COPS3 Gene

HGNC Family	COP9 signalosome (COPS)
Name	COP9 signalosome subunit 3
Description	The protein encoded by this gene possesses kinase activity that phosphorylates regulators involved in signal transduction. It phosphorylates I kappa-Balpha, p105, and c-Jun. It acts as a docking site for complex-mediated phosphorylation. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]
Summary	{"type": "root", "children": [{"type": "t", "text": "<head>\n <meta charset=\"UTF-8\">\n <title>COPS3 Function Summary</title>\n </head>\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n COPS3, which encodes the third subunit of the COP9 signalosome, is emerging as a multifunctional protein with critical roles in both development and disease. In embryonic systems, COPS3 is vital for maintaining the integrity of the COP9 complex and ensuring proper cell cycle progression and survival. Disruption of COPS3 in mouse embryos leads to loss of complex stability, accumulation of cell cycle regulators (such as Cyclin B1 and Securin), and compromised genome integrity during early cleavage stages, ultimately causing embryonic lethality."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, COPS3 is frequently amplified or overexpressed, notably in osteosarcoma, where its upregulation correlates with enhanced metastasis. Mechanistically, elevated COPS3 promotes oncogenesis through modulation of key signaling pathways – for example, by interacting directly with Raf-1 to activate the MEK/ERK cascade, facilitating epithelial–mesenchymal transition, and by enhancing the degradation of the tumor suppressor p53."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similar oncogenic roles have been documented in kidney and prostate cancers where high COPS3 expression contributes to cell proliferation, migration, and poor prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, genomic studies in osteosarcoma and multiple myeloma have identified COPS3 as a candidate driver gene whose amplification is linked to genomic instability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n COPS3 also participates in differentiation processes. In epidermal cells, it associates with desmosomal components such as Desmoglein1 and Desmoplakin to regulate EGFR de‐neddylation, thereby contributing to proper epidermal differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In cardiac myocytes, yeast two-hybrid studies have revealed specific interaction of COPS3 with the beta1D integrin cytoplasmic domain, suggesting roles in heart muscle differentiation and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, proteomic profiling in immune cells following exercise training has shown that COPS3 expression can be upregulated in natural killer cells, potentially linking its function to adaptive responses in immune cell signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Collectively, these diverse studies underscore that COPS3 acts as a key regulator of protein turnover and signal transduction, with roles that extend from ensuring genome integrity during early development to driving oncogenic processes and modulating cell differentiation and immune responses.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jiong Yan, Katherina Walz, Hisashi Nakamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "COP9 signalosome subunit 3 is essential for maintenance of cell proliferation in the mouse embryonic epiblast."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.19.6798-6808.2003"}], "href": "https://doi.org/10.1128/MCB.23.19.6798-6808.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12972600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12972600"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eunju Kim, Se-Jin Yoon, Eun-Young Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Function of COP9 signalosome in regulation of mouse oocytes meiosis by regulating MPF activity and securing degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0025870"}], "href": "https://doi.org/10.1371/journal.pone.0025870"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21991377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21991377"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Steffen Israel, Hannes C A Drexler, Georg Fuellen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The COP9 signalosome subunit 3 is necessary for early embryo survival by way of a stable protein deposit in mouse oocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gaab048"}], "href": "https://doi.org/10.1093/molehr/gaab048"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34264319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34264319"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fan Zhang, Taiqiang Yan, Wei Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel oncogene COPS3 interacts with Beclin1 and Raf-1 to regulate metastasis of osteosarcoma through autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-018-0791-6"}], "href": "https://doi.org/10.1186/s13046-018-0791-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29970115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29970115"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Maaike van Dartel, Theo J M Hulsebos "}, {"type": "b", "children": [{"type": "t", "text": "Amplification and overexpression of genes in 17p11.2 ~ p12 in osteosarcoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Genet Cytogenet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cancergencyto.2004.03.007"}], "href": "https://doi.org/10.1016/j.cancergencyto.2004.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15325100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15325100"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yang Hong, Xiaobo Huang, Lizhe An, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of COPS3 promotes clear cell renal cell carcinoma progression via regulation of Phospho-AKT(Thr308), Cyclin D1 and Caspase-3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2018.02.025"}], "href": "https://doi.org/10.1016/j.yexcr.2018.02.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29477618"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29477618"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhenjie Zhu, Yang Hong, Fengshi Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of COPS3 inhibits the progress of prostate cancer through reducing phosphorylated p38 MAPK expression and impairs the epithelial-mesenchymal transition process."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pros.23907"}], "href": "https://doi.org/10.1002/pros.23907"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31509289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31509289"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Y Xiong, S Wu, Q Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrated analysis of gene expression and genomic aberration data in osteosarcoma (OS)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Gene Ther (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cgt.2015.48"}], "href": "https://doi.org/10.1038/cgt.2015.48"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26427513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26427513"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Joeri Both, Thijs Wu, Anneloor L M A Ten Asbroek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenic Properties of Candidate Oncogenes in Chromosome Region 17p11.2p12 in Human Osteosarcoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cytogenet Genome Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000451046"}], "href": "https://doi.org/10.1159/000451046"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27846620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27846620"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Nicole Ann Najor, Gillian Nicole Fitz, Jennifer Leigh Koetsier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epidermal Growth Factor Receptor neddylation is regulated by a desmosomal-COP9 (Constitutive Photomorphogenesis 9) signalosome complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.22599"}], "href": "https://doi.org/10.7554/eLife.22599"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28891468"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28891468"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Chris Hunter, Jennifer Evans, Maria L Valencik "}, {"type": "b", "children": [{"type": "t", "text": "Subunit 3 of the COP9 signalosome is poised to facilitate communication between the extracellular matrix and the nucleus through the muscle-specific beta1D integrin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Commun Adhes (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15419060802198660"}], "href": "https://doi.org/10.1080/15419060802198660"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18979294"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18979294"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Francisco Llavero, Lidia B Alejo, Carmen Fiuza-Luces, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exercise training effects on natural killer cells: a preliminary proteomics and systems biology approach."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exerc Immunol Rev (2021)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33965896"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33965896"}]}]}]}
Synonyms	SGN3, CSN3
Proteins	CSN3_HUMAN
NCBI Gene ID	8533
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

COPS3 has 7,465 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 118 datasets.

Click the + buttons to view associations for COPS3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

COPS3 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 COPS3 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 COPS3 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 COPS3 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 COPS3 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 COPS3 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 COPS3 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 COPS3 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 COPS3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of COPS3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of COPS3 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 COPS3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with COPS3 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 COPS3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of COPS3 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 COPS3 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 COPS3 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 COPS3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing COPS3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing COPS3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing COPS3 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with COPS3 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 COPS3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing COPS3 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of COPS3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with COPS3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with COPS3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with COPS3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of COPS3 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with COPS3 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 COPS3 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 COPS3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with COPS3 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 COPS3 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 COPS3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of COPS3 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 COPS3 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 COPS3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with COPS3 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 COPS3 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of COPS3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.