COPS6 Gene

HGNC Family	COP9 signalosome (COPS)
Name	COP9 signalosome subunit 6
Description	The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein belongs to translation initiation factor 3 (eIF3) superfamily. It is involved in the regulation of cell cycle and likely to be a cellular cofactor for HIV-1 accessory gene product Vpr. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n COP9 signalosome subunit 6 (CSN6), also known as COPS6, is a critical non‐catalytic component of the COP9 signalosome that regulates the activity of cullin–RING ubiquitin ligases (CRLs) by controlling the neddylation status of cullin proteins. Through this modulation, CSN6 plays a central role in governing the stability of key regulatory proteins involved in cell cycle progression, DNA damage responses, apoptosis, and tumorigenesis. For example, CSN6 promotes degradation of the tumor suppressor p53 by stabilizing its negative regulator MDM2, thereby influencing cell survival and cancer development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, CSN6 facilitates oncogenic signaling by enhancing Myc stability through promoting autoubiquitination and degradation of Fbxw7, the adaptor that normally directs Myc for proteasomal turnover."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " CSN6 also interacts with other ubiquitin ligases such as COP1, resulting in decreased levels of cell cycle inhibitors (such as p27 and p57) and thereby contributing to unrestrained cell proliferation and survival"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " These diverse molecular mechanisms have been documented in a variety of malignancies—including breast, colorectal, glioblastoma, and cervical cancers—where CSN6 overexpression correlates with enhanced oncogenic aggressiveness, poor patient prognosis, and resistance to apoptosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Collectively, these findings underscore the pivotal role of CSN6 in orchestrating ubiquitin‐mediated proteolysis and support its potential as a therapeutic target in cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ruiying Zhao, Sai-Ching J Yeung, Jian Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Subunit 6 of the COP9 signalosome promotes tumorigenesis in mice through stabilization of MDM2 and is upregulated in human cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI44111"}], "href": "https://doi.org/10.1172/JCI44111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21317535"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21317535"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jian Chen, Ji-Hyun Shin, Ruiying Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CSN6 drives carcinogenesis by positively regulating Myc stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms6384"}], "href": "https://doi.org/10.1038/ncomms6384"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25395170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25395170"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "J Hou, Q Deng, J Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CSN6 controls the proliferation and metastasis of glioblastoma by CHIP-mediated degradation of EGFR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2016.280"}], "href": "https://doi.org/10.1038/onc.2016.280"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27546621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27546621"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "H H Choi, C Gully, C-H Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "COP9 signalosome subunit 6 stabilizes COP1, which functions as an E3 ubiquitin ligase for 14-3-3σ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.192"}], "href": "https://doi.org/10.1038/onc.2011.192"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21625211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21625211"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Bo Chen, Ruiying Zhao, Chun-Hui Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDK inhibitor p57 (Kip2) is negatively regulated by COP9 signalosome subunit 6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.22887"}], "href": "https://doi.org/10.4161/cc.22887"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23187808"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23187808"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Hyun Ho Choi, Sergei Guma, Lekun Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulating the stability and localization of CDK inhibitor p27(Kip1) via CSN6-COP1 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15384101.2015.1046655"}], "href": "https://doi.org/10.1080/15384101.2015.1046655"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25945542"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25945542"}]}]}]}
Synonyms	MOV34-34KD, CSN6
Proteins	CSN6_HUMAN
NCBI Gene ID	10980
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

COPS6 has 6,915 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 120 datasets.

Click the + buttons to view associations for COPS6 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

COPS6 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of COPS6 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of COPS6 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of COPS6 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of COPS6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of COPS6 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of COPS6 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of COPS6 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of COPS6 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of COPS6 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of COPS6 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of COPS6 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of COPS6 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with COPS6 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of COPS6 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of COPS6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of COPS6 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing COPS6 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of COPS6 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing COPS6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing COPS6 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing COPS6 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with COPS6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with COPS6 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing COPS6 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of COPS6 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with COPS6 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with COPS6 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of COPS6 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with COPS6 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with COPS6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with COPS6 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with COPS6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with COPS6 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at COPS6 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of COPS6 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of COPS6 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing COPS6 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of COPS6 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with COPS6 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing COPS6 from the GeneSigDB Published Gene Signatures dataset.