions or capsules. In the case of microorganisms, the protein of the invention can be added to the medium in or on which the microorganism is cultured.

Cytokine and Cell Proliferation /Differentiation Activity A protein of the present invention may exhibit cytokine, cell proliferation (either inducing or inhibiting) or ceU differentiation (either inducing or inhibiting) activity or may induce production of other cytokines in certain cell populations. Many protein fadors discovered to date, including all known cytokines, have exhibited activity in one or more factor-dependent cell proliferation assays, and hence the assays serve as a convenient confirmation of cytokine activity. The activity of a protein of the present invention is evidenced by any one of a number of routine factor dependent cell proliferation assays for ceU lines including, without limitation, 32D, DA2, DA1G, T10, B9, B9/11, BaF3, MC9/G, M+ (preB M+), 2E8, RB5, DAI, 123, T1165, HT2, CTLL2, TF-1, Mo7e and CMK.

The activity of a protein of the invention may, among other means, be measured by the following methods: Assays for T-cell or thymocyte proliferation include without limitation those described in: Current Protocols in Immunology, Ed by J. E. CoUgan, A.M. Kruisbeek, D.H. MarguUes, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immimol. 137:3494-3500, 1986; BertagnoUi et al., J. Immimol. 145:1706-1712, 1990; BertagnoUi et al, CeUular Immunology 133:327-341, 1991; BertagnoUi, et al., J. Immunol. 149:3778-3783, 1992; Bowman et al., J. Immunol. 152: 1756-1761, 1994.

Assays for cytokine production and /or proliferation of spleen cells, lymph node ceUs or thymocytes include, without Umitation, those described in: Polyclonal T cell stimulation, Kruisbeek, A.M. and Shevach, E.M. In Current Protocols in Immunology. J.E.e.a.

Coligan eds. Vol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto. 1994; and

Measurement of mouse and human Interferon , Schreiber, R.D. In Current Protocols in

Immunology. J.E.e.a. CoUgan eds. Vol 1 pp. 6.8.1-6.8.8, John WUey and Sons, Toronto. 1994.

Assays for proliferation and differentiation of hematopoietic and lymphopoietic cells include, without limitation, those described in: Measurement of Human and Murine Interleukin 2 and Interleukin 4, Bottomly, K., Davis, L.S. and Lipsky, P.E. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons, Toronto. 1991; deVries et al., J. Exp. Med. 173:1205-1211, 1991; Moreau et al., Nature 336:690-692, 1988; Greenberger et al., Proc. Natl. Acad. Sci. U.S.A. 80:2931-2938, 1983; Measurement of mouse and human interleukin 6 - Nordan, R. In Current Protocols in Immunology. J.E.e.a. CoUgan eds. Vol 1 pp. 6.6.1-6.6.5, John Wiley and Sons, Toronto. 1991; Smith et al., Proc. Natl. Acad. Sci. U.S.A. 83:1857-1861, 1986; Measurement of human Interleukin 11 - Bennett, F., Giannotti, J., Clark, S.C. and Turner, K. J. In Current Protocols in Immunology. ].Ε.e.a. Coligan eds. Vol 1 pp. 6.15.1 John Wiley and Sons, Toronto. 1991; Measurement of mouse and human Interleukin 9 - Ciarletta, A., Giannotti, J., Clark, S.C. and Turner, K.J. In Current Protocols in Immunology. J.E.e.a. Coligan eds. Vol 1 pp. 6.13.1, John Wiley and Sons. Toronto. 1991.

Assays for T-cell clone responses to antigens (which will identify, among others, proteins that affect APC-T cell interactions as well as direct T-cell effects by measuring proliferation and cytokine production) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. CoUgan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, Immunologic studies in Humans); Weinberger et al., Proc. Natl. Acad. Sci. USA 77:6091-6095, 1980; Weinberger et al., Eur. J. Immun. 11:405-411, 1981; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988.

Immune Stimulating or Suppressing Activity

A protein of the present invention may also exhibit immune stimulating or immune suppressing activity, including without limitation the activities for which assays are described herein. A protein may be useful in the treatment of various immune deficiencies and disorders (including severe combined immunodeficiency (SOD)), e.g., in regulating (up or down) growth and proliferation of T and /or B lymphocytes, as well as effecting the cytolytic activity of NK cells and other cell populations. These immune deficiencies may be genetic or be caused by viral (e.g., HIV) as well as bacterial or fungal infections, or may result from autoimmune disorders. More specifically, infectious diseases causes by viral, bacterial, fungal or other infection may be treatable using a protein of the present invention, including infections by HIV, hepatitis viruses, herpesviruses, mycobacteria, Leishmania spp., malaria spp. and various fungal infections such as candidiasis. Of course, in this regard, a protein of the present invention may also be useful where a boost to the immune system generally may be desirable, i.e., in the treatment of cancer.

Autoimmune disorders which may be treated using a protein of the present invention include, for example, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Gυillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes melUtis, myasthenia gravis, graft-versus-host disease and autoimmune inflammatory eye disease. Such a protein of the present invention may also to be useful in the treatment of allergic reactions and conditions, such as asthma (particularly aUergic asthma) or other respiratory problems. Other conditions, in which immune suppression is desired (including, for example, organ transplantation), may also be treatable using a protein of the present invention.

Using the proteins of the invention it may also be possible to regidate immune responses in a number of ways. Down regulation may be in the form of inhibiting or blocking an immune response already in progress or may involve preventing the induction of an immune response. The functions of activated T ceUs may be inhibited by suppressing T cell responses or by inducing specific tolerance in T ceUs, or both. Immunosuppression of T cell responses is generally an active, non-antigen-specific, process which requires continuous exposure of the T cells to the suppressive agent. Tolerance, which involves inducing non-responsiveness or anergy in T ceUs, is distinguishable from immunosuppression in that it is generally antigen-specific and persists after exposure to the tolerizing agent has ceased. OperationaUy, tolerance can be demonstrated by the lack of a T cell response upon reexposure to specific antigen in the absence of the tolerizing agent.

