Secreted and transmembrane polypeptides and nucleic acids encoding the same

• US 20030119129A1
• Filed: 09/17/2002
• Published: 06/26/2003
• Est. Priority Date: 08/10/1999
• Status: Abandoned Application

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Filvaroff, Ellen, Gurney, Austin L., Goddard, Audrey, Eaton, Dan L., Smith, Victoria, Wood, William I., Baker, Kevin P., Zhang, Zemin, Grimaldi, J. Christopher, Fong, Sherman, Watanabe, Colin K., Stephan, Jean Philippe
• Application Number:
  US10/245,479
• Publication Number:
  US 20030119129A1
• Time in Patent Office: Days
• US Class Current: 435/69.1
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C07K 14/435 from animals; from humans
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/705 Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C12N 5/06 Animal cells or tissues; Human cells or tissues preservation of living cells or tissues A01N1/02
• CPC Class Codes: C12N 9/00 Enzymes; Proenzymes; Compositions thereof preparations containing enzymes for cleaning teeth A61K8/66, A61Q11/00; medicinal preparations containing enzymes or proenzymes A61K38/43; enzyme containing detergent compositions C11D; enzymes with nucleic acid structure, e.g. ribozymes, C12N15/113; Processes for preparing, activating, inhibiting, separating or purifying enzymes preparation of malt C12C1/00
• CPC Class Codes: C12P 21/02 having a known sequence of two or more amino acids, e.g. glutathione

Abstract

The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods, for producing the polypeptides of the present invention.

Claims

1. Isolated nucleic acid having at least 80% nucleic acid sequence identity to a nucleotide sequence that encodes an amino acid sequence selected from the group consisting of the amino acid sequence shown in FIG. 2 (SEQ ID NO:

2), FIG. 4 (SEQ ID NO;

     4), FIG. 6 (SEQ ID NO;

     6), FIG. 8 (SEQ ID NO;

     8), FIG. 10 (SEQ ID NO;

     10), FIG. 12 (SEQ ID NO;

     12), FIG. 14 (SEQ ID NO;

     14), FIG. 16 (SEQ ID NO;

     16), FIG. 18 (SEQ ID NO;

     18), FIG. 20 (SEQ ID NO;

     20), FIG. 22 (SEQ ID NO;

     22), FIG. 24 (SEQ ID NO;

     24), FIG. 26 (SEQ ID NO;

     26), FIG. 28 (SEQ ID NO;

     28), FIG. 30 (SEQ ID NO;

     30), FIG. 32 (SEQ ID NO;

     32), FIG. 34 (SEQ ID NO;

     34), FIG. 36 (SEQ ID NO;

     36), FIG. 38 (SEQ ID NO;

     38), FIG. 40 (SEQ ID NO;

     40), FIG. 42 (SEQ ID NO;

     42), FIG. 44 (SEQ ID NO;

     44), FIG. 46 (SEQ ID NO;

     46), FIG. 48 (SEQ ID NO;

     48), FIG. 50 (SEQ ID NO;

     50), FIG. 52 (SEQ ID NO;

     52), FIG. 54 (SEQ ID NO;

     54), FIG. 56 (SEQ ID NO;

     56), FIG. 58 (SEQ ID NO;

     58), FIG. 60 (SEQ ID NO;

     60), FIG. 62 (SEQ ID NO;

     62), FIG. 64 (SEQ ID NO;

     64), FIG. 66 (SEQ ID NO;

     66), FIG. 68 (SEQ ID NO;

     68), FIG. 70 (SEQ ID NO;

     70), FIG. 72 (SEQ ID NO;

     72), FIG. 74 (SEQ ID NO;

     74), FIG. 76 (SEQ ID NO;

     76), FIG. 78 (SEQ ID NO;

     78), FIG. 80 (SEQ ID NO;

     80), FIG. 82 (SEQ ID NO;

     82), FIG. 84 (SEQ ID NO;

     84), FIG. 86 (SEQ ID NO;

     86), FIG. 88 (SEQ ID NO;

     88), FIG. 90 (SEQ ID NO;

     90), FIG. 92 (SEQ ID NO;

     92), FIG. 94 (SEQ ID NO;

     94), FIG. 96 (SEQ ID NO;

     96), FIG. 98 (SEQ ID NO;

     98), FIG. 100 (SEQ ID NO;

     100), FIG. 102 (SEQ ID NO;

     102), FIG. 104 (SEQ ID NO;

     104), FIG. 106 (SEQ ID NO;

     106), FIG. 108 (SEQ ID NO;

     108), FIG. 110 (SEQ ID NO;

     110), FIG. 112 (SEQ ID NO;

     112) and FIG. 114 (SEQ ID NO;

114.

