ORF3c is a gene found in coronaviruses of the subgenus Sarbecovirus, including SARS-CoV and SARS-CoV-2. It was first identified in the SARS-CoV-2 genome and encodes a 41 amino acid non-structural protein of unknown function.[1][2][3] It is also present in the SARS-CoV genome, but was not recognized until the identification of the SARS-CoV-2 homolog.[4]
| ORF3c | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | |||||||
| Symbol | ORF3c | ||||||
| UniProt | P0DTG1 | ||||||
| |||||||
Nomenclature
There has been significant confusion in the scientific literature around the nomenclature used for the accessory proteins of SARS-CoV-2, especially several overlapping genes with ORF3a.[4] The predicted protein product of the ORF3c gene has at least once been referred to as "3b protein",[5] but it is not to be confused with the non-homologous gene ORF3b.[4] It has also been described under the names ORF3h[2] and ORF3a.iORF1.[6] The recommended nomenclature for SARS-CoV-2 uses the term ORF3c for this gene.[4]
Comparative genomics
ORF3c is an overlapping gene whose open reading frame overlaps both ORF3a and ORF3d in the SARS-CoV-2 genome. This potentially represents a rare example of all three possible reading frames of the same sequence region encoding functional proteins.[7][4]
Bioinformatics analyses of Sarbecovirus sequences suggest that the sequence and length of ORF3c are well conserved, indicating that it is likely to encode a functional protein.[1][3][2] It appears to be subject to purifying selection.[1][7]
Properties
Ribosome profiling experiments confirm that the ORF3c gene expresses a protein product.[6] The relatively short 41-residue protein is predicted to contain a transmembrane domain and has features suggestive of a viroporin.[2]