Down regulating or preventing one or more antigen functions (including without limitation B lymphocyte antigen functions (such as , for example, B7)), e.g., preventing high level lymphokine synthesis by activated T cells, will be useful in situations of tissue, skin and organ transplantation and in graft-versus-host disease (GVHD). For example, blockage of T cell function should result in reduced tissue destruction in tissue transplantation. Typically, in tissue transplants, rejection of the transplant is initiated through its recognition as foreign by T cells, foUowed by an immune reaction that destroys the transplant. The administration of a molecule which inhibits or blocks interaction of a B7 lymphocyte antigen with its natural ligand(s) on immune cells (such as a soluble, monomeric form of a peptide having B7-2 activity alone or in conjunction with a monomeric form of a peptide having an activity of another B lymphocyte antigen (e.g., B7- 1, B7-3) or blocking antibody), prior to transplantation can lead to the binding of the molecule to the natural ligand (s) on the immune cells without transmitting the corresponding costimulatory signal. Blocking B lymphocyte antigen function in this matter prevents cytokine synthesis by immune cells, such as T cells, and thus acts as an immunosuppressant. Moreover, the lack of costimulation may also be sufficient to anergize the T cells, thereby inducing tolerance in a subject. Induction of long-term tolerance by B lymphocyte antigen-blocking reagents may avoid the necessity of repeated administration of these blocking reagents. To achieve sufficient immunosuppression or tolerance in a subject, it may also be necessary to block the function of a combination of B lymphocyte antigens. The efficacy of particular blocking reagents in preventing organ transplant rejection or GVHD can be assessed using animal models that are predictive of efficacy in humans. Examples of appropriate systems which can be used include aUogeneic cardiac grafts in rats and xenogeneic pancreatic islet cell grafts in mice, both of which have been used to examine the immunosuppressive effects of CTLA4Ig fusion proteins in vivo as described in Lenschow et al, Science 257:789-792 (1992) and Turka et al, Proc. N atl. Acad. Sci USA, 89:11102-11105 (1992). In addition, murine models of GVHD (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 846-847) can be used to determine the effect of blocking B lymphocyte antigen function in vivo on the development of that disease. Blocking antigen function may also be therapeutically useful for treating autoimmune diseases. Many autoimmune disorders are the result of inappropriate activation of T cells that are reactive against self tissue and which promote the production of cytokines and autoantibodies involved in the pathology of the diseases. Preventing the activation of autoreactive T cells may reduce or eliminate disease symptoms. Administration of reagents which block costimulation of T cells by disrupting receptoπligand interactions of B lymphocyte antigens can be used to inhibit T cell activation and prevent production of autoantibodies or T cell-derived cytokines which may be involved in the disease process. Additionally, blocking reagents may induce antigen-spedfic tolerance of autoreactive T ceUs which could lead to long-term reUef from the disease. The efficacy of blocking reagents in preventing or alleviating autoimmune disorders can be determined using a number of well-characterized animal models of human autoimmune diseases. Examples include murine experimental autoimmune encephalitis, systemic lupus erythmatosis in MRL /Ipr/lpr mice or NZB hybrid mice, murine autoimmune collagen arthritis, diabetes meUitus in NOD mice and BB rats, and murine experimental myasthenia gravis (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 840-856).

Upregulation of an antigen function (preferably a B lymphocyte antigen function), as a means of up regulating immune responses, may also be useful in therapy. Upregulation of immune responses may be in the form of enhancing an existing immune response or eliciting an initial immune response. For example, enhancing an immune response through stimulating B lymphocyte antigen function may be useful in cases of viral infection. In addition, systemic viral diseases such as influenza, the common cold, and encephalitis might be alleviated by the administration of stimulatory forms of B lymphocyte antigens systemically.

Alternatively, anti-viral immune responses may be enhanced in an infected patient by removing T cells from the patient, costimulating the T cells in vitro with viral antigen- pulsed APCs either expressing a peptide of the present invention or together with a stimulatory form of a soluble peptide of the present invention and reintroducing the in vitro activated T cells into the patient. Another method of enhancing anti-viral immune responses would be to isolate infected cells from a patient, transfect them with a nucleic acid encoding a protein of the present invention as described herein such that the cells express all or a portion of the protein on their surface, and reintroduce the transfected cells into the patient. The infected cells would now be capable of delivering a costimulatory signal to, and thereby activate, T cells in vivo.

In another application, up regulation or enhancement of antigen function (preferably B lymphocyte antigen function) may be useful in the induction of tumor immunity. Tumor cells (e.g., sarcoma, melanoma, lymphoma, leukemia, neuroblastoma, carcinoma) transfected with a nucleic acid encoding at least one peptide of the present invention can be administered to a subject to overcome tumor-specific tolerance in the subject. If desired, the tumor cell can be transfected to express a combination of peptides. For example, tumor cells obtained from a patient can be transfected ex vivo with an expression vector directing the expression of a peptide having B7-2-like activity alone, or in conjunction with a peptide having B7-l-like activity and /or B7-3-like activity. The transfected tumor ceUs are returned to the patient to result in expression of the peptides on the surface of the transfected ceU. Alternatively, gene therapy techniques can be used to target a tumor cell for transfection in vivo.

The presence of the peptide of the present invention having the activity of a B lymphocyte antigen(s) on the surface of the tumor cell provides the necessary costimulation signal to T cells to induce a T cell mediated immune response against the transfected tumor cells. In addition, tumor cells which lack MHC class I or MHC class II molecules, or which fail to reexpress sufficient amounts of MHC class I or MHC class II molecules, can be transfected with nucleic acid encoding all or a portion of (e.g., a cytoplasmic-domain truncated portion) of an MHC class I chain protein and - microglobulin protein or an MHC class II chain protein and an MHC class II chain protein to thereby express MHC class I or MHC class II proteins on the cell surface. Expression of the appropriate class I or class II MHC in conjunction with a peptide having the activity of a B lymphocyte antigen (e.g., B7-1, B7-2, B7-3) induces a T cell mediated immune response against the transfected tumor cell. Optionally, a gene encoding an antisense construct which blocks expression of an MHC class II associated protein, such as the invariant chain, can also be cotransfected with a DNA encoding a peptide having the activity of a B lymphocyte antigen to promote presentation of tumor associated antigens and induce tumor specific immunity. Thus, the induction of a T cell mediated immune response in a human subject may be sufficient to overcome tumor-specific tolerance in the subject.

