POXIN_MONPZ
ID POXIN_MONPZ Reviewed; 503 AA.
AC Q8V4S4;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 23-FEB-2022, entry version 51.
DE RecName: Full=Poxin-Schlafen {ECO:0000255|HAMAP-Rule:MF_04143, ECO:0000303|PubMed:30728498};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_04143, ECO:0000269|PubMed:30728498};
GN Name=B4R {ECO:0000312|EMBL:AAL40623.1};
OS Monkeypox virus (strain Zaire-96-I-16) (MPX).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus.
OX NCBI_TaxID=619591;
OH NCBI_TaxID=45479; Cynomys gunnisoni (Gunnison's prairie dog).
OH NCBI_TaxID=99825; Cynomys leucurus (White-tailed prairie dog).
OH NCBI_TaxID=45480; Cynomys ludovicianus (Black-tailed prairie dog).
OH NCBI_TaxID=99826; Cynomys mexicanus (Mexican prairie dog).
OH NCBI_TaxID=99827; Cynomys parvidens (Utah prairie dog).
OH NCBI_TaxID=30650; Gliridae (dormice).
OH NCBI_TaxID=226685; Heliosciurus ruwenzorii (Ruwenzori sun squirrel).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11734207; DOI=10.1016/s0014-5793(01)03144-1;
RA Shchelkunov S.N., Totmenin A.V., Babkin I.V., Safronov P.F.,
RA Ryazankina O.I., Petrov N.A., Gutorov V.V., Uvarova E.A., Mikheev M.V.,
RA Sisler J.R., Esposito J.J., Jahrling P.B., Moss B., Sandakhchiev L.S.;
RT "Human monkeypox and smallpox viruses: genomic comparison.";
RL FEBS Lett. 509:66-70(2001).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 intracellular foreign
CC DNA and blocks the subsequent 2',3'-cGAMP-mediated activation of
CC TMEM173/STING which normally spreads to adjacent cells and activates
CC the interferon and NF-kappa-B immune responses (PubMed:30728498).
CC {ECO:0000255|HAMAP-Rule:MF_04143, 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 -!- 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: In some poxviruses, the poxin is expressed as a poxin-
CC schlafen fusion protein. {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the poxin family.
CC {ECO:0000255|HAMAP-Rule:MF_04143}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the Schlafen protein
CC family. Subgroup poxviridae B3 subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_04143}.
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DR EMBL; AF380138; AAL40623.1; -; Genomic_DNA.
DR RefSeq; NP_536592.1; NC_003310.1.
DR SMR; Q8V4S4; -.
DR GeneID; 928917; -.
DR KEGG; vg:928917; -.
DR Proteomes; UP000101269; 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 Gene3D; 3.30.950.30; -; 1.
DR HAMAP; MF_04143; Poxins; 1.
DR InterPro; IPR031450; B3R.
DR InterPro; IPR006853; Poxin_vir.
DR InterPro; IPR029684; Schlafen.
DR InterPro; IPR007421; Schlafen_AlbA_2_dom.
DR InterPro; IPR038461; Schlafen_AlbA_2_dom_sf.
DR PANTHER; PTHR12155; PTHR12155; 1.
DR Pfam; PF04326; AlbA_2; 1.
DR Pfam; PF17057; B3R; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Nuclease.
FT CHAIN 1..503
FT /note="Poxin-Schlafen"
FT /id="PRO_0000446974"
FT REGION 1..236
FT /note="Poxin-like"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT REGION 237..503
FT /note="Schlafen-like"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT ACT_SITE 15
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT ACT_SITE 136
FT /note="Shared with catalytic histidine of dimeric partner"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT ACT_SITE 140
FT /note="Proton acceptor; shared with catalytic histidine of
FT dimeric partner"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT SITE 58
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT SITE 103
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT SITE 147
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT SITE 167
FT /note="Substrate binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT SITE 180
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"
SQ SEQUENCE 503 AA; 57454 MW; 1EC075E3786A7C8C CRC64;
MFYAHAFGGY DENLHAFPRI SSTVANDVRK YSVVSVYNKK YNIVKNKYMW CNSQVNKRYI
GALLPMFECN EYLQIGDPIH DLEGNQISIV TYRHKNYYAL SGIGYESLDL CLEGVGIHHH
VLETGNAVYG KVQHEYSTIK EKAKEMNALK PGPIIDYHVW IGDCVCQVTT VDVHGKEIMR
MRFKRGAVLP IPNLVKVKVG EENDTINLST SISALLNSGG GTIEVTSKEE RVDYVLMKRL
ESIHHLWSVV YDHLNVVNGE ERCYIHMHSS HQSPMLSTVK TNLYMKTMGA CLQMDSMEAL
EYLSELKESG GRSPRPELQK FEYPDGVKDT ESIERLAEEF FNRSELQAGE SVKFGNSINV
KHTSVSAKQL RTRIRQQLPS ILSSFANTKG GYLFIGVDNN THKVIGFTVG HDYLKLVERD
IEKYIQKLPV VHFCKKKEDI KYACRFIKVY KPGDETTSTY VCAIKVERCC CAVFADWPES
WYMDTSGSMK KYSPDEWVSH IKF