5. A vector comprising the nucleic acid of claim 1.

6. A host cell comprising the vector of claim 5.

7. The host cell of claim 6, wherein said cell is a CHO cell.

8. The host cell of claim 6, wherein said cell is an E. coli.

9. The host cell of claim 6, wherein said cell is a yeast cell.

10. A process for producing a PRO polypeptide comprising culturing the host cell of claim 6 under conditions suitable for expression of said PRO polypeptide and recovering said PRO polypeptide from the cell culture.

2. Isolated nucleic acid having at least 80% nucleic acid sequence identity to a nucleotide sequence selected from the group consisting of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:

1), FIG. 3 (SEQ ID NO;

     3), FIG. 5 (SEQ ID NO;

     5), FIG. 7 (SEQ ID NO;

     7), FIG. 9 (SEQ ID NO;

     9), FIG. 11 (SEQ ID NO;

     11), FIG. 13 (SEQ ID NO;

     13), FIG. 15 (SEQ ID NO;

     15), FIG. 17 (SEQ ID NO;

     17), FIG. 19 (SEQ ID NO;

     19), FIG. 21 (SEQ ID NO;

     21), FIG. 23 (SEQ ID NO;

     23), FIG. 25 (SEQ ID NO;

     25), FIG. 27 (SEQ ID NO;

     27), FIG. 29 (SEQ ID NO;

     29), FIG. 31 (SEQ ID NO;

     31), FIG. 33 (SEQ ID NO;

     33), FIG. 35 (SEQ ID NO;

     35), FIG. 37 (SEQ ID NO;

     37), FIG. 39 (SEQ ID NO;

     39), FIG. 41 (SEQ ID NO;

     41), FIG. 43 (SEQ ID NO;

     43), FIG. 45 (SEQ ID NO;

     45), FIG. 47 (SEQ ID NO;

     47), FIG. 49 (SEQ ID NO;

     49), FIG. 51 (SEQ ID NO;

     51), FIG. 53 (SEQ ID NO;

     53), FIG. 55 (SEQ ID NO;

     55), FIG. 57 (SEQ ID NO;

     57), FIG. 59 (SEQ ID NO;

     59), FIG. 61 (SEQ ID NO;

     61), FIG. 63 (SEQ ID NO;

     63), FIG. 65 (SEQ ID NO;

     65), FIG. 67 (SEQ ID NO;

     67), FIG. 69 (SEQ ID NO;

     69), FIG. 71 (SEQ ID NO;

     71), FIG. 73 (SEQ ID NO;

     73), FIG. 75 (SEQ ID NO;

     75), FIG. 77 (SEQ ID NO;

     77), FIG. 79 (SEQ ID NO;

     79), FIG. 81 (SEQ ID NO;

     81), FIG. 83 (SEQ ID NO;

     83), FIG. 85 (SEQ ID NO;

     85), FIG. 87 (SEQ ID NO;

     87), FIG. 89 (SEQ ID NO;

     89), FIG. 91 (SEQ ID NO;

     91), FIG. 93 (SEQ ID NO;

     93), FIGS. 95A-95B (SEQ ID NO;

     95), FIG. 97 (SEQ ID NO;

     97), FIG. 99 (SEQ ID NO;

     99), FIG. 101 (SEQ ID NO;

     101), FIG. 103 (SEQ ID NO;

     103), FIG. 105 (SEQ ID NO;

     105), FIG. 107 (SEQ ID NO;

     107), FIG. 109 (SEQ ID NO;

     109), FIG. 111 (SEQ ID NO;

     111) and FIG. 113 (SEQ ID NO;

     113).

3. Isolated nucleic acid having at least 80% nucleic acid sequence identity to a nucleotide sequence selected from the group consisting of the full-length coding sequence of the nucleotide sequence shown in FIG. 1 (SEQ ID NO:

1), FIG. 3 (SEQ ID NO;

     3), FIG. 5 (SEQ ID NO;

     5), FIG. 7 (SEQ ID NO;

     7), FIG. 9 (SEQ ID NO;

     9), FIG. 11 (SEQ ID NO;

     11), FIG. 13 (SEQ ID NO;

     13), FIG. 15 (SEQ ID NO;

     15), FIG. 17 (SEQ ID NO;

     17), FIG. 19 (SEQ ID NO;

