ORF9b

There has been inconsistency in the nomenclature used for this gene in the scientific literature. In some work on SARS-CoV, it has been referred to as ORF13. It has also sometimes been referred to as ORF9a, resulting in a downstream ORF of 76 codons in SARS-CoV, also overlapping with the N gene, being designated ORF9b. The recommended nomenclature refers to the longer ORF as 9b and the downstream, shorter ORF as ORF9c.{{cite journal | vauthors = Jungreis I, Nelson CW, Ardern Z, Finkel Y, Krogan NJ, Sato K, Ziebuhr J, Stern-Ginossar N, Pavesi A, Firth AE, Gorbalenya AE, Kellis M | title = Conflicting and ambiguous names of overlapping ORFs in the SARS-CoV-2 genome: A homology-based resolution | journal = Virology | volume = 558 | pages = 145–151 | date = June 2021 | pmid = 33774510 | pmc = 7967279 | doi = 10.1016/j.virol.2021.02.013 }}

The ORF9b protein is 97 amino acid residues long in SARS-CoV and 98 in SARS-CoV-2. It forms a beta sheet-rich homodimer with a hydrophobic cavity in the center that binds lipids. The lipid-binding cavity may serve as an unusual mechanism for anchoring the protein to membranes.

A fragment of the SARS-CoV-2 ORF9b protein has been structurally characterized in a protein complex with Tom70 in which ORF9b forms an alpha helix rather than the beta-sheet structure observed in isolation.{{cite journal | vauthors = Gao X, Zhu K, Qin B, Olieric V, Wang M, Cui S | title = Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests unusual virus-host interactions | journal = Nature Communications | volume = 12 | issue = 1 | pages = 2843 | date = May 2021 | pmid = 33990585 | pmc = 8121815 | doi = 10.1038/s41467-021-23118-8 | bibcode = 2021NatCo..12.2843G }} This fold switching behavior is also consistent with bioinformatics predictions and may also occur for the SARS-CoV homolog.{{cite journal | vauthors = Porter LL | title = Predictable fold switching by the SARS-CoV-2 protein ORF9b | journal = Protein Science | volume = 30 | issue = 8 | pages = 1723–1729 | date = August 2021 | pmid = 33934422 | pmc = 8242659 | doi = 10.1002/pro.4097 }}

ORF9b is one of two overlapping genes fully contained within the open reading frame of the N gene encoding coronavirus nucleocapsid protein, the other being ORF9c. ORF9b is expressed by ribosome leaky scanning from its bicistronic subgenomic RNA.{{cite journal | vauthors = Xu K, Zheng BJ, Zeng R, Lu W, Lin YP, Xue L, Li L, Yang LL, Xu C, Dai J, Wang F, Li Q, Dong QX, Yang RF, Wu JR, Sun B | title = Severe acute respiratory syndrome coronavirus accessory protein 9b is a virion-associated protein | journal = Virology | volume = 388 | issue = 2 | pages = 279–285 | date = June 2009 | pmid = 19394665 | pmc = 7103405 | doi = 10.1016/j.virol.2009.03.032 }} Unlike its neighbor ORF9c, its length is well conserved in sarbecoviruses and there is strong evidence it is a functional protein-coding gene.{{cite journal | vauthors = Jungreis I, Sealfon R, Kellis M | title = SARS-CoV-2 gene content and COVID-19 mutation impact by comparing 44 Sarbecovirus genomes | journal = Nature Communications | volume = 12 | issue = 1 | pages = 2642 | date = May 2021 | pmid = 33976134 | pmc = 8113528 | doi = 10.1038/s41467-021-22905-7 | bibcode = 2021NatCo..12.2642J }}

In SARS-CoV, the protein is localized to the endoplasmic reticulum (ER) and to intracellular vesicles. It does not have a nuclear localization sequence but can enter the cell nucleus by passive diffusion; it does however have a nuclear export sequence for exit from the nucleus. In SARS-CoV-2, it is reportedly associated with the mitochondrial membrane.

The function of the ORF9b protein is not well characterized. It is not essential for viral replication.

The ORF9b protein has been reported to interact with a number of other viral proteins, including ORF6, non-structural protein 5, non-structural protein 14, and coronavirus envelope protein. It has been detected in mature SARS-CoV virions and thus may be a minor viral structural protein.

The ORF9b protein may be involved in modulating the host's immune system response. The SARS-CoV-2 protein has been reported to suppress interferon response via its interactions with Tom70, a component of the mitochondrial translocase of the outer membrane (TOM) complex.{{cite journal | vauthors = Jiang HW, Zhang HN, Meng QF, Xie J, Li Y, Chen H, Zheng YX, Wang XN, Qi H, Zhang J, Wang PH, Han ZG, Tao SC | title = SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting TOM70 | journal = Cellular & Molecular Immunology | volume = 17 | issue = 9 | pages = 998–1000 | date = September 2020 | pmid = 32728199 | pmc = 7387808 | doi = 10.1038/s41423-020-0514-8 }}

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Category:Coronavirus proteins