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Protein

Copper chaperone for superoxide dismutase

Gene

CCS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Delivers copper to copper zinc superoxide dismutase (SOD1).

Cofactori

Protein has several cofactor binding sites:
  • Cu2+Combined sourcesNote: Binds 2 copper ions per subunit.Combined sources
  • Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi22Copper 1Combined sources1
Metal bindingi25Copper 1Combined sources1
Metal bindingi147ZincPROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi155ZincPROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi164ZincPROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi167ZincPROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi244Copper 21
Metal bindingi246Copper 21

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • copper ion binding Source: GO_Central
  • protein disulfide oxidoreductase activity Source: Reactome
  • superoxide dismutase copper chaperone activity Source: GO_Central
  • zinc ion binding Source: GO_Central

GO - Biological processi

  • cellular response to oxidative stress Source: Reactome
  • intracellular copper ion transport Source: ProtInc
  • positive regulation of oxidoreductase activity Source: Ensembl
  • superoxide metabolic process Source: ProtInc

Keywordsi

Molecular functionChaperone
LigandCopper, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3299685. Detoxification of Reactive Oxygen Species.

Names & Taxonomyi

Protein namesi
Recommended name:
Copper chaperone for superoxide dismutase
Alternative name(s):
Superoxide dismutase copper chaperone
Gene namesi
Name:CCS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:1613. CCS.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • nucleus Source: UniProtKB

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi22C → S: Reduces copper binding by half; when associated with S-25. Negligible effect on zinc binding. 1 Publication1
Mutagenesisi25C → S: Reduces copper binding by half; when associated with S-22. Negligible effect on zinc binding. 1 Publication1
Mutagenesisi244C → S: Reduces copper binding by half; when associated with S-246. Negligible effect on zinc binding. 1 Publication1
Mutagenesisi246C → S: Reduces copper binding by half; when associated with S-244. Negligible effect on zinc binding. 1 Publication1

Organism-specific databases

DisGeNETi9973.
OpenTargetsiENSG00000173992.
PharmGKBiPA26177.

Polymorphism and mutation databases

BioMutaiCCS.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002135431 – 274Copper chaperone for superoxide dismutaseAdd BLAST274

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki76Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Disulfide bondi141 ↔ 227Combined sources1 Publication
Cross-linki189Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki216Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki241Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei267PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinion by XIAP/BIRC4 leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. XIAP/BIRC4 preferentially ubiquitinates at Lys-241.1 Publication

Keywords - PTMi

Disulfide bond, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO14618.
MaxQBiO14618.
PaxDbiO14618.
PeptideAtlasiO14618.
PRIDEiO14618.

2D gel databases

OGPiO14618.

PTM databases

iPTMnetiO14618.
PhosphoSitePlusiO14618.
SwissPalmiO14618.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000173992.
CleanExiHS_CCS.
ExpressionAtlasiO14618. baseline and differential.
GenevisibleiO14618. HS.

Organism-specific databases

HPAiCAB008672.
HPA040026.
HPA044090.

Interactioni

Subunit structurei

Homodimer, and heterodimer with SOD1. Interacts with COMMD1. Interacts with XIAP/BIRC4.6 Publications

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi115298. 16 interactors.
MINTiMINT-153485.
STRINGi9606.ENSP00000436318.

Structurei

Secondary structure

1274
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi12 – 18Combined sources7
Helixi23 – 31Combined sources9
Turni32 – 35Combined sources4
Beta strandi41 – 45Combined sources5
Turni46 – 49Combined sources4
Beta strandi50 – 57Combined sources8
Helixi59 – 67Combined sources9
Turni68 – 70Combined sources3
Beta strandi73 – 78Combined sources6
Beta strandi87 – 94Combined sources8
Beta strandi96 – 98Combined sources3
Beta strandi100 – 109Combined sources10
Beta strandi112 – 121Combined sources10
Beta strandi124 – 133Combined sources10
Helixi140 – 142Combined sources3
Beta strandi161 – 163Combined sources3
Beta strandi167 – 173Combined sources7
Beta strandi177 – 187Combined sources11
Helixi190 – 193Combined sources4
Beta strandi196 – 203Combined sources8
Turni213 – 220Combined sources8
Beta strandi224 – 229Combined sources6
Beta strandi231 – 233Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DO5X-ray2.75A/B/C/D84-237[»]
2CRLNMR-A1-85[»]
2RSQNMR-A1-85[»]
ProteinModelPortaliO14618.
SMRiO14618.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14618.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 75HMAPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni88 – 234Superoxide dismutase-likeAdd BLAST147