The activity of a protein of the invention may, among other means, be measured by the following methods:

Suitable assays for thymocyte or splenocyte cytotoxicity include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. CoUgan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J. Immunol. 135:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988; Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J. Immunol. 135:1564-1572, 1985; Takai et al., J. Immunol. 137:3494-3500, 1986; Bowmanet al., J. Virology 61:1992-1998; Takai et al., J. Immunol. 140:508-512, 1988; BertagnoUi et al., Cellular Immunology 133:327-341, 1991; Brown et al., J. Immunol. 153:3079-3092, 1994. Assays for T-cell-dependent immunoglobulin responses and isotype switching (which will identify, among others, proteins that modulate T-ceU dependent antibody responses and that affect Thl /Th2 profiles) include, without limitation, those described in: MaUszewski, J. Immunol. 144:3028-3033, 1990; and Assays for B ceU function: In vitro antibody production, Mond, J.J. and Brunswick, M. In Current Protocols in Immunology. J.E.e.a. CoUgan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and Sons, Toronto. 1994.

Mixed lymphocyte reaction (MLR) assays (which will identify, among others, proteins that generate predominantly Thl and CTL responses) include, without -imitation, those described in: Current Protocols in Immunology, Ed by J. E. CoUgan, A.M. Kruisbeek, D.H. MarguUes, E.M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988; BertagnoUi et al., J. Immunol. 149:3778-3783, 1992.

Dendritic ceU-dependent assays (which will identify, among others, proteins expressed by dendritic cells that activate naive T-cells) include, without limitation, those described in: Guery et al., J. Immunol. 134:536-544, 1995; Inaba et al., Journal of Experimental Medicine 173:549-559, 1991; Macatonia et al., Journal of Immunology 154:5071-5079, 1995; Porgador et al., Journal of Experimental Medicine 182:255-260, 1995; Nair et al., Journal of Virology 67:4062-4069, 1993; Huang et al., Sdence 264:961-965, 1994; Macatonia et al., Journal of Experimental Medicine 169:1255-1264, 1989; Bhardwaj et al., Journal of Clinical Investigation 94:797-807, 1994; and Inaba et al., Journal of Experimental Medicine 172:631-640, 1990.

Assays for lymphocyte survival/apoptosis (which will identify, among others, proteins that prevent apoptosis after superantigen induction and proteins that regulate lymphocyte homeostasis) include, without limitation, those described in: Darzynkiewicz et al., Cytometry 13:795-808, 1992; Gorczyca et al, Leukemia 7:659-670, 1993; Gorczyca et al., Cancer Research 53:1945-1951, 1993; Itoh et al., CeU 66:233-243, 1991; Zacharchuk, Journal of Immunology 145:4037-4045, 1990; Zamai et al., Cytometry 14:891-897, 1993; Gorczyca et al., International Journal of Oncology 1:639-648, 1992.

Assays for proteins that influence early steps of T-cell commitment and development include, without limitation, those described in: Antica et al., Blood 84:111-117, 1994; Fine et al., Cellular Immunology 155:111-122, 1994; Galy et al., Blood 85:2770-2778, 1995; Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551, 1991.

Hematopoiesis Regulating Activity A protein of the present invention may be useful in regulation of hematopoiesis and, consequently, in the treatment of myeloid or lymphoid cell deficiencies. Even marginal biological activity in support of colony forming cells or of factor-dependent cell lines indicates involvement in regulating hematopoiesis, e.g. in supporting the growth and proliferation of erythroid progenitor cells alone or in combination with other cytokines, thereby indicating utility, for example, in treating various anemias or for use in conjunction with inadiation/chemotherapy to stimulate the production of erythroid precursors and/or erythroid ceUs; in supporting the growth and proliferation of myeloid cells such as granulocytes and monocytes/ macrophages (i.e., traditional CSF activity) useful, for example, in conjunction with chemotherapy to prevent or treat consequent myelo-suppression; in supporting the growth and proliferation of megakaryocytes and consequently of platelets thereby allowing prevention or treatment of various platelet disorders such as thrombocytopenia, and generally for use in place of or complimentary to platelet transfusions; and/or in supporting the growth and proliferation of hematopoietic stem cells which are capable of maturing to any and all of the above-mentioned hematopoietic ceUs and therefore find therapeutic utility in various stem ceU disorders (such as those usuaUy treated with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem ceU compartment post irradiation/chemotherapy, either in-vivo or ex-vivo (i.e., in conjunction with bone marrow transplantation or with peripheral progenitor cell transplantation (homologous or heterologous)) as normal cells or genetically manipulated for gene therapy.

Suitable assays for proliferation and differentiation of various hematopoietic lines are cited above.

Assays for embryonic stem cell differentiation (which will identify, among others, proteins that influence embryonic differentiation hematopoiesis) include, without limitation, those described in: Johansson et al. CeUular Biology 15:141-151, 1995; Keller et al., Molecular and Cellular Biology 13:473-486, 1993; McClanahan et al., Blood 81:2903-2915, 1993.

Assays for stem cell survival and differentiation (which will identify, among others, proteins that regulate lympho-hematopoiesis) include, without limitation, those described in: Methylcellulose colony forming assays, Freshney, M.G. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss, Inc., New York, NY. 1994; Hirayama et al., Proc. Natl. Acad. Sci. USA 89:5907-5911, 1992; Primitive hematopoietic colony forming ceUs with high proliferative potential, McNiece, I.K. and Briddell, R.A. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 23-39, Wiley-Liss, Inc., New York, NY. 1994; Neben et al., Experimental Hematology 22:353-359, 1994; Cobblestone area forming cell assay, Ploemacher, R.E. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 1-21, Wiley-Liss, Inc., New York, NY. 1994; Long term bone marrow cultures in the presence of stromal cells, Spooncer, E., Dexter, M. and Allen, T. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 163-179, Wiley-Liss, Inc., New York, NY. 1994; Long term culture initiating cell assay, Sutherland, H.J. In Culture of Hematopoietic Cells. R.I. Freshney, et al. eds. Vol pp. 139-162, Wiley-Liss, Inc., New York, NY. 1994.

Tissue Growth Activity

A protein of the present invention also may have utility in compositions used for bone, cartilage, tendon, Ugament and /or nerve tissue growth or regeneration, as well as for wound healing and tissue repair and replacement, and in the treatment of burns, incisions and ulcers.

