SARS-CoV-2 Protein 3a | SARS-CoV-2 proteins | IUPHAR/BPS Guide to PHARMACOLOGY

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SARS-CoV-2 Protein 3a

Target not currently curated in GtoImmuPdb

Target id: 3115

Nomenclature: SARS-CoV-2 Protein 3a

Family: SARS-CoV-2 proteins

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
SARS-CoV-2 3 275 ORF3a
Previous and Unofficial Names
orf3a
Database Links
Entrez Gene
RefSeq Protein
UniProtKB
Tissue Distribution Comments
SARS-CoV protein 3a localises to the endoplasmic reticulum (ER)-Golgi compartment in host cells, causing ER stress which leads to apoptosis [4].
General Comments
A number of activities have been ascribed to coronavirus protein 3a, particularly based on evidence from study of the original SARS-CoV. It is believed to form homotetrameric potassium sensitive ion channels (viroporins) and may modulate virus release [3]. The viroporin activity of 3a is reported to be critical for 3a-mediated IL-1β secretion via activation of the NLRP3 inflammasome [1]. It may also promote IFN alpha-receptor subunit 1 (IFNAR1) degradation, a function that would attenuate IFN responses and innate immunity [4]. Protein 3a up-regulates expression of fibrinogen subunits in host lung epithelial cells, and this could play some part in the lung tissue damage seen in SARS/COVID-19 patients. It also exhibits pro-apoptotic effects [2].

References

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1. Chen IY, Moriyama M, Chang MF, Ichinohe T. (2019) Severe Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome. Front Microbiol, 10: 50. [PMID:30761102]

2. Law PTW, Wong CH, Au TCC, Chuck CP, Kong SK, Chan PKS, To KF, Lo AWI, Chan JYW, Suen YK et al.. (2005) The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells. J. Gen. Virol., 86 (Pt 7): 1921-1930. [PMID:15958670]

3. Lu W, Zheng BJ, Xu K, Schwarz W, Du L, Wong CK, Chen J, Duan S, Deubel V, Sun B. (2006) Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release. Proc. Natl. Acad. Sci. U.S.A., 103 (33): 12540-5. [PMID:16894145]

4. Minakshi R, Padhan K, Rani M, Khan N, Ahmad F, Jameel S. (2009) The SARS Coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor. PLoS ONE, 4 (12): e8342. [PMID:20020050]

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