Human cdnas and proteins and uses thereof

Abstract

The invention provides polynucleotides and polypeptides encoding an isolated amyloid inhibitor protein (APIP) and compositions thereof. The polypeptides of the subject invention can be used to inhibit the catabolism or sequential cleavage of amyloid beta precursor protein (APP) by sequential cleavage of APP by beta secretase and gamma secretase.

1 . A composition of matter comprising: 
 a) an purified or isolated polynucleotide, or a fragment thereof, comprising: 
 i) any one of the odd SEQ ID NOs:1-111 or polynucleotides at least 80% identical thereto;  
 ii) the sequences of clone inserts of the deposited clone pool or polynucleotides at least 80% identical thereto;  
 iii) the coding sequence of any one of the odd SEQ ID NOs:1-111 or polynucleotides at least 80% identical thereto;  
 iv) the coding sequences of the clone inserts of the deposited clone pool or polynucleotides at least 80% identical thereto;  
 v) a polynucleotide sequence encoding any one of the polypeptides of the even SEQ ID NOs:2-112 or polynucleotides at least 80% identical thereto;  
 vi) a polynucleotide sequence encoding any one of the polypeptides encoded by the clone inserts of the deposited clone pool or polynucleotides at least 80% identical thereto;  
 vii) the genomic sequences coding for the GENSET polypeptides or polynucleotides at least 80% identical thereto;  
 viii) the 5′ transcriptional regulatory regions of GENSET genes; or  
 ix) the 3′ transcriptional regulatory regions of GENSET genes;  
   b) a vector comprising a polynucleotide, or a fragment thereof, comprising: 
 i) any one of the odd SEQ ID NOs:1-111 or polynucleotides at least 80% identical thereto;  
 ii) the sequences of clone inserts of the deposited clone pool or polynucleotides at least 80% identical thereto;  
 iii) the coding sequence of any one of the odd SEQ ID NOs:1-111 or polynucleotides at least 80% identical thereto;  
 iv) the coding sequences of the clone inserts of the deposited clone pool or polynucleotides at least 80% identical thereto;  
 v) a polynucleotide sequence encoding any one of the polypeptides of the even SEQ ID NOs:2-112 or polynucleotides at least 80% identical thereto;  
 vi) a polynucleotide sequence encoding any one of the polypeptides encoded by the clone inserts of the deposited clone pool or polynucleotides at least 80% identical thereto;  
 vii) the genomic sequences coding for the GENSET polypeptides or polynucleotides at least 80% identical thereto;  
 viii) the 5′ transcriptional regulatory regions of GENSET genes; or  
 ix) the 3′ transcriptional regulatory regions of GENSET genes;  
   c) a transformed host cell comprising a polynucleotide, or a fragment thereof, comprising: 
 i) any one of the odd SEQ ID NOs:1-111 or polynucleotides at least 80% identical thereto;  
 ii) the sequences of clone inserts of the deposited clone pool or polynucleotides at least 80% identical thereto;  
 iii) the coding sequence of any one of the odd SEQ ID NOs:1-111 or polynucleotides at least 80% identical thereto;  
 iv) the coding sequences of the clone inserts of the deposited clone pool or polynucleotides at least 80% identical thereto;  
 v) a polynucleotide sequence encoding any one of the polypeptides of the even SEQ ID NOs:2-112 or polynucleotides at least 80% identical thereto;  
 vi) a polynucleotide sequence encoding any one of the polypeptides encoded by the clone inserts of the deposited clone pool or polynucleotides at least 80% identical thereto;  
 vii) the genomic sequences coding for the GENSET polypeptides or polynucleotides at least 80% identical thereto;  
 viii) the 5′ transcriptional regulatory regions of GENSET genes; or  
 ix) the 3′ transcriptional regulatory regions of GENSET genes;  
   d) an isolated polypeptide comprising: 
 i) an amino acid sequence selected from the group consisting of 
 A) any single integer from 6 to 500 amino acids of any one odd SEQ ID NO. or of a polypeptide encoded by a human cDNA of a deposited clone or a polypeptide at least 80% identical thereto;  
 B) a signal peptide sequence of any one odd SEQ ID NO. or encoded by a human cDNA of a deposited clone or a polypeptide at least 80% identical thereto;  
 C) a mature polypeptide sequence of any one odd SEQ ID NO. or encoded by a human cDNA of a deposited clone or a polypeptide at least 80% identical thereto;  
 D) a full length polypeptide sequence of any one odd SEQ ID NO. or encoded by a human cDNA of a deposited clone or a polypeptide at least 80% identical thereto; or  
 E) a polypeptide of a) through d) further comprising a physiologically acceptable carrier; or  
 