A protein of the present invention, which induces cartilage and/or bone growth in circumstances where bone is not normally formed, has application in the healing of bone fractures and cartilage damage or defects in humans and other animals. Such a preparation employing a protein of the invention may have prophylactic use in closed as well as open fracture reduction and also in the improved fixation of artificial joints. De novo bone formation induced by an osteogenic agent contributes to the repair of congenital, trauma induced, or oncologic resection induced craniofacial defects, and also is useful in cosmetic plastic surgery.

A protein of this invention may also be used in the treatment of periodontal disease, and in other tooth repair processes. Such agents may provide an environment to attract bone-forming cells, stimulate growth of bone-forming cells or induce differentiation of progenitors of bone-forming cells. A protein of the invention may also be useful in the treatment of osteoporosis or osteoarthritis, such as through stimulation of bone and /or cartilage repair or by blocking inflammation or processes of tissue destruction (collagenase activity, osteoclast activity, etc.) mediated by inflammatory processes. Another category of tissue regeneration activity that may be attributable to the protein of the present invention is tendon /ligament formation. A protein of the present invention, which induces tendon/ligament-like tissue or other tissue formation in circumstances where such tissue is not normaUy formed, has appUcation in the healing of tendon or Ugament tears, deformities and other tendon or Ugament defects in humans and other animals. Such a preparation employing a tendon/Ugament-like tissue inducing protein may have prophylactic use in preventing damage to tendon or Ugament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or Ugament tissue. De novo tendon/ligament-like tissue formation induced by a composition of the present invention contributes to the repair of congenital, trauma induced, or other tendon or Ugament defeds of other origin, and is also useful in cosmetic plastic surgery for attachment or repair of tendons or Ugaments. The compositions of the present invention may provide an environment to attract tendon- or ligament-forming cells, stimulate growth of tendon- or ligament-forming ceUs, induce differentiation of progenitors of tendon- or ligament-forming ceUs, or induce growth of tendon/Ugament ceUs or progenitors ex vivo for return in vivo to effect tissue repair. The compositions of the invention may also be useful in the treatment of tendinitis, carpal tunnel syndrome and other tendon or ligament defects. The compositions may also indude an appropriate matrix and /or sequestering agent as a carrier as is well known in the art. The protein of the present invention may also be useful for proliferation of neural ceUs and for regeneration of nerve and brain tissue, i.e. for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders, which involve degeneration, death or trauma to neural cells or nerve tissue. More specifically, a protein may be used in the treatment of diseases of the peripheral nervous system, such as peripheral nerve injuries, peripheral neuropathy and locahzed neuropathies, and central nervous system diseases, such as Alzheimer's, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome. Further conditions which may be treated in accordance with the present invention include mechanical and traumatic disorders, such as spinal cord disorders, head trauma and cerebrovascular diseases such as stroke. Peripheral neuropathies resulting from chemotherapy or other medical therapies may also be treatable using a protein of the invention.

Proteins of the invention may also be useful to promote better or faster closure of non-healing wounds, including without limitation pressure ulcers, ulcers associated with vascular insufficiency, surgical and traumatic wounds, and the like.

It is expected that a protein of the present invention may also exhibit activity for generation or regeneration of other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue, or for promoting the growth of cells comprising such tissues. Part of the desired effects may be by inhibition or modulation of fibrotic scarring to allow normal tissue to regenerate. A protein of the invention may also exhibit angiogenic activity.

A protein of the present invention may also be useful for gut protection or regeneration and treatment of lung or Uver fibrosis, reperfusion injury in various tissues, and conditions resulting from systemic cytokine damage.

A protein of the present invention may also be useful for promoting or inhibiting differentiation of tissues described above from precursor tissues or ceUs; or for inhibiting the growth of tissues described above. The activity of a protein of the invention may, among other means, be measured by the following methods:

Assays for tissue generation activity include, without limitation, those described in: International Patent PubUcation No. WO95/16035 (bone, cartilage, tendon); International Patent PubUcation No. W095/ 05846 (nerve, neuronal); International Patent Publication No. W091 /07491 (skin, endothelium ).

Assays for wound healing activity include, without Umitation, those described in: Winter, Epidermal Wound Healing, pps. 71-112 (Maibach, HI and Rovee, DT, eds.), Year Book Medical Publishers, Inc., Chicago, as modified by Eaglstein and Mertz, J. Invest. Dermatol 71:382-84 (1978).

Activin/Inhibin Activity

A protein of the present invention may also exhibit activin- or inhibin-related activities. Inhibins are characterized by their ability to inhibit the release of follicle stimulating hormone (FSH), while activins and are characterized by their ability to stimulate the release of follicle stimulating hormone (FSH). Thus, a protein of the present invention, alone or in heterodimers with a member of the inhibin family, may be useful as a contraceptive based on the ability of inhibins to decrease fertility in female mammals and decrease spermatogenesis in male mammals. Administration of sufficient amounts of other inhibins can induce infertility in these mammals. Alternatively, the protein of the invention, as a homodimer or as a heterodimer with other protein subunits of the inhibin- group, may be useful as a fertility inducing therapeutic, based upon the ability of activin molecules in stimulating FSH release from cells of the anterior pituitary. See, for example, United States Patent 4,798,885. A protein of the invention may also be useful for advancement of the onset of fertility in sexually immature mammals, so as to increase the lifetime reproductive performance of domestic animals such as cows, sheep and pigs.

The activity of a protein of the invention may, among other means, be measured by the following methods: Assays for activin /inhibin activity include, without Umitation, those described in: Vale et al ,. Endocrinology 91:562-572, 1972; Ling et al., Nature 321:779-782, 1986; Vale et al., Nature 321:776-779, 1986; Mason et al., Nature 318:659-663, 1985; Forage et al., Proc. Natl. Acad. Sci. USA 83:3091-3095, 1986.

Chemotactic /Chemokinetic Activity

A protein of the present invention may have chemotactic or chemokinetic activity (e.g., act as a chemokine) for mammalian ceUs, including, for example, monocytes, fibroblasts, neutrophils, T-cells, mast ceUs, eosinophils, epitheUal and/or endothelial cells. Chemotactic and chemokinetic proteins can be used to mobdize or attract a desired cell population to a desired site of action. Chemotactic or chemokinetic proteins provide particular advantages in treatment of wounds and other trauma to tissues, as well as in treatment of locahzed infections. For example, attraction of lymphocytes, monocytes or neutrophils to tumors or sites of infection may result in improved immune responses against the tumor or infecting agent. A protein or peptide has chemotactic activity for a particular cell population if it can stimulate, directly or indiredly, the directed orientation or movement of such cell population. Preferably, the protein or peptide has the ability to directly stimulate directed movement of cells. Whether a particular protein has chemotactic activity for a population of ceUs can be readdy determined by employing such protein or peptide in any known assay for cell chemotaxis.

