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
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
SARS-CoV-2 E pentamer transports Ca2+
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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

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

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

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

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
Mondo
Authored
Shamovsky, V  (2021-10-27)
Reviewed
Messina, F  (2022-02-18)
Created
Shamovsky, V  (2021-09-30)
Cite Us!