     19), FIG. 21 (SEQ ID NO;

     21), FIG. 23 (SEQ ID NO;

     23), FIG. 25 (SEQ ID NO;

     25), FIG. 27 (SEQ ID NO;

     27), FIG. 29 (SEQ ID NO;

     29), FIG. 31 (SEQ ID NO;

     31), FIG. 33 (SEQ ID NO;

     33), FIG. 35 (SEQ ID NO;

     35), FIG. 37 (SEQ ID NO;

     37), FIG. 39 (SEQ ID NO;

     39), FIG. 41 (SEQ ID NO;

     41), FIG. 43 (SEQ ID NO;

     43), FIG. 45 (SEQ ID NO;

     45), FIG. 47 (SEQ ID NO;

     47), FIG. 49 (SEQ ID NO;

     49), FIG. 51 (SEQ ID NO;

     51), FIG. 53 (SEQ ID NO;

     53), FIG. 55 (SEQ ID NO;

     55), FIG. 57 (SEQ ID NO;

     57), FIG. 59 (SEQ ID NO;

     59), FIG. 61 (SEQ ID NO;

     61), FIG. 63 (SEQ ID NO;

     63), FIG. 65 (SEQ ID NO;

     65), FIG. 67 (SEQ ID NO;

     67), FIG. 69 (SEQ ID NO;

     69), FIG. 71 (SEQ ID NO;

     71), FIG. 73 (SEQ ID NO;

     73), FIG. 75 (SEQ ID NO;

     75), FIG. 77 (SEQ ID NO;

     77), FIG. 79 (SEQ ID NO;

     79), FIG. 81 (SEQ ID NO;

     81), FIG. 83 (SEQ ID NO;

     83), FIG. 85 (SEQ ID NO;

     85), FIG. 87 (SEQ ID NO;

     87), FIG. 89 (SEQ ID NO;

     89), FIG. 91 (SEQ ID NO;

     91), FIG. 93 (SEQ ID NO;

     93), FIGS. 95A-95B (SEQ ID NO;

     95), FIG. 97 (SEQ ID NO;

     97), FIG. 99 (SEQ ID NO;

     99), FIG. 101 (SEQ ID NO;

     101), FIG. 103 (SEQ ID NO;

     103), FIG. 105 (SEQ ID NO;

     105), FIG. 107 (SEQ ID NO;

     107), FIG. 109 (SEQ ID NO;

     109), FIG. 111 (SEQ ID NO;

     111) and FIG. 113 (SEQ ID NO;

     113).

4. Isolated nucleic acid having at least 80% nucleic acid sequence identity to the full-length coding sequence of the DNA deposited under any ATCC accession number shown in Table 7.

11. An isolated polypeptide having at least 80% amino acid sequence identity to an amino acid sequence selected from the group consisting of the amino acid sequence shown in FIG. 2 (SEQ ID NO:

2), FIG. 4 (SEQ ID NO;

     4), FIG. 6 (SEQ ID NO;

     6), FIG. 8 (SEQ ID NO;

     8), FIG. 10 (SEQ ID NO;

     10), FIG. 12 (SEQ ID NO;

     12), FIG. 14 (SEQ ID NO;

     14), FIG. 16 (SEQ ID NO;

     16), FIG. 18 (SEQ ID NO;

     18), FIG. 20 (SEQ ID NO;

     20), FIG. 22 (SEQ ID NO;

     22), FIG. 24 (SEQ ID NO;

     24), FIG. 26 (SEQ ID NO;

     26), FIG. 28 (SEQ ID NO;

     28), FIG. 30 (SEQ ID NO;

     30), FIG. 32 (SEQ ID NO;

32 ), FIG. 34 (SEQ ID NO;

     34), FIG. 36 (SEQ ID NO;

     36), FIG. 38 (SEQ ID NO;

     38), FIG. 40 (SEQ ID NO;

     40), FIG. 42 (SEQ ID NO;

     42), FIG. 44 (SEQ ID NO;

     44), FIG. 46 (SEQ ID NO;

     46), FIG. 48 (SEQ ID NO;

     48), FIG. 50 (SEQ ID NO;

     50), FIG. 52 (SEQ ID NO;

     52), FIG. 54 (SEQ ID NO;

     54), FIG. 56 (SEQ ID NO;

     56), FIG. 58 (SEQ ID NO;

     58), FIG. 60 (SEQ ID NO;

     60), FIG. 62 (SEQ ID NO;

     62), FIG. 64 (SEQ ID NO;

