POXIN_VACCW
ID POXIN_VACCW Reviewed; 219 AA.
AC Q01225; Q76ZM1;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 23-FEB-2022, entry version 49.
DE RecName: Full=Poxin {ECO:0000255|HAMAP-Rule:MF_04143, ECO:0000303|PubMed:30728498};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_04143, ECO:0000269|PubMed:30728498};
DE AltName: Full=Immune nuclease {ECO:0000303|PubMed:30728498};
DE AltName: Full=Protein B2;
GN OrderedLocusNames=VACWR184; ORFNames=B2R;
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 [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 X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH NONHYDROLYZABLE 2'3'
RP CGAMP, FUNCTION, DOMAIN, CATALYTIC ACTIVITY, SUBUNIT, ACTIVE SITE,
RP DISRUPTION PHENOTYPE, MUTAGENESIS OF HIS-17; ARG-60; TYR-138; LYS-142;
RP GLN-169; ARG-182; ARG-184 AND LYS-186, AND REACTION MECHANISM.
RX PubMed=30728498; DOI=10.1038/s41586-019-0928-6;
RA Eaglesham J.B., Pan Y., Kupper T.S., Kranzusch P.J.;
RT "Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS-
RT STING signalling.";
RL Nature 566:259-263(2019).
CC -!- FUNCTION: Nuclease that is responsible for viral evasion of host cGAS-
CC STING innate immunity (PubMed:30728498). Cleaves 2',3'-cGAMP which is
CC produced by host cGAS following recognition of cytosolic DNA and blocks
CC the subsequent 2',3'-cGAMP-mediated activation of TMEM173/STING, which
CC normally spreads to adjacent cells and activates the interferon and NF-
CC kappa-B immune responses (PubMed:30728498).
CC {ECO:0000269|PubMed:30728498}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2',3'-cGAMP + H2O = Gp(2'-5')Ap(3') + H(+);
CC Xref=Rhea:RHEA:59472, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:143093, ChEBI:CHEBI:143098; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_04143, ECO:0000269|PubMed:30728498};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59473;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04143,
CC ECO:0000305|PubMed:30728498};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_04143,
CC ECO:0000269|PubMed:30728498}.
CC -!- DOMAIN: The substrate binding site is formed by the N-terminus of a
CC monomer and the C-terminus of the opposite monomer. {ECO:0000255|HAMAP-
CC Rule:MF_04143, ECO:0000269|PubMed:30728498}.
CC -!- DISRUPTION PHENOTYPE: Knockout induces a 40 fold decreased replication
CC of the virus. {ECO:0000269|PubMed:30728498}.
CC -!- SIMILARITY: Belongs to the poxin family. {ECO:0000255|HAMAP-
CC Rule:MF_04143}.
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DR EMBL; D11079; BAA01832.1; -; Genomic_DNA.
DR EMBL; AY243312; AAO89463.1; -; Genomic_DNA.
DR PIR; JQ1796; JQ1796.
DR RefSeq; YP_233066.1; NC_006998.1.
DR PDB; 6EA6; X-ray; 1.70 A; A/B/C/D=1-219.
DR PDB; 6EA8; X-ray; 2.60 A; A/B/C/D/E/F/G/H/I/J=1-219.
DR PDB; 6EA9; X-ray; 2.10 A; A/B/C/D/E=1-219.
DR PDBsum; 6EA6; -.
DR PDBsum; 6EA8; -.
DR PDBsum; 6EA9; -.
DR SMR; Q01225; -.
DR PRIDE; Q01225; -.
DR DNASU; 3707655; -.
DR GeneID; 3707655; -.
DR KEGG; vg:3707655; -.
DR Proteomes; UP000000344; Genome.
DR GO; GO:0061507; F:2',3'-cyclic GMP-AMP binding; IMP:UniProtKB.
DR GO; GO:0004518; F:nuclease activity; IMP:UniProtKB.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IMP:UniProtKB.