Sequence similaritiesi

In the C-terminal section; belongs to the Cu-Zn superoxide dismutase family.Curated

Phylogenomic databases

eggNOGiENOG410IPMW. Eukaryota.
COG2032. LUCA.
GeneTreeiENSGT00530000063226.
HOGENOMiHOG000263450.
HOVERGENiHBG018933.
InParanoidiO14618.
KOiK04569.
OMAiTQRPWSE.
OrthoDBiEOG091G0FQ1.
PhylomeDBiO14618.
TreeFamiTF105184.

Family and domain databases

CDDicd00305. Cu-Zn_Superoxide_Dismutase. 1 hit.
cd00371. HMA. 1 hit.
Gene3Di2.60.40.200. 1 hit.
InterProiView protein in InterPro
IPR006121. HMA_dom.
IPR018152. SOD_Cu/Zn_BS.
IPR001424. SOD_Cu_Zn_dom.
PfamiView protein in Pfam
PF00403. HMA. 1 hit.
PF00080. Sod_Cu. 1 hit.
PRINTSiPR00068. CUZNDISMTASE.
SUPFAMiSSF49329. SSF49329. 1 hit.
SSF55008. SSF55008. 1 hit.
PROSITEiView protein in PROSITE
PS50846. HMA_2. 1 hit.
PS00332. SOD_CU_ZN_2. 1 hit.

Sequencei

Sequence statusi: Complete.

O14618-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASDSGNQGT LCTLEFAVQM TCQSCVDAVR KSLQGVAGVQ DVEVHLEDQM
60 70 80 90 100
VLVHTTLPSQ EVQALLEGTG RQAVLKGMGS GQLQNLGAAV AILGGPGTVQ
110 120 130 140 150
GVVRFLQLTP ERCLIEGTID GLEPGLHGLH VHQYGDLTNN CNSCGNHFNP
160 170 180 190 200
DGASHGGPQD SDRHRGDLGN VRADADGRAI FRMEDEQLKV WDVIGRSLII
210 220 230 240 250
DEGEDDLGRG GHPLSKITGN SGERLACGII ARSAGLFQNP KQICSCDGLT
260 270
IWEERGRPIA GKGRKESAQP PAHL
Length:274
Mass (Da):29,041
Last modified:January 1, 1998 - v1
Checksum:iA392432954B65760
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti116E → D in AAM50090 (PubMed:23625804).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068078163R → W Found in a patient with congenital cataracts, hearing loss, neurodegeneration, neonatal hypotonia and hypoglycemia, pericardial effusion and neurodevelopmental regression after infection; the patient also carries a mutation in SLC33A1; mutant protein does not interact with SOD1. 1 PublicationCorresponds to variant dbSNP:rs142340643Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF002210 mRNA. Translation: AAC51764.1.
AY113179 mRNA. Translation: AAM50090.1.
CR541928 mRNA. Translation: CAG46726.1.
BC105016 mRNA. Translation: AAI05017.1.
BC112055 mRNA. Translation: AAI12056.1.
CCDSiCCDS8146.1.
RefSeqiNP_005116.1. NM_005125.1.
UniGeneiHs.502917.

Genome annotation databases

EnsembliENST00000533244; ENSP00000436318; ENSG00000173992.
GeneIDi9973.
KEGGihsa:9973.
UCSCiuc001oir.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiCCS_HUMAN
AccessioniPrimary (citable) accession number: O14618
Secondary accession number(s): Q2M366, Q8NEV0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: January 1, 1998
Last modified: July 5, 2017
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families