ID ORF9B_SARS2 Reviewed; 97 AA.
AC P0DTD2;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-APR-2020, sequence version 1.
DT 28-JUN-2023, entry version 16.
DE RecName: Full=ORF9b protein;
DE Short=ORF9b;
DE AltName: Full=Accessory protein 9b;
DE AltName: Full=ORF-9b;
DE AltName: Full=Protein 9b;
GN ORFNames=9b;
OS Severe acute respiratory syndrome coronavirus 2 (2019-nCoV) (SARS-CoV-2).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC Betacoronavirus; Sarbecovirus.
OX NCBI_TaxID=2697049;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=32015508; DOI=10.1038/s41586-020-2008-3;
RA Wu F., Zhao S., Yu B., Chen Y.-M., Wang W., Song Z.-G., Hu Y., Tao Z.-W.,
RA Tian J.-H., Pei Y.-Y., Yuan M.-L., Zhang Y.-L., Dai F.-H., Liu Y.,
RA Wang Q.-M., Zheng J.-J., Xu L., Holmes E.C., Zhang Y.-Z.;
RT "A new coronavirus associated with human respiratory disease in China.";
RL Nature 579:265-269(2020).
RN [2]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.05 ANGSTROMS), INTERACTION WITH HUMAN
RP TOMM70, AND SUBCELLULAR LOCATION.
RX PubMed=33060197; DOI=10.1126/science.abe9403;
RG QCRG Structural Biology Consortium;
RG Zoonomia Consortium;
RA Gordon D.E., Hiatt J., Bouhaddou M., Rezelj V.V., Ulferts S., Braberg H.,
RA Jureka A.S., Obernier K., Guo J.Z., Batra J., Kaake R.M., Weckstein A.R.,
RA Owens T.W., Gupta M., Pourmal S., Titus E.W., Cakir M., Soucheray M.,
RA McGregor M., Cakir Z., Jang G., O'Meara M.J., Tummino T.A., Zhang Z.,
RA Foussard H., Rojc A., Zhou Y., Kuchenov D., Huettenhain R., Xu J.,
RA Eckhardt M., Swaney D.L., Fabius J.M., Ummadi M., Tutuncuoglu B.,
RA Rathore U., Modak M., Haas P., Haas K.M., Naing Z.Z.C., Pulido E.H.,
RA Shi Y., Barrio-Hernandez I., Memon D., Petsalaki E., Dunham A.,
RA Marrero M.C., Burke D., Koh C., Vallet T., Silvas J.A., Azumaya C.M.,
RA Billesboelle C., Brilot A.F., Campbell M.G., Diallo A., Dickinson M.S.,
RA Diwanji D., Herrera N., Hoppe N., Kratochvil H.T., Liu Y., Merz G.E.,
RA Moritz M., Nguyen H.C., Nowotny C., Puchades C., Rizo A.N.,
RA Schulze-Gahmen U., Smith A.M., Sun M., Young I.D., Zhao J., Asarnow D.,
RA Biel J., Bowen A., Braxton J.R., Chen J., Chio C.M., Chio U.S.,
RA Deshpande I., Doan L., Faust B., Flores S., Jin M., Kim K., Lam V.L.,
RA Li F., Li J., Li Y.L., Li Y., Liu X., Lo M., Lopez K.E., Melo A.A.,
RA Moss F.R. III, Nguyen P., Paulino J., Pawar K.I., Peters J.K.,
RA Pospiech T.H. Jr., Safari M., Sangwan S., Schaefer K., Thomas P.V.,
RA Thwin A.C., Trenker R., Tse E., Tsui T.K.M., Wang F., Whitis N., Yu Z.,
RA Zhang K., Zhang Y., Zhou F., Saltzberg D., Hodder A.J., Shun-Shion A.S.,
RA Williams D.M., White K.M., Rosales R., Kehrer T., Miorin L., Moreno E.,
RA Patel A.H., Rihn S., Khalid M.M., Vallejo-Gracia A., Fozouni P.,
RA Simoneau C.R., Roth T.L., Wu D., Karim M.A., Ghoussaini M., Dunham I.,
RA Berardi F., Weigang S., Chazal M., Park J., Logue J., McGrath M.,
RA Weston S., Haupt R., Hastie C.J., Elliott M., Brown F., Burness K.A.,
RA Reid E., Dorward M., Johnson C., Wilkinson S.G., Geyer A., Giesel D.M.,
RA Baillie C., Raggett S., Leech H., Toth R., Goodman N., Keough K.C.,
RA Lind A.L., Klesh R.J., Hemphill K.R., Carlson-Stevermer J., Oki J.,
RA Holden K., Maures T., Pollard K.S., Sali A., Agard D.A., Cheng Y.,
RA Fraser J.S., Frost A., Jura N., Kortemme T., Manglik A., Southworth D.R.,
RA Stroud R.M., Alessi D.R., Davies P., Frieman M.B., Ideker T., Abate C.,
RA Jouvenet N., Kochs G., Shoichet B., Ott M., Palmarini M., Shokat K.M.,
RA Garcia-Sastre A., Rassen J.A., Grosse R., Rosenberg O.S., Verba K.A.,
RA Basler C.F., Vignuzzi M., Peden A.A., Beltrao P., Krogan N.J.;
RT "Comparative host-coronavirus protein interaction networks reveal pan-viral
RT disease mechanisms.";
RL Science 0:0-0(2020).
