E3_VACCC
ID E3_VACCC Reviewed; 190 AA.
AC P21081;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 23-FEB-2022, entry version 96.
DE RecName: Full=RNA-binding protein E3 {ECO:0000305};
DE AltName: Full=p25 {ECO:0000250|UniProtKB:P21605};
GN ORFNames=E3L {ECO:0000303|PubMed:15207627};
OS Vaccinia virus (strain Copenhagen) (VACV).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus; Vaccinia virus.
OX NCBI_TaxID=10249;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=2219722; DOI=10.1016/0042-6822(90)90294-2;
RA Goebel S.J., Johnson G.P., Perkus M.E., Davis S.W., Winslow J.P.,
RA Paoletti E.;
RT "The complete DNA sequence of vaccinia virus.";
RL Virology 179:247-266(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Goebel S.J., Johnson G.P., Perkus M.E., Davis S.W., Winslow J.P.,
RA Paoletti E.;
RT "Appendix to 'The complete DNA sequence of vaccinia virus'.";
RL Virology 179:517-563(1990).
RN [3]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=11124948; DOI=10.1074/jbc.m008717200;
RA Smith E.J., Marie I.J., Prakash A., Garcia-Sastre A., Levy D.E.;
RT "IRF3 and IRF7 phosphorylation in virus-infected cells does not require
RT double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is
RT blocked by Vaccinia virus E3L protein.";
RL J. Biol. Chem. 276:8951-8957(2001).
RN [4]
RP FUNCTION.
RX PubMed=15207627; DOI=10.1016/j.virol.2004.03.012;
RA Langland J.O., Jacobs B.L.;
RT "Inhibition of PKR by vaccinia virus: role of the N- and C-terminal domains
RT of E3L.";
RL Virology 324:419-429(2004).
CC -!- FUNCTION: RNA-binding protein that plays a role in the inhibition of
CC multiple cellular antiviral responses activated by double-stranded RNA
CC (dsRNA), such as inhibition of PKR activation, necroptosis, and IFN-
CC mediated antiviral activities (PubMed:11124948, PubMed:15207627).
CC Recognizes and binds Z-RNA structures via its Z-binding domain and
CC dsRNA via its DRBM domain: RNA-binding activity is required to escape
CC host ZBP1-dependent necroptosis (By similarity). Mechanistically, the
CC Z-binding domain binds Z-RNAs that are produced during vaccinia virus
CC infection, thereby competing with Z-RNA detection by host ZBP1,
CC suppressing ZBP1-dependent necroptosis (By similarity). Acts as a key
CC inhibitor of the interferon response by blocking the phosphorylation
CC and subsequent activation of IRF3 and IRF7 kinases that are required
CC for interferon-alpha gene expression (PubMed:11124948,
CC PubMed:15207627). Inhibits NF-kappa-B activation and the ubiquitin-like
CC protein ISG15, which is an early antiviral protein (By similarity). The
CC binding with host ISG15 subsequently blocks host ISGylation (By
CC similarity). {ECO:0000250|UniProtKB:P21605,
CC ECO:0000269|PubMed:11124948, ECO:0000269|PubMed:15207627}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Long;
CC IsoId=P21081-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P21081-2; Sequence=VSP_018956;
CC -!- DEVELOPMENTAL STAGE: Detected at early times, by 2 hours post
CC infection, peaks at 5 hours post infection, and decreases during the
CC late phase of virus replication. {ECO:0000269|PubMed:11124948}.
CC -!- DOMAIN: The Z-binding domain recognizes and binds Z-RNA structures.
CC {ECO:0000250|UniProtKB:P21605}.
CC -!- SIMILARITY: Belongs to the poxviridae E3 protein family. {ECO:0000305}.
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DR EMBL; M35027; AAA48040.1; -; Genomic_DNA.
DR PIR; G42508; G42508.
DR SMR; P21081; -.
DR Proteomes; UP000008269; Genome.
DR GO; GO:0003726; F:double-stranded RNA adenosine deaminase activity; IEA:InterPro.
DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0019050; P:suppression by virus of host apoptotic process; ISS:UniProtKB.
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; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Alternative initiation; Host-virus interaction;
KW 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="RNA-binding protein E3"
FT /id="PRO_0000099447"
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"
FT VAR_SEQ 1..37
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_018956"
SQ SEQUENCE 190 AA; 21504 MW; 470D0610ACB4D44F CRC64;
MSKIYIDERS DAEIVCAAIK NIGIEGATAA QLTRQLNMEK REVNKALYDL QRSAMVYSSD
DIPPRWFMTT EADKPDADAM ADVIIDDVSR EKSMREDHKS FDDVIPAKKI IDWKDANPVT
IINEYCQITK RDWSFRIESV GPSNSPTFYA CVDIDGRVFD KADGKSKRDA KNNAAKLAVD
KLLGYVIIRF
