ORF6

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Betacoronavirus ORF6 protein
Top 10 structural models of the SARS-CoV-2's ORF6 protein obtained by Solid-state NMR. The alpha-helix is highlighted in cyan and the disordered regions are coloured in pink.[1] PDB: 9A8Y
Identifiers
SymbolbCoV_NS6
PfamPF12133
InterProIPR022736
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

ORF6 is a gene that encodes a viral accessory protein in coronaviruses of the subgenus Sarbecovirus, including SARS-CoV and SARS-CoV-2. It is not present in MERS-CoV. It is thought to reduce the immune system response to viral infection through interferon antagonism.[2][3][4]

The ORF6 protein is fairly small, consisting of 63 amino acid residues in SARS-CoV[3] and 61 in SARS-CoV-2.[4] The ORF6 sequence is not well conserved, sharing only about 66% of the sequence between the two viruses.[5] However, from the emergence of SARS-CoV-2 in 2019 until 2025, the ORF6 sequence has only stably conserved one mutation: the last aspartate has mutated into a leucine (D61L).[6]

Its approximately 20-residue C-terminal tail is polar, extends into the cytosol. This region contains the conserved Methionine 58 needed for the interaction with RAE1 and NUP98[7] and signal sequences for protein trafficking.[2][3] The rest of the protein is amphipathic: the first 10 N-terminal residues act as a membrane anchor, while residues 11-45 form and amphiphilic alpha helix that associates with the membrane as an Integral monotopic membrane protein.[1]

Expression and localization

Function

References

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