ORF10 explained

Symbol:	Orf10_SARS-CoV-2
Orf10 protein, 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]

Properties

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.

Expression and function

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]

Evolution

Some studies of SARS-CoV-2 genomes have described ORF10 as likely to be functional and under positive selection. 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. Loss of ORF10 has also shown no effect on replication under experimental conditions in vitro. 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. 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.

Notes and References

1. Redondo N, Zaldívar-López S, Garrido JJ, Montoya M . SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns . Frontiers in Immunology . 12 . 708264 . 7 July 2021 . 34305949 . 8293742 . 10.3389/fimmu.2021.708264 . free .
2. Xu J, Zhao S, Teng T, Abdalla AE, Zhu W, Xie L, Wang Y, Guo X . Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV . Viruses . 12 . 2 . 244 . February 2020 . 32098422 . 7077191 . 10.3390/v12020244 . free .
3. Cagliani R, Forni D, Clerici M, Sironi M . Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses . Infection, Genetics and Evolution . 83 . 104353 . September 2020 . 32387562 . 7199688 . 10.1016/j.meegid.2020.104353 . 2020InfGE..8304353C .
4. Jungreis I, Sealfon R, Kellis M . SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes . Nature Communications . 12 . 1 . 2642 . May 2021 . 33976134 . 8113528 . 10.1038/s41467-021-22905-7 . 2021NatCo..12.2642J .
5. Finkel Y, Mizrahi O, Nachshon A, Weingarten-Gabbay S, Morgenstern D, Yahalom-Ronen Y, Tamir H, Achdout H, Stein D, Israeli O, Beth-Din A, Melamed S, Weiss S, Israely T, Paran N, Schwartz M, Stern-Ginossar N . The coding capacity of SARS-CoV-2 . Nature . 589 . 7840 . 125–130 . January 2021 . 32906143 . 10.1038/s41586-020-2739-1 . 221624633 . free . 2021Natur.589..125F .
6. Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZ, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJ, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JC, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu-Ozturk D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ . A SARS-CoV-2 protein interaction map reveals targets for drug repurposing . Nature . 583 . 7816 . 459–468 . July 2020 . 32353859 . 7431030 . 10.1038/s41586-020-2286-9 . 2020Natur.583..459G .
7. Mena EL, Donahue CJ, Vaites LP, Li J, Rona G, O'Leary C, Lignitto L, Miwatani-Minter B, Paulo JA, Dhabaria A, Ueberheide B, Gygi SP, Pagano M, Harper JW, Davey RA, Elledge SJ . ORF10-Cullin-2-ZYG11B complex is not required for SARS-CoV-2 infection . Proceedings of the National Academy of Sciences of the United States of America . 118 . 17 . e2023157118 . April 2021 . 33827988 . 8092598 . 10.1073/pnas.2023157118 . free . 2021PNAS..11823157M .
8. Pancer K, Milewska A, Owczarek K, Dabrowska A, Kowalski M, Łabaj PP, Branicki W, Sanak M, Pyrc K . The SARS-CoV-2 ORF10 is not essential in vitro or in vivo in humans . PLOS Pathogens . 16 . 12 . e1008959 . December 2020 . 33301543 . 7755277 . 10.1371/journal.ppat.1008959 . free .