Secreted proteins and polynucleotides encoding them

Novel polynucleotides and the proteins encoded thereby are disclosed.

DETAILED DESCRIPTION 
Isolated Proteins and Polynucleotides 
Nucleotide and amino acid sequences are reported below for each clone and 
protein disclosed in the present application. In some instances the 
sequences are preliminary and may include some incorrect or ambiguous 
bases or amino acids. The actual nucleotide sequence of each clone can 
readily be determined by sequencing of the deposited clone in accordance 
with known methods. The predicted amino acid sequence (both full length 
and mature) 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. Because of the partial 
ambiguity in reported sequence information, reported protein sequences 
include "Xaa" designators. These "Xaa" designators indicate either (1) a 
residue which cannot be identified because of nucleotide sequence 
ambiguity or (2) a stop codon in the determined nucleotide sequence where 
applicants believe one should not exist (if the nucleotide sequence were 
determined more accurately). 
As used herein a "secreted" protein is one which, when expressed in a 
suitable host cell, is transported across or through a membrane, including 
transport as a result of signal sequences in its amino acid sequence. 
"Secreted" proteins include without limitation proteins secreted wholly 
(e.g., soluble proteins) or partially (e.g., receptors) from the cell in 
which they are expressed. "Secreted" proteins also include without 
limitation proteins which are transported across the membrane of the 
endoplasmic reticulum. 
Clone "AJ26 3" 
A polynucleotide of the present invention has been identified as clone 
"AJ26.sub.-- 3". AJ26.sub.-- 3 was isolated from a human adult testes cDNA 
library using methods which are selective for cDNAs encoding secreted 
proteins. AJ26.sub.-- 3 is a full-length clone, including the entire 
coding sequence of a secreted protein (also referred to herein as 
"AJ26.sub.-- 3 protein"). 
The nucleotide sequence of the 5' portion of AJ26.sub.-- 3 as presently 
determined is reported in SEQ ID NO1. What applicants presently believe is 
the proper reading frame for the coding region is indicated in SEQ ID 
NO:2. The predicted acid sequence of the AJ26.sub.-- 3 protein 
corresponding to the foregoing nucleotide sequence is reported in SEQ ID 
NO:2. Additional nucleotide sequence from the 3' portion of AJ26.sub.-- 3, 
including the polyA tail, is reported in SEQ ID NO:3. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone AJ26.sub.-- 3 should be approximately 2320 bp. 
The nucleotide sequence disclosed herein for AJ26.sub.-- 3 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. AJ26.sub.-- 3 demonstrated at least some homology with Xenopus 
CTX protein (U43394, J01917, BlastX). Based upon homology, AJ26.sub.-- 3 
proteins and each homologous protein or peptide may share at least some 
activity. 
Clone "BL89 10" 
A polynucleotide of the present invention has been identified as clone 
"BL89.sub.-- 10". BL89.sub.-- 10 was isolated from a human adult testes 
cDNA library using methods which are selective for cDNAs encoding secreted 
proteins. BL89.sub.-- 10 is a full-length clone, including the entire 
coding sequence of a secreted protein (also referred to herein as 
"BL89.sub.-- 10 protein"). 
The nucleotide sequence of the 5' portion of BL89.sub.-- 10 as presently 
determined is reported in SEQ ID NO:4. An additional internal nucleotide 
sequence from BL89.sub.-- 10 as presently determined is reported in SEQ ID 
NO:5. What applicants believe is the proper reading frame and the 
predicted amino acid sequence encoded by such internal sequence is 
reported in SEQ ID NO:6. Additional nucleotide sequence from the 3' 
portion of BL89.sub.-- 10, including the polyA tail, is reported in SEQ ID 
NO:7. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone BL89.sub.-- 10 should be approximately 3290 bp. 
The nucleotide sequence disclosed herein for BL89.sub.-- 10 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. No hits were found in the database. 
Clone "BV239 2" 
A polynucleotide of the present invention has been identified as clone 
"BV239.sub.-- 2". BV239.sub.-- 2 was isolated from a human adult brain 
cDNA library using methods which are selective for cDNAs encoding secreted 
proteins. BV239.sub.-- 2 is a full-length clone, including the entire 
coding sequence of a secreted protein (also referred to herein as 
"BV239.sub.-- 2 protein"). 
The nucleotide sequence of BV239.sub.-- 2 as presently determined is 
reported in SEQ ID NO:8. What applicants presently believe to be the 
proper reading frame and the predicted amino acid sequence of the 
BV239.sub.-- 2 protein corresponding to the foregoing nucleotide sequence 
is reported in SEQ ID NO:9. 
The EcoRInotI restriction fragment obtainable from the deposit containing 
clone BV239.sub.-- 2 should be approximately 300 bp. 
The nucleotide sequence disclosed herein for BV239.sub.-- 2 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. No hits were found in the database. 
Clone "BL341 4" 
A polynucleotide of the present invention has been identified as clone 
"BL341.sub.-- 4". BL341.sub.-- 4 was isolated from a human adult testes 
cDNA library using methods which are selective for cDNAs encoding secreted 
proteins. BL341.sub.-- 4 is a full-length clone, including the entire 
coding sequence of a secreted protein (also referred to herein as 
"BL341.sub.-- 4 protein"). 
The partial nucleotide sequence of BL341.sub.-- 4, including its 3' end and 
any identified polA tail, as presently determined is reported in SEQ ID 
NO:11. What applicants presently believe is the proper reading frame for 
the coding region is indicated in SEQ ID NO:12. The predicted acid 
sequence of the BL341.sub.-- 4 protein corresponding to the foregoing 
nucleotide sequence is reported in SEQ ID NO:12. Additional nucleotide 
sequence from the 5' portion of BL341.sub.-- 4 is reported in SEQ ID 
NO:10. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone BL341.sub.-- 4 should be approximately 600 bp. 
The nucleotide sequence disclosed herein for BL341.sub.-- 4 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. No hits were found in the database. 
Clone "CC25 16" 
A polynucleotide of the present invention has been identified as clone 
"CC25.sub.-- 16". CC25.sub.-- 16 was isolated from a human adult brain 
cDNA library using methods which are selective for cDNAs encoding secreted 
proteins. CC25.sub.-- 16 is a full-length clone, including the entire 
coding sequence of a secreted protein (also referred to herein as 
"CC25.sub.-- 16 protein"). 
The nucleotide sequence of CC25.sub.-- 16 as presently determined is 
reported in SEQ ID NO:13. What applicants presently believe to be the 
proper reading frame and the predicted amino acid sequence of the 
CC25.sub.-- 16 protein corresponding to the foregoing nucleotide sequence 
is reported in SEQ ID NO:14. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone CC25.sub.-- 16 should be approximately 280 bp. 
The nucleotide sequence disclosed herein for CC25.sub.-- 16 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. No hits were found in the database. 
Clone "CC397 11" 
A polynucleotide of the present invention has been identified as clone 
"CC397.sub.-- 11". CC397.sub.-- 11 was isolated from a human adult brain 
cDNA library using methods which are selective for cDNAs encoding secreted 
proteins. CC397.sub.-- 11 is a full-length clone, including the entire 
coding sequence of a secreted protein (also referred to herein as 
"CC397.sub.-- 11 protein"). 
The nucleotide sequence of the 5' portion of CC397.sub.-- 11 as presently 
determined is reported in SEQ ID NO:15. An additional internal nucleotide 
sequence from CC397.sub.-- 11 as presently determined is reported in SEQ 
ID NO:16. What applicants believe is the proper reading frame and the 
predicted amino acid sequence encoded by such internal sequence is 
reported in SEQ ID NO:17. Additional nucleotide sequence from the 3' 
portion of CC397.sub.-- 11, including the polyA tail, is reported in SEQ 
ID NO:18. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone CC397.sub.-- 11 should be approximately 2300 bp. 
The nucleotide sequence disclosed herein for CC397.sub.-- 11 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. No hits were found in the database. 
Clone "D305 2" 
A polynucleotide of the present invention has been identified as clone 
"D305.sub.-- 2". D305.sub.-- 2 was isolated from a human PBMC cDNA library 
using methods which are selective for cDNAs encoding secreted proteins. 
D305.sub.-- 2 is a full-length clone, including the entire coding sequence 
of a secreted protein (also referred to herein as "D305.sub.-- 2 
protein"). 
The nucleotide sequence of the 5' portion of D305.sub.-- 2 as presently 
determined is reported in SEQ ID NO:19. An additional internal nucleotide 
sequence from D305.sub.-- 2 as presently determined is reported in SEQ ID 
NO:20. What applicants believe is the proper reading frame and the 
predicted amino acid sequence encoded by such internal sequence is 
reported in SEQ ID NO:21. Amino acids 1 to 15 of SEQ ID NO:21 are a 
predicted leader/signal sequence, with the predicted mature amino acid 
sequence beginning at amino acid 16. Additional nucleotide sequence from 
the 3' portion of D305.sub.-- 2, including the polyA tail, is reported in 
SEQ ID NO:22. 
The nucleotide sequence disclosed herein for D305.sub.-- 2 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. D305.sub.-- 2 demonstrated at least some homology with an EST 
identified as "yi14g05.s1 Homo sapiens cDNA clone 139526 3'" (R68684, 
BlastN). Based upon homology, D305.sub.-- 2 proteins and each homologous 
protein or peptide may share at least some activity. 
Clone "G55 1" 
A polynucleotide of the present invention has been identified as clone 
"G55.sub.-- 1"G55.sub.-- 1 was isolated from a human PBMC cDNA library 
using methods which are selective for cDNAs encoding secreted proteins. 
G55.sub.-- 1 is a full-length clone, including the entire coding sequence 
of a secreted protein (also referred to herein as "G55.sub.-- 1 protein"). 
The nucleotide sequence of the 5' portion of G55.sub.-- 1 as presently 
determined is reported in SEQ ID NO:23. What applicants presently believe 
is the proper reading frame for the coding region is indicated in SEQ ID 
NO:24. The predicted acid sequence of the G55.sub.-- 1 protein 
corresponding to the foregoing nucleotide sequence is reported in SEQ ID 
NO:24. Amino acids 1 to 110 are the predicted leader/signal sequence, with 
the predicted mature amino acid sequence beginning at amino acid 111. 
Additional nucleotide sequence from the 3' portion of G55.sub.-- 1, 
including the polyA tail, is reported in SEQ ID NO:25. 
The nucleotide sequence disclosed herein for G55.sub.-- 1 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. G55.sub.-- 1 demonstrated at least some identity with an EST 
identified as "yp16a07.r1 Homo sapiens cDNA clone 187572 5'" (R83586, 
BlastN). Based upon identity, G55.sub.-- 1 proteins and each identical 
protein or peptide may share at least some activity. 
Clone "K39 2" 
A polynucleotide of the present invention has been identified as clone 
"K39.sub.-- 2". K39.sub.-- 2 was isolated from a murine bone marrow 
(stromal cell line FCM-4) cDNA library using methods which are selective 
for cDNAs encoding secreted proteins. K39.sub.-- 2 is a full-length clone, 
including the entire coding sequence of a secreted protein (also referred 
to herein as "K39.sub.-- 2 protein"). 
The nucleotide sequence of the 5' portion of K39.sub.-- 2 as presently 
determined is reported in SEQ ID NO:26. What applicants presently believe 
is the proper reading frame for the coding region is indicated in SEQ ID 
NO:27. The predicted acid sequence of the K39.sub.-- 2 protein 
corresponding to the foregoing nucleotide sequence is reported in SEQ ID 
NO:27. Amino acids 1 to 15 are the predicted leader/signal sequence, with 
the predicted mature amino acid sequence beginning at amino acid 16. 
Additional nucleotide sequence from the 3' portion of K39.sub.-- 2, 
including the polyA tail, is reported in SEQ ID NO:28. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone K39.sub.-- 2 should be approximately 1675 bp. 
The nucleotide sequence disclosed herein for K39.sub.-- 2 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. K39.sub.-- 2 demonstrated at least some identity with an EST 
identified as "Mouse 3'-directed cDNA MUSGS01125, clone Mc0564" (D18935, 
BlastN). Based upon identity, K39.sub.-- 2 proteins and each identical 
protein or peptide may share at least some activity. 
Clone "K330 2" 
A polynucleotide of the present invention has been identified as clone 
"K330.sub.-- 2". K330.sub.-- 2 was isolated from a murine bone marrow 
(stromal cell line FCM-4) cDNA library using methods which are selective 
for cDNAs encoding secreted proteins. K330.sub.-- 2 is a full-length 
clone, including the entire coding sequence of a secreted protein (also 
referred to herein as "K330.sub.-- 2 protein"). 
The nucleotide sequence of the 5' portion of K330.sub.-- 2 as presently 
determined is reported in SEQ ID NO:29. What applicants presently believe 
is the proper reading frame for the coding region is indicated in SEQ ID 
NO:30. The predicted acid sequence of the K330.sub.-- 2 protein 
corresponding to the foregoing nucleotide sequence is reported in SEQ ID 
NO:30. Additional nucleotide sequence from the 3' portion of K330.sub.-- 
2, including the polyA tail, is reported in SEQ ID NO:31. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone K330.sub.-- 2 should be approximately 1300 bp. 
The nucleotide sequence disclosed herein for K330.sub.-- 2 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. K330.sub.-- 2 demonstrated at least some homology with an EST 
identified as "yf82c07.s1 Homo sapiens cDNA clone 28939 3'" (R40824, 
BlastN). Based upon homology, K330.sub.-- 2 proteins and each homologous 
protein or peptide may share at least some activity. 
Clone "K363 2" 
A polynucleotide of the present invention has been identified as clone 
"K363.sub.-- 2". K363.sub.-- 2 was isolated from a murine bone marrow 
(stromal cell line FCM-4) cDNA library using methods which are selective 
for cDNAs encoding secreted proteins. K363.sub.-- 2 is a full-length 
clone, including the entire coding sequence of a secreted protein (also 
referred to herein as "K363.sub.-- 2 protein"). 
The nucleotide sequence of the 5' portion of K363.sub.-- 2 as presently 
determined is reported in SEQ ID NO:32. What applicants presently believe 
is the proper reading frame for the coding region is indicated in SEQ ID 
NO:33. The predicted acid sequence of the K363.sub.-- 2 protein 
corresponding to the foregoing nucleotide sequence is reported in SEQ ID 
NO:33. Additional nucleotide sequence from the '' portion of K363.sub.-- 
2, including the polyA tail, is reported in SEQ ID NO:34. 
The nucleotide sequence disclosed herein for K363.sub.-- 2 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. K363.sub.-- 2 demonstrated at least some homology with a 
sequence identified as "mouse embryonal carcinoma cell line DNA 67F09" 
(D21554, BlastN). Based upon homology, K363.sub.-- 2 proteins and each 
homologous protein or peptide may share at least some activity. 
Clone "K446 2" 
A polynucleotide of the present invention has been identified as clone 
"K446.sub.-- 2". K446.sub.-- 2 was isolated from a murine bone marrow 
(stromal cell line FCM-4) cDNA library using methods which are selective 
for cDNAs encoding secreted proteins. K446.sub.-- 2 is a full-length 
clone, including the entire coding sequence of a secreted protein (also 
referred to herein as "K446.sub.-- 2 protein"). 
The nucleotide sequence of the 5' portion of K446.sub.-- 2 as presently 
determined is reported in SEQ ID NO:35. What applicants presently believe 
is the proper reading frame for the coding region is indicated in SEQ ID 
NO:36. The predicted acid sequence of the K446.sub.-- 2 protein 
corresponding to the foregoing nucleotide sequence is reported in SEQ ID 
NO:36. Additional nucleotide sequence from the 3' portion of K446.sub.-- 
2, including the polyA tail, is reported in SEQ ID NO:37. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone K446.sub.-- 2 should be approximately 800 bp. 
