SARS-CoV-2 E pentamer transports Ca2+

Stable Identifier
R-HSA-9754616
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
cytosol, endoplasmic reticulum-Golgi intermediate compartment
ReviewStatus
5/5
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SARS-CoV-2 E pentamer transports Ca2+
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This SARS-CoV-2 event was manually inferred from the event of homologous SARS-CoV-1 E protein, which forms Ca2+ permeable protein‑lipid channels in ERGIC/Golgi membranes (Nieto‑Torres JL et al. 2015). The E protein of SARS-CoV-2 shares a high level of homology with SARS-CoV-1 (Cao Y et al. 2021). NMR spectroscopy identified the pentameric structure of transmembrane domain of SARS‐CoV‐2 E protein in lipid bilayers (Mandala VS et al. 2020). Further, hexamethylene amiloride (HMA), an ion channel blocker, was found to bind to the N-terminal region of SARS-CoV-2 E protein and reduced infection in SARS-CoV-2-infected African green monkey kidney Vero E6 cells (Park SH et al. 2021). Computational electrophysiology simulations further confirmed that the E protein forms a functional ion channel (Cao Y et al. 2020). Release of Ca2+ from ERGIC/Golgi lumen to the cytosol disrupts Ca2+ balance within cells contributing to the activation of the NLRP3 inflammasome (reviewed by Zhou Y et al. 2020).

This Reactome event describes the ion channel activity of the SARS-CoV-2 E protein, although it remains to be shown in vivo.

Literature References
PubMed ID Title Journal Year
33813796 Characterization of the SARS-CoV-2 E Protein: Sequence, Structure, Viroporin, and Inhibitors

Meng, X, Lee, I, Cao, Y, Yang, R, Zhang, W, Wang, W, Sun, J

Protein Sci 2021
33173781 Computational Study of the Ion and Water Permeation and Transport Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel

Zhang, R, Meng, X, Lee, I, Cao, Y, Yang, R, Zhang, W, Wang, W, Xu, B, Sun, J

Front Mol Biosci 2020
Participants
Input
Output
Participates
as an event of
Catalyst Activity

monoatomic cation channel activity of Ub-3xPalmC-E pentamer [Golgi membrane]

Physical Entity
Ub-3xPalmC-E pentamer [Golgi membrane] (Severe acute respiratory syndrome coronavirus 2)
Activity
monoatomic cation channel activity (GO:0005261)
Inferred From
SARS-CoV-1 E transports Ca2+ (Homo sapiens)
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Cross References
Rhea
Authored
Shamovsky, V  (2021-10-27)
Reviewed
Messina, F  (2022-02-18)
Created
Shamovsky, V  (2021-09-30)
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