Assays for chemotactic activity (which will identify proteins that induce or prevent chemotaxis) consist of assays that measure the ability of a protein to induce the migration of cells across a membrane as weU as the ability of a protein to induce the adhesion of one cell population to another ceU population. Suitable assays for movement and adhesion include, without Umitation, those described in: Current Protocols in Immunology, Ed by J.E. Coligan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W.Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 6J2, Measurement of alpha and beta Chemokines 6J2J-6J2.28; Taub et al. j. Clin. Invest. 95:1370-1376, 1995; Lind et al. APMIS 103:140-146, 1995; Muller et al Eur. j. Immunol. 25: 1744-1748; Gruber et al. j. of Immunol. 152:5860-5867, 1994; Johnston et al. J. of Immunol. 153: 1762-1768, 1994.

Hemostatic and Thrombolytic Activity

A protein of the invention may also exhibit hemostatic or thrombolytic activity. As a result, such a protein is expected to be useful in treatment of various coagulation disorders (including hereditary disorders, such as hemophiUas) or to enhance coagulation and other hemostatic events in treating wounds resulting from trauma, surgery or other causes. A protein of the mvention may also be useful for dissolving or inhibiting formation of thromboses and for treatment and prevention of conditions resulting therefrom (such as, for example, infarction of cardiac and central nervous system vessels (e.g., stroke). The activity of a protein of the invention may, among other means, be measured by the following methods:

Assay for hemostatic and thrombolytic activity include, without limitation, those described in: Linet et al., J. Clin. Pharmacol. 26:131-140, 1986; Burdick et al., Thrombosis Res. 45:413-419, 1987; Humphrey et al., Fibrinolysis 5:71-79 (1991); Schaub, Prostaglandins 35:467-474, 1988.

Receptor /Ligand Activity

A protein of the present invention may also demonstrate activity as receptors, receptor ligands or inhibitors or agonists of receptor/ligand interactions. Examples of such receptors and ligands include, without limitation, cytokine receptors and their ligands, receptor kinases and their Ugands, receptor phosphatases and their ligands, receptors involved in cell-cell interactions and their Ugands (including without Umitation, ceUular adhesion molecules (such as selectins, integrins and their ligands) and receptor/ligand pairs involved in antigen presentation, antigen recognition and development of ceUular and humoral immune responses). Receptors and Ugands are also useful for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction. A protein of the present invention (including, without limitation, fragments of receptors and ligands) may themselves be useful as inhibitors of receptor/ligand interactions.

Suitable assays for receptor-Ugand activity include without limitation those described in:Current Protocols in Immunology, Ed by J.E. CoUgan, A.M. Kruisbeek, D.H. Margulies, E.M. Shevach, W.Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 7.28, Measurement of Cellular Adhesion under static conditions 7.28.1-7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84:6864-6868, 1987; Bierer et al., J. Exp. Med. 168:1145-1156, 1988; Rosenstein et al., J. Exp. Med. 169:149-160 1989; Stoltenborg et al., J. Immunol. Methods 175:59-68, 1994; Stitt et al., CeU 80:661-670, 1995.

Anti-Inflammatory Activity

Proteins of the present invention may also exhibit anti-inflammatory activity. The anti-inflammatory activity may be achieved by providing a stimulus to cells involved in the inflammatory response, by inhibiting or promoting cell-cell interactions (such as, for example, cell adhesion), by inhibiting or promoting chemotaxis of cells involved in the inflammatory process, inhibiting or promoting ceU extravasation, or by stimulating or suppressing production of other factors which more directly inhibit or promote an inflammatory response. Proteins exhibiting such activities can be used to treat inflammatory conditions including chronic or acute conditions), including without limitation inflammation assodated with infection (such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or resulting from over production of cytokines such as TNF or IL-1. Proteins of the invention may also be useful to treat anaphylaxis and hypersensitivity to an antigenic substance or material.

Cadherin /Tumor Invasion Suppressor Activity Cadherins are calcium-dependent adhesion molecules that appear to play major roles during development, particularly in defining specific cell types. Loss or alteration of normal cadherin expression can lead to changes in cell adhesion properties linked to tumor growth and metastasis. Cadherin malfunction is also implicated in other human diseases, such as pemphigus vulgaris and pemphigus fohaceus (auto-immune blistering skin diseases), Crohn's disease, and some developmental abnormaUties.

The cadherin superfamily includes well over forty members, each with a distinct pattern of expression. All members of the superfamily have in common conserved extraceUular repeats (cadherin domains), but structural differences are found in other parts of the molecule. The cadherin domains bind calcium to form their tertiary structure and thus calcium is required to mediate their adhesion. Only a few amino adds in the first cadherin domain provide the basis for homophilic adhesion; modification of this recognition site can change the specificity of a cadherin so that instead of recognizing only itself, the mutant molecule can now also bind to a different cadherin. In addition, some cadherins engage in heterophilic adhesion with other cadherins. E-cadherin, one member of the cadherin superfamily, is expressed in epithelial cell types. Pathologically, if E-cadherin expression is lost in a tumor, the maUgnant ceUs become invasive and the cancer metastasizes. Transfection of cancer ceU lines with polynucleotides expressing E-cadherin has reversed cancer-associated changes by returning altered ceU shapes to normal, restoring ceUs' adhesiveness to each other and to their substrate, decreasing the ceU growth rate, and drastically reducing anchorage-independent cell growth. Thus, reintroducing E-cadherin expression reverts carcinomas to a less advanced stage. It is likely that other cadherins have the same invasion suppressor role in carcinomas derived from other tissue types. Therefore, proteins of the present invention with cadherin activity, and polynucleotides of the present invention encoding such proteins, can be used to treat cancer. Introducing such proteins or polynucleotides into cancer cells can reduce or eliminate the cancerous changes observed in these cells by providing normal cadherin expression.

