CCS copper chaperone for superoxide dismutase [Homo sapiens (human)] - Gene

Summary

Official Symbol: CCSprovided by HGNC
Official Full Name: copper chaperone for superoxide dismutaseprovided by HGNC
Primary source: HGNC:HGNC:1613
See related: Ensembl:ENSG00000173992 MIM:603864; AllianceGenome:HGNC:1613
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: Copper chaperone for superoxide dismutase specifically delivers Cu to copper/zinc superoxide dismutase and may activate copper/zinc superoxide dismutase through direct insertion of the Cu cofactor. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in liver (RPKM 18.8), spleen (RPKM 17.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.2

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (66593185..66606019)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (66589431..66602265)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (66360656..66373490)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The E3 ligase TRIM22 functions as a tumor suppressor in breast cancer by targeting CCS for proteasomal degradation to inhibit STAT3 signaling.
Title: The E3 ligase TRIM22 functions as a tumor suppressor in breast cancer by targeting CCS for proteasomal degradation to inhibit STAT3 signaling.
CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress.
Title: CRISPR/Cas9 screens unravel miR-3689a-3p regulating sorafenib resistance in hepatocellular carcinoma via suppressing CCS/SOD1-dependent mitochondrial oxidative stress.
The copper chaperone CCS facilitates copper binding to MEK1/2 to promote kinase activation.
Title: The copper chaperone CCS facilitates copper binding to MEK1/2 to promote kinase activation.
Mutations in Superoxide Dismutase 1 (Sod1) Linked to Familial Amyotrophic Lateral Sclerosis Can Disrupt High-Affinity Zinc-Binding Promoted by the Copper Chaperone for Sod1 (Ccs).
Title: Mutations in Superoxide Dismutase 1 (Sod1) Linked to Familial Amyotrophic Lateral Sclerosis Can Disrupt High-Affinity Zinc-Binding Promoted by the Copper Chaperone for Sod1 (Ccs).
Here, we show that DCAC50, a recently developed small-molecule inhibitor of the intracellular copper chaperones, ATOX1 and CCS, reduces cell proliferation and elevates oxidative stress, triggering apoptosis in a panel of triple-negative breast cancer (TNBC) cells.
Title: Inhibition of Copper Transport Induces Apoptosis in Triple-Negative Breast Cancer Cells and Suppresses Tumor Angiogenesis.
Molecular recognition and maturation of SOD1 by its evolutionarily destabilized cognate chaperone CCS has been reported.
Title: Molecular recognition and maturation of SOD1 by its evolutionarily destabilised cognate chaperone hCCS.
CCS-D2 forms a stable complex with zinc-bound SOD1 in human cells, that has a twofold stabilizing effect: it both prevents the accumulation of unstructured mutant SOD1 and promotes zinc binding. CCS-D2 interacts with apo-SOD1 in vitro, suggesting that in cells CCS stabilizes mutant apo-SOD1 prior to zinc binding.
Title: A molecular chaperone activity of CCS restores the maturation of SOD1 fALS mutants.
In addition to Atox1, the human cytoplasm also contains Cu chaperones for loading of superoxide dismutase 1 (i.e. CCS) and cytochrome c oxidase in mitochondria (i.e. Cox17). [review]
Title: Extended functional repertoire for human copper chaperones.
Human cytoplasmic copper chaperones Atox1 and CCS exchange copper ions in vitro
Title: Human cytoplasmic copper chaperones Atox1 and CCS exchange copper ions in vitro.
Coexpression of hCCS in the presence of copper restores the correct maturation of the SOD1 mutants and prevents the formation of the unstructured species, confirming that hCCS also acts as a molecular chaperone.
Title: In-cell NMR reveals potential precursor of toxic species from SOD1 fALS mutants.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC107843P1 (e-PCR)
- UniSTS:270120

PMC107843P2 (e-PCR)
- UniSTS:270121

PMC107843P3 (e-PCR)
- UniSTS:270122

PMC107843P4 (e-PCR)
- UniSTS:270123

PMC107843P5 (e-PCR)
- UniSTS:270124

PMC107843P6 (e-PCR)
- UniSTS:270125

RH41832 (e-PCR)
- UniSTS:9577

NoName (e-PCR)
- UniSTS:488088

WI-19549 (e-PCR)
- UniSTS:3546

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cadherin binding	HDA more info	PubMed
enables copper ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables copper ion binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-disulfide reductase activity	TAS Traceable Author Statement more info
enables superoxide dismutase copper chaperone activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in cellular response to oxidative stress	TAS Traceable Author Statement more info
involved_in protein maturation by copper ion transfer	TAS Traceable Author Statement more info	PubMed
involved_in removal of superoxide radicals	IBA Inferred from Biological aspect of Ancestor more info
involved_in superoxide metabolic process	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: copper chaperone for superoxide dismutase

Names: superoxide dismutase copper chaperone

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008733.1 RefSeqGene

Range

4967..17801

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005125.2 → NP_005116.1 copper chaperone for superoxide dismutase

See identical proteins and their annotated locations for NP_005116.1

Status: REVIEWED

Source sequence(s)

AF002210, AP001157

Consensus CDS

CCDS8146.1

UniProtKB/Swiss-Prot

O14618, Q2M366, Q8NEV0

UniProtKB/TrEMBL

J3KNF4

Related

ENSP00000436318.1, ENST00000533244.6

Conserved Domains (3) summary

PLN02957
Location:14 → 253

PLN02957; copper, zinc superoxide dismutase

cd00305
Location:89 → 227

Cu-Zn_Superoxide_Dismutase; Copper/zinc superoxide dismutase (SOD). superoxide dismutases catalyse the conversion of superoxide radicals to molecular oxygen. Three evolutionarily distinct families of SODs are known, of which the copper/zinc-binding family is one. Defects in the ...

cd00371
Location:15 → 73

HMA; Heavy-metal-associated domain (HMA) is a conserved domain of approximately 30 amino acid residues found in a number of proteins that transport or detoxify heavy metals, for example, the CPx-type heavy metal ATPases and copper chaperones. HMA domain ...