RN [3]
RP FUNCTION, AND INTERACTION WITH HOST TOMM70.
RX PubMed=32728199; DOI=10.1038/s41423-020-0514-8;
RA Jiang H.W., Zhang H.N., Meng Q.F., Xie J., Li Y., Chen H., Zheng Y.X.,
RA Wang X.N., Qi H., Zhang J., Wang P.H., Han Z.G., Tao S.C.;
RT "SARS-CoV-2 Orf9b suppresses type I interferon responses by targeting
RT TOM70.";
RL Cell. Mol. Immunol. 17:998-1000(2020).
RN [4]
RP FUNCTION, MUTAGENESIS OF SER-53, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP HOST TOMM70.
RX PubMed=34502139; DOI=10.3390/ijms22179233;
RA Brandherm L., Kobas A.M., Kloehn M., Brueggemann Y., Pfaender S.,
RA Rassow J., Kreimendahl S.;
RT "Phosphorylation of SARS-CoV-2 Orf9b Regulates Its Targeting to Two Binding
RT Sites in TOM70 and Recruitment of Hsp90.";
RL Int. J. Mol. Sci. 22:0-0(2021).
RN [5] {ECO:0007744|PDB:6Z4U}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS), AND HOMODIMERIZATION.
RA Weeks S.D., De Graef S., Munawar A.;
RT "X-ray Crystallographic Structure of Orf9b from SARS-CoV-2.";
RL Submitted (MAY-2020) to the PDB data bank.
RN [6]
RP STRUCTURE BY ELECTRON MICROSCOPY (2.20 ANGSTROMS) OF 1-97, AND INTERACTION
RP WITH HOST TOMM70.
RX PubMed=33990585; DOI=10.1038/s41467-021-23118-8;
RA Gao X., Zhu K., Qin B., Olieric V., Wang M., Cui S.;
RT "Crystal structure of SARS-CoV-2 Orf9b in complex with human TOM70 suggests
RT unusual virus-host interactions.";
RL Nat. Commun. 12:2843-2843(2021).
CC -!- FUNCTION: Plays a role in inhibiting the host innate immune response by
CC targeting the mitochondrial-associated innate immune response. Acts by
CC binding to host TOMM70, inhibiting its binding to HSP90AB1 thereby
CC disrupting the interferon activation pathway.
CC {ECO:0000269|PubMed:32728199, ECO:0000269|PubMed:34502139}.
CC -!- SUBUNIT: Homodimer (Ref.5). Interacts with host TOMM70
CC (PubMed:33060197, PubMed:32728199, PubMed:34502139, PubMed:33990585);
CC the interaction occurs only with monomer (PubMed:33990585).
CC {ECO:0000269|PubMed:32728199, ECO:0000269|PubMed:33060197,
CC ECO:0000269|PubMed:33990585, ECO:0000269|PubMed:34502139,
CC ECO:0000269|Ref.5}.
CC -!- INTERACTION:
CC P0DTD2; P0DTD2: 9b; NbExp=5; IntAct=EBI-25475909, EBI-25475909;
CC P0DTD2; Q9Y6K9: IKBKG; Xeno; NbExp=3; IntAct=EBI-25475909, EBI-81279;
CC P0DTD2; O94826: TOMM70; Xeno; NbExp=27; IntAct=EBI-25475909, EBI-2800236;
CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:32728199,
CC ECO:0000269|PubMed:33060197, ECO:0000269|PubMed:34502139}. Host
CC mitochondrion {ECO:0000269|PubMed:32728199,
CC ECO:0000269|PubMed:33060197}.
CC -!- POLYMORPHISM: Variant Omicron/BA.1 and BA.2 belong to a lineage first
CC isolated in South Africa (November 2021). {ECO:0000305}.
CC -!- POLYMORPHISM: Variant Omicron/BQ.1.1 belongs to a lineage first
CC isolated in Nigeria (November 2022). {ECO:0000305}.
CC -!- POLYMORPHISM: Variant Omicron/XBB.1.5 belongs to a lineage first
CC isolated in United States (November 2022). It is the result of
CC recombination between omicron BJ.1 and BM.1.1. Moreover XBB.1.5 do not
CC express ORF8. {ECO:0000305}.
CC -!- MISCELLANEOUS: The open reading frame (ORF) encoding for this protein
CC overlaps with the N ORF. {ECO:0000269|PubMed:32015508}.
CC -!- SIMILARITY: Belongs to the coronavirus group 2 protein 9b family.
