POXIN_CWPXB
ID POXIN_CWPXB Reviewed; 505 AA.
AC Q8QMP8;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 23-FEB-2022, entry version 66.
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=CPXV197 CDS {ECO:0000312|EMBL:AAM13636.1};
OS Cowpox virus (strain Brighton Red) (CPV).
OC Viruses; Varidnaviria; Bamfordvirae; Nucleocytoviricota; Pokkesviricetes;
OC Chitovirales; Poxviridae; Chordopoxvirinae; Orthopoxvirus.
OX NCBI_TaxID=265872;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
OH NCBI_TaxID=9685; Felis catus (Cat) (Felis silvestris catus).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9785; Loxodonta africana (African elephant).
OH NCBI_TaxID=29092; Microtus agrestis (Short-tailed field vole).
OH NCBI_TaxID=10090; Mus musculus (Mouse).
OH NCBI_TaxID=447135; Myodes glareolus (Bank vole) (Clethrionomys glareolus).
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=6961398; DOI=10.1073/pnas.79.23.7112;
RA Pickup D.J., Bastia D., Stone H.O., Joklik W.K.;
RT "Sequence of terminal regions of cowpox virus DNA: arrangement of repeated
RT and unique sequence elements.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:7112-7116(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=2309453; DOI=10.1016/0042-6822(90)90187-v;
RA Parsons B.L., Pickup D.J.;
RT "Transcription of orthopoxvirus telomeres at late times during infection.";
RL Virology 175:69-80(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=2014645; DOI=10.1016/0042-6822(91)90905-q;
RA Hu F.Q., Pickup D.J.;
RT "Transcription of the terminal loop region of vaccinia virus DNA is
RT initiated from the telomere sequences directing DNA resolution.";
RL Virology 181:716-720(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=8091665; DOI=10.1006/viro.1994.1539;
RA Hu F.Q., Smith C.A., Pickup D.J.;
RT "Cowpox virus contains two copies of an early gene encoding a soluble
RT secreted form of the type II TNF receptor.";
RL Virology 204:343-356(1994).
RN [5]
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. 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 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; AF482758; AAM13636.1; -; Genomic_DNA.
DR RefSeq; NP_619978.1; NC_003663.2.
DR SMR; Q8QMP8; -.
DR GeneID; 1486076; -.
DR KEGG; vg:1486076; -.
DR Proteomes; UP000152733; 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.
DR Pfam; PF04766; Baculo_p26; 1.
PE 1: Evidence at protein level;
KW Hydrolase; Nuclease.
FT CHAIN 1..505
FT /note="Poxin-Schlafen"
FT /id="PRO_0000446973"
FT REGION 1..238
FT /note="Poxin-like"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
FT REGION 239..505
FT /note="Schlafen-like"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04143"
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 149
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"
SQ SEQUENCE 505 AA; 57535 MW; E648EB3FDBBE37C3 CRC64;
MAMFYAHAFG GYDENLHAFP GISSTVANDV RKYSVVSVYN NKYDIVKDKY MWCYSYVNKR
YIGALLPMFE CNEYLQIGDP IHDLEGNQIS IVTYRHKNYY ALSGIGYESL DLCLEGVGIH
HHTLEAGNAV YGKVQHDYST IKEKAKEMNS LSPGPIIDYH VWIGDCVCQV TAVDVHGKEI
MRMRFKKGAV LPIPNLVKVK LGEENDTVNL STSISALLNS GGGTIEVTSK EERVDYVLMK
RLESIRHLWS VVYDHFDVVN GKERCYVHMH SSNQSPMLST VKTNLYMKTM GACLQMDYME
ALEYLSELKE SGGRSPRPEL PEFEYPDGVE DAGSIERLAE EFFSRSELQA DEPVNFCNSI
NVKHTSVSAK QLRTRIRQQL PSILSSFANT DGGYLFIGVD NNTHKVVGFT VGQDYLKLVE
SDIEKYIKRL RVVHFCEKKE DIKYACRFIK VYKPGEETTS TYVCAIKVER CCCAVFADWP
ESWYMDTSGS MKKYSPDEWV SHIKF
