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

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31Orf10NAE1Proteasome DegradationpevonedistatUBA3SubstrateN8UbCUL2N8ELOCELOBRBX1E2UbZYG11B2NAECUL2(ZYG11B)


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 <a href="https://en.wikipedia.org/wiki/Neddylation">neddylation</a> (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

  1. 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
  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''; Nature, 2020 PubMed Europe PMC Scholia
  4. 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

View all...
CompareRevisionActionTimeUserComment
134353view05:40, 21 July 2024EgonwRemoved a template comment
124635view12:41, 18 November 2022IsabelWassinkChanged shape of viral protein to standard rounded rectangle
124633view12:40, 18 November 2022IsabelWassinkChanged viral protein shape in to standard rectangle shape
124430view12:45, 27 October 2022Mkutmonlower case SARS-CoV-2 protein names
120599view21:37, 17 December 2021EweitzRefine case
120277view13:17, 23 November 2021EgonwReplaced a DOI with the respective PMID
120276view13:17, 23 November 2021EgonwReplaced a DOI with the respective PMID
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

DataNodes

View all...
NameTypeDatabase referenceComment
CUL2GeneProductENSG00000108094 (Ensembl)
E2GeneProductENSG00000067955 (Ensembl)
ELOBGeneProductENSG00000103363 (Ensembl)
ELOCGeneProductENSG00000154582 (Ensembl)
NAE1GeneProductENSG00000159593 (Ensembl)
Orf10A0A663DJA2 (Uniprot-TrEMBL)
Proteasome DegradationPathwayWP183 (WikiPathways)
RBX1GeneProductENSG00000100387 (Ensembl)
SubstrateGeneProduct
UBA3GeneProductENSG00000144744 (Ensembl)
ZYG11BGeneProductENSG00000162378 (Ensembl)
pevonedistatMetaboliteQ27166792 (Wikidata)

Annotated Interactions

No annotated interactions

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