     64), FIG. 66 (SEQ ID NO;

     66), FIG. 68 (SEQ ID NO;

     68), FIG. 70 (SEQ ID NO;

     70), FIG. 72 (SEQ ID NO;

     72), FIG. 74 (SEQ ID NO;

     74), FIG. 76 (SEQ ID NO;

     76), FIG. 78 (SEQ ID NO;

     78), FIG. 80 (SEQ ID NO;

     80), FIG. 82 (SEQ ID NO;

     82), FIG. 84 (SEQ ID NO;

     84), FIG. 86 (SEQ ID NO;

     86), FIG. 88 (SEQ ID NO;

     88), FIG. 90 (SEQ ID NO;

     90), FIG. 92 (SEQ ID NO;

     92), FIG. 94 (SEQ ID NO;

     94), FIG. 96 (SEQ ID NO;

     96), FIG. 98 (SEQ ID NO;

     98), FIG. 100 (SEQ ID NO;

     100), FIG. 102 (SEQ ID NO;

     102), FIG. 104 (SEQ ID NO;

     104), FIG. 106 (SEQ ID NO;

     106), FIG. 108 (SEQ ID NO;

     108), FIG. 110 (SEQ ID NO;

     110), FIG. 112 (SEQ ID NO;

     112) and FIG. 114 (SEQ ID NO;

     114).

13. A chimeric molecule comprising a polypeptide according to claim 11 fused to a heterologous amino acid sequence.

14. The chimeric molecule of claim 13, wherein said heterologous amino acid sequence is an epitope tag sequence.

15. The chimeric molecule of claim 13, wherein said heterologous amino acid sequence is a Fc region of an immunoglobulin.

16. An antibody which specifically binds to a polypeptide according to claim 11.

17. The antibody of claim 16, wherein said antibody is a monoclonal antibody, a humanized antibody or a single-chain antibody.

12. An isolated polypeptide having at least 80% amino acid sequence identity to an amino acid sequence encoded by the full-length coding sequence of the DNA deposited under any ATCC accession number shown in Table 7.

18. Isolated nucleic acid having at least 80% nucleic acid sequence identity to:

(a) a nucleotide sequence encoding the polypeptide shown in FIG. 2 (SEQ ID NO;

     2), FIG. 4 (SEQ ID NO;

     4), FIG. 6 (SEQ ID NO;

     6), FIG. 8 (SEQ ID NO;

     8), FIG. 10 (SEQ ID NO;

     10), FIG. 12 (SEQ ID NO;

     12), FIG. 14 (SEQ ID NO;

     14), FIG. 16 (SEQ ID NO;

     16), FIG. 18 (SEQ ID NO;

     18), FIG. 20 (SEQ ID NO;

     20), FIG. 22 (SEQ ID NO;

     22), FIG. 24 (SEQ ID NO;

     24), FIG. 26 (SEQ ID NO;

     26), FIG. 28 (SEQ ID NO;

     28), FIG. 30 (SEQ ID NO;

     30), FIG. 32 (SEQ ID NO;

     32), FIG. 34 (SEQ ID NO;

     34), FIG. 36 (SEQ ID NO;

     36), FIG. 38 (SEQ ID NO;

     38), FIG. 40 (SEQ ID NO;

     40), FIG. 42 (SEQ ID NO;

     42), FIG. 44 (SEQ ID NO;

     44), FIG. 46 (SEQ ID NO;

     46), FIG. 48 (SEQ ID NO;

     48), FIG. 50 (SEQ ID NO;

     50), FIG. 52 (SEQ ID NO;

     52), FIG. 54 (SEQ ID NO;

     54), FIG. 56 (SEQ ID NO;

     56), FIG. 58 (SEQ ID NO;

     58), FIG. 60 (SEQ ID NO;

     60), FIG. 62 (SEQ ID NO;

     62), FIG. 64 (SEQ ID NO;

     64), FIG. 66 (SEQ ID NO;

     66), FIG. 68 (SEQ ID NO;

     68), FIG. 70 (SEQ ID NO;

     70), FIG. 72 (SEQ ID NO;

     72), FIG. 74 (SEQ ID NO;

     74), FIG. 76 (SEQ ID NO;

     76), FIG. 78 (SEQ ID NO;

     78), FIG. 80 (SEQ ID NO;

     80), FIG. 82 (SEQ ID NO;

     82), FIG. 84 (SEQ ID NO;

     84), FIG. 86 (SEQ ID NO;

     86), FIG. 88 (SEQ ID NO;

