Gene Symbol: CCS1
Description: copper chaperone CCS1
Alias: LYS7, copper chaperone CCS1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Lamb A, Wernimont A, Pufahl R, Culotta V, O Halloran T, Rosenzweig A. Crystal structure of the copper chaperone for superoxide dismutase. Nat Struct Biol. 1999;6:724-9 pubmed
    ..In the crystal, two SOD1-like domains interact to form a dimer. The subunit interface is remarkably similar to that in SOD1, suggesting a structural basis for target recognition by this metallochaperone. ..
  2. Culotta V, Klomp L, Strain J, Casareno R, Krems B, Gitlin J. The copper chaperone for superoxide dismutase. J Biol Chem. 1997;272:23469-72 pubmed
    ..copper/zinc superoxide dismutase (SOD1) is mediated through a soluble factor identified as Saccharomyces cerevisiae LYS7 and human CCS (copper chaperone for SOD)...
  3. Reddehase S, Grumbt B, Neupert W, Hell K. The disulfide relay system of mitochondria is required for the biogenesis of mitochondrial Ccs1 and Sod1. J Mol Biol. 2009;385:331-8 pubmed publisher
    ..The biogenesis of functional Sod1 is dependent on its copper chaperone, Ccs1, which introduces a disulfide bond and a copper ion into Sod1...
  4. Sturtz L, Diekert K, Jensen L, Lill R, Culotta V. A fraction of yeast Cu,Zn-superoxide dismutase and its metallochaperone, CCS, localize to the intermembrane space of mitochondria. A physiological role for SOD1 in guarding against mitochondrial oxidative damage. J Biol Chem. 2001;276:38084-9 pubmed
    ..Cu,Zn-SOD1 in the mitochondria appears important for reactive oxygen physiology and may have critical implications for SOD1 mutations linked to the fatal neurodegenerative disorder, amyotrophic lateral sclerosis. ..
  5. Lamb A, Torres A, O Halloran T, Rosenzweig A. Heterodimeric structure of superoxide dismutase in complex with its metallochaperone. Nat Struct Biol. 2001;8:751-5 pubmed
    ..This domain is linked to SOD1 by an intermolecular disulfide bond that may facilitate or regulate copper delivery. ..
  6. Schmidt P, Kunst C, Culotta V. Copper activation of superoxide dismutase 1 (SOD1) in vivo. Role for protein-protein interactions with the copper chaperone for SOD1. J Biol Chem. 2000;275:33771-6 pubmed
    ..Our data are consistent with a model in which prefolded dimers of apoSOD1 serve as substrate for the CCS copper chaperone. ..
  7. Pope C, De Feo C, Unger V. Cellular distribution of copper to superoxide dismutase involves scaffolding by membranes. Proc Natl Acad Sci U S A. 2013;110:20491-6 pubmed publisher
  8. Lamb A, Torres A, O Halloran T, Rosenzweig A. Heterodimer formation between superoxide dismutase and its copper chaperone. Biochemistry. 2000;39:14720-7 pubmed
    ..These findings, taken together with structural, biochemical, and genetic studies, strongly suggest that in vivo copper loading of yeast SOD1 occurs via a heterodimeric intermediate. ..
  9. Wei W, Smith N, Wu X, Kim H, Seravalli J, Khalimonchuk O, et al. YCF1-mediated cadmium resistance in yeast is dependent on copper metabolism and antioxidant enzymes. Antioxid Redox Signal. 2014;21:1475-89 pubmed publisher

More Information


  1. Gross D, Burgard C, Reddehase S, Leitch J, Culotta V, Hell K. Mitochondrial Ccs1 contains a structural disulfide bond crucial for the import of this unconventional substrate by the disulfide relay system. Mol Biol Cell. 2011;22:3758-67 pubmed publisher
    The copper chaperone for superoxide dismutase 1 (Ccs1) provides an important cellular function against oxidative stress. Ccs1 is present in the cytosol and in the intermembrane space (IMS) of mitochondria...
  2. Fetherolf M, Boyd S, Taylor A, Kim H, Wohlschlegel J, Blackburn N, et al. Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site. J Biol Chem. 2017;292:12025-12040 pubmed publisher
    ..The copper chaperone for superoxide dismutase (Ccs1) activates immature copper-zinc superoxide dismutase (Sod1) by delivering copper and facilitating the oxidation of ..
  3. Muid K, Karakaya H, Koc A. Absence of superoxide dismutase activity causes nuclear DNA fragmentation during the aging process. Biochem Biophys Res Commun. 2014;444:260-3 pubmed publisher
    ..In this study, we investigated the roles of SOD1, SOD2 and CCS1 genes in preserving genomic integrity in replicatively old yeast cells using the single cell comet assay...
  4. Klöppel C, Suzuki Y, Kojer K, Petrungaro C, Longen S, Fiedler S, et al. Mia40-dependent oxidation of cysteines in domain I of Ccs1 controls its distribution between mitochondria and the cytosol. Mol Biol Cell. 2011;22:3749-57 pubmed publisher
    ..Maturation of Sod1 depends on its copper chaperone (Ccs1)...
  5. Brady G, Galban S, Liu X, Basrur V, Gitlin J, Elenitoba Johnson K, et al. Regulation of the copper chaperone CCS by XIAP-mediated ubiquitination. Mol Cell Biol. 2010;30:1923-36 pubmed publisher
    ..Collectively, our results reveal novel links among apoptosis, copper metabolism, and redox regulation through the XIAP-CCS complex. ..
  6. Leitch J, Jensen L, Bouldin S, Outten C, Hart P, Culotta V. Activation of Cu,Zn-superoxide dismutase in the absence of oxygen and the copper chaperone CCS. J Biol Chem. 2009;284:21863-71 pubmed publisher
    ..In this manner, Cu,Zn-SOD from metazoans may retain activity over a wide range of physiological oxygen tensions. ..
  7. Varabyova A, Topf U, Kwiatkowska P, Wrobel L, Kaus Drobek M, Chacinska A. Mia40 and MINOS act in parallel with Ccs1 in the biogenesis of mitochondrial Sod1. FEBS J. 2013;280:4943-59 pubmed publisher
    ..Sod1 requires its specific chaperone Ccs1 and disulfide bond formation in order to be retained in the intermembrane space...
  8. Wood L, Thiele D. Transcriptional activation in yeast in response to copper deficiency involves copper-zinc superoxide dismutase. J Biol Chem. 2009;284:404-13 pubmed publisher
    ..Here we show that the copper-dependent enzyme Sod1 (Cu,Zn-superoxide dismutase) and its intracellular copper chaperone Ccs1 function in the activation of Mac1 in response to an external copper deficiency...
  9. Carter C, Kitchen L, Au W, Babic C, Basrai M. Loss of SOD1 and LYS7 sensitizes Saccharomyces cerevisiae to hydroxyurea and DNA damage agents and downregulates MEC1 pathway effectors. Mol Cell Biol. 2005;25:10273-85 pubmed
    ..We show that loss of the Cu,Zn-dependent superoxide dismutase, SOD1, or its copper chaperone, LYS7, confers oxygen-dependent sensitivity to replication arrest and DNA damage in Saccharomyces cerevisiae...