pfam11289: bCoV_viroporin (This model is not part of the current CDD release)
Betacoronavirus viroporin
This entry represents protein 3a encoded by Orf3/3a, also known as X1, which forms homotetrameric potassium, sodium or calcium sensitive ion channels (viroporin) that causes ER-stress in host cells and may modulate virus release. This is a pro-apoptosis-inducing protein that localises to the endoplasmic reticulum (ER)-Golgi compartment. SARS-CoV causes apoptosis of infected cells through NLRP3 inflammasome activation. Protein 3a also promotes the ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) mediated by its interaction with TNF receptor-associated factor 3 (TRAF3). This protein induces NF-kappa B activation and upregulates fibrinogen secretion with high cytokine production. Through the activation of the PERK pathway of unfolded protein response (UPR), this protein causes phosphorylation of eIF2-alpha leading to reduced translation of cellular proteins and as the activation of pro-apoptotic downstream effectors (i.e ATF4, CHOP).
Jiyao W et al.(2023). "The conserved domain database in 2023.",