ORF10

From Wikipedia, the free encyclopedia
Orf10 protein, SARS-CoV-2
Identifiers
SymbolOrf10_SARS-CoV-2
InterProIPR044342

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.[1]

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.[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]

References[]

  1. ^ a b Redondo, Natalia; Zaldívar-López, Sara; Garrido, Juan J.; Montoya, Maria (7 July 2021). "SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns". Frontiers in Immunology. 12: 708264. doi:10.3389/fimmu.2021.708264. PMC 8293742. PMID 34305949.
  2. ^ Xu, Jiabao; Zhao, Shizhe; Teng, Tieshan; Abdalla, Abualgasim Elgaili; Zhu, Wan; Xie, Longxiang; Wang, Yunlong; Guo, Xiangqian (22 February 2020). "Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV". Viruses. 12 (2): 244. doi:10.3390/v12020244. PMC 7077191.
  3. ^ a b Cagliani, Rachele; Forni, Diego; Clerici, Mario; Sironi, Manuela (September 2020). "Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses". Infection, Genetics and Evolution. 83: 104353. doi:10.1016/j.meegid.2020.104353. PMC 7199688.
  4. ^ a b c d Jungreis, Irwin; Sealfon, Rachel; Kellis, Manolis (December 2021). "SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes". Nature Communications. 12 (1): 2642. doi:10.1038/s41467-021-22905-7. PMC 8113528.
  5. ^ Finkel, Yaara; Mizrahi, Orel; Nachshon, Aharon; Weingarten-Gabbay, Shira; Morgenstern, David; Yahalom-Ronen, Yfat; Tamir, Hadas; Achdout, Hagit; Stein, Dana; Israeli, Ofir; Beth-Din, Adi; Melamed, Sharon; Weiss, Shay; Israely, Tomer; Paran, Nir; Schwartz, Michal; Stern-Ginossar, Noam (7 January 2021). "The coding capacity of SARS-CoV-2". Nature. 589 (7840): 125–130. doi:10.1038/s41586-020-2739-1.
  6. ^ Gordon, David E.; Jang, Gwendolyn M.; Bouhaddou, Mehdi; Xu, Jiewei; Obernier, Kirsten; White, Kris M.; O’Meara, Matthew J.; Rezelj, Veronica V.; Guo, Jeffrey Z.; Swaney, Danielle L.; Tummino, Tia A.; Hüttenhain, Ruth; Kaake, Robyn M.; Richards, Alicia L.; Tutuncuoglu, Beril; Foussard, Helene; Batra, Jyoti; Haas, Kelsey; Modak, Maya; Kim, Minkyu; Haas, Paige; Polacco, Benjamin J.; Braberg, Hannes; Fabius, Jacqueline M.; Eckhardt, Manon; Soucheray, Margaret; Bennett, Melanie J.; Cakir, Merve; McGregor, Michael J.; Li, Qiongyu; Meyer, Bjoern; Roesch, Ferdinand; Vallet, Thomas; Mac Kain, Alice; Miorin, Lisa; Moreno, Elena; Naing, Zun Zar Chi; Zhou, Yuan; Peng, Shiming; Shi, Ying; Zhang, Ziyang; Shen, Wenqi; Kirby, Ilsa T.; Melnyk, James E.; Chorba, John S.; Lou, Kevin; Dai, Shizhong A.; Barrio-Hernandez, Inigo; Memon, Danish; Hernandez-Armenta, Claudia; Lyu, Jiankun; Mathy, Christopher J. P.; Perica, Tina; Pilla, Kala Bharath; Ganesan, Sai J.; Saltzberg, Daniel J.; Rakesh, Ramachandran; Liu, Xi; Rosenthal, Sara B.; Calviello, Lorenzo; Venkataramanan, Srivats; Liboy-Lugo, Jose; Lin, Yizhu; Huang, Xi-Ping; Liu, YongFeng; Wankowicz, Stephanie A.; Bohn, Markus; Safari, Maliheh; Ugur, Fatima S.; Koh, Cassandra; Savar, Nastaran Sadat; Tran, Quang Dinh; Shengjuler, Djoshkun; Fletcher, Sabrina J.; O’Neal, Michael C.; Cai, Yiming; Chang, Jason C. J.; Broadhurst, David J.; Klippsten, Saker; Sharp, Phillip P.; Wenzell, Nicole A.; Kuzuoglu-Ozturk, Duygu; Wang, Hao-Yuan; Trenker, Raphael; Young, Janet M.; Cavero, Devin A.; Hiatt, Joseph; Roth, Theodore L.; Rathore, Ujjwal; Subramanian, Advait; Noack, Julia; Hubert, Mathieu; Stroud, Robert M.; Frankel, Alan D.; Rosenberg, Oren S.; Verba, Kliment A.; Agard, David A.; Ott, Melanie; Emerman, Michael; Jura, Natalia; von Zastrow, Mark; Verdin, Eric; Ashworth, Alan; Schwartz, Olivier; d’Enfert, Christophe; Mukherjee, Shaeri; Jacobson, Matt; Malik, Harmit S.; Fujimori, Danica G.; Ideker, Trey; Craik, Charles S.; Floor, Stephen N.; Fraser, James S.; Gross, John D.; Sali, Andrej; Roth, Bryan L.; Ruggero, Davide; Taunton, Jack; Kortemme, Tanja; Beltrao, Pedro; Vignuzzi, Marco; García-Sastre, Adolfo; Shokat, Kevan M.; Shoichet, Brian K.; Krogan, Nevan J. (16 July 2020). "A SARS-CoV-2 protein interaction map reveals targets for drug repurposing". Nature. 583 (7816): 459–468. doi:10.1038/s41586-020-2286-9. PMC 7431030.
  7. ^ Mena, Elijah L.; Donahue, Callie J.; Vaites, Laura Pontano; Li, Jie; Rona, Gergely; O’Leary, Colin; Lignitto, Luca; Miwatani-Minter, Bearach; Paulo, Joao A.; Dhabaria, Avantika; Ueberheide, Beatrix; Gygi, Steven P.; Pagano, Michele; Harper, J. Wade; Davey, Robert A.; Elledge, Stephen J. (27 April 2021). "ORF10–Cullin-2–ZYG11B complex is not required for SARS-CoV-2 infection". Proceedings of the National Academy of Sciences. 118 (17): e2023157118. doi:10.1073/pnas.2023157118. PMC 8092598.
  8. ^ a b Pancer, Katarzyna; Milewska, Aleksandra; Owczarek, Katarzyna; Dabrowska, Agnieszka; Kowalski, Michał; Łabaj, Paweł P.; Branicki, Wojciech; Sanak, Marek; Pyrc, Krzysztof (10 December 2020). "The SARS-CoV-2 ORF10 is not essential in vitro or in vivo in humans". PLOS Pathogens. 16 (12): e1008959. doi:10.1371/journal.ppat.1008959. PMID 33301543.
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