Nucleic acids encoding zinc metalloproteases

Abstract

Isolated mammalian proteins having disintegrin-like and metalloprotease domains with thrombospondin type I motifs, i.e., ADAMTS proteins, are provided. The proteins are ADAMTS-5, ADAMTS-6, ADAMTS-7, ADAMTS-8, ADAMTS-9 and ADAMTS-10, collectively referred to as 5 “ADAMTS-N”. The present invention also provides isolated polynucleotides which encode an ADAMTS-N protein or a variant thereof, polynucleotide sequences complementary to such polynucleotides, vectors containing such polynucleotides, and host cells transformed or transfected with such vectors. The present invention also relates to antibodies which are immunospecific for one or more of the ADAMTS-N proteins. The present invention also relates to a protein referred to hereinafter as ADAMTS-R1 (ADAM-TS Related protein-1) and the polynucleotides which encode such protein.

What is claimed is:  
     
         1 . An isolated mammalian protein selected from the group consisting of an ADAMTS-5 protein, 5 an ADAMTS-6 protein, an ADAMTS-7 protein, an ADAMTS-8 protein,. an ADAMTS-9 protein, an ADAMTS-10 protein, and an ADAMTS-R1 protein.  
     
     
         2 . The isolated mammalian protein of  claim 1  wherein said protein comprises an amino acid sequence which is at least 95% identical to a sequence selected from the group consisting of amino acid 262 through amino acid 930 of SEQ ID NO: 2; amino acid 1 through amino acid 518 of SEQ ID NO: 4; amino acid 245 through amino acid 860 of SEQ ID NO: 6; amino acid 233 through amino acid 997 of SEQ ID NO: 8; amino acid 229 through amino acid 905 of SEQ ID NO: 10; amino acid 1 through amino acid 245 of SEQ ID NO: 12; amino acid 236 through amino acid 1882 of SEQ ID NO: 14; amino acid 1 through amino acid 874 of SEQ ID NO: 16; amino acid 212 through amino acid 1081 of SEQ ID NO: 18; amino acid 1 through amino acid 450 of SEQ ID NO: 20; and amino acid 1 through amino acid 547 of SEQ ID NO: 22.  
     
     
         3 . The isolated protein of  claim 2  wherein said amino acid sequence further comprises a prepropeptide sequence at the amino terminus thereof.  
     
     
         4 . The isolated protein of  claim 1  wherein said protein is a human ADAMTS-5 protein or a mouse ADAMTS-5 protein.  
     
     
         5 . The isolated protein of  claim 1  wherein said protein is a human ADAMTS-6 protein.  
     
     
         6 . The isolated protein of  claim 1  wherein said protein is a human ADAMTS-7 protein.  
     
     
         7 . The isolated protein of  claim 1  wherein said protein is a mouse ADAMTS-8 or a human ADAMTS-8 protein.  
     
     
         8 . The isolated protein of  claim 1  wherein said protein is a human ADAMTS-9 or a mouse ADAMTS-9 protein.  
     
     
         9 . The isolated protein of  claim 1  wherein said protein is a human ADAMTS-10 or a mouse ADAMTS-10 protein.  
     
     
         10 . The isolated protein of  claim 1  wherein said protein is a human ADAMTS-R1 protein.  
     
     
         11 . An isolated polynucleotide comprising a sequence which encodes a mammalian protein 30 selected from the group consisting of an ADAMTS-5 protein, an ADAMTS-6 protein, an ADAMTS-7 protein, an ADAMTS-8 protein, an ADAMTS-9 protein, an ADAMTS-10 protein, and an ADAMTS-R1 protein.  
     
     
         12 . The isolated polynucleotide of  claim 11  wherein said protein comprises an amino acid sequence which is at.least 95% identical to a sequence selected from the group consisting of: amino acid 262 through amino acid 930 of SEQ ID NO: 2; amino acid -1 through amino acid 518 of SEQ ID NO: 4; amino acid 245 through amino acid 860 of SEQ ID NO: 6; amino acid 233 through amino acid 997 of SEQ ID NO: 8; amino acid 229 through amino acid 905 of SEQ ID NO: 10; amino acid 1 through amino acid 245 of SEQ ID NO: 12; amino acid 236 through amino acid.1882 of SEQ ID NO: 14; amino acid 1 through amino acid 874 of SEQ ID NO: 16; amino acid 212 through amino acid 1081 of SEQ ID NO: 18; amino acid 1 through amino acid 450 of SEQ ID NO: 20; and amino acid 1 through amino acid 547 of SEQ ID NO: 22.  
     
