A46_VACCW
ID A46_VACCW Reviewed; 240 AA.
AC P26672; Q76ZN1;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 23-FEB-2022, entry version 68.
DE RecName: Full=Protein A46;
GN OrderedLocusNames=VACWR172; ORFNames=A46R;
OS Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain
OS WR)).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus; Vaccinia virus.
OX NCBI_TaxID=10254;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1870190; DOI=10.1128/jvi.65.9.4598-4608.1991;
RA Blasco R., Cole N.B., Moss B.;
RT "Sequence analysis, expression, and deletion of a vaccinia virus gene
RT encoding a homolog of profilin, a eukaryotic actin-binding protein.";
RL J. Virol. 65:4598-4608(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2045793; DOI=10.1099/0022-1317-72-6-1349;
RA Smith G.L., Chan Y.S., Howard S.T.;
RT "Nucleotide sequence of 42 kbp of vaccinia virus strain WR from near the
RT right inverted terminal repeat.";
RL J. Gen. Virol. 72:1349-1376(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Esposito J.J., Frace A.M., Sammons S.A., Olsen-Rasmussen M., Osborne J.,
RA Wohlhueter R.;
RT "Sequencing of the coding region of Vaccinia-WR to an average 9-fold
RT redundancy and an error rate of 0.16/10kb.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16509968; DOI=10.1186/1743-422x-3-10;
RA Yoder J.D., Chen T.S., Gagnier C.R., Vemulapalli S., Maier C.S.,
RA Hruby D.E.;
RT "Pox proteomics: mass spectrometry analysis and identification of Vaccinia
RT virion proteins.";
RL Virol. J. 3:10-10(2006).
RN [5]
RP FUNCTION, AND INTERACTION WITH HOST MYD88; TRF4; TICAM2 AND MAL.
RX PubMed=20802145; DOI=10.4049/jimmunol.1002013;
RA Lysakova-Devine T., Keogh B., Harrington B., Nagpal K., Halle A.,
RA Golenbock D.T., Monie T., Bowie A.G.;
RT "Viral inhibitory peptide of TLR4, a peptide derived from vaccinia protein
RT A46, specifically inhibits TLR4 by directly targeting MyD88 adaptor-like
RT and TRIF-related adaptor molecule.";
RL J. Immunol. 185:4261-4271(2010).
RN [6]
RP FUNCTION, AND SUBUNIT.
RX PubMed=27973613; DOI=10.1371/journal.ppat.1006079;
RA Fedosyuk S., Bezerra G.A., Radakovics K., Smith T.K., Sammito M., Bobik N.,
RA Round A., Ten Eyck L.F., Djinovic-Carugo K., Uson I., Skern T.;
RT "Vaccinia Virus Immunomodulator A46: A Lipid and Protein-Binding Scaffold
RT for Sequestering Host TIR-Domain Proteins.";
RL PLoS Pathog. 12:E1006079-E1006079(2016).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 87-229.
RX PubMed=24356965; DOI=10.1074/jbc.m113.512756;
RA Fedosyuk S., Grishkovskaya I., de Almeida Ribeiro E. Jr., Skern T.;
RT "Characterization and structure of the vaccinia virus NF-kappaB antagonist
RT A46.";
RL J. Biol. Chem. 289:3749-3762(2014).
CC -!- FUNCTION: BCL2-like protein which disrupts the host immune response by
CC inhibiting the TLR4 signaling pathway leading to NF-kappa-B activation.
CC Acts close to the plasma membrane and targets several host TIR-domain
CC containing adaptor proteins including MYD88, TIRAP, TRIF and TICAM2. In
CC turn, blocks the host NF-kappa-B and TRIF-mediated IRF3 activation.
CC {ECO:0000269|PubMed:20802145, ECO:0000269|PubMed:27973613}.
CC -!- SUBUNIT: Tetramer (PubMed:27973613). Interacts with host MYD88, TRF4,
CC TICAM2 and MAL (PubMed:20802145). {ECO:0000269|PubMed:20802145,
CC ECO:0000269|PubMed:27973613}.
CC -!- SIMILARITY: Belongs to the poxviridae A46R protein family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M72474; AAA48313.1; -; Genomic_DNA.
DR EMBL; D11079; BAA01820.1; -; Genomic_DNA.
DR EMBL; AY243312; AAO89451.1; -; Genomic_DNA.
DR PIR; JQ1784; JQ1784.
DR RefSeq; YP_233054.1; NC_006998.1.
DR PDB; 4LQK; X-ray; 1.99 A; A/B/C/D=87-229.
DR PDB; 5EZU; X-ray; 1.55 A; A/B=1-83.
DR PDBsum; 4LQK; -.
DR PDBsum; 5EZU; -.
DR SASBDB; P26672; -.
DR SMR; P26672; -.
DR ELM; P26672; -.
DR DNASU; 3707702; -.
DR GeneID; 3707702; -.
DR KEGG; vg:3707702; -.
DR Proteomes; UP000000344; 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 1: Evidence at protein level;
KW 3D-structure; Host-virus interaction;
KW 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_0000099335"
FT STRAND 2..8
FT /evidence="ECO:0007829|PDB:5EZU"
FT STRAND 13..20
FT /evidence="ECO:0007829|PDB:5EZU"
FT TURN 21..24
FT /evidence="ECO:0007829|PDB:5EZU"
FT STRAND 25..32
FT /evidence="ECO:0007829|PDB:5EZU"
FT STRAND 35..41
FT /evidence="ECO:0007829|PDB:5EZU"
FT STRAND 47..54
FT /evidence="ECO:0007829|PDB:5EZU"
FT TURN 55..58
FT /evidence="ECO:0007829|PDB:5EZU"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:5EZU"
FT STRAND 71..75
FT /evidence="ECO:0007829|PDB:5EZU"
FT HELIX 91..101
FT /evidence="ECO:0007829|PDB:4LQK"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:4LQK"
FT HELIX 108..114
FT /evidence="ECO:0007829|PDB:4LQK"
FT HELIX 117..124
FT /evidence="ECO:0007829|PDB:4LQK"
FT HELIX 127..132
FT /evidence="ECO:0007829|PDB:4LQK"
FT TURN 133..135
FT /evidence="ECO:0007829|PDB:4LQK"
FT HELIX 142..150
FT /evidence="ECO:0007829|PDB:4LQK"
FT TURN 151..156
FT /evidence="ECO:0007829|PDB:4LQK"
FT HELIX 158..173
FT /evidence="ECO:0007829|PDB:4LQK"
FT TURN 174..176
FT /evidence="ECO:0007829|PDB:4LQK"
FT HELIX 178..191
FT /evidence="ECO:0007829|PDB:4LQK"
FT HELIX 194..208
FT /evidence="ECO:0007829|PDB:4LQK"
SQ SEQUENCE 240 AA; 27635 MW; 0D5F3324E187A665 CRC64;
MAFDISVNAS KTINALVYFS TQQNKLVIRN EVNDTHYTVE FDRDKVVDTF ISYNRHNDTI
EIRGVLPEET NIGCAVNTPV SMTYLYNKYS FKLILAEYIR HRNTISGNIY SALMTLDDLA
IKQYGDIDLL FNEKLKVDSD SGLFDFVNFV KDMICCDSRI VVALSSLVSK HWELTNKKYR
CMALAEHISD SIPISELSRL RYNLCKYLRG HTESIEDKFD YFEDDDSSTC SAVTDRETDV
