Novel protein and DNA thereof

Abstract

The present invention relates to a novel protein belonging to an ADAM family, a partial peptide thereof or a salt thereof, a DNA encoding the protein, a recombinant vector comprising the DNA, a transformant, a method for producing the protein, a medicine comprising the protein or the DNA, an antibody against the protein, a method/kit for screening for a compound or a salt thereof which promotes or inhibits the protease activity or the extracellular metric degrading enzyme activity (preferably, the peptidoglycan degrading enzyme activity) of the protein, a compound obtained by the screening, and a medicine comprising the compound. The present protein and a DNA encoding it can be used, for example, as an agent for treating or preventing various diseases such as disc herniation, ischialgia, glomerular nephritis, diabetic nephropathy, hepatic fibrosis, pulmonary fibrosis or osteopetrosis. In addition, the present antibody can be used for quantitating the present protein in a test solution. Further, the present protein is useful as a reagent for screening for a compound which promotes or inhibits the protease activity of the present protein.

1 . An isolated protein or a salt thereof which has an amino acid sequence represented by SEQ ID No: 15.  
     
     
         2 . The isolated protein or a salt thereof according to  claim 1 , which belongs to an ADAM family.  
     
     
         3 . The isolated protein or a salt thereof according to  claim 1 , which has a protease activity.  
     
     
         4 . A DNA having a base sequence encoding a protein according to  claim 1 .  
     
     
         5 . A recombinant vector which has the DNA encoding for a protein according to  claim 1 .  
     
     
         6 . A transformant host cell transformed with the recombinant vector according to  claim 5 .  
     
     
         7 . A method for producing the isolated protein or a salt according to  claim 1 , which comprises culturing a transformant host cell transformed with a recombinant vector comprising an expressible DNA encoding for said protein, and culturing said host cell under suitable conditions for sufficient time to produce said protein.  
     
     
         8 . An antibody against the protein or a salt thereof according to  claim 1  or the partial peptide or a salt thereof.  
     
     
         9 . A diagnostic agent which comprises a DNA encoding for the protein according to  claim 1  or an antibody which binds to said protein.  
     
     
         10 . An agent which comprises the protein or a salt thereof according to  claim 1  or the partial peptide or a salt thereof.  
     
     
         11 . A medicine which comprises the protein or a salt thereof according to  claim 1  or the partial peptide or a salt thereof and a pharmaceutically acceptable carrier, excipient or diluent.  
     
     
         12 . A method for preventing or treating disc herniation, ischialgia, glomerular nephritis, diabetic nephropathy, hepatic fibrosis, pulmonary fibrosis or osteopetrosis, said method comprising administering a medicine according to  claim 11  to a patient in need thereof.  
     
     
         13 . A method for screening for a compound or a salt thereof which promotes or inhibits the protease activity, which comprises using the protein according to  claim 1  or a salt thereof.  
     
     
         14 . A kit for screening for a compound or a salt thereof which promotes or inhibits the protease activity, which comprises the protein according to  claim 1  or a salt thereof.  
     
     
         15 . A compound or a salt thereof which promotes or inhibits the protease activity and is obtainable by using the method for screening according to  claim 19 .  
     
     
         16 . A medicine which comprises a compound or a salt thereof which promotes or inhibits the protease activity and is obtainable by the screening method according to  claim 19 .  
     
     
         17 . A method for detecting a proteoglycan degrading enzyme gene, which comprises mixing and culturing a transformant in which a test gene is introduced and an animal-derived cell producing cartilage or cartilage matrix, and measuring glycosaminoglyean sulfate in the culture supernatant.  
     
     
         18 . A method for screening an agent for inhibiting or promoting the proteoglycan degrading enzyme activity, which comprises mixing and culturing (i) a recombinant in which a gene encoding a protein having the proteoglycan degrading enzyme activity is introduced, (ii) an animal-derived cell producing cartilage or cartilage matrix, and (iii) a test compound, and measuring glycosaminoglycan sulfate in the culture supernatant.  
     
     
         19 . A method for screening an agent for inhibiting or promoting the activity of proteoglycan degrading enzyme, which comprises mixing and culturing (i) an animal cell comprising (a) the DNA according to  claim 7 , or (b) a DNA comprising a DNA having a base sequence encoding a protein having an amino acid sequence identical or substantially identical to an amino acid sequence represented by SEQ ID No: 5, (ii) an animal-derived cell producing cartilage or cartilage matrix, and (iii) a test compound, and measuring an amount of glycosaminoglycon sulfate in the supernatant.  
     
     
         20 . A non-human mammal which has a DNA having a DNA having a base sequence encoding an protein having an amino acid sequence identical or substantially identical to an amino acid sequence represented by SEQ ID No: 15, or a its mutated DNA.