     
         13 . The isolated polynucleotide of  claim 11  wherein said nucleotide sequence encodes a protein having a signal sequence at the amino terminus thereof.  
     
     
         14 . The isolated polynucleotide of  claim 11  wherein said polynucleotide comprises a sequence selected from the group consisting of: nucleotide 800 through nucleotide 2810 of SEQ ID NO: 1 or an allelic variant thereof; nucleotide 1 through nucleotide 1519 of SEQ ID NO: 3 or an allelic variant thereof; nucleotide 754 through nucleotide 2602 of SEQ ID NO: 5 or an allelic variant thereof; nucleotide 708 through nucleotide 3003 of SEQ ID NO: 7 or an allelic variant thereof; nucleotide 962 through nucleotide 2992 of SEQ ID NO: 9 or an allelic variant thereof; nucleotide 1 through nucleotide 739 of SEQ ID NO: 11 or an allelic variant thereof; nucleotide 708 through nucleotide 5648 of SEQ ID NO: 13 or an allelic variant thereof; nucleotide 1 through nucleotide 2625 of SEQ ID NO: 15 or an allelic variant thereof; nucleotide 634 through nucleotide 3243 of SEQ ID NO: 17 or an allelic variant thereof; nucleotide 1 through nucleotide 1642 of SEQ ID NO: 19 or an allelic variant thereof, and nucleotide 51 through nucleotide 1625 of SEQ ID NO: 21 or an allelic variant thereof.  
     
     
         15 . The isolated polynucleotide of  claim 11  wherein said polynucleotide hybridizes under stringent conditions to a nucleic acid molecule comprising a sequence complementary to the protein encoding sequence of SEQ ID NO: 1; SEQ ID NO: 3; SEQ ID NO: 5; SEQ ID NO: 7; SEQ ID NO: 9; SEQ ID NO: 11; SEQ ID NO: 13; SEQ ID NO: 15; SEQ ID NO: 17; SEQ ID NO: 19; or SEQ ID NO: 21.  
     
     
         16 . An isolated polynucleotide having a sequence which is complementary to the protein encoding sequence of the polynucleotide of  claim 11 .  
     
     
         17 . An expression vector comprising a polynucleotide of  claim 11 .  
     
     
         18 . A host cell transformed or transfected with an expression vector of  claim 17 .  
     
     
         19 . A method for producing an ADAMTS-N protein or an ADAMTS-RI protein, said method comprising the steps of 
 (a) culturing a host cell of  claim 18  under conditions suitable for expression of an ADAMTS-N protein or an ADAMTS-R1 protein; and    (b) recovering said ADAMTS-N protein or said ADAMTS-R1 protein from the host cell culture.    
     
     
         20 . An antibody that binds to a protein selected from the group consisting of an ADAMTS-5 protein, an ADAMTS-6 protein, an ADAMTS-7 protein, an ADAMTS-8 protein, an ADAMTS-9 protein, an ADAMTS-10 protein and an ADAMTS-RI protein.  
     
     
         21 . An oligopeptide for producing an antibody that binds to an ADAMTS-N protein or an ADAMTS-R1 protein wherein said oligopeptide has a sequence selected from the group consisting of: 
 a) SVSIERFVETLVVADK, SEQ ID NO: 23;    b) EVAEAANFLALRSEDPDKY, SEQ ID NO: 24;    c) VKEDVENPKAVVDGDWGP, SEQ ID NO: 25;    d) QHPFQNEDYRPRSASPSRTH, SEQ ID NO: 26;    e) PQNCKEVKRLKGASEDGEYF, SEQ ID NO: 27.    f) QELEEGAAVSEEPS, SEQ ID NO: 28    g) YYPENIKPKPKLQE; SEQ ID NO: 29.    h) HIKVRQFKAKDQTRF; and    i) CEAKNGYQSDAKGVKTFVEWVPKYAG, SEQ ID NO: 30.