ID   C6_VACCW                Reviewed;         151 AA.
AC   P17362; Q76ZY6;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   23-FEB-2022, entry version 62.
DE   RecName: Full=Protein C6;
GN   OrderedLocusNames=VACWR022; ORFNames=C6L;
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=2849238; DOI=10.1016/s0042-6822(88)90115-8;
RA   Kotwal G.J., Moss B.;
RT   "Analysis of a large cluster of nonessential genes deleted from a vaccinia
RT   virus terminal transposition mutant.";
RL   Virology 167:524-537(1988).
RN   [2]
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   [3]
RP   FUNCTION, AND INTERACTION WITH HOST TANK; TBKBP1 AND AZI2.
RX   PubMed=21931555; DOI=10.1371/journal.ppat.1002247;
RA   Unterholzner L., Sumner R.P., Baran M., Ren H., Mansur D.S., Bourke N.M.,
RA   Randow F., Smith G.L., Bowie A.G.;
RT   "Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor
RT   proteins and inhibits activation of IRF3 and IRF7.";
RL   PLoS Pathog. 7:E1002247-E1002247(2011).
RN   [4]
RP   FUNCTION, AND INTERACTION WITH HOST STAT2.
RX   PubMed=27907166; DOI=10.1371/journal.ppat.1005955;
RA   Stuart J.H., Sumner R.P., Lu Y., Snowden J.S., Smith G.L.;
RT   "Vaccinia Virus Protein C6 Inhibits Type I IFN Signalling in the Nucleus
RT   and Binds to the Transactivation Domain of STAT2.";
RL   PLoS Pathog. 12:E1005955-E1005955(2016).
CC   -!- FUNCTION: Prevents establishment of cellular antiviral state by
CC       blocking virus-induced phosphorylation and activation of interferon
CC       regulatory factors 3/IRF3 and 7/IRF7, transcription factors critical
CC       for the induction of interferons alpha and beta. This blockage is
CC       produced through the inhibition of host TBK1, by binding host TBK1
CC       adapter proteins TBKBP1 and AZI2, thereby producing a strong inhibition
CC       of the phosphorylation and activation of IRF3 and IRF7. Acts also as an
CC       inhibitor of the cellular response to type I IFN by interacting with
CC       host STAT2. Mechanistically, exerts its inhibitory effect after host
CC       ISGF3 complex (composed of STAT1, STAT2 and IRF9) binding to the
CC       interferon stimulated response element (ISRE).
CC       {ECO:0000269|PubMed:21931555, ECO:0000269|PubMed:27907166}.
CC   -!- SUBUNIT: Interacts with host TANK, TBKBP1 AND AZI2; these interactions
CC       prevent interferon production (PubMed:21931555). Interacts with host
CC       STAT2 (PubMed:27907166). {ECO:0000269|PubMed:21931555,
CC       ECO:0000269|PubMed:27907166}.
CC   -!- INTERACTION:
CC       P17362; Q9H6S1: AZI2; Xeno; NbExp=2; IntAct=EBI-9519257, EBI-359973;
CC       P17362; Q92844: TANK; Xeno; NbExp=2; IntAct=EBI-9519257, EBI-356349;
CC       P17362; A7MCY6: TBKBP1; Xeno; NbExp=2; IntAct=EBI-9519257, EBI-359969;
CC   -!- SIMILARITY: Belongs to the orthopoxvirus C6 protein family.
CC       {ECO:0000305}.
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DR   EMBL; M22812; AAA69602.1; -; Genomic_DNA.
DR   EMBL; AY243312; AAO89301.1; -; Genomic_DNA.
DR   PIR; B33348; WZVZB2.
DR   RefSeq; YP_232904.1; NC_006998.1.
DR   SMR; P17362; -.
DR   IntAct; P17362; 3.
DR   DNASU; 3707637; -.
DR   GeneID; 3707637; -.
DR   KEGG; vg:3707637; -.
DR   Proteomes; UP000000344; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IDA:UniProtKB.
DR   GO; GO:0042025; C:host cell nucleus; IDA:UniProtKB.
DR   GO; GO:0039722; P:suppression by virus of host toll-like receptor signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IDA:UniProtKB.
DR   GO; GO:0039723; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity; IDA:UniProtKB.
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   Early protein; 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 TBK1 by virus; Inhibition of host TLR pathway by virus;
KW   Reference proteome; Viral immunoevasion.
FT   CHAIN           1..151
FT                   /note="Protein C6"
FT                   /id="PRO_0000099384"
SQ   SEQUENCE   151 AA;  17322 MW;  27E1BD3C222AF5DE CRC64;
     MNAYNKADSF SLESDSIKDV IHDYICWLSM TDEMRPSIGN VFKAMETFKI DAVRYYDGNI
     YELAKDINAM SFDGFIRSLQ TIASKKDKLT VYGTMGLLSI VVDINKGCDI SNIKFAAGII
     ILMEYIFDDT DMSHLKVALY RRIQRRDDVD R