The nucleotide sequence disclosed herein for K446.sub.-- 2 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. No hits were found in the database. 
Clone "K464 3" 
A polynucleotide of the present invention has been identified as clone 
"K464.sub.-- 3". K464.sub.-- 3 was isolated from a murine bone marrow 
(stromal cell line FCM-4) cDNA library using methods which are selective 
for cDNAs encoding secreted proteins. K464.sub.-- 3 is a full-length 
clone, including the entire coding sequence of a secreted protein (also 
referred to herein as "K464.sub.-- 3 protein"). 
The nucleotide sequence of the 5' portion of K464.sub.-- 3 as presently 
determined is reported in SEQ ID NO:38. What applicants presently believe 
is the proper reading frame for the coding region is indicated in SEQ ID 
NO:39. The predicted acid sequence of the K464.sub.-- 3 protein 
corresponding to the foregoing nucleotide sequence is reported in SEQ ID 
NO:39. Additional nucleotide sequence from the 3' portion of K464.sub.-- 
3, including the polyA tail, is reported in SEQ ID NO:40. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone K464.sub.-- 3 should be approximately 750 bp. 
The nucleotide sequence disclosed herein for K464.sub.-- 3 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. K464.sub.-- 3 demonstrated at least some homology with the 
following sequences: MHC T7 class I antigen (X16213, BlastX); murine 
cytotoxic T lymphocyte-specific serine protease (M22527, BlastN); an EST 
identified as "zc066b11.s1 Soares parathyroid tumor NbHPA Homo sapiens" 
(W32699, BlastN); and an EST identified as "mb82b10.r1 Soares mouse 
p3NMF19.5 Mus musculus cDNA clone 335899" (W36926, Fasta). Based upon 
homology, K464.sub.-- 3 proteins and each homologous protein or peptide 
may share at least some activity. 
Clone "K483 1" 
A polynucleotide of the present invention has been identified as clone 
"K483.sub.-- 1"K483.sub.-- 1 was isolated from a murine bone marrow 
(stromal cell line FCM-4) cDNA library using methods which are selective 
for cDNAs encoding secreted proteins. K483.sub.-- 1 is a full-length 
clone, including the entire coding sequence of a secreted protein (also 
referred to herein as "K483.sub.-- 1 protein"). 
The nucleotide sequence of the 5' portion of K483.sub.-- 1 as presently 
determined is reported in SEQ ID NO:41. What applicants presently believe 
is the proper reading frame for the coding region is indicated in SEQ ID 
NO:42. The predicted acid sequence of the K483.sub.-- 1 protein 
corresponding to the foregoing nucleotide sequence is reported in SEQ ID 
NO:42. Additional nucleotide sequence from the 3' portion of K483.sub.-- 
1, including the polyA tail, is reported in SEQ ID NO:43. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone K483.sub.-- 1 should be approximately 1500 bp. 
The nucleotide sequence disclosed herein for K483.sub.-- 1 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. K483.sub.-- 1 demonstrated at least some homology with an EST 
identified as "yw86b03.r1 Homo sapiens cDNA clone 259085 5'" (N41895, 
BlastN). Based upon homology, K483.sub.-- 1 proteins and each homologous 
protein or peptide may share at least some activity. 
Clone "L69 2" 
A polynucleotide of the present invention has been identified as clone 
"L69.sub.-- 2". L69.sub.-- 2 was isolated from a murine adult thymus cDNA 
library using methods which are selective for cDNAs encoding secreted 
proteins. L69.sub.-- 2 is a full-length clone, including the entire coding 
sequence of a secreted protein (also referred to herein as "L69.sub.-- 2 
protein"). 
The nucleotide sequence of the 5' portion of L69.sub.-- 2 as presently 
determined is reported in SEQ ID NO:44. What applicants presently believe 
is the proper reading frame for the coding region is indicated in SEQ ID 
NO:45. The predicted acid sequence of the L69.sub.-- 2 protein 
corresponding to the foregoing nucleotide sequence is reported in SEQ ID 
NO:45. Amino acids 1 to 19 are the predicted leader/signal sequence, with 
the predicted mature amino acid sequence beginning at amino acid 20. 
Additional nucleotide sequence from the 3' portion of L69.sub.-- 2, 
including the polyA tail, is reported in SEQ ID NO:46. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone L69.sub.-- 2 should be approximately 1200 bp. 
The nucleotide sequence disclosed herein for L69.sub.-- 2 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. L69.sub.-- 2 demonstrated at least some homology with the 
following sequences: human tissue specific secretory protein (A18921, 
BlastX; X67698, BlastN) and an EST identified as "md91b10.r1 Soares mouse 
embryo NbME13.5 14.5 Mus musculus" (W74864, BlastN). Based upon homology, 
L69.sub.-- 2 proteins and each homologous protein or peptide may share at 
least some activity. 
Clone "AJ172 2" 
A polynucleotide of the present invention has been identified as clone 
"AJ172.sub.-- 2". AJ172.sub.-- 2 was isolated from a human adult testes 
cDNA library using methods which are selective for cDNAs encoding secreted 
proteins. AJ172.sub.-- 2 is a full-length clone, including the entire 
coding sequence of a secreted protein (also referred to herein as 
"AJ172.sub.-- 2 protein"). 
The nucleotide sequence of the 5' portion of AJ172.sub.-- 2 as presently 
determined is reported in SEQ ID NO:47. An additional integral nucleotide 
sequence from AJ172.sub.-- 2 as presently determined is reported in SEQ ID 
NO:48. What applicants believe is the proper reading frame and the 
predicted amino acid sequence encoded by such internal sequence is 
reported in SEQ ID NO:49. Amino acids 1 to 20 of SEQ ID NO:49 are a 
predicted leader/signal sequence, with the predicted mature amino acid 
sequence beginning at amino acid 21. Additional nucleotide sequence from 
the 3' portion of AJ172.sub.-- 2, including the polyA tail, is reported in 
SEQ ID NO:50. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone AJ172.sub.-- 2 should be approximately 2700 bp. 
The nucleotide sequence disclosed herein for AJ172.sub.-- 2 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. AJ172.sub.-- 2 demonstrated at least some homology with the 
following sequences: Friend murine leukemiz virus (M93134, BlastX); 
Moloney murine leukemia virus genome (J02255, BlastN); pol protein, Gibbon 
leukemia virus (M26927, BlastX); and EST identified as "yh46a09.s1 Homo 
sapiens cDNA clone 132760 3'" (R27389, BlastN). Based upon homology, 
AJ172.sub.-- 2 proteins and each homologous protein or peptide may share 
at least some activity. 
Clone "AP224 2" 
A polynucleotide of the present invention has been identified as clone 
"AP224.sub.-- 2". AP224.sub.-- 2 was isolated from a human adult placenta 
cDNA library using methods which are selective for cDNAs encoding secreted 
proteins. AP224.sub.-- 2 is a full-length clone, including the entire 
coding sequence of a secreted protein (also referred to herein as 
"AP224.sub.-- 2 protein"). 
The nucleotide sequence of the 5' portion of AP224.sub.-- 2 as presently 
determined is reported in SEQ ID NO:51. An additional internal nucleotide 
sequence from AP224.sub.-- 2 as presently determined is reported in SEQ ID 
NO:52. What applicants believe is the proper reading frame and the 
predicted amino acid sequence encoded by such internal sequence is 
reported in SEQ ID NO:53. Additional nucleotide sequence from the 3' 
portion of AP224.sub.-- 2, including the polyA tail, is reported in SEQ ID 
NO:54. 
The EcoRI/NotI restriction fragment obtainable from the deposit containing 
clone AP224.sub.-- 2 should be approximately 2100 bp. 
The nucleotide sequence disclosed herein for AP224.sub.-- 2 was searched 
against the GenBank database using BLASTA/BLASTX and FASTA search 
protocols. AP224.sub.-- 2 demonstrated at least some identity with an EST 
identified as "yf61f08.s1 Homo sapiens cDNA clone 26687 3'" (R37675, 
BlastN). Based upon identity, AP224.sub.-- 2 proteins and each identical 
protein or peptide may share at least some activity. 
Deposit of Clones 
Clones AJ26.sub.-- 3, BL89.sub.-- 10, BV239.sub.-- 2, BL341.sub.-- 4, 
CC25.sub.-- 16, CC397.sub.-- 11, D305.sub.-- 2, G55.sub.-- 1, K39.sub.-- 
2, K330.sub.-- 2, K363.sub.-- 2, K446.sub.-- 2, K464.sub.-- 3, K483.sub.-- 
1, L69.sub.-- 2, AJ172.sub.-- 2, and AP224.sub.-- 2 were deposited on Jul. 
25, 1996 with the American Type Culture Collection under accession number 
ATCC 98115, from which each clone comprising a particular polynucleotide 
is obtainable. Each clone has been transfected into separate bacterial 
cells (E. coli) in this composite deposit. Each done can be removed from 
the vector in which it was deposited by performing an EcoRI/NotI digestion 
(5' cite, EcoRI; 3' cite, NotI) to produce the appropriately sized 
fragment for such clone (approximate clone size fragment are identified 
below). Bacterial cells containing a particular clone can be obtained from 
the composite deposit as follows: 
An oligonucleotide probe or probes should be designed to the sequence that 
is known for that particular clone. This sequence can be derived from the 
sequences provided herein, or from a combination of those sequences. The 
sequence of the oligonucleotide probe that was used to isolate each 
full-length clone is identified below, and should be most reliable in 
isolating the clone of interest. 
______________________________________ 
Clone Probe Sequence 
______________________________________ 
AJ26.sub.-- 3 SEQ ID NO:55 
BL89.sub.-- 10 SEQ ID NO:56 
BV239.sub.-- 2 SEQ ID NO:57 
BL341.sub.-- 4 SEQ ID NO:58 
CC25.sub.-- 16 SEQ ID NO:59 
CC397.sub.-- 11 SEQ ID NO:60 
D305.sub.-- 2 SEQ ID NO:61 
G55.sub.-- 1 SEQ ID NO:62 
K39.sub.-- 2 SEQ ID NO:63 
K330.sub.-- 2 SEQ ID NO:64 
K363.sub.-- 2 SEQ ID NO:65 
K446.sub.-- 2 SEQ ID NO:66 
K464.sub.-- 3 SEQ ID NO:67 
K483.sub.-- 1 SEQ ID NO:68 
L69.sub.-- 2 SEQ ID NO:69 
AJ172.sub.-- 2 SEQ ID NO:70 
AP224.sub.-- 2 SEQ ID NO:71 
______________________________________ 
In the sequences listed above which include an N at position 2, that 
position is occupied in preferred probes/primers by a biotinylated 
phosphoaramidite residue rather than a nucleotide (such as, for example, 
that produced by use of biotin phosphoramidite 
(1-dimethoxytrityloxy-2-(N-biotinyl-4-aminobutyl)-propyl-3-O-(2-cyanoethyl 
)-(N,N-diisopropyl)-(phosphoramadite) (Glen Research, cat. no. 10-1953)). 
The design of the oligonucleotide probe should preferably follow these 
parameters: 
(a) It should be designed to an area of the sequence which has the fewest 
ambiguous bases ("N's"), if any; 
(b) It should be designed to have a T.sub.m of approx. 80.degree. C. 
(assuming 2.degree. for each A or T and 4 degrees for each G or C). The 
oligonucleotide should preferably be labeled with g-.sup.32 p 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 .mu.l of the stock used to inoculate a 
sterile culture flask containing 25 ml of sterile L-broth containing 
ampicillin at 100 .mu.g/mL. The culture should preferably be grown to 
saturation at 37.degree. 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 
.mu.g/ml and agar at 1.5% in a 150 mm petri dish when grown overnight at 
37.degree. 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.degree. C. for 1 hour with 
gentle agitation in 6.times.SSC (20.times.stock is 175.3 g NaCl/liter, 
88.2 g Na citrate/liter, adjusted to pH 7.0 with NaOH) containing 0.5% 
SDS, 100 .mu.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 1e+6 dpm/mL. The filter is 
then preferably incubated at 65.degree. C. with gentle agitation 
overnight. The filter is then preferably washed in 500 mL of 
2.times.SSC/0.5% SDS at room temperature without agitation, preferably 
followed by 500 mL of 2.times.SSC/0.1% SDS at room temperature with gentle 
shaking for 15 minutes. A third wash with 0.1.times.SSC/0.5% SDS at 
65.degree. 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 of such protein may be 
obtained by expression of the disclosed full-length polynucleotide 
(preferably those deposited with ATCC) in a suitable mammalian cell or 
other host cell. The sequence of the mature form of the protein may also 
be determinable from the amino acid sequence of the full-length form. 
The present invention also provides genes corresponding to the cDNA 
sequences disclosed herein. The corresponding genes can be isolated in 
accordance with known methods using the sequence information disclosed 
herein. Such methods include the preparation of probes or primers from the 
disclosed sequence information for identification and/or amplification of 
genes in appropriate genomic libraries or other sources of genomic 
materials. 
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. 
Species homologs of the disclosed polynucleotides and proteins are also 
provided by the present invention. Species homologs 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. 
The invention also encompasses allelic variants of the disclosed 
polynucleotides or proteins; that is, naturally-occurring alternative 
forms of the isolated polynucleotide which also encode proteins which are 
identical, homologous or related to that encoded by the polynucleotides. 
The isolated polynucleotide of the invention may be operably linked to an 
expression control sequence such as the pMT2 or pED expression vectors 
disclosed in Kaufman et al., Nucleic Acids Res. 19, 4485-4490 (1991), in 
order to produce the protein recombinantly. Many suitable expression 
control sequences are known in the art. General methods of expressing 
recombinant proteins are also known and are exemplified in R. Kaufman, 
Methods in Enzymology 185, 537-566 (1990). As defined herein "operably 
linked" means that the isolated polynucleotide of the invention and an 
expression control sequence are situated within a vector or cell in such a 
way that the protein is expressed by a host cell which has been 
transformed (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 cells, human Colo205 cells, 3T3 cells, CV-1 cells, other transformed 
primate cell lines, normal diploid cells, cell strains derived from in 
vitro culture of primary tissue, primary explants, HeLa cells, mouse L 
cells, BHK, HL-60, U937, HaK or Jurkat cells. 
Alternatively, it may be possible to produce the protein in lower 
eukaryotes such as yeast or in prokaryotes such as bacteria. Potentially 
suitable yeast strains include Saccharomyces cerevisiae, 
Schizosaccharomyces pombe, Kluyveromyces strains, Candida, or any yeast 
strain capable of expressing heterologous proteins. Potentially suitable 
bacterial strains include Escherichia coli, Bacillus subtills, Salmonella 
typhimurium, or any bacterial strain capable of expressing heterologous 
proteins. If the protein is made in yeast or bacteria, it may be necessary 
to modify the protein produced therein, for example by phosphorylation or 
glycosylation of the appropriate sites, in order to obtain the functional 
protein. Such covalent attachments may be accomplished using known 
chemical or enzymatic methods. 
The protein may also be produced by operably linking the isolated 
polynucleotide of the invention to suitable control sequences in one or 
more insect expression vectors, and employing an insect expression system. 
Materials and methods for baculovirus/insect cell expression systems are 
commercially available in kit form from, e.g., Invitrogen, San Diego, 
Calif., U.S.A. (the MaxBac.RTM. kit), and such methods are well known in 
the art, as described in Summers and Smith, Texas Agricultural Experiment 
Station Bulletin No. 1555 (1987), incorporated herein by reference. As 
used herein, an insect cell capable of expressing a polynucleotide of the 
present invention is "transformed." 
