pfam02723: CoV_E (This model is not part of the current CDD release)
Coronavirus small envelope protein E
This family includes E proteins, well conserved among Coronavirus strains. They are small, integral membrane proteins involved in several aspects of the virus' life cycle, such as assembly, budding, envelope formation, and pathogenesis. They act as a viroporin by oligomerizing after insertion in host membranes to create a hydrophilic pore that allows ion transport. SARS-CoV E protein forms a Ca2+ permeable channel in the endoplasmic reticulum Golgi apparatus intermediate compartment (ERGIC)/Golgi membranes. The E protein ion channel activity alters Ca2+ homeostasis within cells boosting the activation of the NLRP3 inflammasome, leading to the overproduction of IL-beta. SARS-CoV overstimulates the NF-kappaB inflammatory pathway, triggering p38 MARK activation. CoV E proteins have a short hydrophilic N terminus, followed by a large hydrophobic transmembrane (TM) domain, and end with a long, hydrophilic C-terminal which comprises the majority of the protein. The hydrophobic region of the TM domain contains at least one predicted amphipathic alpha-helix that pentamerizes to form an ion-conductive pore in membranes. CoV E proteins are involved in the secretory pathway, altering lumenal environments and rearranging secretory organelles and leading to efficient trafficking of virions, and they may also play a role protein-protein interactions and targeting, among other roles.
Jiyao W et al.(2023). "The conserved domain database in 2023.",