Novel human kallikrein-like genes

Abstract

The invention relates to nucleic acid molecules, kallikrein-like proteins encoded by such nucleic acid molecules; and use of the proteins and nucleic acid molecules.

1 . An isolated nucleic acid molecule comprising a sequence selected from the group consisting of: 
 (a) the nucleic acid sequence of SEQ ID NO: 1, 21, 43, 56 or 65;    (b) a nucleic acid sequence encoding a protein having substantial sequence identity with an amino acid sequence of a protein of SEQ ID NO: 2, 3, 14, 22, 23, 44, 45, 57, 58, 59, 60, 66, or 67;    (c) a nucleic acid sequence complementary to the sequence of (a) or (b);    (d) a nucleic acid sequence that is at least 30 nucleotides in length and is a fragment of the sequence of any of (a) through (c);    (e) a nucleic acid sequence that is at least 30 nucleotides in length and that hybridizes under stringent hybridization conditions to a sequence of any of (a) through (d);    (f) a nucleic acid sequence of any of (a) through (e), wherein in each occurrence in said sequence, T is U;    (g) a nucleic acid sequence which differs from any of the nucleic acid sequences of (a) through (f) in codon sequences due to the degeneracy of the genetic code;    (h) a degenerate form of a nucleic acid sequence of any of (a) through (g); and    (i) a nucleic acid sequence encoding a truncation, an analog, an allelic or species variation of a protein encoded by any of the nucleic acid sequences of (a) through (h).    
     
     
         2 . The isolated nucleic acid molecule of  claim 2 , wherein said nucleic acid sequence comprises a regulatory sequence.  
     
     
         3 . The isolated nucleic acid molecule of  claim 3 , further comprising a nucleic acid which encodes a heterologous protein fused to said regulatory sequence.  
     
     
         4 . A vector comprising a nucleic acid molecule of  claim 1 .  
     
     
         5 . A host cell comprising a nucleic acid molecule of  claim 1 .  
     
     
         6 . An isolated protein comprising: 
 (a) an amino acid sequence encoded by an isolated nucleic acid molecule of  claim 1;     (b) an amino acid sequence selected from the group consisting of SEQ ID NO: 2, 3, 14, 22, 23, 44, 45, 57, 58, 59, 60, 66 and 67, and a fragment thereof; or    (c) an amino acid sequence having at least 65% sequence identity to the amino acid sequence of (b).    
     
     
         7 . An antibody that specifically binds a protein of  claim 6 .  
     
     
         8 . The antibody according to  claim 7  which is labeled with a detectable substance and used to detect the protein in biological samples, tissues, and cells.  
     
     
         9 . A method for preparing an isolated protein, said method comprising: 
 (i) transferring the vector of  claim 4  into a host cell;    (ii) selecting transformed host cells from untransformed host cells;    (iii) culturing a selected transformed host cell under conditions which allow expression of the protein; and    (iv) isolating the protein.    
     
     
         10 . A method of diagnosing and monitoring conditions mediated by the protein of  claim 6  by determining the presence of a nucleic acid molecule encoding said protein or determining the presence of said protein.  
     
     
         11 . The method according to  claim 10  wherein the condition is cancer.  
     
     
         12 . A method for identifying a substance which associates with the protein of  claim 6 , comprising: 
 (i) reacting said protein with at least one substance which potentially can associate with the protein, under conditions which permit the association between the substance and protein, and    (ii) removing or detecting the protein associated with the substance, wherein detection of associated protein and substance indicates the substance associates with the protein.    
     
     
         13 . A method for evaluating a compound for its ability to modulate the biological activity of the protein of  claim 6 , comprising: 
 (i) providing a known concentration of said protein with a substance which associates with the protein and a test compound under conditions which permit the formation of complexes between the substance and protein; and    (ii) removing and/or detecting said complexes.    
     
     
         14 . A method for detecting a nucleic acid molecule encoding a protein of  claim 6  in a biological sample, comprising the steps of: 
 (i) hybridizing the nucleic acid molecule encoding said protein to nucleic acids of the biological sample, thereby forming a hybridization complex; and    (ii) detecting the hybridization complex;    wherein the presence of the hybridization complex correlates with the presence of a nucleic acid molecule encoding the protein in the biological sample.    
     
     
         15 . The method according to  claim 14 , wherein said nucleic acids of the biological sample are amplified by the polymerase chain reaction prior to the hybridizing step.  
     
     
         16 . A method for treating a condition mediated by an isolated protein comprising an amino acid sequence of  claim 6 , comprising administering an effective amount of a composition selected from the group consisting of: 
 (i) an antibody having specificity against an epitope of said protein; and    (ii) a substance or compound identified by the method of  claim 13 .    
     
     
         17 . A method for treating a condition mediated by an isolated protein comprising an amino acid sequence of  claim 6 , comprising administering an effective amount of a composition selected from the group consisting of: 
 (i) an antibody having specificity against an epitope of said protein; and    (ii) a substance or compound identified by the method of  claim 14 .    
     
     
         18 . A composition comprising the nucleic acid molecule of  claim 1  and a pharmaceutically acceptable carrier, excipient or diluent.  
     
     
         19 . A composition comprising the protein of  claim 6  and a pharmaceutically acceptable carrier, excipient or diluent.  
     
     
         20 . A transgenic non-human mammal which does not express the protein of  claim 6 .  
     
     
         21 . A transgenic animal assay system which provides a model system for testing for an agent that reduces or inhibits a protein associated pathology comprising: 
 (i) administering said agent to the transgenic non-human animal of  claim 20;  and    (ii) determining whether said agent reduces or inhibits the protein associated pathology in the transgenic non-human animal relative to a transgenic non-human animal of step (i) which has not been administered the agent.