Cancer ceUs have also been shown to express cadherins of a different tissue type than their origin, thus allowing these cells to invade and metastasize in a different tissue in the body. Proteins of the present invention with cadherin activity, and polynucleotides of the present invention encoding such proteins, can be substituted in these cells for the inappropriately expressed cadherins, restoring normal cell adhesive properties and reducing or eliminating the tendency of the cells to metastasize. AdditionaUy, proteins of the present invention with cadherin activity, and polynucleotides of the present invention encoding such proteins, can used to generate antibodies recognizing and binding to cadherins. Such antibodies can be used to block the adhesion of inappropriately expressed tumor-ceU cadherins, preventing the ceUs from forming a tumor elsewhere. Such an anti-cadherin antibody can also be used as a marker for the grade, pathological type, and prognosis of a cancer, i.e. the more progressed the cancer, the less cadherin expression there will be, and this decrease in cadherin expression can be detected by the use of a cadherin-binding antibody.

Fragments of proteins of the present invention with cadherin activity, preferably a polypeptide comprising a decapeptide of the cadherin recognition site, and poly-nucleotides of the present invention encoding such protein fragments, can also be used to block cadherin function by binding to cadherins and preventing them from binding in ways that produce undesirable effects. Additionally, fragments of proteins of the present invention with cadherin activity, preferably truncated soluble cadherin fragments which have been found to be stable in the circulation of cancer patients, and polynucleotides encoding such protein fragments, can be used to disturb proper cell-cell adhesion.

Assays for cadherin adhesive and invasive suppressor activity include, without Umitation, those described in: Hortsch et al. J Biol Chem 270 (32): 18809-18817, 1995; Miyaki et al. Oncogene 11: 2547-2552, 1995; Ozawa et al. Cell 63: 1033-1038, 1990.

Tumor Inhibition Activity

In addition to the activities described above for immunological treatment or prevention of tumors, a protein of the invention may exhibit other anti-tumor activities. A protein may inhibit tumor growth directly or indirectly (such as, for example, via antibody-dependent ceU-mediated cytotoxidty (ADCQ). A protein may exhibit its tumor inhibitory activity by acting on tumor tissue or tumor precursor tissue, by inhibiting formation of tissues necessary to support tumor growth (such as, for example, by inhibiting angiogenesis), by causing production of other factors, agents or cell types which inhibit tumor growth, or by suppressing, eliminating or inhibiting factors, agents or cell types which promote tumor growth.

Other Activities

A protein of the invention may also exhibit one or more of the following additional activities or effects: inhibiting the growth, infection or function of, or killing, infectious agents, including, without limitation, bacteria, viruses, fungi and other parasites; effecting (suppressing or enhancing) bodily characteristics, including, without limitation, height, weight, hair color, eye color, skin, fat to lean ratio or other tissue pigmentation, or organ or body part size or shape (such as, for example, breast augmentation or diminution, change in bone form or shape); effecting biorhythms or caricadic cycles or rhythms; effecting the fertility of male or female subjects; effecting the metabolism, catabolism, anabohsm, processing, utilization, storage or elimination of dietary fat, Upid, protein, carbohydrate, vitamins, minerals, cofactors or other nutritional factors or component(s); effecting behavioral characteristics, induding, without limitation, appetite, libido, stress, cognition (including cognitive disorders), depression (including depressive disorders) and violent behaviors; providing analgesic effects or other pain reducing effects; promoting differentiation and growth of embryonic stem ceUs in lineages other than hematopoietic lineages; hormonal or endocrine activity; in the case of enzymes, conecting deficiendes of the enzyme and treating deficiency-related diseases; treatment of hyperproliferative disorders (such as, for example, psoriasis); immunoglobulin-like activity (such as, for example, the ability to bind antigens or complement); and the ability to act as an antigen in a vaccine composition to raise an immune response against such protein or another material or entity which is cross-reactive with such protein.

ADMINISTRATION AND DOSING

A protein of the present invention (from whatever source derived, including without limitation from recombinant and non-recombinant sources) may be used in a pharmaceutical composition when combined with a pharmaceuticaUy acceptable carrier. Such a composition may also contain (in addition to protein and a carrier) diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. The term "pharmaceutically acceptable" means a non-toxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s). The characteristics of the carrier will depend on the route of administration. The pharmaceutical composition of the invention may also contain cytokines, lymphokines, or other hematopoietic factors such as M-CSF, GM-CSF, TNF, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IFN, TNFO, TNF1, TNF2, G-CSF, Meg-CSF, thrombopoietin, stem cell factor, and erythropoietin. The pharmaceutical composition may further contain other agents which either enhance the activity of the protein or compliment its activity or use in treatment. Such additional factors and /or agents may be included in the pharmaceutical composition to produce a synergistic effect with protein of the invention, or to minimize side effects. Conversely, protein of the present invention may be included in formulations of the particular cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent to minimize side effects of the cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent.

A protein of the present invention may be active in multimers (e.g., heterodimers or homodimers) or complexes with itself or other proteins. As a result, pharmaceutical compositions of the invention may comprise a protein of the invention in such multimeric or complexed form.

The pharmaceutical composition of the invention may be in the form of a complex of the protein(s) of present invention along with protein or peptide antigens. The protein and /or peptide antigen will deliver a stimulatory signal to both B and T lymphocytes. B lymphocytes will respond to antigen through their surface immunoglobulin receptor. T lymphocytes will respond to antigen through the T cell receptor (TCR) following presentation of the antigen by MHC proteins. MHC and structurally related proteins including those encoded by class I and class II MHC genes on host cells will serve to present the peptide antigen(s) to T lymphocytes. The antigen components could also be supplied as purified MHC-peptide complexes alone or with co-stimulatory molecules that can directly signal T cells. Alternatively antibodies able to bind surface immunolgobulin and other molecules on B ceUs as weU as antibodies able to bind the TCR and other molecules on T cells can be combined with the pharmaceutical composition of the invention. The pharmaceutical composition of the invention may be in the form of a liposome in which protein of the present invention is combined, in addition to other pharmaceutically acceptable carriers, with amphipathic agents such as lipids which exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution. Suitable Upids for Uposomal formulation include, without Umitation, monoglycerides, diglycerides, sulfatides, lysoledthin, phospholipids, saponin, bile acids, and the like. Preparation of such Uposomal formulations is within the level of skill in the art, as disclosed, for example, in U.S. Patent No. 4,235,871; U.S. Patent No. 4,501,728; U.S. Patent No. 4,837,028; and U.S. Patent No. 4,737,323, all of which are incorporated herein by reference.

