ID   B14_VACCW               Reviewed;         149 AA.
AC   P24772; Q76ZK9;
DT   01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-1992, sequence version 1.
DT   25-MAY-2022, entry version 82.
DE   RecName: Full=Protein B14;
GN   OrderedLocusNames=VACWR196; ORFNames=B14R;
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=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   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1846491; DOI=10.1016/0042-6822(91)90077-o;
RA   Howard S.T., Chan Y.S., Smith G.L.;
RT   "Vaccinia virus homologues of the Shope fibroma virus inverted terminal
RT   repeat proteins and a discontinuous ORF related to the tumor necrosis
RT   factor receptor family.";
RL   Virology 180:633-647(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   INTERACTION WITH HOST IKBKB.
RX   PubMed=18266467; DOI=10.1371/journal.ppat.0040022;
RA   Chen R.A., Ryzhakov G., Cooray S., Randow F., Smith G.L.;
RT   "Inhibition of IkappaB kinase by vaccinia virus virulence factor B14.";
RL   PLoS Pathog. 4:E22-E22(2008).
RN   [5]
RP   SIMILARITY.
RX   PubMed=20230632; DOI=10.1186/1743-422x-7-59;
RA   Gonzalez J.M., Esteban M.;
RT   "A poxvirus Bcl-2-like gene family involved in regulation of host immune
RT   response: sequence similarity and evolutionary history.";
RL   Virol. J. 7:59-59(2010).
RN   [6]
RP   FUNCTION, SUBUNIT, AND MUTAGENESIS OF TYR-35 AND PHE-130.
RX   PubMed=21474453; DOI=10.1074/jbc.m111.231381;
RA   Benfield C.T., Mansur D.S., McCoy L.E., Ferguson B.J., Bahar M.W.,
RA   Oldring A.P., Grimes J.M., Stuart D.I., Graham S.C., Smith G.L.;
RT   "Mapping the I{kappa}B Kinase {beta} (IKK{beta})-binding interface of the
RT   B14 protein, a vaccinia virus inhibitor of IKK{beta}-mediated activation of
RT   nuclear factor {kappa}B.";
RL   J. Biol. Chem. 286:20727-20735(2011).
RN   [7]
RP   FUNCTION, AND INTERACTION WITH HOST IKBKB.
RX   PubMed=29748387; DOI=10.1074/jbc.ra118.002817;
RA   Tang Q., Chakraborty S., Xu G.;
RT   "Mechanism of vaccinia viral protein B14 mediated inhibition of IkappaB
RT   kinase beta activation.";
RL   J. Biol. Chem. 293:10344-10352(2018).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.69 ANGSTROMS).
RX   PubMed=18704168; DOI=10.1371/journal.ppat.1000128;
RA   Graham S.C., Bahar M.W., Cooray S., Chen R.A., Whalen D.M., Abrescia N.G.,
RA   Alderton D., Owens R.J., Stuart D.I., Smith G.L., Grimes J.M.;
RT   "Vaccinia virus proteins A52 and B14 Share a Bcl-2-like fold but have
RT   evolved to inhibit NF-kappaB rather than apoptosis.";
RL   PLoS Pathog. 4:E1000128-E1000128(2008).
CC   -!- FUNCTION: Contributes to virulence by binding to the host IKBKB subunit
CC       of the IKK complex and preventing host NF-kappa-B activation in
CC       response to pro-inflammatory stimuli such as TNF-alpha or IL1B.
CC       Mechanistically, sterically hinders the direct contact between the
CC       kinase domains of IKBKB in the IKK complex containing IKBKB, CHUK/IKKA
CC       and NEMO (PubMed:29748387). {ECO:0000269|PubMed:21474453,
CC       ECO:0000269|PubMed:29748387}.
CC   -!- SUBUNIT: Homodimers. Interaction with host IKBKB; this interaction
CC       inhibits host NF-kappa-B activation. {ECO:0000269|PubMed:21474453,
CC       ECO:0000269|PubMed:29748387}.
CC   -!- INTERACTION:
CC       P24772; O15111: CHUK; Xeno; NbExp=3; IntAct=EBI-4291651, EBI-81249;
CC       P24772; O14920: IKBKB; Xeno; NbExp=3; IntAct=EBI-4291651, EBI-81266;
CC       P24772; O88522: Ikbkg; Xeno; NbExp=2; IntAct=EBI-4291651, EBI-998011;
CC   -!- SIMILARITY: Belongs to the orthopoxvirus B14 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; D11079; BAA01844.1; -; Genomic_DNA.
DR   EMBL; M58053; AAA47964.1; -; Genomic_DNA.
DR   EMBL; AY243312; AAO89475.1; -; Genomic_DNA.
DR   PIR; JQ1808; JQ1808.
DR   RefSeq; YP_233078.1; NC_006998.1.
DR   PDB; 2VVY; X-ray; 2.69 A; A/B/C/D=1-149.
DR   PDBsum; 2VVY; -.
DR   SMR; P24772; -.
DR   IntAct; P24772; 17.
DR   DNASU; 3707573; -.
DR   GeneID; 3707573; -.
DR   KEGG; vg:3707573; -.
DR   EvolutionaryTrace; P24772; -.
DR   Proteomes; UP000000344; Genome.
DR   GO; GO:0039644; P:suppression by virus of host NF-kappaB cascade; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.437.20; -; 1.
DR   InterPro; IPR011212; Poxvirus_B14/B22/C16.
DR   InterPro; IPR022819; Poxvirus_Bcl-2-like.
DR   InterPro; IPR043018; Poxvirus_sf.
DR   Pfam; PF06227; Poxvirus; 1.
DR   PIRSF; PIRSF017324; UCP017324; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Early protein; Host-virus interaction;
KW   Inhibition of host NF-kappa-B by virus; Reference proteome.
FT   CHAIN           1..149
FT                   /note="Protein B14"
FT                   /id="PRO_0000099365"
FT   MUTAGEN         35
FT                   /note="Y->E: Disrupts self-association."
FT                   /evidence="ECO:0000269|PubMed:21474453"
FT   MUTAGEN         130
FT                   /note="F->K: Disrupts self-association and NF-kappa-B
FT                   inhibition by B14."
FT                   /evidence="ECO:0000269|PubMed:21474453"
FT   HELIX           23..25
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   HELIX           26..36
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   TURN            37..39
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   HELIX           40..42
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   HELIX           49..55
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   HELIX           57..65
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   HELIX           68..74
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   HELIX           80..90
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   HELIX           98..115
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   STRAND          118..120
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   HELIX           123..135
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   HELIX           138..144
FT                   /evidence="ECO:0007829|PDB:2VVY"
FT   HELIX           145..147
FT                   /evidence="ECO:0007829|PDB:2VVY"
SQ   SEQUENCE   149 AA;  17382 MW;  A6118A960A0B6973 CRC64;
     MTANFSTHVF SPQHCGCDRL TSIDDVRQCL TEYIYWSSYA YRNRQCAGQL YSTLLSFRDD
     AELVFIDIRE LVKNMPWDDV KDCAEIIRCY IPDEQKTIRE ISAIIGLCAY AATYWGGEDH
     PTSNSLNALF VMLEMLNYVD YNIIFRRMN