22438, 23553, 25278, and 26212 novel human sulfatases

Abstract

The present invention relates to newly identified human sulfatases. In particular, the invention relates to sulfatase polypeptides and polynucleotides, methods of detecting the sulfatase polypeptides and polynucleotides, and methods of diagnosing and treating sulfatase-related disorders. Also provided are vectors, host cells, and recombinant methods for making and using the novel molecules.

That which is claimed:  
     
         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 60% identical to the nucleotide sequence of SEQ ID NO:2, 4, 6, 8, 11, 12, 13, or 14, or the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1639 or PTA-1846, wherein said nucleotide sequence encodes a polypeptide having biological activity;    b) a nucleic acid molecule comprising a fragment of at least 20 nucleotides of the nucleotide sequence of SEQ ID NO:2, 4, 6, 8, 11, 12, 13, or 14, or the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1639 or PTA-1846;    c) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:1, 3, 5, or 7, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Patent Deposit Number PTA-1639 or PTA-1846;    d) a nucleic acid molecule which encodes a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:1, 3, 5, 7, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Patent Deposit Number PTA-1639 or PTA-1846, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:1, 3, 5, or 7, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Patent Deposit Number PTA-1639 or PTA-1846;    e) a nucleic acid molecule which encodes a naturally occurring allelic variant of a biologically active polypeptide comprising the amino acid sequence of SEQ ID NO:1, 3, 5, or 7, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Patent Deposit Number PTA-1639 or PTA-1846, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule comprising the complement of SEQ ID NO:2, 4, 6, 8, 11, 12, 13, or 14 under stringent conditions; and    f) a nucleic acid molecule comprising the complement of a), b), c), d), or e).    
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , which is selected from the group consisting of: 
 a) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:2, 4, 6, 8, 11, 12, 13, 14, the cDNA insert of any one the plasmids deposited with ATCC as Patent Deposit Number PTA-1639 or PTA-1846, or a complement thereof; and    b) a nucleic acid molecule which encodes a polypeptide comprising the amino acid sequence of SEQ ID NO:1, 3, 5, or 7, or an amino acid sequence encoded by the cDNA insert of any of the plasmids deposited with ATCC as Patent Deposit Number PTA-1639 or PTA-1846.    
     
     
         3 . The nucleic acid molecule of  claim 1  further comprising vector nucleic acid sequences.  
     
     
         4 . The nucleic acid molecule of  claim 1  further comprising nucleic acid sequences encoding a heterologous polypeptide.  
     
     
         5 . A host cell which contains the nucleic acid molecule of  claim 1 .  
     
     
         6 . The host cell of  claim 5  which is a mammalian host cell.  
     
     
         7 . A nonhuman mammalian host cell containing the nucleic acid molecule of  claim 1 .  
     
     
         8 . An isolated polypeptide selected from the group consisting of: 
 a) a biological active polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 60% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:2, 4, 6, 8, 11, 12, 13, or 14 or the nucleotide sequence of the cDNA insert of the plasmid deposited with ATCC as Patent Deposit Number PTA-1639 or PTA-1846;    b) a naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:1, 3, 5, or 7, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Patent Deposit Number PTA-1639 or PTA-1846, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising the complement of SEQ ID NO: 2, 4, 6, 8, 11, 12, 13, or 14 under stringent conditions; and,    c) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO:1, 3, 5, or 7, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Patent Deposit Number PTA-1639 or PTA-1846, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:1, 3, 5, or 7; and    d) a polypeptide having at least 60% sequence identity to the amino acid sequence SEQ ID NO:1, 3, 5, or 7, wherein the polypeptide has biological activity.    
     
     
         9 . The isolated polypeptide of  claim 8  comprising the amino acid sequence of SEQ ID NO:1, 3, 5, or 7, or an amino acid sequence encoded by the cDNA insert of any of the plasmids deposited with ATCC as Patent Deposit Number PTA-1639 or PTA-1846.  
     
