ID   A46_VACCC               Reviewed;         214 AA.
AC   P21066;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   23-FEB-2022, entry version 58.
DE   RecName: Full=Protein A46;
GN   ORFNames=A46R;
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).
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; M35027; AAA48177.1; -; Genomic_DNA.
DR   PIR; C42522; C42522.
DR   SMR; P21066; -.
DR   Proteomes; UP000008269; 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..214
FT                   /note="Protein A46"
FT                   /id="PRO_0000099334"
SQ   SEQUENCE   214 AA;  24684 MW;  8738EC4CEBD703E9 CRC64;
     MAFDISVNAS KTINALVYFS TQQNKLVIRN EVNDTHYTVE FDRDKVVDTF ISYNRHNDTI
     EIRGVLPEET NIGCAVNTPV SMTYLYNKYS FKLILAEYIR HRNTISGNIY SALMTLDDLA
     IKQYGDIDLL FNEKLKVDSD SGLFDFVNFV KDMICCDSRI VVALSSLVSK HWELTNKKYR
     CMALANIYLI VFQYLSYLDY DTIYVSIYAG TLRA