ID   CAP12_LACSX             Reviewed;         316 AA.
AC   P0DUE0;
DT   10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT   10-FEB-2021, sequence version 1.
DT   25-MAY-2022, entry version 5.
DE   RecName: Full=CD-NTase-associated protein 12 {ECO:0000305};
DE            Short=Cap12 {ECO:0000305};
DE   AltName: Full=NAD(+) hydrolase {ECO:0000250|UniProtKB:A0A2T5Y4G4};
DE            EC=3.2.2.5 {ECO:0000250|UniProtKB:A0A2T5Y4G4};
DE   AltName: Full=TIR-STING {ECO:0000303|PubMed:32877915};
DE            Short=LbSTING {ECO:0000303|PubMed:32877915};
GN   Name=cap12 {ECO:0000305}; ORFNames=Ga0313508_15007, IMG 2800731183;
OS   Lachnospiraceae bacterium (strain RUG226).
OC   Bacteria; Firmicutes; Clostridia; Eubacteriales; Lachnospiraceae.
OX   NCBI_TaxID=2778090;
RN   [1]
RP   C-DI-GMP-BINDING, NUCLEOTIDE-BINDING, AND DOMAIN.
RX   PubMed=32877915; DOI=10.1038/s41586-020-2719-5;
RA   Morehouse B.R., Govande A.A., Millman A., Keszei A.F.A., Lowey B., Ofir G.,
RA   Shao S., Sorek R., Kranzusch P.J.;
RT   "STING cyclic dinucleotide sensing originated in bacteria.";
RL   Nature 586:429-433(2020).
RN   [2]
RP   CLASSIFICATION AND NOMENCLATURE.
RX   PubMed=32839535; DOI=10.1038/s41564-020-0777-y;
RA   Millman A., Melamed S., Amitai G., Sorek R.;
RT   "Diversity and classification of cyclic-oligonucleotide-based anti-phage
RT   signalling systems.";
RL   Nat. Microbiol. 5:1608-1615(2020).
CC   -!- FUNCTION: CBASS (cyclic oligonucleotide-based antiphage signaling
CC       system) provides immunity against bacteriophage. The CD-NTase protein
CC       synthesizes cyclic nucleotides in response to infection; these serve as
CC       specific second messenger signals. The signals activate a diverse range
CC       of effectors, leading to bacterial cell death and thus abortive phage
CC       infection. A type I-D(GG) CBASS system (PubMed:32839535).
CC       {ECO:0000303|PubMed:32839535, ECO:0000305|PubMed:32877915}.
CC   -!- FUNCTION: The effector protein for this CBASS system. Binds c-di-GMP
CC       (synthesized by the cognate CdnE encoded upstream in the same operon)
CC       but not c-di-AMP, 2'-3'-cGAMP, 3'-3'-cGAMP or cUMP-AMP (tested without
CC       the N-terminal TIR domain) (PubMed:32877915). Upon activation by c-di-
CC       GMP forms filaments which hydrolyze NAD(+); filament formation is
CC       required for enzyme activation (By similarity).
CC       {ECO:0000250|UniProtKB:A0A2T5Y4G4, ECO:0000269|PubMed:32877915}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC         Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.5;
CC         Evidence={ECO:0000250|UniProtKB:A0A2T5Y4G4};
CC   -!- ACTIVITY REGULATION: NAD(+) hydrolase activity is strongly stimulated
CC       by c-di-GMP, weakly by 3'3'-cGAMP, very weakly by c-di-AMP but not at
CC       all by 2'3'-cGAMP (Probable). Self-association of TIR domains is
CC       required for NADase activity (By similarity).
CC       {ECO:0000250|UniProtKB:A0A2T5Y4G4, ECO:0000305|PubMed:32877915}.
CC   -!- DOMAIN: The TIR domain mediates NAD(+) hydrolase (NADase) activity. The
CC       cyclic nucleotide binds in the C-terminal bacterial STING region.
CC       {ECO:0000305|PubMed:32877915}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the bacterial STING
CC       family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=IMG gene page for 2800731183;
CC       URL="https://img.jgi.doe.gov/cgi-bin/m/main.cgi?section=GeneDetail&page=genePageMainFaa&gene_oid=2800731183";
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DR   AlphaFoldDB; P0DUE0; -.
DR   SMR; P0DUE0; -.
DR   GO; GO:0061810; F:NAD glycohydrolase activity; IEA:UniProtKB-EC.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR   GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR   InterPro; IPR019302; TIR-like_dom.
DR   Pfam; PF10137; TIR-like; 1.
PE   1: Evidence at protein level;
KW   Antiviral defense; Hydrolase; Nucleotide-binding.
FT   CHAIN           1..316
FT                   /note="CD-NTase-associated protein 12"
FT                   /id="PRO_0000451879"
FT   DOMAIN          4..121
FT                   /note="TIR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204,
FT                   ECO:0000305|PubMed:32877915"
SQ   SEQUENCE   316 AA;  36248 MW;  6BA358C7C1059942 CRC64;
     MKTRIFIGSS SEGIDVAKRI KTFFAPEYDC FLWTDDIFRN NESFLETLVK SASLFDFGFM
     VFSADDKTTI RDQHFESPRD NVLFEYGLFL GRVGLDRAFV IAETDAKIPT DMLGITQTRY
     ETIVNSKGIK VATDSLESSL QKLKKQIDEN VQLGHLGLLP STVIAISYFE GFVKLAAEWL
     VENTPELMIN NHKFNKASLK IVMPESLDTD IKRSAMMYYK RHGLEEARID TKHRNYPIHF
     ASKTEDGILE VYDMPTILTG IDKAIDMYFR VGHIGKTNEQ KLAEDHEMNN FKRVLQLLIN
     EDAFCRECVE IIEPQP