{PDOC51964} {PS51964; SARS_ORF8_IG} {BEGIN} *********************************************************************** * SARS ORF8 accessory protein immunoglobulin (Ig)-like domain profile * *********************************************************************** Coronaviruses (CoVs) are enveloped positive-strand RNA viruses that infect many species, including humans, other mammals, and birds. After infection, the host may develop respiratory, bowel, liver, and neurological diseases. Coronaviruses are divided into four genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. The ideal hosts of AlphaCoV and BetaCoV are mammals, and GammaCoV primarily infects birds, while DeltaCoV has been identified in both mammals and birds. SARS, SARS-CoV-2, BatCoV RaTG13 and Bat-SARS-like coronavirus (BATSL-CoVZXC21 and BAT-SL-CoVZC45) belong to the Sarbecovirus subgenus of BetaCoV [E1]. All coronaviruses have a similar genomic structure. At the 5' end, two-thirds of the genome comprises two large open reading frames (ORFs) (ORF1a and ORF1b) encoding the coronavirus replicase, which is highly conserved among genera. At the 3' end, the genome encodes four structural proteins (S, E, M and N) and a variable number of accessory proteins. Accessory proteins play an important role in virus–host interactions, especially in antagonizing or regulating host immunity and virus adaptation to the host. There are large variations in the number of accessory proteins (1–10) among coronaviruses. The number of accessory proteins of the AlphaCoVs is relatively lower, between 1 and 5, while BetaCoVs have 3–5 accessory proteins, except for SARS-CoV and SARS-CoV-2, which possess the largest number of accessory proteins among all coronaviruses (10 and 9, respectively). ORF8 is the most variable accessory protein among those encoded by SARS related coronaviruses (SARSr-CoVs) and is not shared by all members of subgenus Sarbecovirus. SARSr ORF8 accessory proteins are characterized by the presence of an N-terminal hydrophobic signal peptide, a conserved N-glycosylation site, and enough cysteine residues with the potential to form disulfide bonds, drawing their picture as structurally stable potential ER-resident proteins. There is functional overlap between these proteins with involvement in immune modulation, which is probably accomplished through involvement in protein quality control. When ORF8 is exogenously overexpressed in cells, it disrupts IFN-I signaling. Unlike ORF8a/b of SARS-CoV, the SARS-CoV-2 ORF8 downregulates MHC-I in cells. The SARSr ORF8 contains an immunoglobulin (Ig)-like domain (see ) [1,2,3,4,5]. The profile we developed covers the entire SARS ORF8 accessory protein Ig-like domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: April 2021 / First entry. [ 1] Arya R., Kumari S., Pandey B., Mistry H., Bihani S.C., Das A., Prashar V., Gupta G.D., Panicker L., Kumar M. "Structural insights into SARS-CoV-2 proteins." J. Mol. Biol. 433:166725-166725(2021). PubMed=33245961; DOI=10.1016/j.jmb.2020.11.024 [ 2] Zinzula L. "Lost in deletion: The enigmatic ORF8 protein of SARS-CoV-2." Biochem. Biophys. Res. Commun. 538:116-124(2021). PubMed=33685621; DOI=10.1016/j.bbrc.2020.10.045 [ 3] Lin X., Fu B., Yin S., Li Z., Liu H., Zhang H., Xing N., Wang Y., Xue W., Xiong Y., Zhang S., Zhao Q., Xu S., Zhang J., Wang P., Nian W., Wang X., Wu H. "ORF8 contributes to cytokine storm during SARS-CoV-2 infection by activating IL-17 pathway." iScience 24:102293-102293(2021). PubMed=33723527; DOI=10.1016/j.isci.2021.102293 [ 4] Hussain M., Shabbir S., Amanullah A., Raza F., Imdad M.J., Zahid S. "Immunoinformatic analysis of structural and epitope variations in the spike and Orf8 proteins of SARS-CoV-2/B.1.1.7." J. Med. Virol. 0:0-0(2021). PubMed=33704818; DOI=10.1002/jmv.26931 [ 5] Flower T.G., Buffalo C.Z., Hooy R.M., Allaire M., Ren X., Hurley J.H. "Structure of SARS-CoV-2 ORF8, a rapidly evolving coronavirus protein implicated in immune evasion." bioRxiv 0:0-0(2020). PubMed=32869027; DOI=10.1101/2020.08.27.270637 [E1] https://viralzone.expasy.org/30?outline=all_by_species -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}