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'''ORF3c''' is a [[gene]] found in [[coronavirus]]es 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]] [[viral nonstructural protein|non-structural protein]] of unknown function.<ref name="firth_2020">{{cite journal |last1=Firth |first1=Andrew E. |title=A putative new SARS-CoV protein, 3c, encoded in an ORF overlapping ORF3a |journal=Journal of General Virology |date=1 October 2020 |volume=101 |issue=10 |pages=1085–1089 |pmid=32667280|doi=10.1099/jgv.0.001469}}</ref><ref name="cagliani_2020">{{cite journal |last1=Cagliani |first1=Rachele |last2=Forni |first2=Diego |last3=Clerici |first3=Mario |last4=Sironi |first4=Manuela |title=Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses |journal=Infection, Genetics and Evolution |date=September 2020 |volume=83 |pages=104353 |doi=10.1016/j.meegid.2020.104353|pmc=7199688 }}</ref><ref name="jungreis_2021_natcom">{{cite journal |last1=Jungreis |first1=Irwin |last2=Sealfon |first2=Rachel |last3=Kellis |first3=Manolis |title=SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes |journal=Nature Communications |date=December 2021 |volume=12 |issue=1 |pages=2642 |doi=10.1038/s41467-021-22905-7|pmc=8113528|hdl=1721.1/130581 |hdl-access=free }}</ref> It is also present in the SARS-CoV genome, but was not recognized until the identification of the SARS-CoV-2 [[homology (biology)|homolog]].<ref name="jungreis_2021">{{cite journal |last1=Jungreis |first1=Irwin |last2=Nelson |first2=Chase W. |last3=Ardern |first3=Zachary |last4=Finkel |first4=Yaara |last5=Krogan |first5=Nevan J. |last6=Sato |first6=Kei |last7=Ziebuhr |first7=John |last8=Stern-Ginossar |first8=Noam |last9=Pavesi |first9=Angelo |last10=Firth |first10=Andrew E. |last11=Gorbalenya |first11=Alexander E. |last12=Kellis |first12=Manolis |title=Conflicting and ambiguous names of overlapping ORFs in the SARS-CoV-2 genome: A homology-based resolution |journal=Virology |date=June 2021 |volume=558 |pages=145–151 |pmid=33774510 | doi=10.1016/j.virol.2021.02.013|pmc=7967279 |hdl=1721.1/130363 |hdl-access=free }}</ref> |
'''ORF3c''' is a [[gene]] found in [[coronavirus]]es 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]] [[viral nonstructural protein|non-structural protein]] of unknown function.<ref name="firth_2020">{{cite journal |last1=Firth |first1=Andrew E. |title=A putative new SARS-CoV protein, 3c, encoded in an ORF overlapping ORF3a |journal=Journal of General Virology |date=1 October 2020 |volume=101 |issue=10 |pages=1085–1089 |pmid=32667280|doi=10.1099/jgv.0.001469 |pmc=7660454}}</ref><ref name="cagliani_2020">{{cite journal |last1=Cagliani |first1=Rachele |last2=Forni |first2=Diego |last3=Clerici |first3=Mario |last4=Sironi |first4=Manuela |title=Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses |journal=Infection, Genetics and Evolution |date=September 2020 |volume=83 |pages=104353 |doi=10.1016/j.meegid.2020.104353|pmc=7199688 }}</ref><ref name="jungreis_2021_natcom">{{cite journal |last1=Jungreis |first1=Irwin |last2=Sealfon |first2=Rachel |last3=Kellis |first3=Manolis |title=SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes |journal=Nature Communications |date=December 2021 |volume=12 |issue=1 |pages=2642 |doi=10.1038/s41467-021-22905-7|pmc=8113528|hdl=1721.1/130581 |hdl-access=free }}</ref> It is also present in the SARS-CoV genome, but was not recognized until the identification of the SARS-CoV-2 [[homology (biology)|homolog]].<ref name="jungreis_2021">{{cite journal |last1=Jungreis |first1=Irwin |last2=Nelson |first2=Chase W. |last3=Ardern |first3=Zachary |last4=Finkel |first4=Yaara |last5=Krogan |first5=Nevan J. |last6=Sato |first6=Kei |last7=Ziebuhr |first7=John |last8=Stern-Ginossar |first8=Noam |last9=Pavesi |first9=Angelo |last10=Firth |first10=Andrew E. |last11=Gorbalenya |first11=Alexander E. |last12=Kellis |first12=Manolis |title=Conflicting and ambiguous names of overlapping ORFs in the SARS-CoV-2 genome: A homology-based resolution |journal=Virology |date=June 2021 |volume=558 |pages=145–151 |pmid=33774510 | doi=10.1016/j.virol.2021.02.013|pmc=7967279 |hdl=1721.1/130363 |hdl-access=free }}</ref> |
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==Nomenclature== |
==Nomenclature== |
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| ORF3c | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | SARS-CoV-2 | ||||||
| Symbol | ORF3c | ||||||
| UniProt | P0DTG1 | ||||||
| |||||||
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]
There has been significant confusion in the scientific literature around the nomenclature used for the accessory proteinsofSARS-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]
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]
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]
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