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Gene Review

CCC2  -  Cu(2+)-transporting P-type ATPase CCC2

Saccharomyces cerevisiae S288c

Synonyms: Copper-transporting ATPase, Cu(2+)-ATPase, D9954.6, YDR270W
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Disease relevance of CCC2


High impact information on CCC2

  • Instead, CCC2 mutant cells lacked a copper-dependent oxidase activity associated with the extracytosolic domain of the FET3-encoded protein, a ceruloplasmin homologue previously shown to be necessary for high-affinity iron uptake in yeast [1].
  • These results suggest that the CCC2-encoded protein is required for the export of copper from the cytosol into an extracytosolic compartment, supporting the proposal that intracellular copper transport is impaired in Wilson disease and Menkes disease [1].
  • The results from additional genetic studies using the sphingolipid hydroxylase and copper transporter genes, SCS7 and CCC2, respectively, suggest a second possible point of sterol regulation at the level of complex sphingolipid hydroxylation [3].
  • Most noteworthy, the first 44 residues display significant homology to the methionine- and histidine-rich copper binding domain of three bacterial copper binding proteins, among these a copper transporting ATPase [4].
  • Regulation of CaCCC2 and the phenotype of the homozygous CaCCC2 deletion indicate that it is required for high-affinity iron import, making it the bona fide CCC2 homologue of C. albicans [5].

Biological context of CCC2


Anatomical context of CCC2

  • Accessory genes required for the functioning of this transport system include a plasma-membrane copper transporter (CTR1), an intracellular copper transporter (CCC2), and a putative transcription factor (AFT1) [8].

Regulatory relationships of CCC2

  • Increased expression of CCC2 or increased Cu2+ concentration in the growth medium enhances the Ca2+ tolerance of csg1 mutants, suggesting that accumulation of IPC-C renders csg1 cells Ca2+ sensitive [9].

Other interactions of CCC2

  • RESULTS: Genes in the upstream group encoded the regulator of copper transport, MAC1, and two copper transporters, CTR1 and CCC2 [10].
  • The CCC2 gene in the yeast Saccharomyces cerevisiae encodes a P-type ATPase (Ccc2p) required for the export of cytosolic copper to the extracytosolic domain of a copper-dependent oxidase, Fet3p [11].


  1. The Menkes/Wilson disease gene homologue in yeast provides copper to a ceruloplasmin-like oxidase required for iron uptake. Yuan, D.S., Stearman, R., Dancis, A., Dunn, T., Beeler, T., Klausner, R.D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  2. Caenorhabditis elegans cDNA for a Menkes/Wilson disease gene homologue and its function in a yeast CCC2 gene deletion mutant. Sambongi, Y., Wakabayashi, T., Yoshimizu, T., Omote, H., Oka, T., Futai, M. J. Biochem. (1997) [Pubmed]
  3. Sterol-dependent regulation of sphingolipid metabolism in Saccharomyces cerevisiae. Swain, E., Baudry, K., Stukey, J., McDonough, V., Germann, M., Nickels, J.T. J. Biol. Chem. (2002) [Pubmed]
  4. Molecular characterization of a putative Arabidopsis thaliana copper transporter and its yeast homologue. Kampfenkel, K., Kushnir, S., Babiychuk, E., Inzé, D., Van Montagu, M. J. Biol. Chem. (1995) [Pubmed]
  5. Deletion of the copper transporter CaCCC2 reveals two distinct pathways for iron acquisition in Candida albicans. Weissman, Z., Shemer, R., Kornitzer, D. Mol. Microbiol. (2002) [Pubmed]
  6. clap1, a gene encoding a copper-transporting ATPase involved in the process of infection by the phytopathogenic fungus Colletotrichum lindemuthianum. Parisot, D., Dufresne, M., Veneault, C., Laugé, R., Langin, T. Mol. Genet. Genomics (2002) [Pubmed]
  7. Sequence, mapping and disruption of CCC2, a gene that cross-complements the Ca(2+)-sensitive phenotype of csg1 mutants and encodes a P-type ATPase belonging to the Cu(2+)-ATPase subfamily. Fu, D., Beeler, T.J., Dunn, T.M. Yeast (1995) [Pubmed]
  8. Molecular biology of iron acquisition in Saccharomyces cerevisiae. Askwith, C.C., de Silva, D., Kaplan, J. Mol. Microbiol. (1996) [Pubmed]
  9. SUR1 (CSG1/BCL21), a gene necessary for growth of Saccharomyces cerevisiae in the presence of high Ca2+ concentrations at 37 degrees C, is required for mannosylation of inositolphosphorylceramide. Beeler, T.J., Fu, D., Rivera, J., Monaghan, E., Gable, K., Dunn, T.M. Mol. Gen. Genet. (1997) [Pubmed]
  10. Genetic analysis of iron uptake in the yeast Saccharomyces cerevisiae. Dancis, A. J. Pediatr. (1998) [Pubmed]
  11. Restriction of copper export in Saccharomyces cerevisiae to a late Golgi or post-Golgi compartment in the secretory pathway. Yuan, D.S., Dancis, A., Klausner, R.D. J. Biol. Chem. (1997) [Pubmed]
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