The protein of the invention may be prepared by culturing transformed host 
cells under culture conditions suitable to express the recombinant 
protein. The resulting expressed protein may then be purified from such 
culture (i.e., from culture medium or cell extracts) using known 
purification processes, such as gel filtration and ion exchange 
chromatography. The purification of the protein may also include an 
affinity column containing agents which will bind to the protein; one or 
more column steps over such affinity resins as concanavalin A-agarose, 
heparin-toyopearl.RTM. or Cibacrom blue 3GA Sepharose.RTM.; 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 matlose 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 BioLab (Beverly, Mass.), Pharmacia (Piscataway, N.J.) and 
InVitrogen, 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 Kodak 
(New Haven, Conn.). 
Finally, one or more reverse-phase high performance liquid chromatography 
(RP-HPLC) steps employing hydrophobic RP-HPLC media, e.g., silica gel 
having pendant methyl or other aliphatic groups, can be employed to 
further purify the protein. Some or all of the foregoing purification 
steps, in various combinations, can also be employed to provide a 
substantially homogeneous isolated recombinant protein. The protein thus 
purified is substantially free of other mammalian proteins and is defined 
in accordance with the present invention as an "isolated protein." 
The protein of the invention may also be expressed as a product of 
transgenic animals, e.g., as a component of the milk of transgenic cows, 
goats, pigs, or sheep which are characterized by somatic or germ cells 
containing a nucleotide sequence encoding the protein. 
The protein may also be produced by known conventional chemical synthesis. 
Methods for constructing the proteins of the present invention by 
synthetic means are known to those skilled in the art. The 
synthetically-constructed protein sequences, by virtue of sharing primary, 
secondary or tertiary structural and/or conformational characteristics 
with proteins may possess biological properties in common therewith, 
including protein activity. Thus, they may be employed as biologically 
active or immunological substitutes for natural, purified proteins in 
screening of therapeutic compounds and in immunological processes for the 
development of antibodies. 
The proteins provided herein also include proteins characterized by amino 
acid sequences similar to those of purified proteins but into which 
modification are naturally provided or deliberately engineered. For 
example, modifications in the peptide or DNA sequences can be made by 
those skilled in the art using known techniques. Modifications of interest 
in the protein sequences may include the alteration, substitution, 
replacement, insertion or deletion of a selected amino acid residue in the 
coding sequence. For example, one or more of the cysteine residues may be 
deleted or replaced with another amino acid to alter the conformation of 
the molecule. Techniques for such alteration, substitution, replacement, 
insertion or deletion are well known to those skilled in the art (see, 
e.g., U.S. Pat. No. 4,518,584). Preferably, such alteration, substitution, 
replacement, insertion or deletion retains the desired activity of the 
protein. 
Other fragments and derivatives of the sequences of proteins which would be 
expected to retain protein activity in whole or in part and may thus be 
useful for screening or other immunological methodologies may also be 
easily made by those skilled in the art given the disclosures herein. Such 
modifications are believed to be encompassed by the present invention. 
Uses and Biological Activity 
The polynucleotides and proteins of the present invention are expected to 
exhibit one or more of the uses or biological activities (including those 
associated with assays cited herein) identified below. Uses or activities 
described for proteins of the present invention may be provided by 
administration or use of such proteins or by administration or use of 
polynucleotides encoding such proteins (such as, for example, in gene 
therapies or vectors suitable for introduction of DNA). 
Research Uses and Utilities 
The polynucleotides provided by the present invention can be used by the 
research community for various purposes. The polynucleotides can be used 
to express recombinant protein for analysis, characterization or 
therapeutic use; as markers for tissues in which the corresponding protein 
is preferentially expressed (either constitutively or at a particular 
stage of tissue differentiation or development or in disease states); as 
molecular weight markers on Southern gels; as chromosome markers or tags 
(when labeled) to identify chromosomes or to map related gene positions; 
to compare with endogenous DNA sequences in patients to identify potential 
genetic disorders; as probes to hybridize and thus discover novel, related 
DNA sequences; as a source of information to derive PCR primers for 
genetic fingerprinting; as a probe to "subtract-out" known sequences in 
the process of discovering other novel polynucleotides; for selecting and 
making oligomers for attachment to a "gene chip" or other support, 
including for examination of expression patterns; to raise anti-protein 
antibodies using DNA immunization techniques; and as an antigen to raise 
anti-DNA antibodies or elicit another immune response. Where the 
polynucleotide encodes a protein which binds or potentially binds to 
another protein (such as, for example, in a receptor-ligand interaction), 
the polynucleotide can also be used in interaction trap assays (such as, 
for example, that described in Gyuris et al., Cell 75:791-803 (1993)) to 
identify polynucleotides encoding the other protein with which binding 
occurs or to identify inhibitors of the binding interaction. 
The proteins provided by the present invention can similarly be used in 
assay to determine biological activity, including in a panel of multiple 
proteins for high-throughput screening; to raise antibodies or to elicit 
another immune response; as a reagent (including the labeled reagent) in 
assays designed to quantitatively determine levels of the protein (or its 
receptor) in biological fluids; as markers for tissues in which the 
corresponding protein is preferentially expressed (either constitutively 
or at a particular stage of tissue differentiation or development or in a 
disease state); and, of course, to isolate correlative receptors or 
ligands. Where the protein binds or potentially binds to another protein 
(such as, for example, in a receptor-ligand interaction), the protein can 
be used to identify the other protein with which binding occurs or to 
identify inhibitors of the binding interaction. Proteins involved in these 
binding interactions can also be used to screen for peptide or small 
molecule inhibitors or agonists of the binding interaction. 
Any or all of these research utilities are capable of being developed into 
reagent grade or kit format for commercialization as research products. 
Methods for performing the uses listed above are well known to those 
skilled in the art. References disclosing such methods include without 
limitation "Molecular Cloning: A Laboratory Manual", 2d ed., Cold Spring 
Harbor Laboratory Press, Sambrook, J., E. F. Fritsch and T. Maniatis eds., 
1989, and "Methods in Enzymology: Guide to Molecular Cloning Techniques", 
Academic Press, Berger, S. L. and A. R. Kimmel eds., 1987. 
Nutritional Uses 
Polynucleotides and proteins of the present invention can also be used as 
nutritional sources or supplements. Such uses include without limitation 
use as a protein or amino acid supplement, use as a carbon source, use as 
a nitrogen source and use as a source of carbohydrate. In such cases the 
protein or polynucleotide of the invention can be added to the feed of a 
particular organism or can be administered as a separate solid or liquid 
preparation, such as in the form of powder, pills, solutions, suspensions 
or capsules. In the case of microorganisms, the protein or polynucleotide 
of the invention can be added to the medium in or on which the 
microorganism is cultured. 
Cytokine and Cell Proliferation/Differentiation Activity 
A protein of the present invention may exhibit cytokine, cell proliferation 
(either inducing or inhibiting) or cell differentiation (either inducing 
or inhibiting) activity or may induce production of other cytokines in 
certain cell populations. Many protein factors discovered to date, 
including all known cytokines, have exhibited activity in one or more 
factor dependent cell proliferation assays, and hence the assays serve as 
a convenient confirmation of cytokine activity. The activity of a protein 
of the present invention is evidenced by any one of a number of routine 
factor dependent cell proliferation assays for cell lines including, 
without limitation, 32D, DA2, DA1G, T10, B9, B9/11, BaF3, MC9/G, M+ (preB 
M+), 2E8, RB5, DA1, 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. Coilgan, 
A. M. Kruisbeek, D. H. Marguiles, 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; Bertagnoili et 
al., J. Immunol. 145:1706-1712, 1990; Bertagnolli et al., Cellular 
Immunology 133:327-341, 1991; Bertagnolli, et al., J. Immunol. 
149:3778-3783, 1992; Bowman et al., J. Immunol. 152:1756-1761, 1994. 
Assays for cytokine production and/or proliferation of spleen cells, lymph 
node cells or thymocytes include, without limitation, those described in: 
Polyclonal T cell stimulation, Kruisbeek, A. M. and Shevach, E. M. In 
Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 
3.12.1-3.12.14, John Wiley and Sons, Toronto. 1994; and Measurement of 
mouse and human Interferon .gamma., Schreiber, R. D. In Current Protocols 
in Immunology. J. E. e.a. Coilgan eds. Vol 1 pp. 6.8.1-6.8.8, John Wiley 
and Sons, Toronto. 1994. 
Assays for proliferation and differentiation of hematopoietic and 
lymphopoietic cells include, without limitation, those described in: 
Measurement of Human and Murine Interleukin 2 and Interleukin 4, Bottomly, 
K., Davis, L. S. and Lipsky, P. E. In Current Protocols in Immunology. J. 
E. e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons, Toronto. 
1991; deVries et al., J. Exp. Med. 173:1205-1211, 1991; Moreau et al., 
Nature 336:690-692, 1988; Greenberger et al., Proc. Natl. Acad. Sci. 
U.S.A. 80:2931-2938, 1983; Measurement of mouse and human interleukin 
6-Nordan, R. In Current Protocols in Immunology. J. E. e.a. Coligan eds. 
Vol 1 pp. 6.6.1-6.6.5, John Wiley and Sons, Toronto. 1991; Smith et al., 
Proc. Natl. Acad. Sci. U.S.A. 83:1857-1861, 1986; Measurement of human 
Interleukin 11-Bennett, F., Giannotti, J., Clark, S. C. and Tumer, K. J. 
In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 
6.15.1 John Wiley and Sons, Toronto. 1991; Measurement of mouse and human 
Interleukin 9-Ciarletta, A., Giannotti, J., Clark, S. C. and Turner, K. J. 
In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 
6.13.1, John Wiley and Sons, Toronto. 1991. 
Assays for T-cell clone responses to antigens (which will identify, among 
others, proteins that affect APC-T cell interactions as well as direct 
T-cell effects by measuring proliferation and cytokine production) 
include, without limitation, those described in: Current Protocols in 
Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Marguiles, E. M. 
Shevach, W Strober, Pub. Greene Publishing Associates and 
Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte 
Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, 
Immunologic studies in Humans); Weinberger et al., Proc. Natl. Acad. Sci. 
USA 77:6091-6095, 1980; Weinberger et al., Eur. J. Immun. 11:405-411, 
1981; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. 
Immunol. 140:508-512, 1988. 
Immune Stimulating or Suppressing Activity 
A protein of the present invention may also exhibit immune stimulating or 
immune suppressing activity, including without limitation the activities 
for which assays are described herein. A protein may be useful in the 
treatment of various immune deficiencies and disorders (including severe 
combined immunodeficiency (SCID)), e.g., in regulating (up or down) growth 
and proliferation of T and/or B lymphocytes, as well as effecting the 
cytolytic activity of NK cells and other cell populations. These immune 
deficiencies may be genetic or be caused by vital (e.g., HIV) as well as 
bacterial or fungal infections, or may result from autoimmune disorders. 
More specifically, infectious diseases causes by vital, 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, Guillain-Barre syndrome, autoimmune thyroiditis, 
insulin dependent diabetes mellitis, myasthenia gravis, graft-versus-host 
disease and autoimmune inflammatory eye disease. Such a protein of the 
present invention may also to be useful in the treatment of allergic 
reactions and conditions, such as asthma (particularly allergic asthma) or 
other respiratory problems. Other conditions, in which immune suppression 
is desired (including, for example, organ transplantation), may also be 
treatable using a protein of the present invention. 
Using the proteins of the invention it may also be possible to immune 
responses, in a number of ways. Down regulation may be in the form of 
inhibiting or blocking an immune response already in progress or may 
involve preventing the induction of an immune response. The functions of 
activated T cells may be inhibited by suppressing T cell responses or by 
inducing specific tolerance in T cells, or both. Immunosuppression of T 
cell responses is generally an active, non-antigen-specific, process which 
requires continuous exposure of the T cells to the suppressive agent. 
Tolerance, which involves inducing non-responsiveness or anergy in T 
cells, is distinguishable from immunosuppression in that it is generally 
antigen-specific and persists after exposure to the tolerizing agent has 
ceased. Operationally, tolerance can be demonstrated by the lack of a T 
cell response upon reexposure to specific antigen in the absence of the 
tolerizing agent. 
Down regulating or preventing one or more antigen functions (including 
without limitation B lymphocyte antigen functions (such as, for example, 
B7)), e.g., preventing high level lymphokine synthesis by activated T 
cells, will be useful in situations of tissue, skin and organ 
transplantation and in graft-versus-host disease (GVHD). For example, 
blockage of T cell function should result in reduced tissue destruction in 
tissue transplantation. Typically, in tissue transplants, rejection of the 
transplant is initiated through its recognition as foreign by T cells, 
followed by an immune reaction that destroys the transplant. The 
administration of a molecule which inhibits or blocks interaction of a B7 
lymphocyte antigen with its natural ligand(s) on immune cells (such as a 
soluble, monomeric form of a peptide having B7-2 activity alone or in 
conjunction with a monomeric form of a peptide having an activity of 
another B lymphocyte antigen (e.g., B7-1, B7-3) or blocking antibody), 
prior to transplantation can lead to the binding of the molecule to the 
natural ligand(s) on the immune cells without 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 of B lymphocyte antigens. 
The efficacy of particular blocking reagents in preventing organ transplant 
rejection or GVHD can be assessed using animal models that are predictive 
of efficacy in humans. Examples of appropriate systems which can be used 
include allogeneic cardiac grafts in rats and xenogeneic pancreatic islet 
cell grafts in mice, both of which have been used to examine the 
immunosuppressive effects of CTLA4Ig fusion proteins in vivo as described 
in Lenschow et al., Science 257:789-792 (1992) and Turka et al., Proc. 
Natl. Acad. Sci USA, 89:11102-11105 (1992). In addition, murine models of 
GVHD (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, 
pp. 846-847) can be used to 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 receptor:ligand interactions of B lymphocyte antigens can be 
used to inhibit T cell activation and prevent production of autoantibodies 
or T cell-derived cytokines which may be involved in the disease process. 
Additionally, blocking reagents may induce antigen-specific tolerance of 
autoreactive T cells which could lead to long-term relief from the 
disease. The efficacy of blocking reagents in preventing or alleviating 
autoimmune disorders can be determined using a number of 
well-characterized animal models of human autoimmune diseases. Examples 
include murine experimental autoimmune encephalitis, systemic lupus 
erythmatosis in MRL/lpr/lpr mice or NZB hybrid mice, murine autoimmune 
collagen arthritis, diabetes mellitus in NOD mice and BB rats, and murine 
experimental myasthenia gravis (see Paul ed., Fundamental Immunology, 
Raven Press, New York, 1989, pp. 840-856). 
Upregulation of an antigen function (preferably a B lymphocyte antigen 
function), as a means of up regulating immune responses, may also be 
useful in therapy. Upregulation of immune responses may be in the form of 
enhancing an existing immune response or eliciting an initial immune 
response. For example, enhancing an immune response through stimulating B 
lymphocyte antigen function may be useful in cases of viral infection. In 
addition, systemic vital 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-vital 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 B7-1-like activity and/or B7-3-like activity. The 
transfected tumor cells are returned to the patient to result in 
expression of the peptides on the surface of the transfected cell. 
Alternatively, gene therapy techniques can be used to target a tumor cell 
for transfection in vivo. 
The presence of the peptide of the present invention having the activity of 
a B lymphocyte 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 .alpha. chain 
protein and .beta..sub.2 microglobulin protein or an MHC class II .alpha. 
chain protein and an MHC class II .beta. chain protein to thereby express 
MHC class I or MHC class II proteins on the cell surface. Expression of 
the appropriate class I or class II MHC in conjunction with a peptide 
having the activity of a B lymphocyte antigen (e.g., B7-1, B7-2, B7-3) 
induces a T cell mediated immune response against the transfected tumor 
cell. Optionally, a gene encoding an antisense construct which blocks 
expression of an MHC class II associated protein, such as the invariant 
chain, can also be cotransfected with a DNA encoding a peptide having the 
activity of a B lymphocyte antigen to promote presentation of tumor 
associated antigens and induce tumor specific immunity. Thus, the 
induction of a T cell mediated immune response in a human subject may be 
sufficient to overcome tumor-specific tolerance in the subject. 