     88), FIG. 90 (SEQ ID NO;

     90), FIG. 92 (SEQ ID NO;

     92), FIG. 94 (SEQ ID NO;

     94), FIG. 96 (SEQ ID NO;

     96), FIG. 98 (SEQ ID NO;

     98), FIG. 100 (SEQ ID NO;

     100), FIG. 102 (SEQ ID NO;

     102), FIG. 104 (SEQ ID NO;

     104), FIG. 106 (SEQ ID NO;

     106), FIG. 108 (SEQ ID NO;

     108), FIG. 110 (SEQ ID NO;

     110), FIG. 112 (SEQ ID NO;

     112) or FIG. 114 (SEQ ID NO;

     114), lacking its associated signal peptide;

(b) a nucleotide sequence encoding an extracellular domain of the polypeptide shown in FIG. 2 (SEQ ID NO;

     2), FIG. 4 (SEQ ID NO;

     4), FIG. 6 (SEQ ID NO;

     6), FIG. 8 (SEQ ID NO;

     8), FIG. 10 (SEQ ID NO;

     10), FIG. 12 (SEQ ID NO;

     12), FIG. 14 (SEQ ID NO;

     14), FIG. 16 (SEQ ID NO;

     16), FIG. 18 (SEQ ID NO;

     18), FIG. 20 (SEQ ID NO;

     20), FIG. 22 (SEQ ID NO;

     22), FIG. 24 (SEQ ID NO;

     24), FIG. 26 (SEQ ID NO;

     26), FIG. 28 (SEQ ID NO;

     28), FIG. 30 (SEQ ID NO;

     30), FIG. 32 (SEQ ID NO;

     32), FIG. 34 (SEQ ID NO;

     34), FIG. 36 (SEQ ID NO;

     36), FIG. 38 (SEQ ID NO;

     38), FIG. 40 (SEQ ID NO;

     40), FIG. 42 (SEQ ID NO;

     42), FIG. 44 (SEQ ID NO;

     44), FIG. 46 (SEQ ID NO;

     46), FIG. 48 (SEQ ID NO;

     48), FIG. 50 (SEQ ID NO;

     50), FIG. 52 (SEQ ID NO;

     52), FIG. 54 (SEQ ID NO;

     54), FIG. 56 (SEQ ID NO;

     56), FIG. 58 (SEQ ID NO;

     58), FIG. 60 (SEQ ID NO;

     60), FIG. 62 (SEQ ID NO;

     62), FIG. 64 (SEQ ID NO;

     64), FIG. 66 (SEQ ID NO;

     66), FIG. 68 (SEQ ID NO;

     68), FIG. 70 (SEQ ID NO;

     70), FIG. 72 (SEQ ID NO;

     72), FIG. 74 (SEQ ID NO;

     74), FIG. 76 (SEQ ID NO;

     76), FIG. 78 (SEQ ID NO;

     78), FIG. 80 (SEQ ID NO;

     80), FIG. 82 (SEQ ID NO;

     82), FIG. 84 (SEQ ID NO;

     84), FIG. 86 (SEQ ID NO;

     86), FIG. 88 (SEQ ID NO;

     88), FIG. 90 (SEQ ID NO;

     90), FIG. 92 (SEQ ID NO;

     92), FIG. 94 (SEQ ID NO;

     94), FIG. 96 (SEQ ID NO;

     96), FIG. 98 (SEQ ID NO;

     98), FIG. 100 (SEQ ID NO;

     100), FIG. 102 (SEQ ID NO;

     102), FIG. 104 (SEQ ID NO;

     104), FIG. 106 (SEQ ID NO;

     106), FIG. 108 (SEQ ID NO;

     108), FIG. 110 (SEQ ID NO;

     110), FIG. 112 (SEQ ID NO;

     112) or FIG. 114 (SEQ ID NO;

     114), with its associated signal peptide;

or

(c) a nucleotide sequence encoding an extracellular domain of the polypeptide shown in FIG. 2 (SEQ ID NO;

     2), FIG. 4 (SEQ ID NO;

     4), FIG. 6 (SEQ ID NO;

     6), FIG. 8 (SEQ ID NO;

     8), FIG. 10 (SEQ ID NO;

     10), FIG. 12 (SEQ ID NO;

     12), FIG. 14 (SEQ ID NO;

     14), FIG. 16 (SEQ ID NO;

     16), FIG. 18 (SEQ ID NO;

     18), FIG. 20 (SEQ ID NO;

