SEQUENCE, MAPPING AND DISRUPTION OF CCC2, A GENE THAT CROSS-COMPLEMENTS THE CA2+-SENSITIVE PHENOTYPE OF CSG1 MUTANTS AND ENCODES A P-TYPE ATPASE BELONGING TO THE CU2+-ATPASE SUBFAMILY

We have isolated, sequenced, mapped and disrupted a gene, CCC2, from Saccharomyces cerevisiae. This gene displays non-allelic complementation of the Ca2+-sensitive phenotype conferred by the csg1 mutation. 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. The ability of this gene, in two or more copies, to reverse the csg1 defect suggests that Ca2+-induced death of csg1 mutant cells is related to Cu2+ metabolism. Cells without CCC2 require increased Cu2+ concentrations for growth. Therefore CCC2p may function to provide Cu2+ to a cellular compartment rather than in removal of excess Cu2+. The sequence of CCC2 is available through GenBank under accession number L36317.