CAP12_SPHFK
ID CAP12_SPHFK Reviewed; 323 AA.
AC A0A2T5Y4G4;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 18-JUL-2018, sequence version 1.
DT 25-MAY-2022, entry version 10.
DE RecName: Full=CD-NTase-associated protein 12 {ECO:0000305};
DE Short=Cap12 {ECO:0000305};
DE AltName: Full=NAD(+) hydrolase {ECO:0000303|PubMed:32877915};
DE EC=3.2.2.5 {ECO:0000269|PubMed:32877915};
DE AltName: Full=TIR-STING {ECO:0000303|PubMed:32877915};
DE Short=SfSTING {ECO:0000303|PubMed:32877915};
GN Name=cap12 {ECO:0000305}; ORFNames=C8N37_104320, SF1_08920;
OS Sphingobacterium faecium (strain DSM 11690 / JCM 21820 / NBRC 15299 / NCIMB
OS 13408 / KS 0470).
OC Bacteria; Bacteroidetes; Sphingobacteriia; Sphingobacteriales;
OC Sphingobacteriaceae; Sphingobacterium.
OX NCBI_TaxID=1220575;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 11690 / JCM 21820 / NBRC 15299 / NCIMB 13408 / KS 0470;
RA Goeker M.;
RT "Genomic Encyclopedia of Archaeal and Bacterial Type Strains, Phase II
RT (KMG-II): from individual species to whole genera.";
RL Submitted (APR-2018) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 11690 / JCM 21820 / NBRC 15299 / NCIMB 13408 / KS 0470;
RA Hosoyama A., Uohara A., Ohji S., Ichikawa N.;
RT "Whole genome shotgun sequence of Sphingobacterium faecium NBRC 15299.";
RL Submitted (JUL-2019) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION AS AN NAD HYDROLASE, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, C-DI-GMP-BINDING,
RP NUCLEOTIDE-BINDING, DOMAIN, AND MUTAGENESIS OF GLU-84; ASN-163; PHE-165;
RP LYS-167; ARG-168; 201-LEU--ASP-203; ARG-234; ASP-259; SER-262; THR-263;
RP 275-LEU--GLN-282 AND 307-ARG--ALA-309.
RC STRAIN=DSM 11690 / JCM 21820 / NBRC 15299 / NCIMB 13408 / KS 0470;
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 [4]
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. Upon activation
CC by c-di-GMP forms filaments which hydrolyze NAD(+); filament formation
CC is required for enzyme activation. Induction in an E.coli strain that
CC synthesizes c-di-GMP leads to significant growth inhibition. Binds c-
CC di-GMP and 3'3'-cGAMP (3'3'-cyclic GMP-AMP), but not c-di-AMP, 2'3'-
CC cGAMP or cUMP-AMP. {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:0000269|PubMed:32877915};
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 and not at
CC all by 2'3'-cGAMP. Self-association of TIR domains is required for
CC NADase activity. {ECO:0000269|PubMed:32877915}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=27 uM for NAD(+) {ECO:0000269|PubMed:32877915};
CC Note=kcat is 2.3 sec(-1). {ECO:0000269|PubMed:32877915};
CC -!- SUBUNIT: Forms homodimers in equilibrium with homotetramers. In vitro,
CC in the presence of c-di-GMP, forms filaments 25-30 nm in length with an
CC ordered array of parallel-stacked homodimers. 3'3'-cGAMP weakly induces
CC filament formation, while 2'3'-cGAMP does not.
CC {ECO:0000269|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; QBKH01000004; PTX11039.1; -; Genomic_DNA.
DR EMBL; BJXG01000002; GEM62910.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A2T5Y4G4; -.
DR EnsemblBacteria; PTX11039; PTX11039; C8N37_104320.
DR Proteomes; UP000244226; Unassembled WGS sequence.
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..323
FT /note="CD-NTase-associated protein 12"
FT /id="PRO_0000451881"
FT DOMAIN 4..120
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204,
FT ECO:0000305|PubMed:32877915"
FT MUTAGEN 84
FT /note="E->A: Loss of NAD(+) cleavage, still forms filaments
FT in the presence of c-di-GMP and weakly with 3'3'-cGAMP."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 163
FT /note="N->A: Requires 10X more c-di-GMP for activation."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 165
FT /note="F->A: Poorly activated by c-di-GMP."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 167
FT /note="K->A: About wild-type activation by c-di-GMP."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 168
FT /note="R->A: Requires 100X more c-di-GMP for activation."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 201..203
FT /note="LDD->RDR: Binds c-di-GMP, no longer forms filaments,
FT no NAD(+) cleavage."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 234
FT /note="R->A: Loss of NAD(+) cleavage."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 259
FT /note="D->A: Loss of NAD(+) cleavage, does not inhibit
FT E.coli growth."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 262
FT /note="S->A: Requires 100X more c-di-GMP for activation."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 263
FT /note="T->A: About wild-type activation by c-di-GMP."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 275..282
FT /note="Missing: Binds c-di-GMP, no longer forms filaments,
FT no NAD(+) cleavage."
FT /evidence="ECO:0000269|PubMed:32877915"
FT MUTAGEN 307..309
FT /note="RNA->ENR: Binds c-di-GMP, no longer forms filaments,
FT no NAD(+) cleavage."
FT /evidence="ECO:0000269|PubMed:32877915"
SQ SEQUENCE 323 AA; 35943 MW; EB13C0CEA71A33E1 CRC64;
MKKRIFIGSS SEQLTILNEI VDLLGDDVEC IPWTDAFALN KSGLDSLIKQ TRLADYSILI
ATKDDLTKQR GESLTKPRDN VVFEFGLFLG AAGPEKCYLI AEEDTDLPTD LDGITVAKFT
RNSGQYNSLD KIVESIRTHL VKIAEMSQLG LLPSTALAIG YYNSFIKRVC EEIHGSECVE
LEGKKIKVKS FRVDVVIPET LDDNGVGNFT TLYNKRYGLS KATTCTNPAL LGTRGFPFHF
KVDPPDANQE SPVDIHLLDI PSTLSTIVES LKLYLPSNQV GQDFDMDYLE MRELENFAKV
LKYLIGRNAA TKGYVNVLTN VKL
