23484, a novel human ubiquitin protease

Abstract

The present invention relates to a newly identified human ubiquitin protease belonging to the family of mammalian deubiquitinating enzymes. The invention also relates to polynucleotides encoding the ubiquitin protease. The invention further relates to methods using the ubiquitin protease polypeptides and polynucleotides as a target for diagnosis and treatment in ubiquitin-mediated or -related disorders. The invention further relates to drug-screening methods using the ubiquitin protease polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the ubiquitin protease polypeptides and polynucleotides. The invention further relates to procedures for producing the ubiquitin protease polypeptides and polynucleotides.

That which is claimed:  
     
         1 . An isolated polypeptide having an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence set forth in SEQ ID NO:1; and    (b) the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1 849.    
     
     
         2 . An isolated polypeptide having an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence of a sequence variant of the amino acid sequence set forth in SEQ ID NO:1, wherein said sequence variant has ubiquitin protease activity and is encoded by a nucleotide sequence having at least about 70% sequence identity to the nucleotide sequence set forth in SEQ ID NO:2;    (b) the amino acid sequence of a sequence variant of the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1 849, wherein said sequence variant has ubiquitin protease activity and is encoded by a nucleotide sequence having at least about 70% sequence identity to the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1 849;    (c) the amino acid sequence of a sequence variant of the amino acid sequence set forth in SEQ ID NO:1, wherein said sequence variant has ubiquitin protease activity and is encoded by a nucleotide sequence having at least about 80% sequence identity to the nucleotide sequence set forth in SEQ ID NO:2;    (d) the amino acid sequence of a sequence variant of the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1849, wherein said sequence variant has ubiquitin protease activity and is encoded by a nucleotide sequence having at least about 80% sequence identity to the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1849;    (e) the amino acid sequence of a sequence variant of the amino acid sequence set forth in SEQ ID NO:1, wherein said sequence variant has ubiquitin protease activity and is encoded by a nucleotide sequence having at least about 90% sequence identity to the nucleotide sequence set forth in SEQ ID NO:2; and,    (f) the amino acid sequence of a sequence variant of the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1849, wherein said sequence variant has ubiquitin protease activity and is encoded by a nucleotide sequence having at least about 90% sequence identity to the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1849.    
     
     
         3 . An isolated polypeptide having an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence of a sequence variant of the amino acid sequence shown in SEQ ID NO:1, wherein the sequence variant has ubiquitin protease activity and is encoded by a nucleic acid molecule hybridizing to the complement of the nucleotide sequence set forth in SEQ ID NO:2 under stringent conditions; and,    (b) the amino acid sequence of a sequence variant of the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA- 1849, wherein the sequence variant has ubiquitin protease activity and is encoded by a nucleotide sequence that hybridizes to the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1849; 
 said stringent conditions comprising hybridization in 6× SSC at about 45° C. followed by one or more washes in 0.2× SSC/0.1% SDS at 65° C.  
   
     
     
         4 . An isolated polypeptide having an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence of a fragment of the amino acid sequence set forth in SEQ ID NO:1, wherein said fragment consists of at least 11 contiguous amino acids of the amino acid sequence set forth in SEQ ID NO:1; and,    (b) the amino acid sequence of a fragment of the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1 849, wherein said fragment consists of at least 11 contiguous amino acids of the amino acid sequence encoded by the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1 849.    
     
     
         5 . An isolated polypeptide having an amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence having at least 70% sequence identity to the sequence set forth in SEQ ID NO:1, wherein said amino acid sequence has ubiquitin protease activity;    (b) the amino acid sequence having at least 70% sequence identity to the polypeptide encoded by the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA- 1849, wherein said amino acid sequence has ubiquitin protease activity;    (c) the amino acid sequence having at least 80% sequence identity to the sequence set forth in SEQ ID NO:1, wherein said amino acid sequence has ubiquitin protease activity;    (d) the amino acid sequence having at least 80% sequence identity to the polypeptide encoded by the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1849, wherein said amino acid sequence has ubiquitin protease activity;    (e) the amino acid sequence having at least 90% sequence identity to the sequence set forth in SEQ ID NO:1, wherein said amino acid sequence has ubiquitin protease activity; and,    (f) the amino acid sequence having at least 90% sequence identity to the polypeptide encoded by the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1849, wherein said amino acid sequence has ubiquitin protease activity.    
     
     
         6 . A composition comprising the polypeptide in  claim 1 .  
     
     
         7 . The composition of  claim 6  further comprising a pharmaceutical carrier.