Hijack of ubiquitination by SARS-CoV-2 (Homo sapiens)
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Description
SARS-CoV-2 includes a novel Orf10 that interacts with muliple members of the Cullin 2 ubiquitin ligase complex as determined by AP-MS (Gordon 2020). The strongest interaction is with ZYG11B, a substrate adaptor for CUL2. By binding this complex, Orf10 might be able to hijack its activity. The hijacking of ubiquitination machinery is a common strategy of viruses to direct the degradation of viral restriction factors, for example. Also depicted here is the required neddylation (N8) of CUL2 by the NAE enzyme complex. The ability of this enzyme to transfer N8 to CUL2 is inhibited by the small molecule Pevonedistat.
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Ontology Terms
Bibliography
- David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, et al; '' A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug Repurposing''; Nature, 2020 PubMed Europe PMC Scholia
- Edelmann MJ, Nicholson B, Kessler BM; ''Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases.''; Expert Rev Mol Med, 2011 PubMed Europe PMC Scholia
- David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, et al.; '' A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug Repurposing''; Nature, 2020 PubMed Europe PMC Scholia
- Vasudevan S, Starostina NG, Kipreos ET; ''The Caenorhabditis elegans cell-cycle regulator ZYG-11 defines a conserved family of CUL-2 complex components.''; EMBO Rep, 2007 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
CUL2 | GeneProduct | ENSG00000108094 (Ensembl) | |
E2 | GeneProduct | ENSG00000067955 (Ensembl) | |
ELOB | GeneProduct | ENSG00000103363 (Ensembl) | |
ELOC | GeneProduct | ENSG00000154582 (Ensembl) | |
NAE1 | GeneProduct | ENSG00000159593 (Ensembl) | |
Pevonedistat | Metabolite | ||
RBX1 | GeneProduct | ENSG00000100387 (Ensembl) | |
Substrate | GeneProduct | ||
UBA3 | GeneProduct | ENSG00000144744 (Ensembl) | |
ZYG11B | GeneProduct | ENSG00000162378 (Ensembl) |
Annotated Interactions
No annotated interactions