The activity of a protein of the invention may, among other means, be 
measured by the following methods: 
Suitable assays for thymocyte or splenocyte cytotoxicity include, without 
limitation, those described in: Current Protocols in Immunology, Ed by J. 
E. Coligan, A. M. Kruisbeek, D. H. Marguiles, 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; Bowman et al., J. 
Virology 61:1992-1998; Takai et al., J. Immunol. 140:508-512, 1988; 
Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Brown et al., 
J. Immunol. 153:3079-3092, 1994. 
Assays for T-cell-dependent immunoglobulin responses and isotype switching 
(which will identify, among others, proteins that modulate T-cell 
dependent antibody responses and that affect Th1/Th2 profiles) include, 
without limitation, those described in: Maliszewski, J. Immunol. 
144:3028-3033, 1990; and Assays for B cell function: In vitro antibody 
production, Mond, J. J. and Brunswick, M. In Current Protocols in 
Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and 
Sons, Toronto. 1994. 
Mixed lymphocyte reaction (MLR) assays (which will identify, among others, 
proteins that generate predominantly Th1 and CTL responses) include, 
without limitation, those described in: Current Protocols in Immunology, 
Ed by J. E. Coilgan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W 
Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 
3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, 
Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 
1986; Takai et al., J. Immunol. 140:508-512, 1988; Bertagnolli et al., J. 
Immunol. 149:3778-3783, 1992. 
Dendritic cell-dependent assays (which will identify, among others, 
proteins expressed by dendritic cells that activate naive T-cells) 
include, without limitation, those described in: Guery et al., J. Immunol. 
134:536-544, 1995; Inaba et al., Journal of Experimental Medicine 
173:549-559, 1991; Macatonia et al., Journal of Immunology 154:5071-5079, 
1995; Porgador et al., Journal of Experimental Medicine 182:255-260, 1995; 
Nair et al., Journal of Virology 67:4062-4069, 1993; Huang et al., Science 
264:961-965, 1994; Macatonia et al., Journal of Experimental Medicine 
169:1255-1264, 1989; Bhardwaj et al., Journal of Clinical investigation 
94:797-807, 1994; and Inaba et al., Journal of Experimental Medicine 
172:631-640, 1990. 
Assays for lymphocyte survival/apoptosis (which will identify, among 
others, proteins that prevent apoptosis after superantigen induction and 
proteins that regulate lymphocyte homeostasis) include, without 
limitation, those described in: Darzynkiewicz et al., Cytometry 
13:795-808, 1992; Gorczyca et al., Leukemia 7:659-670, 1993; Gorczyca et 
al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cell 66:233-243, 
1991; Zacharchuk, Journal of Immunology 145:4037-4045, 1990; Zamai et al., 
Cytometry 14:891-897, 1993; Gorczyca et al., International Journal of 
Oncology 1:639-648, 1992. 
Assays for proteins that influence early steps of T-cell commitment and 
development include, without limitation, those described in: Antica et 
al., Blood 84:111-117, 1994; Fine et al., Cellular Immunology 155: 
111-122, 1994; Galy et al., Blood 85:2770-2778, 1995; Toki et al., Proc. 
Nat. Acad Sci. USA 88:7548-7551, 1991. 
Hematopoiesis Regulating Activity 
A protein of the present invention may be useful in regulation of 
hematopoiesis and, consequently, in the treatment of myeloid or lymphoid 
cell deficiencies. Even marginal biological activity in support of colony 
forming cells or of factor-dependent cell lines indicates involvement in 
regulating hematopoiesis, e.g. in supporting the growth and proliferation 
of erythroid progenitor cells alone or in combination with other 
cytokines, thereby indicating utility, for example, in treating various 
anemias or for use in conjunction with irradiation/chemotherapy to 
stimulate the production of erythroid precursors and/or erythroid cells; 
in supporting the growth and proliferation of myeloid cells such as 
granulocytes and monocytes/macrophages (i.e., traditional CSF activity) 
useful, for example, in conjunction with chemotherapy to prevent or treat 
consequent myelo-suppression; in supporting the growth and proliferation 
of megakaryocytes and consequently of platelets thereby allowing 
prevention or treatment of various platelet disorders such as 
thrombocytopenia, and generally for use in place of or complimentary to 
platelet transfusions; and/or in supporting the growth and proliferation 
of hematopoietic stem cells which are capable of maturing to any and all 
of the above-mentioned hematopoietic cells and therefore find therapeutic 
utility in various stem cell disorders (such as those usually treated with 
transplantation, including, without limitation, aplastic anemia and 
paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem 
cell compartment post irradiation/chemotherapy, either in-vivo or ex-vivo 
(i.e., in conjunction with bone marrow transplantation or with peripheral 
progenitor cell transplantation (homologous or heterologous)) as normal 
cells or genetically manipulated for gene therapy. 
The activity of a protein of the invention may, among other means, be 
measured by the following methods: 
Suitable assays for proliferation and differentiation of various 
hematopoietic lines are cited above. 
Assays for embryonic stem cell differentiation (which will identify, among 
others, proteins that influence embryonic differentiation hematopoiesis) 
include, without limitation, those described in: Johansson et al. Cellular 
Biology 15:141-151, 1995; Keller et al., Molecular and Cellular Biology 
13:473-486, 1993; McClanahan et al., Blood 81:2903-2915, 1993. 
Assays for stem cell survival and differentiation (which will identify, 
among others, proteins that regulate lympho-hematopoiesis) include, 
without limitation, those described in: Methylcellulose colony forming 
assays, Freshney, M. G. In Culture of Hematopoietic Cells. R. I. Freshney, 
et al. eds. Vol pp. 265-268, Wiley-Liss, Inc., New York, N.Y. 1994; 
Hirayama et al., Proc. Natl. Acad. Sci. USA 89:5907-5911, 1992; Primitive 
hematopoietic colony forming cells with high proliferative potential, 
McNiece, I. K. and Briddeli, R. A. In Culture of Hematopoietic Cells. R. 
I. Freshney, et al. eds. Vol pp. 23-39, Wiley-Liss, Inc., New York, N.Y. 
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, N.Y. 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. Freshhey, et al. eds. Vol pp. 163-179, Wiley-Liss, Inc., New 
York, N.Y. 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, N.Y. 1994. 
Tissue Growth Activity 
A protein of the present invention also may have utility in compositions 
used for bone, cartilage, tendon, ligament and/or nerve tissue growth or 
regeneration, as well as for wound healing and tissue repair and 
replacement, and in the treatment of burns, incisions and ulcers. 
A protein of the present invention, which induces cartilage and/or bone 
growth in circumstances where bone is not normally formed, has application 
in the healing of bone fractures and cartilage damage or defects in humans 
and other animals. Such a preparation employing a protein of the invention 
may have prophylactic use in closed as well as open fracture reduction and 
also in the improved fixation of artificial joints. De novo bone formation 
induced by an osteogenic agent contributes to the repair of congenital, 
trauma induced, or oncologic resection induced craniofacial defects, and 
also is useful in cosmetic plastic surgery. 
A protein of this invention may also be used in the treatment of 
periodontal disease, and in other tooth repair processes. Such agents may 
provide an environment to attract bone-forming cells, stimulate growth of 
bone-forming cells or induce differentiation of progenitors of 
bone-forming cells. A protein of the invention may also be useful in the 
treatment of osteoporosis or osteoarthritis, such as through stimulation 
of bone and/or cartilage repair or by blocking inflammation or processes 
of tissue destruction (collagenase activity, osteoclast activity, etc.) 
mediated by inflammatory processes. 
Another category of tissue regeneration activity that may be attributable 
to the protein of the present invention is tendon/ligament formation. A 
protein of the present invention, which induces tendon/ligament-like 
tissue or other tissue formation in circumstances where such tissue is not 
normally formed, has application in the healing of tendon or ligament 
tears, deformities and other tendon or ligament defects in humans and 
other animals. Such a preparation employing a tendon/ligament-like tissue 
inducing protein may have prophylactic use in preventing damage to tendon 
or ligament tissue, as well as use in the improved fixation of tendon or 
ligament to bone or other tissues, and in repairing defects to tendon or 
ligament tissue. De novo tendon/ligament-like tissue formation induced by 
a composition of the present invention contributes to the repair of 
congenital, trauma induced, or other tendon or ligament defects of other 
origin, and is also useful in cosmetic plastic surgery for attachment or 
repair of tendons or ligaments. The compositions of the present invention 
may provide an environment to attract tendon- or ligament-forming cells, 
stimulate growth of tendon- or ligament-forming cells, induce 
differentiation of progenitors of tendon- or ligament-forming cells, or 
induce growth of tendon/ligament cells or progenitors ex vivo for return 
in vivo to effect tissue repair. The compositions of the invention may 
also be useful in the treatment of tendinitis, carpal tunnel syndrome and 
other tendon or ligament defects. The compositions may also include an 
appropriate matrix and/or sequestering agent as a career as is well known 
in the art. 
The protein of the present invention may also be useful for proliferation 
of neural cells and for regeneration of nerve and brain tissue, i.e. for 
the treatment of central and peripheral nervous system diseases and 
neuropathies, as well as mechanical and traumatic disorders, which involve 
degeneration, death or trauma to neural cells or nerve tissue. More 
specifically, a protein may be used in the treatment of diseases of the 
peripheral nervous system, such as peripheral nerve injuries, peripheral 
neuropathy and localized neuropathies, and central nervous system 
diseases, such as Alzheimer's, Parkinson's disease, Huntington's disease, 
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 liver fibrosis, reperfusion injury 
in various tissues, and conditions resulting from systemic cytokine 
damage. 
A protein of the present invention may also be useful for promoting or 
inhibiting differentiation of tissues described above from precursor 
tissues or cells; or for inhibiting the growth of tissues described above. 
The activity of a protein of the invention may, among other means, be 
measured by the following methods: 
Assays for tissue generation activity include, without limitation, those 
described in: International Patent Publication No. WO95/16035 (bone, 
cartilage, tendon); International Patent Publication No. WO95/05846 
(nerve, neuronal); International Patent Publication No. WO91/07491 (skin, 
endothelium). 
Assays for wound healing activity include, without limitation, those 
described in: Winter, Epidermal Wound Healing, pps. 71-112 (Maibach, H I 
and Rovee, D T, eds.), Year Book Medical Publishers, Inc., Chicago, as 
modified by Eaglstein and Menz, 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 .alpha. 
family, may be useful as a contraceptive based on the ability of inhibins 
to decrease fertility in female mammals and decrease spematogenesis 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-.beta. 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, U.S. 
Pat. No. 4,798,885. A protein of the invention may also be useful for 
advancement of the onset of fertility in sexually immature mammals, so as 
to increase the lifetime reproductive performance of domestic animals such 
as cows, sheep and pigs. 
The activity of a protein of the invention may, among other means, be 
measured by the following methods: 
Assays for activin/inhibin activity include, without limitation, those 
described in: Vale et al., Endocrinology 91:562-572, 1972; Ling et al., 
Nature 321:779-782, 1986; Vale et al., Nature 321:776-779, 1986; Mason et 
al., Nature 318:659-663, 1985; Forage et al., Proc. Natl. Acad. Sci. USA 
83:3091-3095, 1986. 
Chemotactic/Chemokinetic Activity 
A protein of the present invention may have chemotactic or chemokinetic 
activity (e.g., act as a chemokine) for mammalian cells, including, for 
example, monocytes, fibroblasts, neutrophils, T-cells, mast cells, 
eosinophils, epithelial and/or endothelial cells. Chemotactic and 
chemokinetic proteins can be used to mobilize or attract a desired cell 
population to a desired site of action. Chemotactic or chemokinetic 
proteins provide particular advantages in treatment of wounds and other 
trauma to tissues, as well as in treatment of localized infections. For 
example, attraction of lymphocytes, monocytes or neutrophils to tumors or 
sites of infection may result in improved immune responses against the 
tumor or infecting agent. 
A protein or peptide has chemotactic activity for a particular cell 
population if it can stimulate, directly or indirectly, the directed 
orientation or movement of such cell population. Preferably, the protein 
or peptide has the ability to directly stimulate directed movement of 
cells. Whether a particular protein has chemotactic activity for a 
population of cells can be readily determined by employing such protein or 
peptide in any known assay for cell chemotaxis. 
The activity of a protein of the invention may, among other means, be 
measured by following methods: 
Assays for chemotactic activity (which will identify proteins that induce 
or prevent chemotaxis) consist of assays that measure the ability of a 
protein to induce the migration of cells across a membrane as well as the 
ability of a protein to induce the adhesion of one cell population to 
another cell population. Suitable assays for movement and adhesion 
include, without limitation, those described in: Current Protocols in 
Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. 
Shevach, W. Strober, Pub. Greene Publishing Associates and 
Wiley-Interscience (Chapter 6.12, Measurement of alpha and beta Chemokines 
6.12.1-6.12.28; Taub et al. J. Clin. Invest. 95:1370-1376, 1995; Lind et 
al. APMIS 103:140-146, 1995; Muller et al Eur. J. Immunol. 25: 1744-1748; 
Gruberet al. J. of Immunol. 152:5860-5867, 1994; Johnston et al. J. of 
Immunol. 153: 1762-1768, 1994. 
Hemostatic and Thrombolytic Activity 
A protein of the invention may also exhibit hemostatic or thrombolytic 
activity. As a result, such a protein is expected to be useful in 
treatment of various coagulation disorders (including hereditary 
disorders, such as hemophilias) or to enhance coagulation and other 
hemostatic events in treating wounds resulting from trauma, surgery or 
other causes. A protein of the invention may also be useful for dissolving 
or inhibiting formation of thromboses and for treatment and prevention of 
conditions resulting therefrom (such as, for example, infarction of 
cardiac and central nervous system vessels (e.g., stroke). 
The activity of a protein of the invention may, among other means, be 
measured by the following methods: 
Assay for hemostatic and thrombolytic activity include, without limitation, 
those described in: Linet et al., J. Clin. Pharmacol. 26:131-140, 1986; 
Burdick et al., Thrombosis Res. 45:413-419, 1987; Humphrey et al., 
Fibrinolysis 5:71-79 (1991); Schaub, Prostaglandins 35:467-474, 1988. 
Receptor/Ligand Activity 
A protein of the present invention may also demonstrate activity as 
receptors, receptor ligands or inhibitors or agonists of receptor/ligand 
interactions. Examples of such receptors and ligands include, without 
limitation, cytokine receptors and their ligands, receptor kinases and 
their ligands, receptor phosphatases and their ligands, receptors involved 
in cell--cell interactions and their ligands (including without 
limitation, cellular adhesion molecules (such as selectins, integrins and 
their ligands) and receptor/ligand pairs involved in antigen presentation, 
antigen recognition and development of cellular and humoral immune 
responses). Receptors and ligands are also useful for screening of 
potential peptide or small molecule inhibitors of the relevant 
receptor/ligand interaction. A protein of the present invention 
(including, without limitation, fragments of receptors and ligands) may 
themselves be useful as inhibitors of receptor/iigand interactions. 
The activity of a protein of the invention may, among other means, be 
measured by the following methods: 
Suitable assays for receptor-ligand activity include without limitation 
those described in:Current Protocols in Immunology, Ed by J. E. Coligan, 
A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W.Strober, Pub. Greene 
Publishing Associates and Wiley-Interscience (Chapter 7.28, Measurement of 
Cellular Adhesion under static conditions 7.28.1-7.28.22), Takai et al., 
Proc. Natl. Acad. Sci. USA 84:6864-6868, 1987; Bierer et al., J. Exp. Med. 
168:1145-1156, 1988; Rosenstein et al., J. Exp. Med. 169:149-160 1989; 
Stoltenborg et al., J. Immunol. Methods 175:59-68, 1994; StiTt et al., 
Cell 80:661-670, 1995. 
