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FLASH GENE
Symbol CCS contributors: mct - updated : 21-10-2017
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
DNA
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
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 1068 29 274 - 1999 10221913
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineneuroendocrinepituitary  highly
Nervousnerve   highly
Urinarybladder   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 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 (30–40 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
    HOMOLOGY
    interspecies ortholog to yeast S.cerevisiae LYS7
    Homologene
    FAMILY
  • Cu-Zn superoxide dismutase family
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,interspace
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • 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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism metal
    signaling
    a component
  • homodimer, and heterodimer with SOD1
  • XIAP-CCS complex implicated in apoptosis, copper metabolism, and redox regulation
  • INTERACTION
    DNA
    RNA
    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)
  • copper chaperone for SOD1 (CCS) is a dedicated and specific chaperone that assists SOD1 folding and maturation to produce the active enzyme
  • cell & other
    REGULATION
    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)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • 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