DR HAMAP; MF_04143; Poxins; 1.
DR InterPro; IPR006853; Poxin_vir.
DR Pfam; PF04766; Baculo_p26; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Nuclease; Reference proteome.
FT CHAIN 1..219
FT /note="Poxin"
FT /id="PRO_0000099354"
FT ACT_SITE 17
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143,
FT ECO:0000269|PubMed:30728498"
FT ACT_SITE 138
FT /note="Shared with catalytic histidine of dimeric partner"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143,
FT ECO:0000269|PubMed:30728498"
FT ACT_SITE 142
FT /note="Proton acceptor; shared with catalytic histidine of
FT dimeric partner"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143,
FT ECO:0000269|PubMed:30728498"
FT SITE 60
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143,
FT ECO:0000269|PubMed:30728498"
FT SITE 105
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143,
FT ECO:0000269|PubMed:30728498"
FT SITE 149
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143,
FT ECO:0000269|PubMed:30728498"
FT SITE 169
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143,
FT ECO:0000269|PubMed:30728498"
FT SITE 182
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143,
FT ECO:0000269|PubMed:30728498"
FT SITE 184
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143,
FT ECO:0000269|PubMed:30728498"
FT SITE 186
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143,
FT ECO:0000269|PubMed:30728498"
FT MUTAGEN 17
FT /note="H->A: Complete loss of 2',3'-cGAMP cleavage."
FT /evidence="ECO:0000269|PubMed:30728498"
FT MUTAGEN 60
FT /note="R->A: Stalls the 2',3'-cGAMP cleavage reaction at an
FT intermediary stage."
FT /evidence="ECO:0000269|PubMed:30728498"
FT MUTAGEN 138
FT /note="Y->A: Stalls the 2',3'-cGAMP cleavage reaction at an
FT intermediary stage."
FT /evidence="ECO:0000269|PubMed:30728498"
FT MUTAGEN 142
FT /note="K->A: Complete loss of 2',3'-cGAMP cleavage."
FT /evidence="ECO:0000269|PubMed:30728498"
FT MUTAGEN 169
FT /note="Q->A: No effect on 2',3'-cGAMP cleavage reaction."
FT /evidence="ECO:0000269|PubMed:30728498"
FT MUTAGEN 182
FT /note="R->A: Stalls the 2',3'-cGAMP cleavage reaction at an
FT intermediary stage."
FT /evidence="ECO:0000269|PubMed:30728498"
FT MUTAGEN 184
FT /note="R->A: Complete loss of 2',3'-cGAMP cleavage."
FT /evidence="ECO:0000269|PubMed:30728498"
FT MUTAGEN 186
FT /note="K->A: Stalls the 2',3'-cGAMP cleavage reaction at an
FT intermediary stage."
FT /evidence="ECO:0000269|PubMed:30728498"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:6EA6"
FT HELIX 7..9
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 16..19
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 22..26
FT /evidence="ECO:0007829|PDB:6EA6"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 50..57
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 60..66
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 99..101
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 107..113
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 118..124
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:6EA6"
FT HELIX 138..149
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 158..166
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 168..173
FT /evidence="ECO:0007829|PDB:6EA6"
FT STRAND 179..185
FT /evidence="ECO:0007829|PDB:6EA6"
SQ SEQUENCE 219 AA; 24625 MW; 67D5099D4C9357B2 CRC64;
MAMFYAHALG GYDENLHAFP GISSTVANDV RKYSVVSVYN NKYDIVKDKY MWCYSQVNKR
YIGALLPMFE CNEYLQIGDP IHDQEGNQIS IITYRHKNYY ALSGIGYESL DLCLEGVGIH
HHVLETGNAV YGKVQHDYST IKEKAKEMNA LSPGPIIDYH VWIGDCICQV TAVDVHGKEI
MRMRFKKGAV LPIPNLVKVK LGENDTENLS STISAAPSR