     20), FIG. 22 (SEQ ID NO;

     22), FIG. 24 (SEQ ID NO;

     24), FIG. 26 (SEQ ID NO;

     26), FIG. 28 (SEQ ID NO;

     28), FIG. 30 (SEQ ID NO;

     30), FIG. 32 (SEQ ID NO;

     32), FIG. 34 (SEQ ID NO;

     34), FIG. 36 (SEQ ID NO;

     36), FIG. 38 (SEQ ID NO;

     38), FIG. 40 (SEQ ID NO;

     40), FIG. 42 (SEQ ID NO;

     42), FIG. 44 (SEQ ID NO;

     44), FIG. 46 (SEQ ID NO;

     46), FIG. 48 (SEQ ID NO;

     48), FIG. 50 (SEQ ID NO;

     50), FIG. 52 (SEQ ID NO;

     52), FIG. 54 (SEQ ID NO;

     54), FIG. 56 (SEQ ID NO;

     56), FIG. 58 (SEQ ID NO;

     58), FIG. 60 (SEQ ID NO;

     60), FIG. 62 (SEQ ID NO;

     62), FIG. 64 (SEQ ID NO;

     64), FIG. 66 (SEQ ID NO;

     66), FIG. 68 (SEQ ID NO;

6

     8), FIG. 70 (SEQ ID NO;

     70), FIG. 72 (SEQ ID NO;

     72), FIG. 74 (SEQ ID NO;

     74), FIG. 76 (SEQ ID NO;

     76), FIG. 78 (SEQ ID NO;

     78), FIG. 80 (SEQ ID NO;

     80), FIG. 82 (SEQ ID NO;

     82), FIG. 84 (SEQ ID NO;

     84), FIG. 86 (SEQ ID NO;

     86), FIG. 88 (SEQ ID NO;

     88), FIG. 90 (SEQ ID NO;

     90), FIG. 92 (SEQ ID NO;

     92), FIG. 94 (SEQ ID NO;

     94), FIG. 96 (SEQ ID NO;

     96), FIG. 98 (SEQ ID NO;

9

     8), FIG. 100 (SEQ ID NO;

     100), FIG. 102 (SEQ ID NO;

     102), FIG. 104 (SEQ ID NO;

     104), FIG. 106 (SEQ ID NO;

     106), FIG. 108 (SEQ ID NO;

     108), FIG. 110 (SEQ ID NO;

     110), FIG. 112 (SEQ ID NO;

     112) or FIG. 114 (SEQ ID NO;

     114), lacking its associated signal peptide.

19. An isolated polypeptide having at least 80% amino acid sequence identity to:

(a) an amino acid sequence of the polypeptide shown in FIG. 2 (SEQ ID NO;

     2), FIG. 4 (SEQ ID NO;

     4), FIG. 6 (SEQ ID NO;

     6), FIG. 8 (SEQ ID NO;

     8), FIG. 10 (SEQ ID NO;

     10), FIG. 12 (SEQ ID NO;

     12), FIG. 14 (SEQ ID NO;

     14), FIG. 16 (SEQ ID NO;

     16), FIG. 18 (SEQ ID NO;

     18), FIG. 20 (SEQ ID NO;

     20), FIG. 22 (SEQ ID NO;

     22), FIG. 24 (SEQ ID NO;

     24), FIG. 26 (SEQ ID NO;

     26), FIG. 28 (SEQ ID NO;

     28), FIG. 30 (SEQ ID NO;

     30), FIG. 32 (SEQ ID NO;

     32), FIG. 34 (SEQ ID NO;

     34), FIG. 36 (SEQ ID NO;

     36), FIG. 38 (SEQ ID NO;

     38), FIG. 40 (SEQ ID NO;

     40), FIG. 42 (SEQ ID NO;

     42), FIG. 44 (SEQ ID NO;

     44), FIG. 46 (SEQ ID NO;

     46), FIG. 48 (SEQ ID NO;

     48), FIG. 50 (SEQ ID NO;

     50), FIG. 52 (SEQ ID NO;

     52), FIG. 54 (SEQ ID NO;

     54), FIG. 56 (SEQ ID NO;

     56), FIG. 58 (SEQ ID NO;

     58), FIG. 60 (SEQ ID NO;

     60), FIG. 62 (SEQ ID NO;

     62), FIG. 64 (SEQ ID NO;

     64), FIG. 66 (SEQ ID NO;

     66), FIG. 68 (SEQ ID NO;

     68), FIG. 70 (SEQ ID NO;

