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Symbol CCS contributors: mct - updated : 21-10-2015
HGNC name copper chaperone for superoxide dismutase
HGNC id 1613
Location 11q13.2      Physical location : 66.360.689 - 66.373.489
Synonym name superoxide dismutase copper chaperone
Synonym symbol(s) MGC138260, CCS1
TYPE functioning gene
SPECIAL FEATURE arranged in tandem
STRUCTURE 12.86 kb     8 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map cen - D11S913 - CST6 - CCS - PPP1CA - D11S1337 - FOLR1 - D11S1314 - D11S4184 - D11S916 - qter
Physical map
KLC2 11q13.1 pyruvate carboxylase RAB1B 11q12 RAB1B, member RAS oncogene family MGC50896 11q13.1 hypothetical protein MGC50896 YIF1 11q13 Yip1 interacting factor homolog (S. cerevisiae) MGC33486 11q13.1 hypothetical protein MGC33486 LOC387783 11 LOC387783 CD164L1 11q13 CD164 sialomucin-like 1 RIN1 11q13.2 Ras and Rab interactor 1 BRMS1 14q13.1 breast cancer metastasis-suppressor 1 B3GNT6 11q13.1 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 6 SLC29A2 11q13 solute carrier family 29 (nucleoside transporters), member 2 LOC387784 11 LOC387784 NXF 11q13 HLH-PAS transcription factor NXF MRPL11 11q13.3 mitochondrial ribosomal protein L11 MGC35521 11q13.1 pellino 3 alpha DPP3 11q12-q13.1 dipeptidylpeptidase 3 BBS1 11q13 Bardet-Biedl syndrome 1 LOC254359 11q13.1 hypothetical protein LOC254359 ACTN3 11q13 actinin, alpha 3 CTSF 11q13.1-q13.3 cathepsin F FLJ10786 11q13.1 hypothetical protein FLJ10786 CCS 11q13 copper chaperone for superoxide dismutase RBM14 11q12.1 RNA binding motif protein 14 MGC15912 11q13.1 hypothetical protein MGC15912 RBM4 11q13 RNA binding motif protein 4 MGC10871 11q13 hypothetical protein similar to RNA-binding protein lark SPTBN2 11q13 spectrin, beta, non-erythrocytic 2 FLJ22531 11q13.1 hypothetical protein FLJ22531 RCE1 11q13 RCE1 homolog, prenyl protein protease (S. cerevisiae) PC 11q13.3 pyruvate carboxylase MGC3103
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 1068 29 274 - 1999 10221913
Type ubiquitous
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineneuroendocrinepituitary  highly
Nervousnerve   highly
Urinarybladder   highly
cell lineage
cell lines
  • N terminal domain (I) containing a putative copper-binding motif, essential for SOD1 copper acquisition
  • an internal domain (II), structurally similar to SOD1 and has been postulated to be critical for CCS-SOD1 protein recognition
  • a HMA domain
  • a C terminal domain (III), a short polypeptide segment (3040 amino acids) lacking secondary structure but containing a CXC motif (Cys-244 and Cys-246 in hCCS) essential for CCS-dependent activation of SOD1
  • conjugated MetalloP
    mono polymer homomer , heteromer , dimer
    interspecies ortholog to yeast S.cerevisiae LYS7
  • Cu-Zn superoxide dismutase family
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
  • colocalyzing with SOD1
  • CCS localization in the cytosol prevents SOD1 mitochondrial import, whereas CCS in mitochondria increases it
  • mitochondrial distribution is regulated by the CHCHD40 disulfide relay system in a redox-dependent manner
  • present in the cytosol and in the intermembrane space of mitochondria
  • CCS import depends on the presence of mature CCS in the mitochondria
  • basic FUNCTION
  • mediating copper incorporation in superoxide dismutase
  • may activate copper/zinc superoxide dismutase through direct insertion of the Cu cofactor
  • may be playing a role in prioritizing the utilization of copper when it is scarce
  • likely exhibits disulfide isomerase activity
  • involved in one activation pathway of SOD1 (CCS-dependent pathway)
  • necessary for expression of an active, copper-bound form of superoxide dismutase (SOD1) in spite of the high affinity of SOD1 for copper and the high intracellular concentrations of both SOD1 and copper
  • metallochaperone protein activating the target enzyme through direct insertion of the copper cofactor and apparently functions to protect the metal ion from binding to intracellular copper scavengers
  • mediator of copper delivery to XIAP in cells
  • promotes SOD1 maturation and retention in the intermembrane space
  • specifically delivers copper (Cu) to copper, zinc superoxide dismutase (SOD1) in cytoplasm of mammalian cells
  • the amount of CCS protein exceeds that required to supply Cu to SOD1 in the cells
  • CCS is the physiological partner for the complex mechanism of SOD1 maturation
  • facilitates copper trafficking to the mitochondria, but does not affect the transfer of copper to the cytochrome c oxidase (CCO)
  • serves as a specialized import receptor in mitochondria that facilitates the import and folding of SOD1 and CCS, thereby extending the substrate spectrum of oxidation-dependent protein import in the mitochondrial intermembrane space
    metabolism metal
    a component
  • homodimer, and heterodimer with SOD1
  • XIAP-CCS complex implicated in apoptosis, copper metabolism, and redox regulation
    small molecule metal binding,
  • 2 copper ions per subunit
  • 1 zinc ion per subunit , and zinc binding is essential to human CCS (hCCS) function, most likely contributing to protein stabilization
  • protein
  • target of the E3 ubiquitin ligase activity of XIAP, although interestingly, ubiquitination of CCS by XIAP was found to lead to enhancement of its chaperone activity toward its physiologic target, superoxide dismutase 1, rather than proteasomal degradation)
  • cell & other
    inhibited by copper supplementation that decreased the protein levels of ATOX1 and CCS
    Other regulated by copper (regulates CCS expression by modulating its degradation by the 26 S proteosome)
    corresponding disease(s)
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • dual transgenic mice overexpressing both G93A and CCS copper chaperone (G93A/CCS) exhibit no SOD1-positive aggregates yet show accelerated ALS1 symptoms with enhanced mitochondrial pathology compared to G93A mice