PROSITE documentation PDOC51966
Coronavirus (CoV) 3a-like viroporin transmembrane (TM) and cytosolic (CD) domains profiles


Coronaviruses (CoVs) are enveloped positive-strand RNA viruses that infect many species, including humans, other mammals, and birds. After infection, the host may develop respiratory, bowel, liver, and neurological diseases. Coronaviruses are divided into four genera: αcoronavirus, βcoronavirus, γcoronavirus, and Deltacoronavirus. The ideal hosts of αCoV and βCoV are mammals, and γCoV primarily infects birds, while DeltaCoV has been identified in both mammals and birds. SARS, SARS-CoV-2, BatCoV RaTG13 and Bat-SARS-like coronavirus (BATSL-CoVZXC21 and BAT-SL-CoVZC45) belong to the Sarbecovirus subgenus of βCoV [E1].

All coronaviruses have a similar genomic structure. At the 5' end, two-thirds of the genome comprises two large open reading frames (ORFs) (ORF1a and ORF1b) encoding the coronavirus replicase, which is highly conserved among genera. At the 3' end, the genome encodes four structural proteins (S, E, M and N) and a variable number of accessory proteins. Accessory proteins play an important role in virus-host interactions, especially in antagonizing or regulating host immunity and virus adaptation to the host. There are large variations in the number of accessory proteins (1-10) among coronaviruses. The number of accessory proteins of the αCoVs is relatively lower, between 1 and 5, while βCoVs have 3-5 accessory proteins, except for SARS-CoV and SARS-CoV-2, which possess the largest number of accessory proteins among all coronaviruses (10 and 9, respectively). 3a-like accessory proteins are found in multiple αCoV and βCoV lineages that infect bats and humans. They are transmembrane proteins of the viroporin family that form ion channels in the host membrane and have been implicated in inducing apoptosis, pathogenicity, and virus release. The induction of cytokine storms in COVID-19 patients might be linked to ORF3a mediated activation of inflammasome. 3a-like viroporins contain a transmembrane domain (TM) and a cytosolic domain (CD) [1,2,3,4,5,6,7].

The 3a-like viroporin TM domain is composed of three helices and the CD domain of two anti-parallel β-sheets forming a β-sandwich (see <PDB:6XDC>). The 3a-like viroporin forms a dimer and the six transmembrane helices of the dimer form an ion channel with polar/charged residues in the interior of the channel capable of conducting cations [3].

The profiles we developed cover respectively the entire CoV 3a-like viroporin TM and CD domains.

Last update:

March 2021 / First entry.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

COV_VIROPORIN_3A_CD, PS51967; Coronavirus (CoV) 3a-like viroporin cytosolic (CD) domain profile  (MATRIX)

COV_VIROPORIN_3A_TM, PS51966; Coronavirus (CoV) 3a-like viroporin trans-membrane (TM) domain profile  (MATRIX)


1AuthorsArya R. Kumari S. Pandey B. Mistry H. Bihani S.C. Das A. Prashar V. Gupta G.D. Panicker L. Kumar M.
TitleStructural insights into SARS-CoV-2 proteins.
SourceJ. Mol. Biol. 433:166725-166725(2021).
PubMed ID33245961

2AuthorsAzad G.K. Khan P.K.
TitleVariations in Orf3a protein of SARS-CoV-2 alter its structure and function.
SourceBiochem. Biophys. Rep. 26:100933-100933(2021).
PubMed ID33527091

3AuthorsKern D.M. Sorum B. Hoel C.M. Sridharan S. Remis J.P. Toso D.B. Brohawn S.G.
TitleCryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs.
SourcebioRxiv 0:0-0(2020).
PubMed ID32587976

4AuthorsShang J. Han N. Chen Z. Peng Y. Li L. Zhou H. Ji C. Meng J. Jiang T. Wu A.
TitleCompositional diversity and evolutionary pattern of coronavirus accessory proteins.
SourceBrief. Bioinform. 0:0-0(2020).
PubMed ID33126244

5AuthorsMcClenaghan C. Hanson A. Lee S.-J. Nichols C.G.
TitleCoronavirus Proteins as Ion Channels: Current and Potential Research.
SourceFront. Immunol. 11:573339-573339(2020).
PubMed ID33154751

6AuthorsChen I.-Y. Moriyama M. Chang M.-F. Ichinohe T.
TitleSevere Acute Respiratory Syndrome Coronavirus Viroporin 3a Activates the NLRP3 Inflammasome.
SourceFront. Microbiol. 10:50-50(2019).
PubMed ID30761102

7AuthorsOuzounis C.A.
TitleA recent origin of Orf3a from M protein across the coronavirus lineage arising by sharp divergence.
SourceComput. Struct. Biotechnol. J. 18:4093-4102(2020).
PubMed ID33363705


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