ID   ORF4A_MERS1             Reviewed;         109 AA.
AC   K9N4V0;
DT   29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT   06-MAR-2013, sequence version 1.
DT   23-FEB-2022, entry version 34.
DE   RecName: Full=Non-structural protein ORF4a;
DE            Short=ORF4a;
GN   Name=ORF4a;
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].
RA   Nishi O., Iiyama K., Yasunaga-Aoki C., Shimizu S.;
RT   "The phylogenetic status and pathogenicity of a new isolate of Metarhizium
RT   sp. from a fruit beetle larvae in Japan.";
RL   Submitted (NOV-2012) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION.
RX   PubMed=24027320; DOI=10.1128/jvi.01845-13;
RA   Niemeyer D., Zillinger T., Muth D., Zielecki F., Horvath G., Suliman T.,
RA   Barchet W., Weber F., Drosten C., Mueller M.A.;
RT   "Middle East respiratory syndrome coronavirus accessory protein 4a is a
RT   type I interferon antagonist.";
RL   J. Virol. 87:12489-12495(2013).
RN   [3]
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   [4]
RP   FUNCTION, AND INTERACTION WITH HOST PRKRA/PACT.
RX   PubMed=24522921; DOI=10.1128/jvi.03649-13;
RA   Siu K.L., Yeung M.L., Kok K.H., Yuen K.S., Kew C., Lui P.Y., Chan C.P.,
RA   Tse H., Woo P.C., Yuen K.Y., Jin D.Y.;
RT   "Middle east respiratory syndrome coronavirus 4a protein is a double-
RT   stranded RNA-binding protein that suppresses PACT-induced activation of
RT   RIG-I and MDA5 in the innate antiviral response.";
RL   J. Virol. 88:4866-4876(2014).
CC   -!- FUNCTION: DsRNA-binding protein that plays a role in the inhibition of
CC       host innate response. Suppresses host PACT-induced activation of DDX58
CC       and MDA5 and thereby circumvents the production of type I inteferons.
CC       Prevents also the activation of host NF-kappaB.
CC       {ECO:0000269|PubMed:24027320, ECO:0000269|PubMed:24318862,
CC       ECO:0000269|PubMed:24522921}.
CC   -!- SUBUNIT: Interacts with host PRKRA/PACT. {ECO:0000269|PubMed:24522921}.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:24318862}.
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DR   EMBL; KC164505; AFY13309.1; -; Genomic_RNA.
DR   SMR; K9N4V0; -.
DR   BioGRID; 4383882; 48.
DR   IntAct; K9N4V0; 51.
DR   Proteomes; UP000139997; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR   GO; GO:0039526; P:modulation by virus of host apoptotic process; IEA:UniProtKB-KW.
DR   GO; GO:0039646; P:modulation by virus of host G0/G1 transition checkpoint; IEA:UniProtKB-KW.
DR   GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IDA:UniProtKB.
DR   GO; GO:0039501; P:suppression by virus of host type I interferon production; IDA:UniProtKB.
PE   1: Evidence at protein level;
KW   Apoptosis; G0/G1 host cell cycle checkpoint dysregulation by virus;
KW   Host cytoplasm; Host-virus interaction;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host NF-kappa-B by virus;
KW   Modulation of host cell apoptosis by virus;
KW   Modulation of host cell cycle by virus; Viral immunoevasion.
FT   CHAIN           1..109
FT                   /note="Non-structural protein ORF4a"
FT                   /id="PRO_0000422436"
SQ   SEQUENCE   109 AA;  12233 MW;  3213D44AC3D9623F CRC64;
     MDYVSLLNQI WQKYLNSPYT TCLYIPKPTA KYTPLVGTSL HPVLWNCQLS FAGYTESAVN
     STKALAKQDA AQRIAWLLHK DGGIPDGCSL YLRHSSLFAQ SEEEESFSN