   e) an antibody that specifically binds to: 
 i) an amino acid sequence selected from the group consisting of 
 A) any single integer from 6 to 500 amino acids of any one odd SEQ ID NO. or of a polypeptide encoded by a human cDNA of a deposited clone or a polypeptide at least 80% identical thereto;  
 B) a signal peptide sequence of any one odd SEQ ID NO. or encoded by a human cDNA of a deposited clone or a polypeptide at least 80% identical thereto;  
 C) a mature polypeptide sequence of any one odd SEQ ID NO. or encoded by a human cDNA of a deposited clone or a polypeptide at least 80% identical thereto; or  
 D) a full length polypeptide sequence of any one odd SEQ ID NO. or encoded by a human cDNA of a deposited clone or a polypeptide at least 80% identical thereto.  
 
   
     
     
         2 . A method of making a polypeptide, said method comprising a) providing a population of host cells according to  claim 1;  b) culturing said population of host cells under conditions conducive to the production of a polypeptide within said host cells; and c) purifying said polypeptide from said population of host cells.  
     
     
         3 . A method of making a polypeptide, said method comprising: a) providing a population of cells comprising a polynucleotide encoding the polypeptide of  claim 1 , operably linked to a promoter; b) culturing said population of cells under conditions conducive to the production of said polypeptide within said cells; and c) purifying said polypeptide from said population of cells.  
     
     
         4 . A method of binding a polypeptide to an antibody, comprising contacting an antibody of  claim 1  with an antibody under conditions in which antibody can specifically bind to said polypeptide.  
     
     
         5 . A method of determining whether a GENSET gene is expressed within a mammal, said method comprising the steps of: a) providing a biological sample from said mammal b) contacting said biological sample with either of: i) a polynucleotide that hybridizes under stringent conditions to the polynucleotide of  claim 1;  or ii) an antibody that specifically binds to the polypeptide of  claim 1;  and c) detecting the presence or absence of hybridization between said polynucleotide and an RNA species within said sample, or the presence or absence of binding of said polypeptide to a an antibody within said sample; wherein a detection of said hybridization or of said binding indicates that said GENSET gene is expressed within said mammal.  
     
     
         6 . The method of  claim 5 , wherein said polynucleotide is a primer, and wherein said hybridization is detected by detecting the presence of an amplification product comprising the sequence of said primer.  
     
     
         7 . A method of determining whether a mammal has an elevated or reduced level of GENSET gene expression, said method comprising the steps of: a) providing a biological sample from said mammal; and b) comparing the amount of the polypeptide of  claim 1 , or of an RNA species encoding said polypeptide, within said biological sample with a level detected in or expected from a control sample; wherein an increased amount of said polypeptide or said RNA species within said biological sample compared to said level detected in or expected from said control sample indicates that said mammal has an elevated level of said GENSET gene expression, and wherein a decreased amount of said polypeptide or said RNA species within said biological sample compared to said level detected in or expected from said control sample indicates that said mammal has a reduced level of said GENSET gene expression.  
     
     
         8 . A method of identifying a candidate modulator of a GENSET polypeptide, said method comprising: a) contacting the polypeptide of  claim 1  with a test compound; and b) determining whether said compound specifically binds to said polypeptide; wherein a detection that said compound specifically binds to said polypeptide indicates that said compound is a candidate modulator of said GENSET polypeptide.  
     
     
         9 . The method of  claim 8 , further comprising testing the biological activity of said GENSET polypeptide in the presence of said candidate modulator, wherein an alteration in the biological activity of said GENSET polypeptide in the presence of said compound in comparison to the activity in the absence of said compound indicates that the compound is a modulator of said GENSET polypeptide.  
     
     
         10 . A method for the production of a pharmaceutical composition comprising a) identifying a modulator of a GENSET polypeptide using the method of  claim 9;  and b) combining said modulator with a physiologically acceptable carrier.