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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| SARS-CoV-2 | 1 | 75 | Orf4 | E | Envelope protein | |
| SARS-CoV | 1 | 76 | Orf4 | E | Envelope protein | |
| Previous and Unofficial Names |
| envelope small membrane protein | orf4 |
| Database Links |
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| Entrez Gene | 43740570 (SARS-CoV-2), 1489671 (SARS-CoV) |
| RefSeq Protein | YP_009825054 (SARS-CoV), YP_009724392 (SARS-CoV-2) |
| UniProtKB | P0DTC4 (SARS-CoV-2), P59637 (SARS-CoV) |
Download all structure-activity data for this target as a CSV file 
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| General Comments |
| By similarity to other coronavirus E proteins, SARS-CoV-2 E is predicted to constitute a single transmembrane (potentially homopentameric) ion channel (or viroporin). These channels are required for viral assembly, release, and pathogenesis [2-3], and have demonstrated selectivity for monovalent cations over monovalent anions [6,8-10]. The SARS-CoV E protein's ion channel function has been linked to calcium entry into endoplasmic reticulum/Golgi membrane complexes and the subsequent activation of the NLRP3 inflammasome and interleukin-β (IL-1β) production [4]. SARS-CoV-2 E protein can be blocked by gliclazide (a sulfonylurea receptor K+ channel blocker) and memantine (a NMDA channel antagonist) [7], which suggests that inhibiting viriporin function may offer a mechanism to reduce viral entry into host cells. Anti-infection activity has been reported for dual-mechanism small molecules that block SARS-CoV-2 E channels and chemically modify the S (spike) protein to disrupt ACE2 binding [5]. Peptides that bind and inhibit E protein are proposed for therapeutic potential against human coronaviruses including SARS-CoV-2 [1]. |
1. Bekdash R, Yoshida K, Nair MS, Qiu L, Ahdout J, Tsai HY, Uryu K, Soni RK, Huang Y, Ho DD et al.. (2024) Developing inhibitory peptides against SARS-CoV-2 envelope protein. PLoS Biol, 22 (3): e3002522. [PMID:38483887]
2. DeDiego ML, Alvarez E, Almazán F, Rejas MT, Lamirande E, Roberts A, Shieh WJ, Zaki SR, Subbarao K, Enjuanes L. (2007) A severe acute respiratory syndrome coronavirus that lacks the E gene is attenuated in vitro and in vivo. J Virol, 81 (4): 1701-13. [PMID:17108030]
3. Devantier K, Kjaer VMS, Griffin S, Kragelund BB, Rosenkilde MM. (2024) Advancing the field of viroporins—Structure, function and pharmacology: IUPHAR Review 39. British Journal of Pharmacology, Epub ahead of pring. DOI: 10.1111/bph.17317
4. Nieto-Torres JL, Verdiá-Báguena C, Jimenez-Guardeño JM, Regla-Nava JA, Castaño-Rodriguez C, Fernandez-Delgado R, Torres J, Aguilella VM, Enjuanes L. (2015) Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome. Virology, 485: 330-9. [PMID:26331680]
5. Oh CK, Nakamura T, Beutler N, Zhang X, Piña-Crespo J, Talantova M, Ghatak S, Trudler D, Carnevale LN, McKercher SR et al.. (2023) Targeted protein S-nitrosylation of ACE2 inhibits SARS-CoV-2 infection. Nat Chem Biol, 19 (3): 275-283. [PMID:36175661]
6. Pervushin K, Tan E, Parthasarathy K, Lin X, Jiang FL, Yu D, Vararattanavech A, Soong TW, Liu DX, Torres J. (2009) Structure and inhibition of the SARS coronavirus envelope protein ion channel. PLoS Pathog, 5 (7): e1000511. [PMID:19593379]
7. Singh Tomar PP, Arkin IT. (2020) SARS-CoV-2 E protein is a potential ion channel that can be inhibited by Gliclazide and Memantine. Biochem Biophys Res Commun, 530 (1): 10-14. [PMID:32828269]
8. Surya W, Li Y, Verdià-Bàguena C, Aguilella VM, Torres J. (2015) MERS coronavirus envelope protein has a single transmembrane domain that forms pentameric ion channels. Virus Res, 201: 61-6. [PMID:25733052]
9. Wilson L, McKinlay C, Gage P, Ewart G. (2004) SARS coronavirus E protein forms cation-selective ion channels. Virology, 330 (1): 322-31. [PMID:15527857]
10. Zhang R, Wang K, Lv W, Yu W, Xie S, Xu K, Schwarz W, Xiong S, Sun B. (2014) The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production. Biochim Biophys Acta, 1838 (4): 1088-95. [PMID:23906728]
