25501, a human transferase family member and uses therefor

Abstract

The invention provides isolated nucleic acids molecules, designated 25501 nucleic acid molecules, which encode novel transferase family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 25501 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 25501 gene has been introduced or disrupted. The invention still further provides isolated 25501 proteins, fusion proteins, antigenic peptides and anti-25501 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

1 . An isolated nucleic acid molecule selected from the group consisting of: 
 a) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:2;    b) a nucleic acid molecule which encodes a polypeptide consisting of a fragment of the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises the transfer domain of 25501 (amino acid residues 280 to 411 of SEQ ID NO:2) and has transferase activity; and    c) a nucleic acid molecule which encodes a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, 3, or a complement thereof, under conditions of 0.5M sodium phosphate, 7% SDS at 65° C., followed by one or more washes at 0.2×SSC, 1% SDS at 65° C. and the variant has transferase activity.    
   
   
       2 . The nucleic acid molecule of  claim 1  further comprising vector nucleic acid sequences.  
   
   
       3 . The nucleic acid molecule of  claim 1  further comprising nucleic acid sequences encoding a heterologous polypeptide.  
   
   
       4 . A host cell which contains the nucleic acid molecule of  claim 1 .  
   
   
       5 . An isolated polypeptide selected from the group consisting of: 
 a) a polypeptide comprising SEQ ID NO:2;    b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the variant is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, 3, or a complement thereof, under conditions of 0.5M sodium phosphate, 7% SDS at 65° C., followed by one or more washes at 0.2×SSC, 1% SDS at 65° C. and the variant has transferase activity; and    c) a fragment of the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises the transfer domain of 25501, wherein the transfer domain of 25501 is amino acid residues 280 to 411 of SEQ ID NO:2, and the fragment has transferase activity.    
   
   
       6 . The isolated polypeptide of  claim 5  comprising an amino acid sequence encoded by SEQ ID NO:1 or SEQ ID NO:3.  
   
   
       7 . The isolated polypeptide of claim  5 c), wherein the fragment further comprises the recognition/binding domain of 25501, wherein the recognition/binding domain of 25501 is amino acid residues 30 to 250 of SEQ ID NO:2.  
   
   
       8 . The polypeptide of  claim 5  further comprising heterologous amino acid sequences.  
   
   
       9 . An antibody which selectively binds to a polypeptide of  claim 5 .  
   
   
       10 . A method for producing a polypeptide selected from the group consisting of: 
 a) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;    b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:2, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising SEQ ID NO:1, 3, or a complement thereof, under conditions of 0.5M sodium phosphate, 7% SDS at 65° C., followed by one or more washes at 0.2×SSC, 1% SDS at 65° C. and the variant has transferase activity; and    c) a fragment of the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises the transfer domain of 25501, wherein the transfer domain of 25501 is amino acid residues 280 to 411 of SEQ ID NO:2, and the fragment has transferase activity;    comprising culturing the host cell of  claim 4  under conditions in which the nucleic acid molecule is expressed.    
   
   
       11 . A method for detecting the presence of a polypeptide of  claim 5  in a sample, comprising: 
 a) contacting the sample with a compound which selectively binds to a polypeptide of  claim 5;  and    b) determining whether the compound binds to the polypeptide in the sample.    
   
   
       12 . The method of  claim 11 , wherein the compound which binds to the polypeptide is an antibody.  
   
   
       13 . A kit comprising a compound which selectively binds to a polypeptide of  claim 5  and instructions for use.  
   
   
       14 . A method for detecting the presence of a nucleic acid molecule of  claim 1  in a sample, comprising the steps of: 
 a) contacting the sample with a nucleic acid probe or primer which selectively hybridizes to the nucleic acid molecule; and    b) determining whether the nucleic acid probe or primer binds to a nucleic acid molecule in the sample.    
   
   
       15 . A method for identifying a compound which binds to a 25501 polypeptide comprising the steps of: 
 a) contacting a 25501 polypeptide, or a cell expressing a 25501 polypeptide with a test compound; and    b) determining whether the polypeptide binds to the test compound, wherein the 25501 polypeptide comprises a polypeptide selected from the group consisting of:    i) a polypeptide encoded by a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3,    ii) a polypeptide having the amino acid sequence of SEQ ID NO:2,    iii) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises the transfer domain of 25501, wherein the transfer domain of 25501 is amino acid residues 280 to 411 of SEQ ID NO:2, and the fragment has transferase activity,    iv) a polypeptide comprising the amino acid sequence shown in SEQ ID NO:2 and a non-25501 polypeptide,    v) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO:2, wherein the fragment comprises the transfer domain of 25501, wherein the transfer domain of 25501 is amino acid residues 280 to 411 of SEQ ID NO:2, and the fragment has transferase activity, and a non-25501 polypeptide, and    vi) a fusion polypeptide encoded by a nucleic acid comprising a nucleotide sequence which encodes SEQ ID NO:2 operably linked to a non-25501 polypeptide.    
   
   
       16 . The method of  claim 15 , wherein the 25501 polypeptide is immobilized on a solid surface.  
   
   
       17 . The method of  claim 15 , wherein the binding of the test compound to the polypeptide is detected by a method selected from the group consisting of: 
 a) detection of binding by direct detecting of test compound/polypeptide binding;    b) detection of binding using a competition binding assay;    c) detection of binding using an assay for 25501-transferase activity; and    d) detection of binding using a two-hybrid assay.    
   
   
       18 . A method for modulating the activity of a polypeptide of  claim 5  comprising contacting a polypeptide or a cell expressing a polypeptide of  claim 5  with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.  
   
   
       19 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 5 , comprising: 
 a) contacting a polypeptide of  claim 5  or a cell expressing a polypeptide of  claim 5  with a test compound; and    b) determining the effect of the test compound on the activity of the polypeptide to thereby identify a compound which modulates the activity of the polypeptide.    
   
   
       20 . The method of  claim 19  wherein the cell is a tumor cell.