Activation of NLRP3 inflammasome by SARS-CoV-2 (Homo sapiens)
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Description
Orf3a from SARS-CoV has been shown to bind TRAF3 and activate the NLRP3 inflammasome. The activation occurs at two points. First, by ubiquinating NF-kB (p105) to stimulate its proteolytic processing into mature NF-kB (p50), which can then go on to promote the transcription of pro-IL-1B together with RELA (p65). And second, by ubiquitinating ASC (PYCARD) in the NLRP3 inflammasome, which leads to its degradtion and the activation of caspase-1 (CASP1) that goes on to catalyze the production of mature IL-1B, leading to a cytokine storm. While Orf3a of SARS-CoV-2 only has 72.7% sequence identity with that of SARS-CoV, the TRAF3 binding motif PxQxS is 100% conserved (https://alexanderpico.github.io/SARS-CoV-2_Alignments/#Orf3a).
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Ontology Terms
Saving...Bibliography
- Siu KL, Yuen KS, Castaño-Rodriguez C, Ye ZW, Yeung ML, Fung SY, Yuan S, Chan CP, Yuen KY, Enjuanes L, Jin DY; ''Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC.''; FASEB J, 2019 PubMed Europe PMC Scholia
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External references
DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| ASC | GeneProduct | ENSG00000103490 (Ensembl)  | |
| CASP1 | GeneProduct | ENSG00000137752 (Ensembl) | |
| IL1B | GeneProduct | ENSG00000125538 (Ensembl) | |
| NFKB1 p105 | GeneProduct | ENSG00000109320 (Ensembl) | |
| NFKB1 | GeneProduct | ENSG00000109320 (Ensembl) | |
| NLRP3 | GeneProduct | ENSG00000162711 (Ensembl) | |
| Orf3a | GeneProduct | 43740569 (Entrez Gene) | |
| RELA | GeneProduct | ENSG00000173039 (Ensembl) | |
| TRAF3 | GeneProduct | ENSG00000131323 (Ensembl) | |
| pro-CASP1 | GeneProduct | ENSG00000137752 (Ensembl) | |
| pro-IL1B | Rna | ENSG00000125538 (Ensembl) |
Annotated Interactions
No annotated interactions