As used herein, the term "therapeuticaUy effective amount" means the total amount of each active component of the pharmaceutical composition or method that is sufficient to show a meaningful patient benefit, i.e., treatment, healing, prevention or ameUoration of the relevant medical condition, or an increase in rate of treatment, healing, prevention or amelioration of such conditions. When applied to an individual active ingredient, administered alone, the term refers to that ingredient alone. When applied to a combination, the term refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, seriaUy or simultaneously.

In practicing the method of treatment or use of the present invention, a therapeutically effective amount of protein of the present invention is administered to a mammal having a condition to be treated. Protein of the present invention may be administered in accordance with the method of the invention either alone or in combination with other therapies such as treatments employing cytokines, lymphokines or other hematopoietic factors. When co-administered with one or more cytokines, lymphokines or other hematopoietic factors, protein of the present invention may be administered either simultaneously with the cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or sequentially. If administered sequentially, the attending physician will decide on the appropriate sequence of administering protein of the present invention in combination with cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors.

Administration of protein of the present invention used in the pharmaceutical composition or to practice the method of the present invention can be carried out in a variety of conventional ways, such as oral ingestion, inhalation, topical application or cutaneous, subcutaneous, intraperitoneal, parenteral or intravenous injection. Intravenous administration to the patient is preferred.

When a therapeutically effective amount of protein of the present invention is administered orally, protein of the present invention will be in the form of a tablet, capsule, powder, solution or eUxir. When administered in tablet form, the pharmaceutical composition of the invention may additionaUy contain a solid carrier such as a gelatin or an adjuvant. The tablet, capsule, and powder contain from about 5 to 95% protein of the present invention, and preferably from about 25 to 90% protein of the present invention. When administered in Uquid form, a Uquid carrier such as water, petroleum, oils of animal or plant origin such as peanut oil, mineral oil, soybean oil, or sesame oil, or synthetic oils may be added. The liquid form of the pharmaceutical composition may further contain physiological saline solution, dextrose or other saccharide solution, or glycols such as ethylene glycol, propylene glycol or polyethylene glycol. When administered in liquid form, the pharmaceutical composition contains from about 0.5 to 90% by weight of protein of the present invention, and preferably from about 1 to 50% protein of the present invention.

When a therapeutically effective amount of protein of the present invention is administered by intravenous, cutaneous or subcutaneous injection, protein of the present invention will be in the form of a pyrogen-free, parenterally acceptable aqueous solution. The preparation of such parenterally acceptable protein solutions, having due regard to pH, isotonicity, stability, and the like, is within the skill in the art. A preferred pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection should contain, in addition to protein of the present invention, an isotonic vehicle such as Sodium Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, Lactated Ringer's Injection, or other vehicle as known in the art. The pharmaceutical composition of the present invention may also contain stabilizers, preservatives, buffers, antioxidants, or other additives known to those of skill in the art.

The amount of protein of the present invention in the pharmaceutical composition of the present invention will depend upon the nature and severity of the condition being treated, and on the nature of prior treatments which the patient has undergone. Ultimately, the attending physician will decide the amount of protein of the present invention with which to treat each individual patient. Initially, the attending physician will administer low doses of protein of the present invention and observe the patient's response. Larger doses of protein of the present invention may be administered until the optimal therapeutic effect is obtained for the patient, and at that point the dosage is not increased further. It is contemplated that the various pharmaceutical compositions used to practice the method of the present invention should contain about 0.01 g to about 100 mg (preferably about OJng to about 10 mg, more preferably about 0J g to about 1 mg) of protein of the present invention per kg body weight. The duration of intravenous therapy using the pharmaceutical composition of the present invention will vary, depending on the severity of the disease being treated and the condition and potential idiosyncratic response of each individual patient. It is contemplated that the duration of each appUcation of the protein of the present invention will be in the range of 12 to 24 hours of continuous intravenous administration. Ultimately the attending physidan will dedde on the appropriate duration of intravenous therapy using the pharmaceutical composition of the present invention.

Protein of the invention may also be used to immunize animals to obtain polyclonal and monoclonal antibodies which specifically react with the protein. Such antibodies may be obtained using either the entire protein or fragments thereof as an immunogen. The peptide immunogens additionally may contain a cysteine residue at the carboxyl terminus, and are conjugated to a hapten such as keyhole limpet hemocyanin (KLH). Methods for synthesizing such peptides are known in the art, for example, as in R.P. Merrifield, J. Amer.Chem.Soc. 85, 2149-2154 (1963); J.L. Krstenansky, et al, FEBS Lett. 211, 10 (1987). Monoclonal antibodies binding to the protein of the invention may be useful diagnostic agents for the immunodetection of the protein. Neutralizing monoclonal antibodies binding to the protein may also be useful therapeutics for both conditions associated with the protein and also in the treatment of some forms of cancer where abnormal expression of the protein is involved. In the case of cancerous cells or leukemic cells, neutralizing monoclonal antibodies against the protein may be useful in detecting and preventing the metastatic spread of the cancerous cells, which may be mediated by the protein.

For compositions of the present invention which are useful for bone, cartilage, tendon or Ugament regeneration, the therapeutic method includes adrriinistering the composition topically, systematically, or locally as an implant or device. When administered, the therapeutic composition for use in this invention is, of course, in a pyrogen-free, physiologically acceptable form. Further, the composition may desirably be encapsulated or injected in a viscous form for delivery to the site of bone, cartilage or tissue damage. Topical administration may be suitable for wound healing and tissue repair. TherapeuticaUy useful agents other than a protein of the invention which may also optionally be included in the composition as described above, may alternatively or additionaUy, be administered simultaneously or sequentially with the composition in the methods of the invention. Preferably for bone and /or cartilage formation, the composition would include a matrix capable of delivering the protein-containing composition to the site of bone and/or cartilage damage, providing a structure for the developing bone and cartilage and optimally capable of being resorbed into the body. Such matrices may be formed of materials presently in use for other implanted medical applications. The choice of matrix material is based on biocompatibility, biodegradability, mechanical properties, cosmetic appearance and interface properties. The particular application of the compositions will define the appropriate formulation. Potential matrices for the compositions may be biodegradable and chemically defined calcium sulfate, tricalciumphosphate, hydroxyapatite, polylactic acid, polyglycolic acid and polyanhydrides. Other potential materials are biodegradable and biologically well-defined, such as bone or dermal collagen. Further matrices are comprised of pure proteins or extracellular matrix components. Other potential matrices are nonbiodegradable and chemically defined, such as sintered hydroxapatite, bioglass, aluminates, or other ceramics. Matrices may be comprised of combinations of any of the above mentioned types of material, such as polylactic acid and hydroxyapatite or coUagen and tricalciumphosphate. The bioceramics may be altered in composition, such as in calcium-aluminate-phosphate and processing to alter pore size, particle size, particle shape, and biodegradability.