Anti-Inflammatory Activity 
Proteins of the present invention may also exhibit anti-inflammatory 
activity. The anti-inflammatory activity may be achieved by providing a 
stimulus to cells involved in the inflammatory response, by inhibiting or 
promoting cell--cell interactions (such as, for example, cell adhesion), 
by inhibiting or promoting chemotaxis of cells involved in the 
inflammatory process, inhibiting or promoting cell extravasation, or by 
stimulating or suppressing production of other factors which more directly 
inhibit or promote an inflammatory response. Proteins exhibiting such 
activities can be used to treat inflammatory conditions including chronic 
or acute conditions), including without limitation inflammation associated 
with infection (such as septic shock, sepsis or systemic inflammatory 
response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin 
lethality, arthritis, complement-mediated hyperacute rejection, nephritis, 
cytokine or chemokine-induced lung injury, inflammatory bowel disease, 
Crohn's disease or resulting from over production of cytokines such as TNF 
or IL-1. Proteins of the invention may also be useful to treat anaphylaxis 
and hypersensitivity to an antigenic substance or material. 
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 ADCC). A protein may exhibit its 
tumor inhibitory activity by acting on tumor tissue or tumor precursor 
tissue, by inhibiting formation of tissues necessary to support tumor 
growth (such as, for example, by inhibiting angiogenesis), by causing 
production of other factors, agents or cell types which inhibit tumor 
growth, or by suppressing, eliminating or inhibiting factors, agents or 
cell types which promote tumor growth. 
Other Activities 
A protein of the invention may also exhibit one or more of the following 
additional activities or effects: inhibiting the growth, infection or 
function of, or killing, infectious agents, including, without limitation, 
bacteria, viruses, fungi and other parasites; effecting (suppressing or 
enhancing) bodily characteristics, including, without limitation, height, 
weight, hair color, eye color, skin, fat to lean ratio or other tissue 
pigmentation, or organ or body part size or shape (such as, for example, 
breast augmentation or diminution, change in bone form or shape); 
effecting biorhythms or caricadic cycles or rhythms; effecting the 
fertility of male or female subjects; effecting the metabolism, 
catabolism, anabolism, processing, utilization, storage or elimination of 
dietary fat, lipid, protein, carbohydrate, vitamins, minerals, cofactors 
or other nutritional factors or component(s); effecting behavioral 
characteristics, including, without limitation, appetite, libido, stress, 
cognition (including cognitive disorders), depression (including 
depressive disorders) and violent behaviors; providing analgesic effects 
or other pain reducing effects; promoting differentiation and growth of 
embryonic stem cells in lineages other than hematopoietic lineages; 
hormonal or endocrine activity; in the case of enzymes, correcting 
deficiencies of the enzyme and treating deficiency-related diseases; 
treatment of hyperproliferative disorders (such as, for example, 
psoriasis); immunoglobulin-like activity (such as, for example, the 
ability to bind antigens or complement); and the ability to act as an 
antigen in a vaccine composition to raise an immune response against such 
protein or another material or entity which is cross-reactive with such 
protein. 
Administration and Dosing 
A protein of the present invention (from whatever source derived, including 
without limitation from recombinant and non-recombinant sources) may be 
used in a pharmaceutical composition when combined with a pharmaceutically 
acceptable career. 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, TNF0, 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 cells as well as antibodies able to bind the TCR and 
other molecules on T cells can be combined with the pharmaceutical 
composition of the invention. 
The pharmaceutical composition of the invention may be in the form of a 
liposome in which protein of the present invention is combined, in 
addition to other pharmaceutically acceptable carriers, with amphipathic 
agents such as lipids which exist in aggregated form as micelles, 
insoluble monolayers, liquid crystals, or lamellar layers in aqueous 
solution. Suitable lipids for liposomal formulation include, without 
limitation, monoglycerides, diglycerides, sulfatides, lysolecithin, 
phospholipids, saponin, bile acids, and the like. Preparation of such 
liposomal formulations is within the level of skill in the art, as 
disclosed, for example, in U.S. Pat. No. 4,235,871; U.S. Pat. No. 
4,501,728; U.S. Pat. No. 4,837,028; and U.S. Pat. No. 4,737,323, all of 
which are incorporated herein by reference. 
As used herein, the term "therapeutically effective amount" means the total 
amount of each active component of the pharmaceutical composition or 
method that is sufficient to show a meaningful patient benefit, i.e., 
treatment, healing, prevention or amelioration of the relevant medical 
condition, or an increase in rate of treatment, healing, prevention or 
amelioration of such conditions. When applied to an individual active 
ingredient, administered alone, the term refers to that ingredient alone. 
When applied to a combination, the term refers to combined amounts of the 
active ingredients that result in the therapeutic effect, whether 
administered in combination, serially or simultaneously. 
In practicing the method of treatment or use of the present invention, a 
therapeutically effective amount of protein of the present invention is 
administered to a mammal having a condition to be treated. Protein of the 
present invention may be administered in accordance with the method of the 
invention either alone or in combination with other therapies such as 
treatments employing cytokines, lymphokines or other hematopoietic 
factors. When co-administered with one or more cytokines, lymphokines or 
other hematopoietic factors, protein of the present invention may be 
administered either simultaneously with the cytokine(s), lymphokine(s), 
other hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or 
sequentially. If administered sequentially, the attending physician will 
decide on the appropriate sequence of administering protein of the present 
invention in combination with cytokine(s), lymphokine(s), other 
hematopoietic factor(s), thrombolytic or anti-thrombotic factors. 
Administration of protein of the present invention used in the 
pharmaceutical composition or to practice the method of the present 
invention can be carried out in a variety of conventional ways, such as 
oral ingestion, inhalation, topical application or cutaneous, 
subcutaneous, intraperitoneal, parenteral or intravenous injection. 
Intravenous administration to the patient is preferred. 
When a therapeutically effective amount of protein of the present invention 
is administered orally, protein of the present invention will be in the 
form of a tablet, capsule, powder, solution or elixir. When administered 
in tablet form, the pharmaceutical composition of the invention may 
additionally contain a solid carrier such as a gelatin or an adjuvant. The 
tablet, capsule, and powder contain from about 5 to 95% protein of the 
present invention, and preferably from about 25 to 90% protein of the 
present invention. When administered in liquid form, a liquid carrier such 
as water, 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 .mu.g to 
about 100 mg (preferably about 0.1 .mu.g to about 10 mg, more preferably 
about 0.1 .mu.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 
application of the protein of the present invention will be in the range 
of 12 to 24 hours of continuous intravenous administration. Ultimately the 
attending physician will decide on the appropriate duration of intravenous 
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 ligament regeneration, the therapeutic method 
includes administering the composition topically, systematically, or 
locally as an implant or device. When administered, the therapeutic 
composition for use in this invention is, of course, in a pyrogen-free, 
physiologically acceptable form. Further, the composition may desirably be 
encapsulated or injected in a viscous form for delivery to the site of 
bone, cartilage or tissue damage. Topical administration may be suitable 
for wound healing and tissue repair. Therapeutically useful agents other 
than a protein of the invention which may also optionally be included in 
the composition as described above, may alternatively or additionally, be 
administered simultaneously or sequentially with the composition in the 
methods of the invention. Preferably for bone and/or cartilage formation, 
the composition would include a matrix capable of delivering the 
protein-containing composition to the site of bone and/or cartilage 
damage, providing a structure for the developing bone and cartilage and 
optimally capable of being resorbed into the body. Such matrices may be 
formed of materials presently in use for other implanted medical 
applications. 
The choice of matrix material is based on biocompatibility, 
biodegradability, mechanical properties, cosmetic appearance and interface 
properties. The particular application of the compositions will define the 
appropriate formulation. Potential matrices for the compositions may be 
biodegradable and chemically defined calcium sulfate, 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, aluminares, or other ceramics. Matrices may be comprised of 
combinations of any of the above mentioned types of material, such as 
polylactic acid and hydroxyapatite or collagen and tricalciumphosphate. 
The bioceramics may be altered in composition, such as in 
calcium-aluminate-phosphate and processing to alter pore size, particle 
size, particle shape, and biodegradability. 
Presently preferred is a 50:50 (mole weight) copolymer of lactic acid and 
glycolic acid in the form of porous particles having diameters ranging 
from 150 to 800 microns. In some applications, it will be useful to 
utilize a sequestering agent, such as carboxymethyl cellulose or 
autologous blood clot, to prevent the protein compositions from 
disassociating from the matrix. 
A preferred family of sequestering agents is cellulosic materials such as 
alkyicelluloses (including hydroxyalkylcelluloses), including 
methylcellulose, ethylcellulose, hydroxyethylcellulose, 
hydroxypropylcellulose, hydroxypropyl-methylcellulose, and 
carboxymethylcellulose, the most preferred being cationic salts of 
carboxymethylcellulose (CMC). Other preferred sequestering agents include 
hyaluronic acid, sodium alginate, 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 cells are prevented from infiltrating the matrix, thereby 
providing the protein the opportunity to assist the osteogenic activity of 
the progenitor cells. 
In further compositions, proteins of the invention may be combined with 
other agents beneficial to the treatment of the bone and/or cartilage 
defect, wound, or tissue in question. These agents include various growth 
factors such as epidermal growth factor (EGF), platelet derived growth 
factor (PDGF), transforming growth factors (TGF-.alpha. and TGF-.beta.), 
