Disease relevance of CCC2

• The CCC2 gene of the yeast Saccharomyces cerevisiae is homologous to the human genes defective in Wilson disease and Menkes disease [1].
• The Saccharomyces cerevisiae mutant with a disrupted CCC2 gene (yeast Menkes/Wilson disease gene homologue) was rescued by the cDNA for the C. elegans Cu2+-ATPase but not by the cDNA with an Asp-786 (an invariant phosphorylation site) to Asn mutation, suggesting that the C. elegans Cu2+-ATPase functions as a copper transporter in yeast [2].

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

• Caenorhabditis elegans cDNA for a Menkes/Wilson disease gene homologue and its function in a yeast CCC2 gene deletion mutant [2].
• Molecular analyses indicated that the mutagenic plasmid had targeted clap1, a gene encoding a putative copper-transporting ATPase sharing 35% identity with the human Menkes and Wilson proteins and the product of the CCC2 gene of Saccharomyces cerevisiae [6].
• Analysis of the CCC2p amino acid sequence reveals that it encodes a member of the P-type ATPase family and is most similar to a subfamily thought to consist of Cu2+ transporters, including the human genes that mutate to cause Wilson disease and Menkes disease [7].

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].

References