ID   CAP12_AGGAC             Reviewed;         317 AA.
AC   A0A5D0EMF2;
DT   10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT   11-DEC-2019, sequence version 1.
DT   25-MAY-2022, entry version 8.
DE   RecName: Full=CD-NTase-associated protein 12 {ECO:0000305};
DE            Short=Cap12;
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=AaSTING {ECO:0000303|PubMed:32877915};
GN   Name=cap12 {ECO:0000305}; ORFNames=FXB68_04755;
OS   Aggregatibacter actinomycetemcomitans (Actinobacillus
OS   actinomycetemcomitans) (Haemophilus actinomycetemcomitans).
OC   Bacteria; Proteobacteria; Gammaproteobacteria; Pasteurellales;
OC   Pasteurellaceae; Aggregatibacter.
OX   NCBI_TaxID=714;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=PN_567;
RA   Nedergaard S., Kobel C.M., Nielsen M.B., Moeller R.T., Jensen A.B.,
RA   Noerskov-Lauritsen N.;
RT   "Whole genome sequencing of Aggregatibacter actinomycetemcomitans cultured
RT   from blood stream infections in Denmark reveals a novel phylogenetic
RT   lineage expressing serotype a membrane O polysaccharide.";
RL   Submitted (AUG-2019) to the EMBL/GenBank/DDBJ databases.
RN   [2]
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   [3]
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       and 3'-3'-cGAMP, but not c-di-AMP, 2'-3'-cGAMP or cUMP-AMP
CC       (PubMed:32877915). Upon activation by c-di-GMP forms filaments which
CC       hydrolyze NAD(+); filament formation is required for enzyme activation
CC       (By similarity). {ECO:0000250|UniProtKB:A0A2T5Y4G4,
CC       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}.
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DR   EMBL; VSEG01000009; TYA35095.1; -; Genomic_DNA.
DR   RefSeq; WP_005552896.1; NZ_VSET01000009.1.
DR   AlphaFoldDB; A0A5D0EMF2; -.
DR   SMR; A0A5D0EMF2; -.
DR   STRING; 694569.D7S_02394; -.
DR   KEGG; aact:ACT75_11015; -.
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..317
FT                   /note="CD-NTase-associated protein 12"
FT                   /id="PRO_0000451876"
FT   DOMAIN          4..128
FT                   /note="TIR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204,
FT                   ECO:0000305|PubMed:32877915"
SQ   SEQUENCE   317 AA;  36211 MW;  2C67B8A2662F182A CRC64;
     MKKKIFIGSS SEELRIAEKV KKILEQDNEF EVTIWNDNSI WDNSVFKLNH NFLTDLLNSS
     LSSDFGILIG TCDDKVIVRG TERLQPRDNV LFELGFFIGK LGLDNCAFLI DKNIHILSDV
     QGITLARANM GDPDELKRAV NCIKEHFKHQ PNSGINFFPS STLASVYHEN FIKPTCQTII
     EDNGILDTAG KKHTNCLVKI IIPNKINIDV NSQFQILKNK ISTNTLSFNY KGRPRNISIE
     IVESSEENTT IIDFPTIISG IYYAISNLLP QDSETDSITY RNILARELDR FVNTLYKFIK
     RDGYDEIVKI VYEDKLY