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, histomorphometric 
determinations and tetracycline labeling. 
Polynucleotides of the present invention can also be used for gene therapy. 
Such polynucleotides can be introduced either in vivo or ex vivo into 
cells for expression in a mammalian subject. Polynucleotides of the 
invention may also be administered by other known methods for introduction 
of nucleic acid into a cell or organism (including, without limitation, in 
the form of viral vectors or naked DNA). 
Cells may also be cultured ex vivo in the presence of proteins of the 
present invention in order to proliferate or to produce a desired effect 
on or activity in such cells. Treated cells can then be introduced in vivo 
for therapeutic purposes. 
Patent and literature references cited herein are incorporated by reference 
as if fully set forth. 
__________________________________________________________________________ 
SEQUENCE LISTING 
(1) GENERAL INFORMATION: 
(iii) NUMBER OF SEQUENCES: 71 
(2) INFORMATION FOR SEQ ID NO:1: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 628 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: 
AAAAAGAGGAGGATTTGATATTCACNTGGCCCGCGGNGATGCCTTTGAGGGNGGCCGCGT60 
CCATNTGGTCAGAAAAGACAATCTTTTTGTTGTCAAGCTTGAGGTGTGGCAGGCTTGAGA120 
TCTGGCCATACACTTGAGTGACAATGACATCCANTTTGCCTTTCTCTCCACAGGTGTCCA180 
NTCCCAGGTCCAACTGCAGANTTCGAATTCGGCCTTCATGGCCTASGCAARCTACTGGCA240 
CCTGCTGYTCTCAACTAACCTCCACACAATGGTGTTCGCATTTTGGAAGGTCTTTCTGAT300 
CCTAAGCTGCCTTGCAGGTCAGGTTAGTGTGGTGCAAGTGACCATCCCAGACGGTTTCGT360 
GAACGTGACTGTTGGATCTAATGTCACTCTCATCTGCATCTACACCACCACTGTGGCCTC420 
CCGAGAACAGCTTTCCATCCAGTGGTCTTTCTTCCATAAGAAGGAGATGGAGCCAATTTC480 
TATTTACTTTTCTCAAGGTGGACAAGCTGTAGCCATCGGGCAATTTAAAGATCGAATTAC540 
AGGGTCCAACGATCCAGGTAATGCATCTATCACTATCTCGCATATGCAGCCAGCAGACAG600 
TGGAATTTACATCTGCGATGTTAACAAC628 
(2) INFORMATION FOR SEQ ID NO:2: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 137 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: 
MetAlaXaaAlaXaaTyrTrpHisLeuLeuXaaSerThrAsnLeuHis 
151015 
ThrMetValPheAlaPheTrpLysValPheLeuIleLeuSerCysLeu 
202530 
AlaGlyGlnValSerValValGlnValThrIleProAspGlyPheVal 
354045 
AsnValThrValGlySerAsnValThrLeuIleCysIleTyrThrThr 
505560 
ThrValAlaSerArgGluGlnLeuSerIleGlnTrpSerPhePheHis 
65707580 
LysLysGluMetGluProIleSerIleTyrPheSerGlnGlyGlyGln 
859095 
AlaValAlaIleGlyGlnPheLysAspArgIleThrGlySerAsnAsp 
100105110 
ProGlyAsnAlaSerIleThrIleSerHisMetGlnProAlaAspSer 
115120125 
GlyIleTyrIleCysAspValAsnAsn 
130135 
(2) INFORMATION FOR SEQ ID NO:3: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 358 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: 
ATGTTATCACNGTGTCNGATGTTATNNACTTNGAAAGGCAGTCCAGAAAAGTGTTCTAAG60 
NGAANTCTTAAGATCTATTTTAGATAATTTCAACTAATTAAATAACCTGTTTTACTGCCT120 
GNACATTCCACATTAATAANGNGATACCAATCTTATANGAATGCTAATATTACTAAAATG180 
CACTGATATCACTTNTTCTTCCCCTGTNGAAAAGCTTTCTCATGATCATATTTCACCCAC240 
ATNTCACCTNGAAGAAACTTACAGGTAGACTTACCTTTTCACTTGTGGAATTAATCATAT300 
TTAAATCTTACTTTAAGGCTCAATAAATAATANTCATAAAAAAAAAAAAAAAAAAAAA358 
(2) INFORMATION FOR SEQ ID NO:4: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 271 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: 
TAATCATGCCTCTTGGAAGTNAGTTAACGGGCGTGATTGTGGAAAATGAAAATATTACCA60 
AAGAAGGTGGCTTATTGGACATGGCCNNNAAANAAAATGACTTNNATGCNGAGCCCNNTT120 
TAAAGCAGACAATTAAAGCAACAGTNNAAAATGGCAANAANGATGGCNTTGCTGTTGATC180 
NTGTTGTNGGCCTGAATACNGAAAAATATGCTGAAACTGTCCAACTTNANCNTAAAAGAA240 
CCCCNGGTNAAGTNAAAGACATTTCCTTGAA271 
(2) INFORMATION FOR SEQ ID NO:5: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 591 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: 
ATGGTNACAGGTGCAGGTGTTNTCCTGGGAGATAATGATGCACCACCAGGAACAAGTGCC60 
AGCCAAGAAGGAGATGGTTCTGTGAATGATGGTACAGAAGGTGAGAGTGCAGTCACCAGC120 
ACGGGGATAACAGAAGATGGAGAGGGGCCAGCAAGTTGCACAGGTTCAGAANATTGCNTC180 
GAAGGCTTTGCTATAAGTTCTGAATCGGAAGAAAATGGAGAGAGTGCAATGGACAGCACA240 
GTGGCCAAAGAAGGCACTAATGTACCATTAGTTGCTGCTGGTCCTTGTGATGATGAAGGC300 
ATTGTGACTAGCACAGGCGCNAAAGAGGAAGACGAGGAAGGGGAGGATGTTGTGACTAGT360 
ACTGGAAGAGGAAATGAAATTGGGCATGCTTCAACTTGTACAGGGTTAGGAGAAGAAAGT420 
GAAGGGGTCTTGATTTGTGAAAGTGCAGAAGGGGACAGTCAGATTGGTACTGTGGTAGAG480 
CATGTGGAAGCTGAGGCTGGAGCTGCCATCATGAATGCAAATGAAAATAATGTTGACAGC540 
ATGAGTGGCACAGAGAAAGGAAGTAAAGACACAGATATCTGCTCCAGTGCC591 
(2) INFORMATION FOR SEQ ID NO:6: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 197 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: 
MetValThrGlyAlaGlyValXaaLeuGlyAspAsnAspAlaProPro 
151015 
GlyThrSerAlaSerGlnGluGlyAspGlySerValAsnAspGlyThr 
202530 
GluGlyGluSerAlaValThrSerThrGlyIleThrGluAspGlyGlu 
354045 
GlyProAlaSerCysThrGlySerGluXaaCysXaaGluGlyPheAla 
505560 
IleSerSerGluSerGluGluAsnGlyGluSerAlaMetAspSerThr 
65707580 
ValAlaLysGluGlyThrAsnValProLeuValAlaAlaGlyProCys 
859095 
AspAspGluGlyIleValThrSerThrGlyAlaLysGluGluAspGlu 
100105110 
GluGlyGluAspValValThrSerThrGlyArgGlyAsnGluIleGly 
115120125 
HisAlaSerThrCysThrGlyLeuGlyGluGluSerGluGlyValLeu 
130135140 
IleCysGluSerAlaGluGlyAspSerGlnIleGlyThrValValGlu 
145150155160 
HisValGluAlaGluAlaGlyAlaAlaIleMetAsnAlaAsnGluAsn 
165170175 
AsnValAspSerMetSerGlyThrGluLysGlySerLysAspThrAsp 
180185190 
IleCysSerSerAla 
195 
(2) INFORMATION FOR SEQ ID NO:7: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 289 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: 
GTATGCCAATTTCCGCCAGCATTGACNGACATGAAGAGAATCAGNTGACTGCAGACAACC60 
CAGAAGGGAACGGTGACTTNTCAGCCACAGAAGTGAGCAAGCACAAGTTCCCCATGCCCA120 
GCTTAATTGCTGAGAATAACTGTCGGTGTCCTGGGCCAGTCAGGGGAGGCAAAGAACTGG180 
GTCCCGTGTTGGCAGTGAGCACCGAGGAGGGGCACAACGGGCCATCAGTCCACAAGCCNT240 
CTGCAGGGCAAGGCCATCAAGTGCTGTTTGTGCGGAAAAAAAAAAAAAA289 
(2) INFORMATION FOR SEQ ID NO:8: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 429 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: 
CTTGGTCCANTTGGTTTNNTTCGNTTCCCCCTTTTTCTTCCCCTTGGTTTTCTTTTTTTT60 
CGGGCAACAATATTTTCCAAGGCTAATACCAAGGCANACCAATTCAACTCCCAAGGNTCG120 
GGAATTTTTAACCTTTTAATTNNATGGCCCCTCCCACTCCTTTTCTACGGCGATTTGTCT180 
GTGTCTGGCCCCCACCCACTGCCCATCCCCCATTGTTGTCTGGATGTGGTTCTATTTTTT240 
ATCGGTCTCCTTTCCCCTCCTCCCCGTTCTCGCCCCCGCCCCACCCCCTGCTCCCACTAC300 
CCTTTGTCTCTTGCTCTTTCTTGGGCTTCTGTACAACTCAACTTGTATACACTGTGTACA360 
CACAACCAGCCAAACGAAAACCCAACGGCRAAMAAAAAAAAAAAAAAAAAAAAAAAAAAA420 
AAAAAAAAA429 
(2) INFORMATION FOR SEQ ID NO:9: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 130 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: 
LeuGlyProXaaGlyXaaXaaArgPheProLeuPheLeuProLeuGly 
151015 
PheLeuPhePheArgAlaThrIlePheSerLysAlaAsnThrLysAla 
202530 
XaaGlnPheAsnSerGlnGlySerGlyIlePheAsnLeuLeuIleXaa 
354045 
TrpProLeuProLeuLeuPheTyrGlyAspLeuSerValSerGlyPro 
505560 
HisProLeuProIleProHisCysCysLeuAspValValLeuPhePhe 
65707580 
IleGlyLeuLeuSerProProProArgSerArgProArgProThrPro 
859095 
CysSerHisTyrProLeuSerLeuAlaLeuSerTrpAlaSerValGln 
100105110 
LeuAsnLeuTyrThrLeuCysThrHisAsnGlnProAsnGluAsnPro 
115120125 
ThrAla 
130 
(2) INFORMATION FOR SEQ ID NO:10: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 368 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: 
TCTGTTCCCGAACTGGAACTGCGTTGGGACCCGTCGGATCGTAAATCCCATGTNNGGTAT60 
CTGCCGTCGGAAAATTTGAACTTTCTAATTGGACACCTAACACCCACANTCCTCCAGGTG120 
GGTCCTAAGGATCTTANGAACAACGATGGGGGGTCCTAANCCAGGGGGGGATGAAGGTCT180 
GGCTCTCAATCCCCGCCTCGCGGGGANTNCCTCCCCCCTCTGCGATGGGGGTCCTAAGAG240 
CCATTGGGGGAACCAGGGGCTGGCTCTCAATCCCTGCCTCGCGGGGGGTGCCTCCCCCCC300 
TGTGATGGGGGTTCTAACAGCCANGGGCGGAANAAGGGATATCTCTCACTCCCCACCTTC360 
NCGGGGGG368 
(2) INFORMATION FOR SEQ ID NO:11: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 396 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: 
GAACTTTCTACTTGGACAACTAACACCCACAGTCCTCCAGACAGAAAGACAACAGGTACA60 
AAGCCCTAAGGATTATAAAGGTATGCTGCTTACCATCATCTTAGTGACCAAGGCAGCGAA120 
GCTGTTTCTGTACCTTGGAACAGTCTTCCCTGACAAGCCAGAGAACAGTGATAAAGCCAC180 
CAGCCTTGGGATCAGGACTGAAAAGGCAAGAGTGATGGAGATTTCTCCTGCGCTAAGCCA240 
AGAGAAGGTTTCAGCACTTCAGACAGCTCCCACCGAAGTAGCCGCGTTCCCAGCTGCTTG300 
CAGATGTTGAAAAGGAAAGCCTCGGTTTGTCTTGAGGTTGTCAGCAGGTGCAAGACACGT360 
AATAAAATGCAATGTGTTCCTAAAAAAAAAAAAAAA396 
(2) INFORMATION FOR SEQ ID NO:12: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 75 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: 
MetLeuLeuThrIleIleLeuValThrLysAlaAlaLysLeuPheLeu 
151015 
TyrLeuGlyThrValPheProAspLysProGluAsnSerAspLysAla 
202530 
ThrSerLeuGlyIleArgThrGluLysAlaArgValMetGluIleSer 
354045 
ProAlaLeuSerGlnGluLysValSerAlaLeuGlnThrAlaProThr 
505560 
GluValAlaAlaPheProAlaAlaCysArgCys 
657075 
(2) INFORMATION FOR SEQ ID NO:13: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 429 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: 
TCAGAAAAGACAATNTTTTAGTAANAAAGNANTGAGGTGTGGCAGGCTNGAGATTTGGCC60 
ANANACTNGAGTGACAANGACATCCACTTTGCCTTTNTCTCCACAGGTGTCCACTCCCAG120 
GTCCAACTGCAGATTTNGAATTCGGCNTTCATGGCCTAGCCCCTTCCACCTCTTCTCCTA180 
NGACTTGGAGGANTCCTCCCTGTCCACCAAGGAGAAGGAAGCAGANTCCCAGAAGGAAAA240 
CAGANACAGCAATTTTGGCAATAACTCTTATCACTCCTCAAGACCCTCATCTGGATCCAG300 
TGTGCCCACCACCCCCACATCATCCGTCTCACCCCCACAGGAGGCCAGGTTGGAAAGGTC360 
ATCACCGAGTGGTCTTCTCACATCATCCTTCAGGCAGCACCAAGAGTCACTGGCAAAAAA420 
AAAAAAAAA429 
(2) INFORMATION FOR SEQ ID NO:14: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 138 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: 
GlnLysArgGlnXaaPheSerXaaLysXaaXaaArgCysGlyArgLeu 
151015 
GluIleTrpProXaaThrXaaValThrXaaThrSerThrLeuProXaa 
202530 
SerProGlnValSerThrProArgSerAsnCysArgPheXaaIleArg 
354045 
XaaSerTrpProSerProPheHisLeuPheSerXaaAspLeuGluXaa 
505560 
SerSerLeuSerThrLysGluLysGluAlaXaaSerGlnLysGluAsn 
65707580 
ArgXaaSerAsnPheGlyAsnAsnSerTyrHisSerSerArgProSer 
859095 
SerGlySerSerValProThrThrProThrSerSerValSerProPro 
100105110 
GlnGluAlaArgLeuGluArgSerSerProSerGlyLeuLeuThrSer 
115120125 
SerPheArgGlnHisGlnGluSerLeuAla 
130135 
(2) INFORMATION FOR SEQ ID NO:15: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 218 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: 
TGGCCTACCTGACCTCAGGTGATCTGCCCGCCTCGGCCTCTGAAAGTGCTGGGATTATAG60 
GCATGAGCCNACATGCCTGACCTGTTATTTATTTTAAATTATATCAGGAATACACACACA120 
CACACACACACACACACACACACACACACAACTTATAAAGATAATGGTCTCCTTGGCACT180 
CCCACCCACCCACCCATCCAAATTTACACAAATTAATC218 
(2) INFORMATION FOR SEQ ID NO:16: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 322 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: 
ATCCAAATTNACACAAGTAAATCTGTAATCAATTTGGTTAGAAGGGATTTATTTTAATAT60 
TTTTGGGGATTGCTTAGATGCAGTATAATTTTTAGTTATATTAGTAGTAATTGGAAATGT120 
GTATTTTTGTGACTGAAGTCACCTTCTAAATAATTTCTAGAATAAAATTTTTATATTGAA180 
GAAGTTGGTNTTAACCATTTTTTTTTCAGGAGCATGCATTTTGAAATCATTCTGTGGGAA240 
GATGAAAACAAATTTAGTTCTATGTCTCCCCTTTTTAGAGATGTTGACACTTTCCTTAAA300 
TGTACCATGCATGATTTGTCTA322 
(2) INFORMATION FOR SEQ ID NO:17: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 27 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: 
MetLysThrAsnLeuValLeuCysLeuProPheLeuGluMetLeuThr 
151015 
LeuSerLeuAsnValProCysMetIleCysLeu 
2025 
(2) INFORMATION FOR SEQ ID NO:18: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 379 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: 
CAGTTTTGATGTAAGTAAATACCCAACAGAAATGCAAACATATACTTACCAAAACTCATG60 
TCCAAGAATATTCGTAGAAGCACAATTCTTATGATAGCAAAAAGGTAGAAAACAACTTAA120 
ATGTTTTTAAGCAGTAGCATAAGAGTAATACCGTGTGGTTTGTTTANACAGTGAGATCCT180 
GTACAGCCATGTAAAAGACCAAAATATTCCCTGTAACAATGAGAATGAATCTCCTGTGCT240 
TGCTTCGGCAGCACATACANTAAAATTGGAACGATACAGAGATTANCATGNCCCCTGTGC300 
AAGGAGAATGAATTTTCGTAATGTTCAGCAAAAGAAGCCAGATATAAATGAATATTCCAT360 
TTTATAAAAANAAAAAAAA379 
(2) INFORMATION FOR SEQ ID NO:19: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 456 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: 