     70), FIG. 72 (SEQ ID NO;

     72), FIG. 74 (SEQ ID NO;

     74), FIG. 76 (SEQ ID NO;

     76), FIG. 78 (SEQ ID NO;

     78), FIG. 80 (SEQ ID NO;

     80), FIG. 82 (SEQ ID NO;

     82), FIG. 84 (SEQ ID NO;

     84), FIG. 86 (SEQ ID NO;

     86), FIG. 88 (SEQ ID NO;

     88), FIG. 90 (SEQ ID NO;

     90), FIG. 92 (SEQ ID NO;

     92), FIG. 94 (SEQ ID NO;

     94), FIG. 96 (SEQ ID NO;

     96), FIG. 98 (SEQ ID NO;

     98), FIG. 100 (SEQ ID NO;

     100), FIG. 102 (SEQ ID NO;

     102), FIG. 104 (SEQ ID NO;

     104), FIG. 106 (SEQ ID NO;

     106), FIG. 108 (SEQ ID NO;

     108), FIG. 110 (SEQ ID NO;

     110), FIG. 112 (SEQ ID NO;

     112) or FIG. 114 (SEQ ID NO;

     114), lacking its associated signal peptide;

(b) an amino acid sequence of an extracellular domain of the polypeptide shown in FIG. 2 (SEQ ID NO;

     2), FIG. 4 (SEQ ID NO;

     4), FIG. 6 (SEQ ID NO;

     6), FIG. 8 (SEQ ID NO;

     8), FIG. 10 (SEQ ID NO;

     10), FIG. 12 (SEQ ID NO;

     12), FIG. 14 (SEQ ID NO;

     14), FIG. 16 (SEQ ID NO;

     16), FIG. 18 (SEQ ID NO;

     18), FIG. 20 (SEQ ID NO;

     20), FIG. 22 (SEQ ID NO;

     22), FIG. 24 (SEQ ID NO;

     24), FIG. 26 (SEQ ID NO;

     26), FIG. 28 (SEQ ID NO;

     28), FIG. 30 (SEQ ID NO;

     30), FIG. 32 (SEQ ID NO;

     32), FIG. 34 (SEQ ID NO;

     34), FIG. 36 (SEQ ID NO;

     36), FIG. 38 (SEQ ID NO;

     38), FIG. 40 (SEQ ID NO;

     40), FIG. 42 (SEQ ID NO;

     42), FIG. 44 (SEQ ID NO;

     44), FIG. 46 (SEQ ID NO;

     46), FIG. 48 (SEQ ID NO;

     48), FIG. 50 (SEQ ID NO;

     50), FIG. 52 (SEQ ID NO;

     52), FIG. 54 (SEQ ID NO;

     54), FIG. 56 (SEQ ID NO;

     56), FIG. 58 (SEQ ID NO;

     58), FIG. 60 (SEQ ID NO;

     60), FIG. 62 (SEQ ID NO;

     62), FIG. 64 (SEQ ID NO;

     64), FIG. 66 (SEQ ID NO;

     66), FIG. 68 (SEQ ID NO;

     68), FIG. 70 (SEQ ID NO;

     70), FIG. 72 (SEQ ID NO;

     72), FIG. 74 (SEQ ID NO;

     74), FIG. 76 (SEQ ID NO;

     76), FIG. 78 (SEQ ID NO;

     78), FIG. 80 (SEQ ID NO;

     80), FIG. 82 (SEQ ID NO;

     82), FIG. 84 (SEQ ID NO;

     84), FIG. 86 (SEQ ID NO;

     86), FIG. 88 (SEQ ID NO;

     88), FIG. 90 (SEQ ID NO;

     90), FIG. 92 (SEQ ID NO;

     92), FIG. 94 (SEQ ID NO;

     94), FIG. 96 (SEQ ID NO;

     96), FIG. 98 (SEQ ID NO;

     98), FIG. 100 (SEQ ID NO;

     100), FIG. 102 (SEQ ID NO;

     102), FIG. 104 (SEQ ID NO;

     104), FIG. 106 (SEQ ID NO;

     106), FIG. 108 (SEQ ID NO;

     108), FIG. 110 (SEQ ID NO;

     110), FIG. 112 (SEQ ID NO;

     112) or FIG. 114 (SEQ ID NO;

     114), with its associated signal peptide;

or

(c) an amino acid sequence of an extracellular domain of the polypeptide shown in FIG. 2 (SEQ ID NO;

     2), FIG. 4 (SEQ ID NO;

