Gene found in coronaviruses of the subgenus Sarbecovirus
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]
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]
References
^ a b c Firth AE (October 2020). "A putative new SARS-CoV protein, 3c, encoded in an ORF overlapping ORF3a" . The Journal of General Virology . 101 (10): 1085–1089. doi :10.1099/jgv.0.001469 . PMC 7660454 . PMID 32667280 .
^ a b c d Cagliani R, Forni D, Clerici M, Sironi M (September 2020). "Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses" . Infection, Genetics and Evolution . 83 : 104353. doi :10.1016/j.meegid.2020.104353 . PMC 7199688 . PMID 32387562 .
^ a b Jungreis I, Sealfon R, Kellis M (May 2021). "SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes" . Nature Communications . 12 (1): 2642. doi :10.1038/s41467-021-22905-7 . hdl :1721.1/130581 . PMC 8113528 . PMID 33976134 .
^ a b c d e Jungreis I, Nelson CW, Ardern Z, Finkel Y, Krogan NJ, Sato K, et al. (June 2021). "Conflicting and ambiguous names of overlapping ORFs in the SARS-CoV-2 genome: A homology-based resolution" . Virology . 558 : 145–151. doi :10.1016/j.virol.2021.02.013 . hdl :1721.1/130363 . PMC 7967279 . PMID 33774510 .
^ Pavesi A (July 2020). "New insights into the evolutionary features of viral overlapping genes by discriminant analysis" . Virology . 546 : 51–66. doi :10.1016/j.virol.2020.03.007 . PMC 7157939 . PMID 32452417 .
^ a b Finkel Y, Mizrahi O, Nachshon A, Weingarten-Gabbay S, Morgenstern D, Yahalom-Ronen Y, et al. (January 2021). "The coding capacity of SARS-CoV-2" . Nature . 589 (7840): 125–130. doi :10.1038/s41586-020-2739-1 . PMID 32906143 .
^ a b Nelson CW, Ardern Z, Goldberg TL, Meng C, Kuo CH, Ludwig C, et al. (October 2020). "Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic" . eLife . 9 : e59633. doi :10.7554/eLife.59633 . PMC 7655111 . PMID 33001029 .