CAP12_CAPGB
ID CAP12_CAPGB Reviewed; 314 AA.
AC A0A381HAP5;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2018, sequence version 1.
DT 25-MAY-2022, entry version 9.
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=CgSTING {ECO:0000303|PubMed:32877915};
GN Name=cap12 {ECO:0000305}; ORFNames=NCTC12948_02565;
OS Capnocytophaga granulosa (strain ATCC 51502 / DSM 11449 / JCM 8566 / LMG
OS 16022 / NCTC 12948 / B0611).
OC Bacteria; Bacteroidetes; Flavobacteriia; Flavobacteriales;
OC Flavobacteriaceae; Capnocytophaga.
OX NCBI_TaxID=641143;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 51502 / DSM 11449 / JCM 8566 / LMG 16022 / NCTC 12948 / B0611;
RG Pathogen Informatics;
RA Doyle S.;
RL Submitted (JUN-2018) to the EMBL/GenBank/DDBJ databases.
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).
RN [3] {ECO:0007744|PDB:6WT5}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 151-314, SUBUNIT, DOMAIN,
RP C-DI-GMP-BINDING, AND NUCLEOTIDE-BINDING.
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).
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-(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-
CC GMP(synthesized by the cognate CdnE encoded upstream in the same
CC operon), and about 10-fold less well 3'3'-cGAMP, but not c-di-AMP, 2'-
CC 3'-cGAMP or cUMP-AMP (tested without the N-terminal TIR domain)
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 -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:32877915}.
CC -!- DOMAIN: The TIR domain mediates NAD(+) hydrolase (NADase) activity. The
CC cyclic nucleotide binds in C-terminal bacterial STING region.
CC Comparison of structures from 2 different bacteria suggests that cyclic
CC nucleotide binding causes domain rotation to form a lid which seals the
CC nucleotide-binding pocket. {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; UFVE01000002; SUX93682.1; -; Genomic_DNA.
DR RefSeq; WP_016421263.1; NZ_KE150243.1.
DR PDB; 6WT5; X-ray; 2.80 A; A/B/C/D=151-314.
DR PDBsum; 6WT5; -.
DR AlphaFoldDB; A0A381HAP5; -.
DR SMR; A0A381HAP5; -.
DR STRING; 641143.HMPREF9331_02454; -.
DR EnsemblBacteria; SUX93682; SUX93682; NCTC12948_02565.
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 3D-structure; Antiviral defense; Hydrolase; Nucleotide-binding.
FT CHAIN 1..314
FT /note="CD-NTase-associated protein 12"
FT /id="PRO_0000451877"
FT DOMAIN 5..129
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204,
FT ECO:0000305|PubMed:32877915"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:6WT5"
FT HELIX 159..170
FT /evidence="ECO:0007829|PDB:6WT5"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:6WT5"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:6WT5"
FT STRAND 192..202
FT /evidence="ECO:0007829|PDB:6WT5"
FT HELIX 210..218
FT /evidence="ECO:0007829|PDB:6WT5"
FT STRAND 224..228
FT /evidence="ECO:0007829|PDB:6WT5"
FT STRAND 235..239
FT /evidence="ECO:0007829|PDB:6WT5"
FT STRAND 247..252
FT /evidence="ECO:0007829|PDB:6WT5"
FT HELIX 255..258
FT /evidence="ECO:0007829|PDB:6WT5"
FT HELIX 259..267
FT /evidence="ECO:0007829|PDB:6WT5"
FT HELIX 279..300
FT /evidence="ECO:0007829|PDB:6WT5"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:6WT5"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:6WT5"
SQ SEQUENCE 314 AA; 36072 MW; F1EF01CE9A3031BC CRC64;
MRGKRIFIGS SSEELRLAEQ AKKILEKNTN YQVTIWNENM WDKAVFRLNN SYLNDLIRAT
LHFDFGILIG TKDDKVIFRG SEEIQPRDNV LFELGLFIGR LGLNNCAFLV DEEIKILSDV
KGISLARFKE KDSDSFNNAV LSIRESFDRQ NDSDINFFPS STLAAVYYEN FIKPTCSHII
NNGGLLDKNG YIYKKCTIKI IIPKKLTSDV NSQFQRIKAK IETKELSFEY LGRPRNINVE
IIAEDGEVMI IDFPTILSGI NYAISNLLPQ DFNSMSVDYE AILSRELERF VYTLKKIALR
DGFDDLIKIV DEDN
