ORF3a
From Wikipedia, the free encyclopedia
| Betacoronavirus viroporin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
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| Identifiers | |||||||||
| Symbol | bCoV_viroporin | ||||||||
| Pfam | PF11289 | ||||||||
| InterPro | IPR024407 | ||||||||
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ORF3a (previously known as X1 or U274)[2] is a gene found in coronaviruses of the subgenus Sarbecovirus, including SARS-CoV[3][2] and SARS-CoV-2.[1][4] It encodes an accessory protein about 275 amino acid residues long, which is thought to function as a viroporin.[1] It is the largest accessory protein[2][4] and was the first of the SARS-CoV accessory proteins to be described.[3]
ORF3a is well conserved within the subgenus Sarbecovirus.[3][2] The protein has 73% sequence identity between SARS-CoV (274 residues) and SARS-CoV-2 (275 residues).[1] Within the ORF3a open reading frame there are several overlapping genes in the genome: ORF3a, ORF3b, and (in SARS-CoV-2 only) ORF3c. In SARS-CoV-2, the overlap between ORF3a, ORF3c, and ORF3d potentially represents a rare example of all three possible reading frames of the same sequence region encoding functional proteins.[5][6]
Although ORF3a is present in Sarbecovirus, it is absent in another Betacoronavirus subgenus, Embecovirus, which includes the human coronaviruses HKU1 and OC43. It may be distantly related to ORF5 in Merbecovirus, which includes MERS-CoV. Distant homologs of ORF3a have been identified in Alphacoronavirus, which includes the human coronaviruses 229E and NL63, but not in Gammacoronavirus or Deltacoronavirus.[1]
Structure
The ORF3a protein is a transmembrane protein that contains three transmembrane domains. It has an N-terminal ectodomain and C-terminal endodomain, which is separated from the transmembrane domain by a cysteine-rich region.[3][2] It is thought to function as a dimer or tetramer, which is assembled at the plasma membrane. It may also form higher-order oligomers, with unknown functional effects.[3][2][1]
Post-translational modifications
In SARS-CoV, post-translational modification of ORF3a by O-glycosylation has been observed.[3][7] In hCoV-NL63, it is N-glycosylated.[8]