     
         10 . The polypeptide of  claim 8  further comprising heterologous amino acid sequences.  
     
     
         11 . An antibody which selectively binds to a polypeptide of  claim 8 .  
     
     
         12 . A method for producing a polypeptide selected from the group consisting of: 
 a) a polypeptide comprising the amino acid sequence of SEQ ID NO:1, 3, 5, or 7, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Patent Deposit Number PTA-1639 or PTA-1846;    b) a polypeptide comprising a fragment of the amino acid sequence of SEQ ID NO:1, 3, 5, or 7, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Patent Deposit Number PTA-1639 or PTA-1846, wherein the fragment comprises at least 15 contiguous amino acids of SEQ ID NO:1, 3, 5, or 7, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Patent Deposit Number PTA-1639 or PTA-1846;    c) a biologically active naturally occurring allelic variant of a polypeptide comprising the amino acid sequence of SEQ ID NO:1, 3, 5, or 7, or the amino acid sequence encoded by the cDNA insert of the plasmid deposited with the ATCC as Patent Deposit Number PTA-1639 or PTA-1846, wherein the polypeptide is encoded by a nucleic acid molecule which hybridizes to a nucleic acid molecule comprising the complement of SEQ ID NO:2, 4, 6, 8, 11, 12, 13, or 14;    d) a polypeptide having at least 60% sequence identity to the amino acid sequence of SEQ ID NO:1, 3, 5, or 7, wherein said polypeptide has biological activity;    comprising culturing the host cell of  claim 5  under conditions in which the nucleic acid molecule is expressed.    
     
     
         13 . The method of  claim 12  wherein said polypeptide comprises the amino acid sequence of SEQ ID NO:1, 3, 5, or 7.  
     
     
         14 . A method for detecting the presence of a polypeptide of  claim 8  in a sample, comprising: 
 a) contacting the sample with a compound which selectively binds to a polypeptide of  claim 8;  and  
 b) determining whether the compound binds to the polypeptide in the sample.  
 
     
     
         15 . The method of  claim 14 , wherein the compound which binds to the polypeptide is an antibody.  
     
     
         16 . A kit comprising a compound which selectively binds to a polypeptide of  claim 8  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 . The method of  claim 17 , wherein the sample comprises mRNA molecules and is contacted with a nucleic acid probe.  
     
     
         19 . A kit comprising a compound which selectively hybridizes to a nucleic acid molecule of  claim 1  and instructions for use.  
     
     
         20 . A method for identifying a compound which binds to a polypeptide of  claim 8  comprising the steps of: 
 a) contacting a polypeptide, or a cell expressing a polypeptide of  claim 8  with a test compound; and  
 b) determining whether the polypeptide binds to the test compound.  
 
     
     
         21 . The method of  claim 20 , 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 sulfatase activity.    
     
     
         22 . A method for modulating the activity of a polypeptide of  claim 8  comprising contacting a polypeptide or a cell expressing a polypeptide of  claim 8  with a compound which binds to the polypeptide in a sufficient concentration to modulate the activity of the polypeptide.  
     
     
         23 . A method for identifying a compound which modulates the activity of a polypeptide of  claim 8 , comprising: 
 a) contacting a polypeptide of  claim 8  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.    
     
     
         24 . A method for identifying an agent that modulates the level of expression of a nucleic acid molecule of  claim 1  in a cell, said method comprising contacting said agent with the cell expressing said nucleic acid molecule such that said level of expression of said nucleic acid molecule can be modulated in said cell by said agent and measuring said level of expression of said nucleic acid molecule.  
     
     
         25 . A method for modulating the level of expression of a nucleic acid molecule of  claim 1 , said method comprising contacting said nucleic acid molecule with an agent under conditions that allow the agent to modulate the level of expression of the nucleic acid molecule.  
     
     
         26 . A pharmaceutical composition containing any of the polypeptides in  claim 8  in a pharmaceutically acceptable carrier.