title: The Saccharomyces cerevisiae copper transport protein (Ctr1p). Biochemical characterization, regulation by copper, and physiologic role in copper uptake.
abstract: The CTR1 gene of Saccharomyces cerevisiae encodes a protein required for high affinity copper uptake. The protein is expressed on the plasma membrane, is heavily glycosylated with O-linkages, and exists as an oligomer in vivo. The transcript abundance is strongly regulated by copper availability, being induced by copper deprivation and repressed by copper excess. Regulation occurs at very low, nontoxic levels of available copper and is independent of ACE1, the trans-inducer of yeast metallothionein. Expression of Ctr1p is limiting for copper uptake, since overexpression from a 2 mu high copy number plasmid increases copper uptake. Mutations in CTR1 result in altered cellular responses to extracellular copper, demonstrating a physiologic role for CTR1 in the delivery of copper to the cytosol. A copper-dependent reporter gene construct, CUP1-lacZ, is not expressed in CTR1 mutants to the same level as in wild-type strains, and Cu,Zn superoxide dismutase activity is deficient in these mutants. The growth arrest that occurs in CTR1 mutants grown aerobically in copper-deficient media is attributable to the defect in Cu,Zn superoxide dismutase activity.
authors.affiliation: Cell Biology and Metabolism Branch, NICHHD, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: A
authors.initials: A
authors.lastname: Dancis
authors.forename: D
authors.initials: D
authors.lastname: Haile
authors.forename: D S
authors.initials: DS
authors.lastname: Yuan
authors.forename: R D
authors.initials: RD
authors.lastname: Klausner
mesh_terms: D000332:Aerobiosis; D001483:Base Sequence; D001692:Biological Transport; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D003600:Cytosol / Q000378:metabolism; D038181:FMN Reductase; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D017930:Genes, Reporter; D006706:Homeostasis; D008565:Membrane Proteins / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010641:Phenotype; D011487:Protein Conformation; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D013482:Superoxide Dismutase / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C490078:CTR1 protein, S cerevisiae; C500769:CUP1-1 protein, S cerevisiae; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D005656:Fungal Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C007121:copper thionein; D003300:Copper; D008668:Metallothionein; D013482:Superoxide Dismutase; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; C023903:ferric citrate iron reductase