Comparison of human CAP and CAP2, homologs of the yeast adenylyl cyclase-associated proteins.
We previously reported the identification of human CAP, a protein that is related to the Saccharomyces cerevisiae and Schizosaccharomyces pombe adenylyl cyclase-associated CAP proteins. The two yeast CAP proteins have similar functions: the N-terminal domains are required for the normal function of adenylyl cyclase, while loss of the C-terminal domains result in morphological and nutritional defects that are unrelated to the cAMP pathways. We have amplified and cloned cDNAs from a human glioblastoma library that encode a second CAP-related protein, CAP2. The human CAP and CAP2 proteins are 64% identical. Expression of either human CAP or CAP2 in S. cerevisiae cap- strains suppresses phenotypes associated with deletion of the C-terminal domain of CAP, but does not restore hyper-activation of adenylyl cyclase by RAS2val19. Similarly, expression of either human CAP or CAP2 in S. pombe cap- strains suppresses the morphological and temperature-sensitive phenotypes associated with deletion of the C-terminal domain of CAP in this yeast. In addition, expression of human CAP, but not CAP2, suppresses the propensity to sporulate due to deletion of the N-terminal domain of CAP in S. pombe. This latter observation suggests that human CAP restores normal adenylyl cyclase activity in S. pombe cap- cells. Thus, functional properties of both N-terminal and C-terminal domains are conserved between the human and S. pombe CAP proteins.
Department of Medical Biochemistry, University of Calgary Health Science Centre, Alberta, Canada.
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001483:Base Sequence; D005075:Biological Evolution; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000235:genetics; D029721:Drosophila Proteins; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D005796:Genes; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D006801:Humans; D008565:Membrane Proteins; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D048868:Adaptor Proteins, Signal Transducing; C489549:CAP1 protein, human; C484231:CAP2 protein, human; C081782:Cap1 protein, rat; C090135:Cap2 protein, S cerevisiae; C484230:Cap2 protein, rat; C410502:Capt protein, Drosophila; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D029721:Drosophila Proteins; D005656:Fungal Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; C073751:SRV2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins