Fail molecules and uses thereof

Abstract

The invention provides isolated nucleic acid molecules, designated FAIL, which encode polypeptide molecules containing Ig and Ig-like domains and which are homologous to FcγRI. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies. Diagnostic, screening 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 comprising a nucleotide sequence which is at least 95% identical to the nucleotide sequence of SEQ ID NO:1 or 2, the cDNA insert of the plasmid deposited with the ATCC® as patent deposit Number PTA-2266, or a complement thereof;    b) a nucleic acid molecule comprising a fragment of at least 25 nucleotides of the nucleotide sequence of SEQ ID NO:1 or 2, the cDNA insert of the plasmid deposited with the ATCC® as patent deposit Number PTA-2266, or a complement thereof;    c) nucleic acid molecule which encodes a polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO:3, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC® as patent deposit Number PTA-2266; and    d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:3, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC® as patent deposit Number PTA-2266, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:3, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC® as patent deposit Number PTA-2266.    
     
     
         2 . A host cell genetically engineered to express the nucleic acid molecule of  claim 1 .  
     
     
         3 . An isolated polypeptide selected from the group consisting of: 
 a) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO:3, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:3;    b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:3, or the amino acid sequence encoded by the cDNA insert of plasmids deposited with the ATCC® as patent deposit Number PTA-2266, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes under hybridization conditions of hybridization in 6×SSC at 45° C. and washing in 0.2×SSC, 0.1% SDS at 65° C. to a nucleic acid molecule comprising SEQ ID NO:2, or a complement thereof;    c) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:2, or at least 98% to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:2, or a complement thereof; and    d) a polypeptide which comprises an amino acid sequence which is at least 90% identical to SEQ ID NO:3.    
     
     
         4 . The polypeptide of  claim 3 , further comprising heterologous amino acid sequences.  
     
     
         5 . A substantially purified antibody or epitope-binding fragment thereof which specifically binds to a polypeptide of  claim 3 .  
     
     
         6 . The antibody or epitope-binding fragment thereof of  claim 5 , wherein the antibody or epitope-binding fragment thereof is a monoclonal antibody or epitope-binding fragment thereof.  
     
     
         7 . The antibody or epitope-binding fragment thereof of  claim 5 , wherein the antibody or epitope-binding fragment thereof is selected from the group consisting of a human antibody, a non-human antibody, a humanized antibody, a single chain antibody and a chimeric antibody or an epitope-binding fragment thereof.  
     
     
         8 . The epitope-binding fragment thereof of  claim 5  which consists of an epitope-binding fragment selected from the group consisting of an Fab fragment, an F(ab′) 2  fragment, and an Fab′ fragment.  
     
     
         9 . The antibody or epitope-binding fragment thereof of  claim 5 , wherein the antibody or epitope-binding fragment thereof is conjugated to a polymer.  
     
     
         10 . The antibody or epitope-binding fragment thereof of  claim 5 , wherein the antibody or epitope-binding fragment thereof is conjugated to a therapeutic moiety.  
     
     
         11 . The antibody or epitope-binding fragment thereof of  claim 5 , wherein the antibody or epitope-binding fragment thereof specifically binds to a polypeptide selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, and SEQ ID NO:34.  
     
     
         12 . A pharmaceutical composition comprising the antibody or epitope-binding fragment thereof of  claim 5  and a pharmaceutically acceptable carrier.  
     
     
         13 . A method for detecting the presence of a polypeptide of  claim 3  in a sample, comprising: 
 a) contacting the sample with a compound which selectively binds to a polypeptide of  claim 3;  and    b) determining whether the compound binds to the polypeptide in the sample.    
     
     
         14 . The method of  claim 13 , wherein the compound which binds to the polypeptide is an antibody or epitope-binding fragment thereof.  
     
     
         15 . The method of  claim 14 , wherein the antibody or epitope-binding fragment thereof is coupled to a detectable substance.  
     
     
         16 . A kit comprising one or more containers comprising an antibody or epitope-binding fragment thereof which selectively binds to a polypeptide of  claim 3 , and instructions for use.  
     
     
         17 . 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.    
     
     
         18 . A method for identifying a compound which binds to a polypeptide of  claim 3  comprising the steps of: 
 a) contacting a polypeptide, or a cell expressing a polypeptide of  claim 3  with a test compound; and    b) determining whether the polypeptide binds to the test compound.    
     
     
         19 . A method of treating a subject for a disorder in the group consisting of immune disorders, autoimmune disorders, inflammatory disorders, and chronic obstructive pulmonary disorders, comprising administering to the subject an agent which modulates the expression or activity of a polypeptide of  claim 3 .  
     
     
         20 . The method of  claim 19 , wherein the agent is an antibody or epitope-binding fragment thereof which specifically binds to the polypeptide.