Presently preferred is a 50:50 (mole weight) copolymer of lactic acid and glycolic acid in the form of porous particles having diameters ranging from 150 to 800 microns. In some applications, it will be useful to utilize a sequestering agent, such as carboxymethyl cellulose or autologous blood clot, to prevent the protein compositions from disassociating from the matrix.

A preferred family of sequestering agents is cellulosic materials such as alkylcelluloses (including hydroxyalkylcelluloses), including methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl-methylcellulose, and carboxymethylceUulose, the most preferred being cationic salts of carboxymethylcellulose (CMC). Other preferred sequestering agents include hyaluronic acid, sodium alginate, poly(ethylene glycol), polyoxyethylene oxide, carboxyvinyl polymer and poly(vinyl alcohol). The amount of sequestering agent useful herein is 0.5-20 wt%, preferably 1-10 wt% based on total formulation weight, which represents the amount necessary to prevent desorbtion of the protein from the polymer matrix and to provide appropriate handling of the composition, yet not so much that the progenitor ceUs are prevented from infiltrating the matrix, thereby providing the protein the opportunity to assist the osteogenic activity of the progenitor cells.

In further compositions, proteins of the invention may be combined with other agents beneficial to the treatment of the bone and /or cartilage defect, wound, or tissue in question. These agents include various growth factors such as epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factors (TGF- and TGF-), and insulin-like growth factor (IGF).

The therapeutic compositions are also presently valuable for veterinary applications. Particularly domestic animals and thoroughbred horses, in addition to humans, are desired patients for such treatment with proteins of the present invention. The dosage regimen of a protein-containing pharmaceutical composition to be used in tissue regeneration will be determined by the attending physician considering various factors which modify the action of the proteins, e.g., amount of tissue weight desired to be formed, the site of damage, the condition of the damaged tissue, the size of a wound, type of damaged tissue (e.g., bone), the patient's age, sex, and diet, the severity of any infection, time of administration and other clinical factors. The dosage may vary with the type of matrix used in the reconstitution and with inclusion of other proteins in the pharmaceutical composition. For example, the addition of other known growth factors, such as IGF I (insulin like growth factor I), to the final composition, may also effect the dosage. Progress can be monitored by periodic assessment of tissue/bone growth and /or repair, for example, X-rays, histomorphomefric determinations and tetracycline labeling.

Polynucleotides of the present invention can also be used for gene therapy. Such polynucleotides can be introduced either in vivo or ex vivo into cells for expression in a mammaUan subject. Polynucleotides of the invention may also be administered by other known methods for introduction of nucleic acid into a cell or organism (including, without limitation, in the form of viral vectors or naked DNA).

Cells may also be cultured ex vivo in the presence of proteins of the present invention in order to prohferate or to produce a desired effect on or activity in such cells. Treated cells can then be introduced in vivo for therapeutic purposes.

Patent and Uterature references dted herein are incorporated by reference as if fully set forth.

Claims

What is claimed is:

1. An isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NOJ;

(b) a polynudeotide comprising the nudeotide sequence of SEQ ID NOJ from nucleotide 19 to nucleotide 561;

(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AK296_li deposited under accession number ATCC 98026;

(e) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:2;

(f) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:2; and

(g) a polynucleotide which is an alleUc variant of a polynucleotide of (a)-(f) above.

2. A composition comprising the protein of claim 1 and a pharmaceutically acceptable carrier.

3. A protein 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 from amino acid 3 to amino acid 181;

(d) the amino acid sequence encoded by the cDNA insert of clone AK296_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins.

4. The protein of claim 3, wherein said protein comprises the amino acid sequence of SEQ ID NO:2.

5. The protein of claim 3, wherein said protein comprises a fragment of the amino acid sequence of SEQ ID NO:2, the fragment comprising eight consecutive amino acids of SEQ ID NO:2.

6. The protein of claim 3, wherein said protein comprises the amino acid sequence of SEQ ID NO:2 from amino acid 3 to amino acid 181.

7. A composition comprising the protein of claim 3 and a pharmaceutically acceptable carrier.

8. An isolated protein encoded by a polynucleotide selected from the group consisting of:

(a) a polynudeotide comprising the nudeotide sequence of SEQ ID NO:21;

(b) a polynudeotide comprising the nudeotide sequence of SEQ ID NO:21 from nucleotide 65 to nucleotide 490;

(c) a polynudeotide comprising the nudeotide sequence of SEQ ID NO:21 from nucleotide 137 to nucleotide 490;

(d) a polynucleotide comprising the nucleotide sequence of the fuU- length protein coding sequence of clone AS34_li deposited under accession number ATCC 98026;

(e) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AS34_li deposited under accession number ATCC 98026;

(f) a polynucleotide comprising the nucleotide sequence of a mature protein coding sequence of clone AS34_li deposited under accession number ATCC 98026;

(g) a polynucleotide encoding a mature protein encoded by the cDNA insert of clone AS34_li deposited under accession number ATCC 98026;

(h) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:22; (i) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:22 having biological activity, the fragment comprising eight consecutive amino acids of SEQ ID NO:22; and

(j) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(g) above.

9. A protein comprising an amino acid sequence selected from the group consisting of:

(a) the amino acid sequence of SEQ ID NO:22;

(c) the amino acid sequence encoded by the cDNA insert of clone AS34_li deposited under accession number ATCC 98026; the protein being substantially free from other mammalian proteins.