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1.A.57.1.1
SARS-CoV Viroporin tetrameric ion channel. Protein 3a (ORF3a) is of 274 aas and 3 TMSs. It activates the Nod-like receptor family members which are pyrin domain-containing 3 (NLRP3)proteins that regulate the secretion of proinflammatory cytokines such as interleukin 1 beta (IL-1beta) and IL-18. K+ efflux and mitochondrial reactive oxygen species are important for SARS-CoV 3a-induced NLRP3 inflammasome activation (Chen et al. 2019). Viroporin 3a exhibits allosteric properties (Tee et al. 2021).  The role of the tyrosine-based sorting signals of the ORF3a protein of SARS-CoV-2 on intracellular trafficking, autophagy, and apoptosis has been examined (Henke et al. 2023). It has been concluded that ORF3a is not an ion channel but a water channel (Michelucci et al. 2025).

Accession Number:P59632
Protein Name:SARS-Caronavirus aka Viroporin aka Protein 3a
Length:274
Molecular Weight:30903.00
Species:Human SARS coronavirus (SARS-CoV) (Severe acute respiratory syndrome coronavirus) [227859]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Virion1 / Multi-pass membrane protein2
Substrate ion

Cross database links:

Gene Ontology

GO:0044178 C:host cell Golgi membrane
GO:0020002 C:host cell plasma membrane
GO:0016021 C:integral to membrane
GO:0019012 C:virion
GO:0006915 P:apoptosis

References (14)

[1] “Characterization of a novel coronavirus associated with severe acute respiratory syndrome.”  Rota P.A.et.al.   12730500
[2] “The genome sequence of the SARS-associated coronavirus.”  Marra M.A.et.al.   12730501
[3] “Coronavirus genomic-sequence variations and the epidemiology of the severe acute respiratory syndrome.”  Tsui S.K.W.et.al.   12853594
[4] “The complete genome sequence of severe acute respiratory syndrome coronavirus strain HKU-39849 (HK-39).”  Zeng F.Y.et.al.   12876307
[5] “Identification of a novel protein 3a from severe acute respiratory syndrome coronavirus.”  Yu C.-J.et.al.   15135062
[6] “A novel severe acute respiratory syndrome coronavirus protein, U274, is transported to the cell surface and undergoes endocytosis.”  Tan Y.-J.et.al.   15194747
[7] “Subcellular localization and membrane association of SARS-CoV 3a protein.”  Yuan X.et.al.   15763150
[8] “The severe acute respiratory syndrome coronavirus 3a is a novel structural protein.”  Shen S.et.al.   15781262
[9] “Severe acute respiratory syndrome coronavirus 3a protein is a viral structural protein.”  Ito N.et.al.   15709039
[10] “The severe acute respiratory syndrome coronavirus 3a protein up-regulates expression of fibrinogen in lung epithelial cells.”  Tan Y.J.et.al.   16014971
[11] “The 3a protein of severe acute respiratory syndrome-associated coronavirus induces apoptosis in Vero E6 cells.”  Law P.T.et.al.   15958670
[12] “Glycosylation of the severe acute respiratory syndrome coronavirus triple-spanning membrane proteins 3a and M.”  Oostra M.et.al.   16474139
[13] “Severe acute respiratory syndrome coronavirus 3a protein is released in membranous structures from 3a protein-expressing cells and infected cells.”  Huang C.et.al.   16352545
[14] “Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release.”  Lu W.et.al.   16894145

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Predict TMSs (Predict number of transmembrane segments)
Window Size: Angle:  
FASTA formatted sequence 
1:	MDLFMRFFTL GSITAQPVKI DNASPASTVH ATATIPLQAS LPFGWLVIGV AFLAVFQSAT 
61:	KIIALNKRWQ LALYKGFQFI CNLLLLFVTI YSHLLLVAAG MEAQFLYLYA LIYFLQCINA 
121:	CRIIMRCWLC WKCKSKNPLL YDANYFVCWH THNYDYCIPY NSVTDTIVVT EGDGISTPKL 
181:	KEDYQIGGYS EDRHSGVKDY VVVHGYFTEV YYQLESTQIT TDTGIENATF FIFNKLVKDP 
241:	PNVQIHTIDG SSGVANPAMD PIYDEPTTTT SVPL