Dendritic cell transmembrane serine protease

Abstract

Isolated Dendritic Cell Transmembrane Serine Proteases (DCTSPs), DNAs encoding such DCTSPs, and pharmaceutical and/or diagnostic compositions made therefrom, are disclosed. The isolated DCTSPs can be used to hydrolyze peptide bonds. The DCTSPs are also useful in screening for inhibitors or agonists thereof.

1 . An isolated nucleic acid selected from the group consisting of: 
 (a) a nucleic acid comprising nucleotides 1 through 1338 of SEQ ID NO:3;    (b) a nucleic acid encoding a Dendritic Cell Transmembrane Serine Protease (DCTSP) polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 1 to 60 inclusive, and y represents an integer from 441 to 446, inclusive;    (c) a nucleic acid encoding polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 91 to 96, inclusive, and y represents an integer from 441 to 446, inclusive;    (d) a nucleic acid encoding a DCTSP polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 174 to 179, inclusive, and y represents an integer from 441 to 446, inclusive;    (e) a nucleic acid encoding a DCTSP polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 174 to 179, inclusive, and y represents an integer from 190 to 195, inclusive; and    (f) a nucleic acid encoding a DCTSP polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 91 to 96, inclusive, and y represents an integer from 190 to 195, inclusive.    
     
     
         2 . The isolated nucleic acid of  claim 1 , selected from the group consisting of: 
 (a) a nucleic acid comprising nucleotides 139 to 1323 of SEQ ID NO:3, inclusive;    (b) a nucleic acid comprising nucleotides 286 to 1323 of SEQ ID NO:3, inclusive;    (c) a nucleic acid comprising nucleotides 535 to 1323 of SEQ ID NO:3, inclusive;    (d) a nucleic acid comprising nucleotides 286 to 570 of SEQ ID NO:3, inclusive;    (e) a nucleic acid comprising at least 17 consecutive nucleotides of SEQ ID NO:3, between nucleotides 525 and 545, inclusive;    (f) a nucleic acid comprising nucleotides 535 to 570 of SEQ ID NO:3, inclusive; and    (g) DNA or RNA complements of the nucleic acids of (a) through (f).    
     
     
         3 . An isolated Dendritic Cell Transmembrane Serine Protease (DCTSP) polypeptide selected from the group consisting of: 
 (a) a polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 1 to 60 inclusive, and y represents an integer from 441 to 446, inclusive;    (b) a polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 91 to 96, inclusive, and y represents an integer from 441 to 446, inclusive; and    (c) a polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 91 to 96, inclusive, and y represents an integer from 190 to 195, inclusive.    
     
     
         4 . The DCTSP polypeptide of  claim 3 , which further comprises a peptide selected from the group consisting of an immunoglobulin Fc domain, an immunoglobulin Fc mutein, a FLAG® tag, a peptide comprising at least about 6 His residues, a leucine zipper, and combinations thereof  
     
     
         5 . An isolated antibody that binds a Dendritic Cell Transmembrane Serine Protease (DCTSP) polypeptide consisting of amino acids 1 to x of SEQ ID NO:2, wherein x represents an integer from 75 to 95, inclusive of SEQ ID NO:2.  
     
     
         6 . The antibody of  claim 5 , which is selected from the group consisting of polyclonal antibodies and monoclonal antibodies.  
     
     
         7 . An isolated antibody that binds a Dendritic Cell Transmembrane Serine Protease (DCTSP) splice variant polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 1 to 60 inclusive, and y represents an integer from 441 to 446, inclusive, and which does not cross react with other DCTSP polypeptides.  
     
     
         8 . The antibody of  claim 7 , which is selected from the group consisting of polyclonal antibodies and monoclonal antibodies.  
     
     
         9 . A method for identifying compounds that alter Dendritic Cell Transmembrane Serine Protease (DCTSP) protease activity comprising: 
 (a) mixing a test compound with a DCTSP polypeptide selected from the group consisting of: 
 (i) a polypeptide comprising amino acids 1 through 477 of SEQ ID NO:2;  
 (ii) a fragment of the polypeptide of (i) comprising amino acids x through y of SEQ ID NO:2, wherein x represents an integer from 1 to 47, inclusive, and y represents an integer from 470 to 477, inclusive, wherein the fragment has DCTSP activity;  
 (iii) a polypeptide consisting of amino acids 1 to x of SEQ ID NO:2, wherein x represents an integer from 75 to 95, inclusive of SEQ ID NO:2;  
 (iv) a polypeptide consisting of amino acids 1 to x of SEQ ID NO:2, wherein x represents an integer from 75 to 95, inclusive of SEQ ID NO:2  
 (v) a polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 1 to 60 inclusive, and y represents an integer from 441 to 446, inclusive;  
 (vi) a polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 91 to 96, inclusive, and y represents an integer from 441 to 446, inclusive; and  
 (vii) a polypeptide comprising amino acids x to y of SEQ ID NO:4, wherein x represents an integer from 91 to 96, inclusive, and y represents an integer from 190 to 195, inclusive;  
   and    (b) determining whether the test compound alters DCTSP protease activity.    
     
     
         10 . The method of  claim 9 , wherein the DCTSP protease activity is inhibited.