Hijack of ubiquitination by SARS-CoV-2 (Homo sapiens)

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34222Orf10NAE1UBA3Proteasome DegradationpevonedistatN8SubstrateUbCUL2N8ELOCELOBRBX1E2ZYG11BUbNAE1CUL2(ZYG11B)


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



  1. 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
  2. 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
  3. 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''; BioRxiv, 2020
  4. 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


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118880view12:08, 3 June 2021EweitzOntology Term : 'peripheral blood mononuclear cell' added !
118874view12:02, 3 June 2021EweitzOntology Term : 'COVID-19' added !
117264view21:41, 19 May 2021EgonwNew Wikidata id.
116363view12:36, 4 May 2021EweitzModified title
115856view15:47, 18 March 2021FinterlyAdded literature references for interactions
111111view09:09, 13 July 2020EgonwMake the pathway clickable
110196view20:36, 23 April 2020EgonwAdded a missing type annotation
109969view18:16, 8 April 2020AlexanderPicoupdated sars nodes per #covidpathways guidelines
109840view01:46, 2 April 2020AlexanderPicoupdated Orf10 protein xref
109828view22:03, 1 April 2020AlexanderPicoupdated Orf10 xref
109739view10:12, 30 March 2020EgonwModified description
109738view10:11, 30 March 2020EgonwModified description
109676view20:00, 28 March 2020AlexanderPicoOntology Term : 'viral infectious disease' added !
109675view20:00, 28 March 2020AlexanderPicoOntology Term : 'disease pathway' added !
109674view19:58, 28 March 2020AlexanderPicoAnnotated pevonedistat
109660view01:41, 28 March 2020AlexanderPicoAdded ref for Pevonedistat inhibition on NAE
109622view17:27, 27 March 2020EgonwAdded the UniProt Orf10 identifier
109621view17:24, 27 March 2020AlexanderPicoadjusting z-order
109620view17:23, 27 March 2020EgonwConverted Orf10 into a DataNode
109619view17:21, 27 March 2020AlexanderPicoAdded Identifier for Orf10
109613view00:29, 27 March 2020AlexanderPicoAdded Proteasome Degradation
109612view00:20, 27 March 2020AlexanderPicoOntology Term : 'regulatory pathway' added !
109611view00:20, 27 March 2020AlexanderPicoOntology Term : 'severe acute respiratory syndrome' added !
109610view00:19, 27 March 2020AlexanderPicoOntology Term : 'altered ubiquitin/proteasome degradation pathway' added !
109607view00:14, 27 March 2020AlexanderPicoadjusting z-order
109606view00:13, 27 March 2020AlexanderPicocentered label
109605view00:11, 27 March 2020AlexanderPicoupdated layout
109604view00:08, 27 March 2020AlexanderPicoModified title
109603view00:07, 27 March 2020AlexanderPicoNew pathway

External references


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NameTypeDatabase referenceComment
CUL2GeneProductENSG00000108094 (Ensembl)
E2GeneProductENSG00000067955 (Ensembl)
ELOBGeneProductENSG00000103363 (Ensembl)
ELOCGeneProductENSG00000154582 (Ensembl)
NAE1GeneProductENSG00000159593 (Ensembl)
Orf10ProteinQ89227548 (Wikidata)
Proteasome DegradationPathwayWP183 (WikiPathways)
RBX1GeneProductENSG00000100387 (Ensembl)
UBA3GeneProductENSG00000144744 (Ensembl)
ZYG11BGeneProductENSG00000162378 (Ensembl)
pevonedistatMetaboliteQ25100575 (Wikidata)

Annotated Interactions

No annotated interactions

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