AAGAAGGAGACTGTAAGCTTGTTTGTACAAAAACATACCATACAGAGAAAGCTGAAGACA60 
AACAAAAGTTAGAATTCTTGAAAAAAAGCATGTTATTGAATTATCAACATCACTGGATTG120 
TGGATAATATGCCTGTAACGTGGTGTTACGATGTTGAAGATGGTCAGGTTCTGTAATCCT180 
GGATTTCCTATTGGCTGTTACATTACAGATAAAGGCCATGCAAAAGATGCCTGTGTTATT240 
AGTTCAGATTTCCATGAAAGAGATACATTTTACATCTTCAACCATGTTGACATCAAAATA300 
TACTATCATGTTGTTGAAACTGGGTCCATGGGAGCAAGATTAGTGGCTGCTAAACTTGAA360 
CCGAAAAGCTTCAAACATACCCATATAGATAAACCAGACTGCTCAGGGCCCCCCATGGAC420 
ATAAGTAACAAGGCTTCTGGGGAGATAAAAATTGCA456 
(2) INFORMATION FOR SEQ ID NO:20: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 519 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: 
CAANTAATAAANCTTTTGTTTCCCTCGNCATTGTNNTCGTTCCCCTGTCCNGCCTTGTTT60 
CCNNNGTCCTGCACCAATATTTCCAAACCNAATACCCAAGCATACAATCCNNACTCCAAG120 
CTNGGAATTCGCCCANAGAGACCGTCGNGGGAAGAANTTGNCTGGAAACTTGTTCATGGT180 
GATATATACCGTCCTCCAAGAAANGGGATGCTGCTATCAGTCTTTCTAGGAGCCGGGANA240 
CAGATATTAATTATGACCTTTGTGACTCTATTTTTCGCTTGCCTGGGAGTTTTGTCACCT300 
CCCANCCGAGGAGCGCTGATGACGTGTGCTGTGGTCCTGTGGGTGCTGCTGGGCACCCCT360 
GCAGGCTATGTTTCTGCCAGATTCTATAAGTCCTTTGGAGGTGAGAAGTGGAAAACAAAT420 
GTTTTATTAACATCATTTCTTTGTCCTGGGATTGTATTTGCTGACTTCTTTATAATGAAT480 
CTGATCCTCTGGTCAACGGCCTCTTTGGCCCTCGAGACA519 
(2) INFORMATION FOR SEQ ID NO:21: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 89 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: 
MetThrPheValThrLeuPhePheAlaCysLeuGlyValLeuSerPro 
151015 
ProXaaArgGlyAlaLeuMetThrCysAlaValValLeuTrpValLeu 
202530 
LeuGlyThrProAlaGlyTyrValSerAlaArgPheTyrLysSerPhe 
354045 
GlyGlyGluLysTrpLysThrAsnValLeuLeuThrSerPheLeuCys 
505560 
ProGlyIleValPheAlaAspPhePheIleMetAsnLeuIleLeuTrp 
65707580 
SerThrAlaSerLeuAlaLeuGluThr 
85 
(2) INFORMATION FOR SEQ ID NO:22: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 507 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: 
TTCTTCCCATACACCTTTCCCCCATAAGATGTGTCTTCAACACTATAAAGCATTTGTATT60 
GTGATTTGATTAAGTATATATTTGGTTGTTCTCAATGAAGAGCAAATTTAAATATTATGT120 
GCATTTGTAAATACAGTAGCTATAAAATTTTCCATACTTCTAATGGCAGAATAGAGGAGG180 
CCATATTAAATAATACTGATGAAAGGCAGGACACTGCATTGTAAATAGGATTTTCTAGGC240 
TCGGTAGGCAGAAAGAATTATTTTTCTTTGAAGGAAATAACTTTTTATCATGGTAATTTT300 
GAAGGATGATTCCTATGATGTGTTCACCAGGGGAATGTGGCTTTTAAAGAAAATCTTCTA360 
TTGGTTGTAACTGTTCATATCTTCTTACTTTTCTGTGTTGACTTCATTATTCCCATGGTA420 
TTGGCCTTTTAAACTATGTGCCTCTGAGTCTTTCAATTTATAAATTTGTATCTTAATAAA480 
TATTATAAAAATGAAAAAAAAAAAAAA507 
(2) INFORMATION FOR SEQ ID NO:23: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 622 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: 
GGTTCTTCGGGACACCCGTGGATGGACACGGNAAGGAAACACCAGGCCAACCACAGNTGG60 
GGATANAATAGNACAACCACACCCTGCCGTCCAGAGCCTCCCAGNCTGTGCCCCGTCCTA120 
GTACCACCAGCAACCATCAATCCCGTCTCCTCCTGCCTCCTCTCCTGCAATCCACCCCGC180 
CACGACTATCGCCATGGCAGCCCTGATCGCAGAGAACTTCCGCTTCCTGTCACTTTTCTT240 
CAAGAGCAAGGATGTGATGATTTTCAACGGCCTGGTGGCACTGGGCACGGTGGGCAGCCA300 
GGAGCTGTTCTCTGTGGTGGCCTTCCACTGCCCCTGCTCGCCGGCCCGGAACTACCTGTA360 
CGGGCTGGCGGCCATCGGCGTGCCCGCCCTGGTGCTCTTCATCATTGGCATCATCCTCAA420 
CAACCACACCTGGAACCTCGTGGCCGAGTGCCAGCACCGGAGGACCAAGAACTGCTCCGC480 
CGCCCCCACCTTCCTCCTTCTAAGCTCCATCCTGGGACGTGCGGCTGTGGCCCCTGTCAC540 
CTGGTCTGTCATCTCCCTGCTGCGTGGTGAGGCTTATGTCTGTGCTCTCAGTGAGTTCGT600 
GGACCCTTCCTCACTCACGGCC622 
(2) INFORMATION FOR SEQ ID NO:24: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 143 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: 
MetAlaAlaLeuIleAlaGluAsnPheArgPheLeuSerLeuPhePhe 
151015 
LysSerLysAspValMetIlePheAsnGlyLeuValAlaLeuGlyThr 
202530 
ValGlySerGlnGluLeuPheSerValValAlaPheHisCysProCys 
354045 
SerProAlaArgAsnTyrLeuTyrGlyLeuAlaAlaIleGlyValPro 
505560 
AlaLeuValLeuPheIleIleGlyIleIleLeuAsnAsnHisThrTrp 
65707580 
AsnLeuValAlaGluCysGlnHisArgArgThrLysAsnCysSerAla 
859095 
AlaProThrPheLeuLeuLeuSerSerIleLeuGlyArgAlaAlaVal 
100105110 
AlaProValThrTrpSerValIleSerLeuLeuArgGlyGluAlaTyr 
115120125 
ValCysAlaLeuSerGluPheValAspProSerSerLeuThrAla 
130135140 
(2) INFORMATION FOR SEQ ID NO:25: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 314 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: 
TTTTAAAAAACTTTTATCTTCTTGGCCAGGGGAAAGGNCCCCCAGGCAANCTGGGGTNTG60 
GANANACCCANAAAACNATGGNANCCCCAACCANCAGGGCCAGGTTACAGTGNAACTCCC120 
CAGTGGGCCCCNTTATGGGACTCNATTCAGTTAANATTTATCTANCTTCANAGGGACACC180 
CANCCCAACAGTTCCCCNCTGGGGAGTGGCCCCCANTTCAACCTCTGGCCTTANTTTAAA240 
AAATTAAANTTTTNANAAAGTTTTTCTTACTAAAAGGGAAAAAAAAAAAAAAAAAAAAAA300 
AAAAAAAAAAAAAA314 
(2) INFORMATION FOR SEQ ID NO:26: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 533 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: 
GGGATATCCCATACAGGTATGAAAAAACCCCNTATGTNATAGTGTTCTATAGCACACAAT60 
ACCTTATGAAGGAAGGGTTTSATGAATACATGGCAGAAGACAATCATGAAAGAMTTATYT120 
TGAGGGGYTAGAARTAATGAGTTTGGAGGTGTGCCCCTTAGGTCCTGARTGTCCTGGGAT180 
CCCTMACCCCTAATTTCTCTCCCARAGCATYATCCCTTCTCAGTATTGGTACTACATGAT240 
TGAACTTTCCTTCTASTGGTCCCTGYTCTTCAGCATTGCCTCTGATGTCWAGCGAAAGGA300 
TTTTAAGGAACAGATCATCCACCATGTGGCCACTATCATTCTCCTCTGCTTCTCCTGGTT360 
TGCCAATTACGTCCGGGCAGGGACCCTCATCATGGCTCTGCATGACGCTTCTGACTACCT420 
GCTGGAGTCTGCCAAGATGTTTAACTACGCGGGATGGAAGAACACCTGCAACAACCTCTT480 
CATTGTGTTCGCCATCGTTTTCATCATCACTCGGCTGGTTATCATGCCTTTCT533 
(2) INFORMATION FOR SEQ ID NO:27: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 44 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: 
MetThrLeuLeuThrThrCysTrpSerLeuProArgCysLeuThrThr 
151015 
ArgAspGlyArgThrProAlaThrThrSerSerLeuCysSerProSer 
202530 
PheSerSerSerLeuGlyTrpLeuSerCysLeuSer 
3540 
(2) INFORMATION FOR SEQ ID NO:28: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 313 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: 
AAANACAAGTCAATGAAGTGAAGGAGGGTATGNANACATGCCCCTCACCATACCCCAGGG60 
ACCATGGTTCCTAGGATCTCACTGCCTCCCTTTNTGGCCTTCCTGTCCCCTCCCTTCAGC120 
TATGACAGCTGGTGTGGAGTAGAAGGGCAACTAGTTCTGTTATTTATTGAACATTTGGGG180 
TTTCAGTTGTAAAGCCACAACTACAGGTAGGACCTGATATTTCGGNGAGGGACCATTTCA240 
GACCAAAATGTACTGTTAATTTTTTTTAATTAAAGTATATTAAAGGTTAAATAAAAAAAA300 
AAAAAAAAAAAAA313 
(2) INFORMATION FOR SEQ ID NO:29: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 525 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: 
AAAGACATCCACTTTGCCTTTNTCTCCACAGGTGTCCACTCCCAGGTCCAANTGNAGGNG60 
AGCCTGAATTCGGCCAAAGAGGCCTAATTACAATCATTTCAAATTTTGAATTTTTAAGTT120 
GATGGGCTCTTAAGTGGTCCGTTCTGAATARAAACCAATTTGCTAGTTTCGGTTTTGTTT180 
TGTTTTGTTTTGTTTTGTTTTGTTTTGTTTTTTTAAGGAATCAGATAGCCAGAAAAAAAA240 
ATGCTATTGCTTGTTTTCATGAACTTCAGTTGTCTCTTTTTAGTAAACCCAGTACTTTCC300 
ACAAAGTCTTCTCTGACCTTCCCCATCACTGGACGGTTCACCCATCTTCTTCTCCAAGTG360 
TTTATCCCCCAGCCCAAGCCTTTCCTGCTGCAAGCCAAGCCTGCTACATTTGTTACAGAC420 
CAAGCTTATACACAGCTCGACAACTGCACTCCCACTGTAGGCTCCGGTGTGTACTCTTGT480 
CTTGTGTTGGGAAGGGGAAGTGAAGTGATAAGCCAGAATTTTTTT525 
(2) INFORMATION FOR SEQ ID NO:30: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 95 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: 
MetLeuLeuLeuValPheMetAsnPheSerCysLeuPheLeuValAsn 
151015 
ProValLeuSerThrLysSerSerLeuThrPheProIleThrGlyArg 
202530 
PheThrHisLeuLeuLeuGlnValPheIleProGlnProLysProPhe 
354045 
LeuLeuGlnAlaLysProAlaThrPheValThrAspGlnAlaTyrThr 
505560 
GlnLeuAspAsnCysThrProThrValGlySerGlyValTyrSerCys 
65707580 
LeuValLeuGlyArgGlySerGluValIleSerGlnAsnPhePhe 
859095 
(2) INFORMATION FOR SEQ ID NO:31: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 270 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: 
AGGTTTCTTGGGAACAGCTCAGCAGATTTTTGAGACCAATCAAATGNCCTCATTAAGAAC60 
TTTATCTGTTNGGAAACATGGCTTCCTTCCNGGNTCTGCTAAACNGAAAGCTCATTTGTT120 
GTTGCTGTTGTTGTTGTTTGTTTGTCCATTTCTCTTTAATTCTAATGTTNACATCATGTC180 
GTGCTGTANGANTCTAGAAAGCCTTAATTNACTTCCACCAAGAAATAAAGCAATATGTTG240 
GTAATNNGAAAAAAAAAAAAAAAAAAAAAA270 
(2) INFORMATION FOR SEQ ID NO:32: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 574 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: 
TTTGGTCANAAAAGACAATTTTTTTGTTNTCAAGCTNGAGGTGTGGCAGGCTNGANATTT60 
GGCCAAANAATNGAGGGACAAAGANATCCACTTTGCCTTTTTTTCCACAGGTGTCCANTC120 
CCAGGTCCAANTGCAGGCGGGTCCACAGGCCGCAGCCATGGGTAGCCGNNTNTCCCGAGN180 
GGARTTCGAATGGGTYTACACGGACCARCCCCACGCCGCCCGGCGCAAGGAGATCTTAGC240 
AAAGTATCCAGANATCAAGTCCTTGATGAAACCTGACCACAATCTGATCTGGATTGTAGC300 
CATGATGCTTCTCGTCCAGCTGGCTTCATTTTACTTAGTCAAAGATTTGGACTGGAAATG360 
GGTCATATTTTGGTCCTATGTCTTTGGCAGCTGCCTTAACCACTCCATGACTCTGGCTAT420 
CCATGAGATTTCCCACAATTTCCCCTTNGGCNCCNCNANGGCCTGTGGAACCGCNGGTTT480 
GGAATGTTTGCTAACCTCTCTCTCCGAATGGCCTACTCCATTTCCTTTAAAAAAAACACA540 
TGGATCACCNCCGGTACTCCGAACGGATAAANTR574 
(2) INFORMATION FOR SEQ ID NO:33: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 138 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: 
MetGlySerArgXaaSerArgXaaGluPheGluTrpValTyrThrAsp 
151015 
GlnProHisAlaAlaArgArgLysGluIleLeuAlaLysTyrProXaa 
202530 
IleLysSerLeuMetLysProAspHisAsnLeuIleTrpIleValAla 
354045 
MetMetLeuLeuValGlnLeuAlaSerPheTyrLeuValLysAspLeu 
505560 
AspTrpLysTrpValIlePheTrpSerTyrValPheGlySerCysLeu 
65707580 
AsnHisSerMetThrLeuAlaIleHisGluIleSerHisAsnPhePro 
859095 
XaaGlyXaaXaaXaaAlaCysGlyThrAlaGlyLeuGluCysLeuLeu 
100105110 
ThrSerLeuSerGluTrpProThrProPheProLeuLysLysThrHis 
115120125 
GlySerProProValLeuArgThrAspLys 
130135 
(2) INFORMATION FOR SEQ ID NO:34: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 216 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: 
ATGAAGTGCTTTTTGGAGGAGCTTTTGTTTAGTCCAACAGGAGTCCAAGGATGCAGATTA60 
GAGTTTTGNGAGTTTGCTGCCCTTGNTGGGCTAGGCATTTCATTGTTGTAACTNCNTCNG120 
AGTAACTGATGATCCTATAAGNAACCCCAATAAATTTTTTGGTTTACTAAAAAAAAAAAA180 
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA216 
(2) INFORMATION FOR SEQ ID NO:35: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 526 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: 
ACAGGNGTCCAATCCCAGGTCCAANTGCAGGGGAGCCTGAATTCGGCCAAAGNGGCCTAG60 
CCTCCCAAGTGSTGGGATTAAAGGSGTGTGCCACCATGCCCCACTTCATATGTTATATTT120 
TTAATGAATAAAGAGTGGAAAAATTATGTATCACATGTGTTAATTTGGGGAGAAGCGCTT180 
TATAACAGAGGGCTTACTYTCAATTAAAGAGAACAAAGGRAAATGTGTTYTACAGGCAGT240 
GTATACCTTTGACCTCTGAAAAAACCTATATAGTTTCTCCTACAGACACCTTGCCAGTAA300 
CCTTACAGGTCTTATAGGAGAGCAGATCCAAGTTGCCAGGCTGATCTGCAAGCACAAACA360 
TTTGTCAAGGGAAAGCACAGGTCGTTACTTTCAGTACAAAATGGTTCTTTGCTATGGATG420 
GATTCTCTTCTTCTTGCCCCATGTCCTGTTCCCAAGGACCGACTTCCTGCAGCACTGTGG480 
TGGACTCTTCTATGAGGAGACAACATCTGGGCCTTATTCAATAGCC526 
(2) INFORMATION FOR SEQ ID NO:36: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 42 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: 
MetValLeuCysTyrGlyTrpIleLeuPhePheLeuProHisValLeu 
151015 
PheProArgThrAspPheLeuGlnHisCysGlyGlyLeuPheTyrGlu 
202530 
GluThrThrSerGlyProTyrSerIleAla 
3540 
(2) INFORMATION FOR SEQ ID NO:37: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 208 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: 
TTTGAAANGGCAACAGAAATATTTTTTGNANTAGAAAAAGGNATGGAACGTGGTNCCAAT60 
TGTTNATTTTCCTTNATTTATTCCCNGTAANTTTGTCNGNNGATAAATTGAANATAACNG120 
NGATTAANGNNTNATGNTAAAAAAAAAAAAAAAAAAAAAANAAAAAAAAAAAAAAAAAAA180 
AAAAAAAAAAAAAAAAAAAAAAAAAAAA208 
(2) INFORMATION FOR SEQ ID NO:38: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 535 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:38: 
ATTTGNTCAGAAAAGACAATTTTTTTGTTNTCAAGCTTGAGGTGTGGCAGGCTTGAGATN60 
TGCCCANACACTTGAGGGACAANGACATCCAATAACCCNTTCTCTCCACAGGTGNCCACT120 
CCCAGGTCCAACTGCAGGCGAGCCNGAATTCGGCCAAAGNGGCCNAAGATCAGTTAGCTC180 
CCTGGGTCGGAACAAGGTGAAAAGCAGCTTTCTTGCTTTTGAAATCATYTTTGTGACAAG240 
GACACATGGGGTCAGGGTAGGGTGTCCARTTAAAATAGTGTCACTGCTTAGAAAGGGGWA300 
CTTGGATTCCTTTAGTTAGCTTAGCTCTGTCTCTTGTTTCATAAAACACACTGGGTTAGA360 
ATARAGGCTCCTGCATTACATGGTTTGTGTCACTGTTTTTTGTTGGGTTTTCTTTTTGGT420 
TTTTCGAGACAGGGTTTCTCTGTATAGCCCTGGCTGTCCTARAACTCACTCTGTAGACCA480 