CC {ECO:0000305}.
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DR EMBL; MN908947; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR PDB; 6Z4U; X-ray; 1.95 A; A/B=1-97.
DR PDB; 7DHG; X-ray; 2.20 A; B=1-97.
DR PDB; 7KDT; EM; 3.05 A; B=1-97.
DR PDB; 7YE7; X-ray; 2.95 A; A/B/C/D=1-97.
DR PDB; 7YE8; X-ray; 3.01 A; A/B/C/D=1-97.
DR PDBsum; 6Z4U; -.
DR PDBsum; 7DHG; -.
DR PDBsum; 7KDT; -.
DR PDBsum; 7YE7; -.
DR PDBsum; 7YE8; -.
DR SMR; P0DTD2; -.
DR BioGRID; 4383874; 545.
DR ComplexPortal; CPX-6100; SARS-CoV-2 9b complex.
DR IntAct; P0DTD2; 42.
DR iPTMnet; P0DTD2; -.
DR Reactome; R-HSA-168928; DDX58/IFIH1-mediated induction of interferon-alpha/beta.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-9727281; Translation of Accessory Proteins.
DR PRO; PR:P0DTD2; -.
DR Proteomes; UP000464024; Genome.
DR GO; GO:0033650; C:host cell mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProt.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:ComplexPortal.
DR GO; GO:0098799; C:outer mitochondrial membrane protein complex; ISO:ComplexPortal.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0140678; F:molecular function inhibitor activity; IDA:UniProt.
DR GO; GO:0140311; F:protein sequestering activity; IDA:UniProt.
DR GO; GO:0050687; P:negative regulation of defense response to virus; IDA:ComplexPortal.
DR GO; GO:0090258; P:negative regulation of mitochondrial fission; ISO:ComplexPortal.
DR GO; GO:2000786; P:positive regulation of autophagosome assembly; ISO:ComplexPortal.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IDA:ComplexPortal.
DR GO; GO:0039545; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity; IDA:UniProt.
DR CDD; cd21955; SARS-CoV_ORF9b; 1.
DR InterPro; IPR018542; Protein_9b_Betacoronavirus.
DR InterPro; IPR037223; Protein_9b_SARS.
DR Pfam; PF09399; bCoV_lipid_BD; 1.
DR SUPFAM; SSF141666; SARS ORF9b-like; 1.
DR PROSITE; PS51920; SARS_9B; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host cytoplasm; Host mitochondrion; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host MAVS by virus; Inhibition of host RLR pathway by virus;
KW Reference proteome; Viral immunoevasion.
FT CHAIN 1..97
FT /note="ORF9b protein"
FT /evidence="ECO:0000250|UniProtKB:P59636"
FT /id="PRO_0000449657"
FT DOMAIN 8..97
FT /note="9b"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01268"
FT MOTIF 45..53
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P59636"
FT VARIANT 10
FT /note="P -> S (in strain: Omicron/BA.1, Omicron/BA.2,
FT Omicron/BA.2.12.1, Omicron/BA.4, Omicron/BA.5, Omicron/
FT XBB.1.5)"
FT /evidence="ECO:0000305"
FT VARIANT 27..29
FT /note="Missing (in strain: Omicron/BA.1, Omicron/BA.2,
FT Omicron/BA.2.12.1, Omicron/BA.4, Omicron/BA.5, Omicron/
FT XBB.1.5)"
FT /evidence="ECO:0000305"
FT VARIANT 60
FT /note="T -> A (in strain: Delta/B.1.617.2)"
FT /evidence="ECO:0000305"
FT VARIANT 77
FT /note="Q -> E (in strain: Gamma/P.1)"
FT /evidence="ECO:0000305"
FT MUTAGEN 53
FT /note="S->E: Complete loss of binding to host TOMM70."
FT /evidence="ECO:0000269|PubMed:34502139"
FT HELIX 5..7
FT /evidence="ECO:0007829|PDB:6Z4U"
FT STRAND 12..15
FT /evidence="ECO:0007829|PDB:6Z4U"
FT STRAND 19..23
FT /evidence="ECO:0007829|PDB:6Z4U"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:6Z4U"
FT STRAND 44..50
FT /evidence="ECO:0007829|PDB:6Z4U"
FT STRAND 52..61
FT /evidence="ECO:0007829|PDB:6Z4U"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:6Z4U"
FT STRAND 68..74
FT /evidence="ECO:0007829|PDB:6Z4U"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:7YE7"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:6Z4U"
FT STRAND 89..96
FT /evidence="ECO:0007829|PDB:6Z4U"
SQ SEQUENCE 97 AA; 10797 MW; 62CFB65C1804545E CRC64;
MDPKISEMHP ALRLVDPQIQ LAVTRMENAV GRDQNNVGPK VYPIILRLGS PLSLNMARKT
LNSLEDKAFQ LTPIAVQMTK LATTEELPDE FVVVTVK
//