     4), FIG. 6 (SEQ ID NO;

     6), FIG. 8 (SEQ ID NO;

     8), FIG. 10 (SEQ ID NO;

     10), FIG. 12 (SEQ ID NO;

     12), FIG. 14 (SEQ ID NO;

     14), FIG. 16 (SEQ ID NO;

     16), FIG. 18 (SEQ ID NO;

     18), FIG. 20 (SEQ ID NO;

     20), FIG. 22 (SEQ ID NO;

     22), FIG. 24 (SEQ ID NO;

     24), FIG. 26 (SEQ ID NO;

     26), FIG. 28 (SEQ ID NO;

     28), FIG. 30 (SEQ ID NO;

     30), FIG. 32 (SEQ ID NO;

     32), FIG. 34 (SEQ ID NO;

     34), FIG. 36 (SEQ ID NO;

     36), FIG. 38 (SEQ ID NO;

     38), FIG. 40 (SEQ ID NO;

     40), FIG. 42 (SEQ ID NO;

     42), FIG. 44 (SEQ ID NO;

     44), FIG. 46 (SEQ ID NO;

     46), FIG. 48 (SEQ ID NO;

     48), FIG. 50 (SEQ ID NO;

     50), FIG. 52 (SEQ ID NO;

     52), FIG. 54 (SEQ ID NO;

     54), FIG. 56 (SEQ ID NO;

     56), FIG. 58 (SEQ ID NO;

     58), FIG. 60 (SEQ ID NO;

     60), FIG. 62 (SEQ ID NO;

     62), FIG. 64 (SEQ ID NO;

     64), FIG. 66 (SEQ ID NO;

     66), FIG. 68 (SEQ ID NO;

     68), FIG. 70 (SEQ ID NO;

     70), FIG. 72 (SEQ ID NO;

     72), FIG. 74 (SEQ ID NO;

     74), FIG. 76 (SEQ ID NO;

     76), FIG. 78 (SEQ ID NO;

     78), FIG. 80 (SEQ ID NO;

     80), FIG. 82 (SEQ ID NO;

     82), FIG. 84 (SEQ ID NO;

     84), FIG. 86 (SEQ ID NO;

     86), FIG. 88 (SEQ ID NO;

     88), FIG. 90 (SEQ ID NO;

     90), FIG. 92 (SEQ ID NO;

     92), FIG. 94 (SEQ ID NO;

     94), FIG. 96 (SEQ ID NO;

     96), FIG. 98 (SEQ ID NO;

     98), FIG. 100 (SEQ ID NO;

     100), FIG. 102 (SEQ ID NO;

     102), FIG. 104 (SEQ ID NO;

     104), FIG. 106 (SEQ ID NO;

     106), FIG. 108 (SEQ ID NO;

     108), FIG. 110 (SEQ ID NO;

     110), FIG. 112 (SEQ ID NO;

     112) or FIG. 114 (SEQ ID NO;

     114), lacking its associated signal peptide.

20. A method for stimulating the proliferation or differentiation of chondrocyte cells, said method comprising contacting said cells with a PRO6018 polypeptide, wherein the proliferation or differentiation of said cells is stimulated.

21. A method for stimulating the proliferation of human microvascular endothelial cells, said method comprising contacting said cells with a PRO1313, PRO20080 or PRO21383 polypeptide, wherein the proliferation of said cells is stimulated.

24. A method for inhibiting the proliferation of human microvascular endothelial cells, said method comprising contacting said cells with a PRO6071, PRO4487 or PRO6006 polypeptide, wherein the proliferation of said cells is inhibited.

25. A method for detecting the presence of tumor in a mammal, said method comprising comparing the level of expression of any PRO polypeptide shown in Table 8 in (a) a test sample of cells taken from said mammal and (b) a control sample of normal cells of the same cell type, wherein a higher level of expression of said PRO polypeptide in the test sample as compared to the control sample is indicative of the presence of tumor in said mammal.

26. The method of claim 25, wherein said tumor is lung tumor, colon tumor, breast tumor, prostate tumor, rectal tumor, kidney tumor or liver tumor.

27. A method for inducing endothelial cell tube formation comprising administering to the endothelial cell a PRO281, PRO1560, PRO189, PRO4499, PRO6308, PRO6000, PRO10275, PRO21207, PRO20933 or PRO34274 polypeptide, or agonist thereof, wherein tube formation in said endothelial cell is induced.

28. An oligonucleotide probe derived from any of the nucleotide sequences shown in the accompanying figures.