ORF4B_MERS1
ID ORF4B_MERS1 Reviewed; 246 AA.
AC K9N643;
DT 29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2013, sequence version 1.
DT 23-FEB-2022, entry version 30.
DE RecName: Full=Non-structural protein ORF4b;
DE Short=ORF4b;
GN Name=ORF4b;
OS Middle East respiratory syndrome-related coronavirus (isolate United
OS Kingdom/H123990006/2012) (MERS-CoV) (Betacoronavirus England 1).
OC Viruses; Riboviria; Orthornavirae; Pisuviricota; Pisoniviricetes;
OC Nidovirales; Cornidovirineae; Coronaviridae; Orthocoronavirinae;
OC Betacoronavirus; Merbecovirus.
OX NCBI_TaxID=1263720;
OH NCBI_TaxID=9838; Camelus dromedarius (Dromedary) (Arabian camel).
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=23078800;
RA Bermingham A., Chand M.A., Brown C.S., Aarons E., Tong C., Langrish C.,
RA Hoschler K., Brown K., Galiano M., Myers R., Pebody R.G., Green H.K.,
RA Boddington N.L., Gopal R., Price N., Newsholme W., Drosten C.,
RA Fouchier R.A., Zambon M.;
RT "Severe respiratory illness caused by a novel coronavirus, in a patient
RT transferred to the United Kingdom from the Middle East, September 2012.";
RL Eurosurveillance 17:20290-20290(2012).
RN [2]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24318862; DOI=10.1007/s13238-013-3096-8;
RA Yang Y., Zhang L., Geng H., Deng Y., Huang B., Guo Y., Zhao Z., Tan W.;
RT "The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of
RT Middle East respiratory syndrome coronavirus (MERS-CoV) are potent
RT interferon antagonists.";
RL Protein Cell 4:951-961(2013).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=24443473; DOI=10.1099/vir.0.062059-0;
RA Matthews K.L., Coleman C.M., van der Meer Y., Snijder E.J., Frieman M.B.;
RT "The ORF4b-encoded accessory proteins of Middle East respiratory syndrome
RT coronavirus and two related bat coronaviruses localize to the nucleus and
RT inhibit innate immune signalling.";
RL J. Gen. Virol. 95:874-882(2014).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26631542; DOI=10.1038/srep17554;
RA Yang Y., Ye F., Zhu N., Wang W., Deng Y., Zhao Z., Tan W.;
RT "Middle East respiratory syndrome coronavirus ORF4b protein inhibits type I
RT interferon production through both cytoplasmic and nuclear targets.";
RL Sci. Rep. 5:17554-17554(2015).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH HOST KPNA4.
RX PubMed=29370303; DOI=10.1371/journal.ppat.1006838;
RA Canton J., Fehr A.R., Fernandez-Delgado R., Gutierrez-Alvarez F.J.,
RA Sanchez-Aparicio M.T., Garcia-Sastre A., Perlman S., Enjuanes L., Sola I.;
RT "MERS-CoV 4b protein interferes with the NF-kappaB-dependent innate immune
RT response during infection.";
RL PLoS Pathog. 14:E1006838-E1006838(2018).
CC -!- FUNCTION: Plays a role in the inhibition of host innate immunity by
CC inhibiting the interaction between host IKBKE and MAVS. In turn, this
CC inhibition prevents the production of host interferon beta.
CC Additionally, inhibits host NF-kappa-B by interacting with host KPNA4
CC and thereby preventing the translocation of the NF-kappa-B complex into
CC the nucleus by this importin (PubMed:29370303).
CC {ECO:0000269|PubMed:24318862, ECO:0000269|PubMed:24443473,
CC ECO:0000269|PubMed:26631542, ECO:0000269|PubMed:29370303}.
CC -!- SUBUNIT: Interacts with host KPNA4; this interaction inhibits the
CC nuclear import of NF-kappa-B complex. {ECO:0000269|PubMed:29370303}.
CC -!- INTERACTION:
CC K9N643; P52294: KPNA1; Xeno; NbExp=3; IntAct=EBI-25641007, EBI-358383;
CC K9N643; P52292: KPNA2; Xeno; NbExp=2; IntAct=EBI-25641007, EBI-349938;
CC K9N643; O00505: KPNA3; Xeno; NbExp=4; IntAct=EBI-25641007, EBI-358297;
CC K9N643; O00629: KPNA4; Xeno; NbExp=7; IntAct=EBI-25641007, EBI-396343;
CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000269|PubMed:24318862,
CC ECO:0000269|PubMed:24443473, ECO:0000269|PubMed:26631542,
CC ECO:0000269|PubMed:29370303}. Host nucleus, host nucleolus
CC {ECO:0000269|PubMed:26631542}. Host cytoplasm
CC {ECO:0000269|PubMed:26631542}. Note=Mainly localized in the host
CC nucleus. {ECO:0000269|PubMed:24318862, ECO:0000269|PubMed:24443473,
CC ECO:0000269|PubMed:26631542}.
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DR EMBL; KC164505; AFY13310.1; -; Genomic_RNA.
DR BioGRID; 4383883; 12.
DR IntAct; K9N643; 12.
DR SIGNOR; K9N643; -.
DR Proteomes; UP000139997; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0044196; C:host cell nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR GO; GO:0039501; P:suppression by virus of host type I interferon production; IDA:UniProtKB.
DR GO; GO:0039724; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IKBKE activity; IEA:UniProtKB-KW.
DR CDD; cd21651; ORF4b_MERS-CoV-like; 1.
DR InterPro; IPR044321; ORF4b_MERS-CoV-like.
PE 1: Evidence at protein level;
KW Host cytoplasm; Host nucleus; Host-virus interaction;
KW Inhibition of host IKBKE by virus;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host NF-kappa-B by virus;
KW Inhibition of host RLR pathway by virus; Viral immunoevasion.
FT CHAIN 1..246
FT /note="Non-structural protein ORF4b"
FT /id="PRO_0000422437"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 22..38
FT /note="Nuclear localization motif"
FT /evidence="ECO:0000269|PubMed:29370303"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 246 AA; 28563 MW; 7529F1F376D53982 CRC64;
MEESLMDVPS TSGTQVYSRK ARKRSHSPTK KLRYVKRRFS LLRPEDLSVI VQPTHYVRVT
FSDPNMWYLR SGHHLHSVHN WLKPYGGQPV SEYHITLALL NLTDEDLARD FSPIALFLRN
VRFELHEFAL LRKTLVLNAS EIYCANIHRF KPVYRVNTAI PTIKDWLLVQ GFSLYHSGLP
LHMSISKLHA LDDVTRNYII TMPCFRTYPQ QMFVTPLAVD VVSIRSSNQG NKQIVHSYPI
LHHPGF
