ORF3c is a

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

found in coronaviruses of the subgenus ''

Sarbecovirus ''Severe acute respiratory syndrome–related coronavirus'' (SARSr-CoV or SARS-CoV)The terms ''SARSr-CoV'' and ''SARS-CoV'' are sometimes used interchangeably, especially prior to the discovery of SARS-CoV-2. This may cause confusion when some ...

'', including

SARS-CoV Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; or Severe acute respiratory syndrome coronavirus, SARS-CoV) is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for ...

and

SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...

. It was first identified in the SARS-CoV-2

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...

and encodes a 41

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

non-structural protein of unknown function. It is also present in the SARS-CoV genome, but was not recognized until the identification of the SARS-CoV-2

homolog In biology, homology is similarity due to shared ancestry between a pair of structures or genes in different taxa. A common example of homologous structures is the forelimbs of vertebrates, where the wings of bats and birds, the arms of prima ...

Nomenclature

There has been significant confusion in the scientific literature around the nomenclature used for the accessory proteins of

, especially several

overlapping gene An overlapping gene (or OLG) is a gene whose expressible nucleotide sequence partially overlaps with the expressible nucleotide sequence of another gene. In this way, a nucleotide sequence may make a contribution to the function of one or more ge ...

s with

ORF3a ORF3a (previously known as X1 or U274) is a gene found in coronaviruses of the subgenus ''Sarbecovirus'', including SARS-CoV and SARS-CoV-2. It encodes an accessory protein about 275 amino acid residues long, which is thought to function as a v ...

. The predicted protein product of the ''ORF3c'' gene has at least once been referred to as "3b protein", but it is not to be confused with the non-homologous gene '' ORF3b''. It has also been described under the names ''ORF3h'' and ''ORF3a.iORF1''. The recommended nomenclature for SARS-CoV-2 uses the term ''ORF3c'' for this gene.

Comparative genomics

ORF3c is an

whose

open reading frame In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...

overlaps both

and ORF3d in the

genome. This potentially represents a rare example of all three possible

reading frame In molecular biology, a reading frame is a way of dividing the sequence of nucleotides in a nucleic acid ( DNA or RNA) molecule into a set of consecutive, non-overlapping triplets. Where these triplets equate to amino acids or stop signals during ...

s of the same sequence region encoding functional proteins. Bioinformatics analyses of ''

'' sequences suggest that the sequence and length of ORF3c are well conserved, indicating that it is likely to encode a functional protein. It appears to be subject to

purifying selection In natural selection, negative selection or purifying selection is the selective removal of alleles that are deleterious. This can result in stabilising selection through the purging of deleterious genetic polymorphisms that arise through random ...

Properties

Ribosome profiling experiments confirm that the ''ORF3c'' gene expresses a protein product. The relatively short 41-

residue Residue may refer to: Chemistry and biology * An amino acid, within a peptide chain * Crop residue, materials left after agricultural processes * Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...

protein is predicted to contain a

transmembrane domain A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bi ...

and has features suggestive of a viroporin.

References

{{Viral proteins Coronavirus proteins Viral nonstructural proteins