ID   A46_VAR67               Reviewed;         240 AA.
AC   P33876;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1994, sequence version 1.
DT   03-AUG-2022, entry version 60.
DE   RecName: Full=Protein A46;
GN   ORFNames=A46R, A52R;
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=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: Bcl-2-like protein which disrupts the host immune response by
CC       inhibiting the TLR4 signaling pathway leading to NF-kappa-B activation.
CC       Targets several host TIR adapters including MYD88, TIRAP, TRIF and
CC       TICAM2 thereby blocking NF-kappa-B and TRIF-mediated IRF3 activation
CC       (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Interacts with host MYD88, TRF4, TICAM2 and MAL.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the poxviridae A46R protein family.
CC       {ECO:0000305}.
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DR   EMBL; X69198; CAA49099.1; -; Genomic_DNA.
DR   PIR; H36853; H36853.
DR   RefSeq; NP_042202.1; NC_001611.1.
DR   SMR; P33876; -.
DR   GeneID; 1486534; -.
DR   KEGG; vg:1486534; -.
DR   Proteomes; UP000002060; Genome.
DR   GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; 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   Gene3D; 1.10.437.20; -; 1.
DR   InterPro; IPR022819; Poxvirus_Bcl-2-like.
DR   InterPro; IPR043018; Poxvirus_sf.
DR   Pfam; PF06227; Poxvirus; 1.
PE   3: Inferred from homology;
KW   Host-virus interaction; Inhibition of host innate immune response by virus;
KW   Inhibition of host IRF3 by virus; Inhibition of host NF-kappa-B by virus;
KW   Inhibition of host RLR pathway by virus; Reference proteome;
KW   Viral immunoevasion.
FT   CHAIN           1..240
FT                   /note="Protein A46"
FT                   /id="PRO_0000099336"
SQ   SEQUENCE   240 AA;  27644 MW;  4770ACC202D5F04C CRC64;
     MAFDISVNAS KTINALVYFS TQQNKLVIRN EVNDTHYTVE FDRDKVVDTF ISYNRHNDSI
     EIRGVLPEET NIGCTVNTPV SMTYLYNKYS FKLILAEYIR HRNTVSGNIY SALMTLDDLV
     IKQYGDIDLL FNEKLKVDSD SGLFDFVNFV KDIICCDSRI VVALSSLVSK HWELTNKKYR
     CMALAEHIAD SIPISELSRP RYNLCKYLRG HTESIEDEFD YFEDDDSSTC SVVTDRETDV