GGCTGGCCTCGAACTCAGAAATCTGCCCGCTTCTGCCTCCCAAGTGCTGGGATTA535 
(2) INFORMATION FOR SEQ ID NO:39: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 52 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:39: 
MetValCysValThrValPheCysTrpValPhePheLeuValPheArg 
151015 
AspArgValSerLeuTyrSerProGlyCysProXaaThrHisSerVal 
202530 
AspGlnAlaGlyLeuGluLeuArgAsnLeuProAlaSerAlaSerGln 
354045 
ValLeuGlyLeu 
50 
(2) INFORMATION FOR SEQ ID NO:40: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 308 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:40: 
GGATTAAAGGCATGTGTCACGTTTTAAATTGATAGTTATAACNTCGATGCCACGAATCCT60 
GCAGTTTCTCCTGTGCTCCTTTCTTTGTGTCAGATGGGTTAAGGGTTATCAGTTNGGGGA120 
AGAATTGTCCTTGNACCCCCTGGAATTATTTTTCTCAAAAATCCAAGACTCCAAAGAACA180 
TGGGAAAAATTGTTCTGTCCACTTTTGACGTTGAAGATTTTGGTTATCCTTTTCGTACTT240 
TCTATGTATTTTCTATGTAAAATTTTACACAATTAAAAATGTTTTTTTGTCTAGTAAAAA300 
AAAAAAAA308 
(2) INFORMATION FOR SEQ ID NO:41: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 520 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: 
CAGCNCGCGGANCCGGCGTCCCGTTGGCGCGCTCTGGYMTGGMWTCGNGGTMGTCGNYTT60 
CGGCCCCGARGAGCCGCTCGCTGTYTCCSGAGCGGCGGARARGATGSTGCGGGGCAGCCS120 
GGGGCCCGCYGCGCGCCGCCGSGAGTGAACAGGGCCAGGCCGCGGGCGTCCGCKGGCTCG180 
AACCSCCAGTYTGCAGGGGCGKTTGCCGSTGGTGGGAAACATGTTCAGTATCAACCCCCT240 
GGAGAACCTGAAGCTGTACATCAGCAGCCGGCCGCCCTTGGTGGTTTTTATGATCAGTGT300 
CAGCGCCATGGCCATCGCCTTCCTCACCCTGGGCTACTTCTTCAAGATCAAGGAGATTAA360 
GTCCCCAGAAATGGCTGAGGATTGGAATACTTTTCTGCTCCGGTTTAATGATTTGGACTT420 
GTGTGTATCAGAAAACGAGACACTGAAGCATCTCTCCAACGATACCACCACACCAGAGAG480 
CACCATGACCGTCGGGCAGGCCAGATCGTCTACCCAGCCG520 
(2) INFORMATION FOR SEQ ID NO:42: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 100 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:42: 
MetPheSerIleAsnProLeuGluAsnLeuLysLeuTyrIleSerSer 
151015 
ArgProProLeuValValPheMetIleSerValSerAlaMetAlaIle 
202530 
AlaPheLeuThrLeuGlyTyrPhePheLysIleLysGluIleLysSer 
354045 
ProGluMetAlaGluAspTrpAsnThrPheLeuLeuArgPheAsnAsp 
505560 
LeuAspLeuCysValSerGluAsnGluThrLeuLysHisLeuSerAsn 
65707580 
AspThrThrThrProGluSerThrMetThrValGlyGlnAlaArgSer 
859095 
SerThrGlnPro 
100 
(2) INFORMATION FOR SEQ ID NO:43: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 244 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:43: 
GCGGCAGAGCAATCCTGAATTTTGCCANGAGAAGGNGGTTNTGGCTGACGCCTAATCNNA60 
CAGCTCCCCATTTTTTGAGAGACCAAGAACCATGATCATTGCCTGCTGAATCGGCCAGGG120 
CCTGGCCANTCTGTGAANACATGATCTTGCAATGTTGGGTTATTCCAGCCAAAGACATTT180 
CAAGTGCCTGTAANTGATTTGTCCATATTTATAAACACTGATNTGGNAAAAAAAAAAAAA240 
AAAA244 
(2) INFORMATION FOR SEQ ID NO:44: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 848 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:44: 
AGCTGTTGGGNTCGCGGTTGAGGACAAATNTTCGCGGTCTTTCCAGTATTCTTGGATCGG60 
AAACCCGTCGGCTTCCGAACGGTACTCCGCCACCGAGGGACCTGAGCGAGTCCGCATCGA120 
CCGGATCGGAAAACCTNTCGACTGTTGGGGTGAGTACTCCCTCTCAAAAGCGGGCATGAC180 
TTNTGCGCTAAGATTGTCAGTTTCCAAAAACGAGGAGGATTTGATATTCACCTGGCCCGC240 
GGTGATGCCTTTGAGGGTGGCCGCGTCCATCTGGTCAGAAAAGACAATCTTTTTGTTGTC300 
AAGCTTGAGGTGTGGCAGGCTTGAGATCTGGCCATACACTTGAGTGACAATGACATCCAC360 
TTTGCCTTTNTCTCCACAGGTGTCCACTCCCAGGTCCAACTGCAGACTTCGAATTCGGCC420 
AAAGAGGCCTACTTTCATATCCACGATGCGTTTTCTGGCCGCCACGATCCTGCTGCTGGC480 
GCTGGTCGCTGCCAGCCAGGCGGAGCCCCTGCACTTCAAGGACTGCGGCTCTAAGGTGGG540 
AGTTATAAAGGAGGTGAATGTGAGCCCATGTCCCACCGATCCCTGTCAGCTGCACAAAGG600 
CCAGTCCTACAGTGTCAACATCACCTTTACCAGCGGCACTCAGTCCCANAACAGCACGGC660 
CTTGGTCCACGGCATCCTGGAAGGGATCCGGGTCCCCTTCCCTATTCCTGANCCTGACGG720 
TTGTNANANTGGAATCAACTGCCCCNTCCAGAAAGACAANGTCTACAGCTACCTGAATAA780 
GCTTCCGGTGAAAAATGAATACCCCTCTATAAAACTGGTGGTGGAATGGAAACTTTGAAN840 
ATGACAAA848 
(2) INFORMATION FOR SEQ ID NO:45: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 130 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:45: 
MetArgPheLeuAlaAlaThrIleLeuLeuLeuAlaLeuValAlaAla 
151015 
SerGlnAlaGluProLeuHisPheLysAspCysGlySerLysValGly 
202530 
ValIleLysGluValAsnValSerProCysProThrAspProCysGln 
354045 
LeuHisLysGlyGlnSerTyrSerValAsnIleThrPheThrSerGly 
505560 
ThrGlnSerXaaAsnSerThrAlaLeuValHisGlyIleLeuGluGly 
65707580 
IleArgValProPheProIleProXaaProAspGlyCysXaaXaaGly 
859095 
IleAsnCysProXaaGlnLysAspXaaValTyrSerTyrLeuAsnLys 
100105110 
LeuProValLysAsnGluTyrProSerIleLysLeuValValGluTrp 
115120125 
LysLeu 
130 
(2) INFORMATION FOR SEQ ID NO:46: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 265 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:46: 
GNGTTACCTCCCCTGTTTCTAAGTGCCTCCTGAGTCCCCAGCCCCTGGCTTATCAGTCAG60 
ATGAGTNTCCTTGGNAGCNTCTGCCCCATCGCTTCAGCAGNAGNGACTAGNTTTCCTCGG120 
NATCCAGACTGGNTGNGGGGCAGTCTGCCGCAGAAANTTGTNTNTGAGTGGNTGNGTCTT180 
TGNGGTNAGCTNTCGTTCNNTGGTAGTNTTNATTAAAGCCAANANTNGGTTGCAAAAAAA240 
AANNGNAAAAAAAAAAAAAAAAAAA265 
(2) INFORMATION FOR SEQ ID NO:47: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 374 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:47: 
GCGGCCGCAGGTCTANAATTCAATCGGGCTGCCTTATCGCCAAGCTCCTTCAGGAGAACA60 
AAGAACAGGCCATTACCCTGGAAAANACTGGCAACTGATTTTACCCACAAGCCCNAACCT120 
CAGGGATTTCAGTATCTACTANTCTGGGTNNATACTTTCACGGGTTGGGCAGAAGCCTTC180 
CCCTGTTGGACAGAAAANGCCCNAGANGTTNTAAAGGCACTAGTTCATGAAATAATTCCC240 
ANATTCGGACTTCCCCGAGGCTTACAGANTGACNATNNCCCTGCTTTCCAGGCCACAGTN300 
ACCCAGGGGAGTNTCCCNGGCGTTNGGTNTACGATATCACTTACACTGCGCCTGAANGCC360 
ACAGTCCTCNGGGA374 
(2) INFORMATION FOR SEQ ID NO:48: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 542 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:48: 
AACAANTTNTTAAAACATTACAAGGAACGTATCCNTGAGNAGAGGGAAAAGAATTATTCC60 
ACCCTTGTGACATGGTATTAGTCAAGTCCATTCCCTATAATTCCCNATCCCTAGANACAT120 
CNTGGGANGGACCNTACCCAGTCATTTTATNTACCCCAACTGCGGTTAAAGTGGCTGGAG180 
TGGAGTCTTGGATACATCACACTTGAGTCAAATCCTGGATACTGCCAAAGGAACCTGAAA240 
ATCCAGGAGACAACGCTAGCTATTCCTGTGAACCTCTAGAGGATTTGCGCCTGCTCTTCA300 
AACAACAACCAGGAGGAAAGTAACTAAAATCATAAATCCCCATGGCCCTCCCTTATCATA360 
TTTTTCTCTTTACTGTTCTTTTACCCTCTTTCACTCTCACTGCACCCCCTCCATGCCGCT420 
GTATGACCAGTAGCTCCCCTTACCAAGAGTTTCTATGGAGAATGCAGCGTCCCGGAAATA480 
TTGATGCCCCATCGTATAGGAGTCTTTCTAAGGGAACCCCCACCTTCACTGCCCACACCC540 
AT542 
(2) INFORMATION FOR SEQ ID NO:49: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 67 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:49: 
MetAlaLeuProTyrHisIlePheLeuPheThrValLeuLeuProSer 
151015 
PheThrLeuThrAlaProProProCysArgCysMetThrSerSerSer 
202530 
ProTyrGlnGluPheLeuTrpArgMetGlnArgProGlyAsnIleAsp 
354045 
AlaProSerTyrArgSerLeuSerLysGlyThrProThrPheThrAla 
505560 
HisThrHis 
65 
(2) INFORMATION FOR SEQ ID NO:50: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 279 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:50: 
RCCACATCCACCTTTAAACACGGGGNTTGCAAANAAGATNACACTTGACCAATCAGAGAG60 
NTCANTAAAATGATNATTNGGCAAAAACAGGAGGTAAAGAAATAGCCAATCATCTATTGC120 
CTGAGAGCACAGCAGGAGGGACAATGATCGGGATATAAACCCAAGTTTTNGAGCCGGCAA180 
CGGCAACCCCCTTTGGGTCCCCTCCCTTTGTATGGGAGCTNTGTTTTCATGCTATTTCAN240 
TNTATTAAATNTTGCAACTGCAAAAAAAAAAAAAAAAAA279 
(2) INFORMATION FOR SEQ ID NO:51: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 338 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:51: 
AGCGGCCGCGCCATCCCCATCAAGCAGGGGATCCTGCTAAAGCGGAGCGGCAAGTCCCTG60 
AACAAGGAGTGGAAGAAGAAGTATGTGACGCTCTGTGACAACGGGCTGCTCACCTATCAC120 
CCCAGCCTGCATCTTGGTGCGCTGTCTGTGCCCTCTGCCAACAGTGGAGGCAGCGAGGAT180 
GAAGAGGAGTGGCAAGGGGTGTCTTGGATGTGGAAAAAAATGTGGGTTGTGGGGTTGGGC240 
TGGGTTTTGGTTTCAGTANANGAAACACAGCCAGCTGGAGANCANAACTCACGGGGGTTG300 
GTGGCTTTTCANAATCACCCGGCTGGTGGCTGANCTAA338 
(2) INFORMATION FOR SEQ ID NO:52: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 387 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:52: 
AAGTAGGCAAGGGATAATAACCAAAGAAGNAAATTTCATGAAGACTAGACATCATAAAGC60 
ATAATTTTAATAGTCACTCAACCAAGTATTTTTTATTTTTTATGGATACTCTGAATGGCA120 
ATTAAATGTGAAACCCAGTTTCTTGGGCAAGTCAAATTSTGGNATCACATCCACCTAAAT180 
TAAAATGACTAGCTCGTATTTTCCCCATCTTCAAGTTTCACATCCTGGTCATCAAAAGAC240 
TCGACAGCAAGACTTAGAATGMAAAAGGGTACTTGTTTATATTAATATTTTTTACTTGAA300 
CACGTGTAGCTTGCAGCAGGTTCTTGATGAATGTGCTTTGTGTCCAAAATGCCTCCCCAT360 
TGTACACAGGTGTACACCATGCATGCA387 
(2) INFORMATION FOR SEQ ID NO:53: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 67 amino acids 
(B) TYPE: amino acid 
(C) STRANDEDNESS: 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: protein 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:53: 
MetThrSerSerTyrPheProHisLeuGlnValSerHisProGlyHis 
151015 
GlnLysThrArgGlnGlnAspLeuGluXaaLysArgValLeuValTyr 
202530 
IleAsnIlePheTyrLeuAsnThrCysSerLeuGlnGlnValLeuAsp 
354045 
GluCysAlaLeuCysProLysCysLeuProIleValHisArgCysThr 
505560 
ProCysMet 
65 
(2) INFORMATION FOR SEQ ID NO:54: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 348 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: double 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: cDNA 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:54: 
CAAACCCTAAACCCTGGCAGGAAGCATGTCGAGGAAGGAGTTCCGGCAACTCCAGAGGNT60 
CCGACAGAANTNTGGGCTGAGCCTGGNTNTCNTNTCCAGCAAGGGTTTCGCCTGAGCCCC120 
AAGGGCATCGGGANTGGNGACTCACCTATGGATGGGGGCCGGGGAGACAGGACACACAGA180 
AGATGAGTTTGTGGGCCAGCCNTGAGCCCCGCGCCNGATTTTNGCCGGCCCAAGAGAGCC240 
CGCCGCAGCTTCCCCCATTTTGCAGCCAGCGGAGCCATTCACACAATCACCTTCTGTTAA300 
TTNTATCTGCAACATCAATTAAATTGTTTGTAGAAACTAAAAAAAAAA348 
(2) INFORMATION FOR SEQ ID NO:55: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:55: 
TNAGATCCAACAGTCACGTTCACGAAACC29 
(2) INFORMATION FOR SEQ ID NO:56: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:56: 
GNTGAAGCATGCCCAATTTCATTTCCTCT29 
(2) INFORMATION FOR SEQ ID NO:57: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:57: 
TNCAAGTTGAGTTGTACAGAAGCCCAAGA29 
(2) INFORMATION FOR SEQ ID NO:58: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:58: 
ANTGTTCTCTGGCTTGTCAGGGAAGACTG29 
(2) INFORMATION FOR SEQ ID NO:59: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:59: 
GNTGTGAGAAGACCACTCGGTGATGACCT29 
(2) INFORMATION FOR SEQ ID NO:60: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:60: 
TNGAGTCTGGGTGGTAGACAAATCATGCA29 
(2) INFORMATION FOR SEQ ID NO:61: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:61: 
ANGGACGGTATATATCACCATGAACAAGT29 
(2) INFORMATION FOR SEQ ID NO:62: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:62: 
ANAGGCAGGAGGAGACGGGATTGATGGTT29 
(2) INFORMATION FOR SEQ ID NO:63: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:63: 
ANAAGCGTCATGCAGAGCCATGATGAGGG29 
(2) INFORMATION FOR SEQ ID NO:64: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:64: 
ANAAATGTAGCAGGCTTGGCTTGCAGCAG29 
(2) INFORMATION FOR SEQ ID NO:65: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:65: 
ANGACCCATTTCCAGTCCAAATCTTTGAC29 
(2) INFORMATION FOR SEQ ID NO:66: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:66: 
GNCAAGGTGTCTGTAGGAGAAACTATATA29 
(2) INFORMATION FOR SEQ ID NO:67: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:67: 
ANCCAGGGCTATACAGAGAAACCCTGTCT29 
(2) INFORMATION FOR SEQ ID NO:68: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:68: 
GNTCTTGAAGAAGTAGCCCAGGGTGAGGA29 
(2) INFORMATION FOR SEQ ID NO:69: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:69: 
CNGGTAAAGGTGATGTTGACACTGTAGGA29 
(2) INFORMATION FOR SEQ ID NO:70: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:70: 
CNTCCTGGTTGTTGTTTGAAGAGCAGGCG29 
(2) INFORMATION FOR SEQ ID NO:71: 
(i) SEQUENCE CHARACTERISTICS: 
(A) LENGTH: 29 base pairs 
(B) TYPE: nucleic acid 
(C) STRANDEDNESS: single 
(D) TOPOLOGY: linear 
(ii) MOLECULE TYPE: other nucleic acid 
(A) DESCRIPTION: /desc ="oligonucleotide" 
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:71: 
TNGCCCAAGAAACTGGGTTTCACATTTAA29 
__________________________________________________________________________