POXIN_VACCA
ID POXIN_VACCA Reviewed; 219 AA.
AC Q6J362; A9J129;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 22-APR-2020, sequence version 2.
DT 23-FEB-2022, entry version 26.
DE RecName: Full=Poxin {ECO:0000255|HAMAP-Rule:MF_04143, ECO:0000303|PubMed:30728498};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_04143};
DE AltName: Full=Immune nuclease {ECO:0000250|UniProtKB:Q01225};
DE AltName: Full=Protein CVA194 {ECO:0000312|EMBL:CAM58358.1};
GN ORFNames=ACAM3000_MVA_168 {ECO:0000312|EMBL:AAT10566.1},
GN CVA194 {ECO:0000312|EMBL:CAM58358.1};
OS Vaccinia virus (strain Ankara) (VACV).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus; Vaccinia virus.
OX NCBI_TaxID=126794;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Vaccine Acambis 3000 Modified Virus Ankara (MVA)
RC {ECO:0000312|EMBL:AAT10566.1};
RA Esposito J.J., Frace M., Sammons S.A., Olsen-Rasmussen M.S., Osborne J.,
RA Khristova M., Wohlhueter R.M.;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|EMBL:CAM58358.1, ECO:0000312|Proteomes:UP000136916}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Chorioallantois vaccinia virus Ankara {ECO:0000312|EMBL:CAM58358.1};
RX PubMed=18024893; DOI=10.1099/vir.0.83156-0;
RA Meisinger-Henschel C., Schmidt M., Lukassen S., Linke B., Krause L.,
RA Konietzny S., Goesmann A., Howley P., Chaplin P., Suter M., Hausmann J.;
RT "Genomic sequence of chorioallantois vaccinia virus Ankara, the ancestor of
RT modified vaccinia virus Ankara.";
RL J. Gen. Virol. 88:3249-3259(2007).
RN [3]
RP CAUTION.
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. Cleaves 2',3'-cGAMP which is produced by host
CC cGAS following recognition of cytosolic DNA and blocks the subsequent
CC 2',3'-cGAMP-mediated activation of TMEM173/STING, which normally
CC spreads to adjacent cells and activates the interferon and NF-kappa-B
CC immune responses. {ECO:0000255|HAMAP-Rule:MF_04143}.
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59473;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04143};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_04143}.
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}.
CC -!- MISCELLANEOUS: The sequence shown comes from the strain chorioallantois
CC vaccinia virus Ankara (CVA), which is the ancestor strain of the
CC modified vaccinia virus Ankara (MVA). {ECO:0000269|PubMed:18024893}.
CC -!- SIMILARITY: Belongs to the poxin family. {ECO:0000255|HAMAP-
CC Rule:MF_04143}.
CC -!- CAUTION: The truncated poxin of the Modified Virus Ankara (MVA) is
CC probably non-functional, since part of its active site is missing.
CC {ECO:0000305|PubMed:30728498}.
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DR EMBL; AY603355; AAT10566.1; -; Genomic_DNA.
DR EMBL; AM501482; CAM58358.1; -; Genomic_DNA.
DR SMR; Q6J362; -.
DR Proteomes; UP000136916; Genome.
DR Proteomes; UP000172909; Genome.
DR GO; GO:0061507; F:2',3'-cyclic GMP-AMP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004518; F:nuclease activity; IEA:UniProtKB-UniRule.
DR GO; GO:0039503; P:suppression by virus of host innate immune response; IEA:UniProtKB-UniRule.
DR HAMAP; MF_04143; Poxins; 1.
DR InterPro; IPR006853; Poxin_vir.
DR Pfam; PF04766; Baculo_p26; 1.
PE 3: Inferred from homology;
KW Hydrolase; Nuclease.
FT CHAIN 1..219
FT /note="Poxin"
FT /id="PRO_0000446975"
FT ACT_SITE 17
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT ACT_SITE 138
FT /note="Shared with catalytic histidine of dimeric partner"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
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 SITE 60
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT SITE 105
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT SITE 169
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT SITE 182
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT SITE 184
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT SITE 186
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT VARIANT 1..91
FT /note="MAMFYAHALGGYDENLHAFPGISSTVANDVRKYSVVSVYNNKYDIVKDKYMW
FT CYSQVNKRYIGALLPMFECNEYLQIGDPIHDQEGNQISI -> MNIYKLEIRSMIKKE
FT (in strain: Vaccine Acambis 3000 Modified Virus Ankara
FT (ACAM3000))"
FT /evidence="ECO:0000269|PubMed:18024893"
FT VARIANT 127
FT /note="G -> E (in strain: Vaccine Acambis 3000 Modified
FT Virus Ankara (ACAM3000))"
FT /evidence="ECO:0000269|PubMed:18024893"
FT VARIANT 149..153
FT /note="STLSP -> NALSS (in strain: Vaccine Acambis 3000
FT Modified Virus Ankara (ACAM3000))"
FT /evidence="ECO:0000269|PubMed:18024893"
SQ SEQUENCE 219 AA; 24628 MW; EEDE3BB44C8F2A23 CRC64;
MAMFYAHALG GYDENLHAFP GISSTVANDV RKYSVVSVYN NKYDIVKDKY MWCYSQVNKR
YIGALLPMFE CNEYLQIGDP IHDQEGNQIS IITYRHKNYY ALSGIGYESL DLCLEGVGIH
HHVLETGNAV YGKVQHDYST IKEKAKEMST LSPGPIIDYH VWIGDCICQV TAVDVHGKEI
MRMRFKKGAV LPIPNLVKVK LGENDTENLS STISAAPSR
