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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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COPS2
COP9 signalosome subunit 2
Chromosome 15 · 15q21.1
NCBI Gene: 9318Ensembl: ENSG00000166200.16HGNC: HGNC:30747UniProt: P61201
166PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingnucleusprotein phosphorylationcytoplasmneurodegenerative diseasePhenotypic abnormalitygoitercancer
✦AI Summary

COPS2 (COP9 signalosome subunit 2) is a multifunctional protein that plays critical roles in cellular regulation and pathological processes. As a component of the COP9 signalosome complex, COPS2 regulates protein stability through deneddylation and ubiquitination pathways 1. In pluripotency maintenance, COPS2 stabilizes Nanog protein by preventing proteasomal degradation and functions as a transcriptional corepressor, being essential for embryonic stem cell maintenance and somatic cell reprogramming 2. COPS2 demonstrates unique autophagy-hijacking capabilities, coordinating both autophagosome entry and autolysosome exocytosis for viral propagation by regulating K11/K48-linked ubiquitination and SNAP29 O-GlcNAcylation 1. In cancer contexts, COPS2 shows complex roles: it serves as a prognostic biomarker in bladder cancer 3, is downregulated in cancer cachexia but normalized by exercise training 4, and functions as a suppressor of break-induced replication, with its knockdown increasing genome instability and mutagenic hotspots 5. Additionally, COPS2 upregulation promotes cell proliferation in response to avian influenza infection 6, highlighting its diverse regulatory functions across development, disease, and cellular stress responses.

Sources cited
1
COPS2 coordinates autophagy hijacking through ubiquitination and SNAP29 regulation for viral propagation
PMID: 41269859
2
COPS2 stabilizes Nanog protein and functions as transcriptional corepressor for pluripotency maintenance
PMID: 27226076
3
COPS2 serves as a prognostic biomarker in bladder cancer
PMID: 40524221
4
COPS2 is downregulated in cancer cachexia but normalized by exercise training
PMID: 32408015
5
COPS2 functions as a suppressor of break-induced replication and genome instability
PMID: 36833325
6
COPS2 upregulation promotes cell proliferation in response to avian influenza
PMID: 29104227
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.45Moderate
Phenotypic abnormalityOpen Targets
0.29Weak
goiterOpen Targets
0.15Weak
cancerOpen Targets
0.08Suggestive
hypothyroidismOpen Targets
0.07Suggestive
hyperthyroidismOpen Targets
0.07Suggestive
lung adenocarcinomaOpen Targets
0.03Suggestive
nontoxic goiterOpen Targets
0.03Suggestive
neoplasmOpen Targets
0.03Suggestive
Toxic Nodular GoiterOpen Targets
0.03Suggestive
response to statinOpen Targets
0.03Suggestive
gastroesophageal reflux diseaseOpen Targets
0.02Suggestive
lung cancerOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.02Suggestive
head and neck squamous cell carcinomaOpen Targets
0.02Suggestive
bacteriemiaOpen Targets
0.02Suggestive
non-small cell lung carcinomaOpen Targets
0.01Suggestive
embryonal carcinomaOpen Targets
0.01Suggestive
bladder transitional cell carcinomaOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CRBNProtein interaction100%CUL3Protein interaction100%ELOCProtein interaction100%CUL1Protein interaction100%ELOBProtein interaction100%LATProtein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Heart
75%
Brain
58%
Ovary
42%
Lung
33%
Liver
32%
Gene Interaction Network
Click a node to explore
COPS2CRBNCUL3ELOCCUL1ELOBLAT
PROTEIN STRUCTURE
Preparing viewer…
PDB6A73 · 2.45 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.14Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.00 [0.00–0.14]
RankingsWhere COPS2 stands among ~20K protein-coding genes
  • #2,685of 20,598
    Most Researched166 · top quartile
  • #161of 17,882
    Most Constrained (LOEUF)0.14 · top 1%
Genes detectedCOPS2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
The coregulator Alien.
PMID: 18174916
Nucl Recept Signal · 2007
1.00
2
Inter-Species Host Gene Expression Differences in Response to Human and Avian Influenza A Virus Strains.
PMID: 29104227
Int J Mol Sci · 2017
0.90
3
COPS2 coordinates biphasic autophagy hijacking for non-lytic propagation of enveloped RNA viruses.
PMID: 41269859
Cell Rep · 2025
0.80
4
Prognostic analysis of bladder cancer with neddylation-related genes.
PMID: 40524221
Hereditas · 2025
0.70
5
Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma.
PMID: 39859203
Int J Mol Sci · 2025
0.68