ORF3c is a

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

found in

coronavirus Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the comm ...

es of the

subgenus In biology, a subgenus ( subgenera) is a taxonomic rank directly below genus. In the International Code of Zoological Nomenclature, a subgeneric name can be used independently or included in a species name, in parentheses, placed between the ge ...

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

'', including

SARS-CoV Severe acute respiratory syndrome–related coronavirus (SARSr-CoV or SARS-CoV'', Betacoronavirus pandemicum'')The terms ''SARSr-CoV'' and ''SARS-CoV'' are sometimes used interchangeably, especially prior to the discovery of SARS-CoV-2. This m ...

and

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

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

genome 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 genes, other functional regions of the genome such as ...

and encodes a 41

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 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 in anatomical structures or genes between organisms of different taxa due to shared ancestry, ''regardless'' of current functional differences. Evolutionary biology explains homologous structures as retained her ...

Nomenclature

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

accessory protein A viral regulatory and accessory protein is a type of viral protein that can play an indirect role in the function of a virus. An example is Nef (protein), Nef. References Further reading

* Viral proteins {{virus-stub ...

s 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 g ...

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 ...

. 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 ORF3b is a gene found in coronaviruses of the subgenus ''Sarbecovirus'', encoding a short non-structural protein. It is present in both SARS-CoV (which causes the disease SARS) and SARS-CoV-2 (which causes COVID-19), though the protein product h ...

''. 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, reading frames 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 reading frames ...

overlaps both

and

ORF3d ORF3d is a gene found in SARS-CoV-2 (the virus that causes COVID-19) and at least one closely related coronavirus found in pangolins, though it is not found in other closely related viruses within the '' Sarbecovirus'' subgenus. It is 57 codons l ...

in the

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

reading frame In molecular biology, a reading frame is a specific choice out of the possible ways to read the nucleic acid sequence, sequence of nucleotides in a nucleic acid (DNA or RNA) molecule as a sequence of triplets. Where these triplets equate to amino ...

s of the same sequence region encoding functional proteins.

Bioinformatics Bioinformatics () is an interdisciplinary field of science that develops methods and Bioinformatics software, software tools for understanding biological data, especially when the data sets are large and complex. Bioinformatics uses biology, ...

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 Ribosome profiling, or Ribo-Seq (also named ribosome footprinting), is an adaptation of a technique developed by Joan Steitz and Marilyn Kozak almost 50 years ago that Nicholas Ingolia and Jonathan Weissman adapted to work with next generation se ...

experiments confirm that the ''ORF3c'' gene expresses a protein product. The relatively short 41- residue protein is predicted to contain a

transmembrane domain A transmembrane domain (TMD, TM domain) is a membrane-spanning protein domain. TMDs may consist of one or several alpha-helices or a transmembrane beta barrel. Because the interior of the lipid bilayer is hydrophobic, the amino acid residues in ...

and has features suggestive of a viroporin.

References

{{Viral proteins Coronavirus proteins Viral nonstructural proteins