ID   E3_VAR67                Reviewed;         190 AA.
AC   P33863;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 1.
DT   03-AUG-2022, entry version 100.
DE   RecName: Full=Protein E3;
GN   ORFNames=E3L;
OS   Variola virus (isolate Human/India/Ind3/1967) (VARV) (Smallpox virus).
OC   Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC   Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus.
OX   NCBI_TaxID=587200;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8109158; DOI=10.1016/0168-1702(93)90093-3;
RA   Shchelkunov S.N., Blinov V.M., Resenchuk S.M., Totmenin A.V.,
RA   Sandakhchiev L.S.;
RT   "Analysis of the nucleotide sequence of a 43 kbp segment of the genome of
RT   variola virus India-1967 strain.";
RL   Virus Res. 30:239-258(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8384129; DOI=10.1016/0014-5793(93)80041-r;
RA   Shchelkunov S.N., Blinov V.M., Sandakhchiev L.S.;
RT   "Genes of variola and vaccinia viruses necessary to overcome the host
RT   protective mechanisms.";
RL   FEBS Lett. 319:80-83(1993).
CC   -!- FUNCTION: Plays a role in the inhibition of multiple cellular antiviral
CC       responses activated by dsRNA, such as inhibition of PKR activation,
CC       apoptosis, and IFN-mediated antiviral activities. Blocks also the
CC       phosphorylation and subsequent activation of IRF3 and IRF7 kinases that
CC       are required for interferon-alpha gene expression. Inhibits NF-kappa-B
CC       activation and the ubiquitin-like protein ISG15, which is an early
CC       antiviral protein. The binding with host ISG15 subsequently blocks host
CC       ISGylation. Inhibits ZBP1-dependent necroptosis via interaction with
CC       host ZBP1. {ECO:0000250|UniProtKB:P21605}.
CC   -!- SUBUNIT: Interacts with host G1P2/ISG15. Interacts with host
CC       EIF2AK2/PKR. Interacts with host ZBP1. {ECO:0000250|UniProtKB:P21605}.
CC   -!- SIMILARITY: Belongs to the poxviridae E3 protein family. {ECO:0000305}.
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DR   EMBL; X69198; CAA48985.1; -; Genomic_DNA.
DR   PIR; F36841; F36841.
DR   RefSeq; NP_042088.1; NC_001611.1.
DR   SMR; P33863; -.
DR   GeneID; 1486409; -.
DR   KEGG; vg:1486409; -.
DR   Proteomes; UP000002060; Genome.
DR   GO; GO:0003726; F:double-stranded RNA adenosine deaminase activity; IEA:InterPro.
DR   GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0039579; P:suppression by virus of host ISG15-protein conjugation; IEA:UniProtKB-KW.
DR   GO; GO:0039580; P:suppression by virus of host PKR signaling; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0039548; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity; IEA:UniProtKB-KW.
DR   GO; GO:0039557; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF7 activity; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.10.10; -; 1.
DR   InterPro; IPR014720; dsRBD_dom.
DR   InterPro; IPR009179; E3L.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   InterPro; IPR042371; Z_dom.
DR   Pfam; PF00035; dsrm; 1.
DR   Pfam; PF02295; z-alpha; 1.
DR   PIRSF; PIRSF004008; VAC_E3L; 1.
DR   SMART; SM00358; DSRM; 1.
DR   SMART; SM00550; Zalpha; 1.
DR   SUPFAM; SSF46785; SSF46785; 1.
DR   PROSITE; PS50137; DS_RBD; 1.
DR   PROSITE; PS50139; Z_BINDING; 1.
PE   3: Inferred from homology;
KW   Host-virus interaction; Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host IRF3 by virus; Inhibition of host IRF7 by virus;
KW   Inhibition of host ISG15 by virus; Inhibition of host PKR by virus;
KW   Inhibition of host RLR pathway by virus; Reference proteome; RNA-binding;
KW   Viral immunoevasion.
FT   CHAIN           1..190
FT                   /note="Protein E3"
FT                   /id="PRO_0000099449"
FT   DOMAIN          5..70
FT                   /note="Z-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00073"
FT   DOMAIN          117..184
FT                   /note="DRBM"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
SQ   SEQUENCE   190 AA;  21664 MW;  67697ED28E1D115B CRC64;
     MSKIYIDERS DAEIVCEAIK NIGLEGVTAV QLTRQLNMEK REVNKALYDL QRSAMVYSSD
     DIPPRWFMTT EADKPDAMTM ADVIIDDVSR EKSMREDHKS FDDVIPAKKI IDWKNANPVT
     IINEYCQITK RDWSFRIESV GPSNSPTFYA CVDIDGRVFD KADGKSKRDA KNNAAKLAVD
     KLLGYVIIRF