Orf10 protein, SARS-CoV-2 | |
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Identifiers | |
Symbol | Orf10_SARS-CoV-2 |
InterPro | IPR044342 |
ORF10 is an open reading frame (ORF) found in the genome of the SARS-CoV-2 coronavirus. It is 38 codons long.[1] It is not conserved in all Sarbecoviruses (including SARS-CoV). In studies prompted by the COVID-19 pandemic, ORF10 attracted research interest as one of two viral accessory protein genes not conserved between SARS-CoV and SARS-CoV-2[2] and was initially described as a protein-coding gene likely under positive selection.[3] However, although it is sometimes included in lists of SARS-CoV-2 accessory genes, experimental and bioinformatics evidence suggests ORF10 is likely not a functional protein-coding gene.[4]
ORF10 is located downstream of the N gene, which encodes coronavirus nucleocapsid protein. It is the annotated open reading frame furthest to the 3' end of the genome. It encodes a 38-amino acid hypothetical protein.[1]
It is unlikely that ORF10 is translated under natural conditions, since subgenomic RNA containing the ORF10 region is not detected, though there is some ribosome footprinting signal.[5] When experimentally overexpressed, the ORF10 protein has been reported to interact with ZYG11B and its cullin-RING ligase protein complex.[6] However, this interaction has been shown to be dispensable in in vitro studies of the viral life cycle.[7]
Some studies of SARS-CoV-2 genomes have described ORF10 as likely to be functional and under positive selection.[3] However, premature stop codons have been identified in SARS-CoV-2 variants[8] and in many Sarbecovirus sequences, suggesting that the putative protein product is not essential for viral replication.[4] Loss of ORF10 has also shown no effect on replication under experimental conditions in vitro.[8] It has been suggested through bioinformatics analysis that apparent sequence conservation in SARS-CoV-2 ORF10 may not be due to a protein-coding function, but instead due to conserved RNA secondary structure in the region.[4] The conserved region, which extends beyond ORF10 itself, overlaps with the coronavirus 3' UTR pseudoknot region, a secondary structure known to be involved in genome replication.[4]