CDAS_BACSU
ID CDAS_BACSU Reviewed; 207 AA.
AC O31854; Q7BV95;
DT 24-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 3.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Cyclic di-AMP synthase CdaS {ECO:0000303|PubMed:22211522};
DE Short=c-di-AMP synthase;
DE EC=2.7.7.85 {ECO:0000255|HAMAP-Rule:MF_00838};
DE AltName: Full=Diadenylate cyclase {ECO:0000255|HAMAP-Rule:MF_00838};
DE Short=DAC {ECO:0000255|HAMAP-Rule:MF_00838};
GN Name=cdaS {ECO:0000303|PubMed:23192352}; Synonyms=dacB, yojJ;
GN OrderedLocusNames=BSU19430;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RA Park S.-H., Shin B.-S., Choi S.-K., Ghim S.-Y.;
RT "DNA sequences of a 15.4 kb fragment covering the 181 degree region of the
RT Bacillus subtilis genome.";
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [3]
RP SEQUENCE REVISION TO C-TERMINUS.
RX PubMed=19383706; DOI=10.1099/mic.0.027839-0;
RA Barbe V., Cruveiller S., Kunst F., Lenoble P., Meurice G., Sekowska A.,
RA Vallenet D., Wang T., Moszer I., Medigue C., Danchin A.;
RT "From a consortium sequence to a unified sequence: the Bacillus subtilis
RT 168 reference genome a decade later.";
RL Microbiology 155:1758-1775(2009).
RN [4]
RP PROBABLE FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=168;
RX PubMed=22211522; DOI=10.1111/j.1365-2958.2011.07953.x;
RA Luo Y., Helmann J.D.;
RT "Analysis of the role of Bacillus subtilis sigma(M) in beta-lactam
RT resistance reveals an essential role for c-di-AMP in peptidoglycan
RT homeostasis.";
RL Mol. Microbiol. 83:623-639(2012).
RN [5]
RP DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=22383849; DOI=10.1126/science.1206848;
RA Nicolas P., Maeder U., Dervyn E., Rochat T., Leduc A., Pigeonneau N.,
RA Bidnenko E., Marchadier E., Hoebeke M., Aymerich S., Becher D.,
RA Bisicchia P., Botella E., Delumeau O., Doherty G., Denham E.L., Fogg M.J.,
RA Fromion V., Goelzer A., Hansen A., Haertig E., Harwood C.R., Homuth G.,
RA Jarmer H., Jules M., Klipp E., Le Chat L., Lecointe F., Lewis P.,
RA Liebermeister W., March A., Mars R.A., Nannapaneni P., Noone D., Pohl S.,
RA Rinn B., Ruegheimer F., Sappa P.K., Samson F., Schaffer M., Schwikowski B.,
RA Steil L., Stuelke J., Wiegert T., Devine K.M., Wilkinson A.J.,
RA van Dijl J.M., Hecker M., Voelker U., Bessieres P., Noirot P.;
RT "Condition-dependent transcriptome reveals high-level regulatory
RT architecture in Bacillus subtilis.";
RL Science 335:1103-1106(2012).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LEU-44.
RC STRAIN=168;
RX PubMed=23192352; DOI=10.1074/jbc.m112.395491;
RA Mehne F.M., Gunka K., Eilers H., Herzberg C., Kaever V., Stuelke J.;
RT "Cyclic di-AMP homeostasis in Bacillus subtilis: both lack and high level
RT accumulation of the nucleotide are detrimental for cell growth.";
RL J. Biol. Chem. 288:2004-2017(2013).
RN [7]
RP FUNCTION, SUBUNIT, DOMAIN, AND MUTAGENESIS OF 1-MET--LYS-39; 1-MET--TYR-69;
RP GLN-41; LEU-44; GLU-46; ALA-61; ALA-76 AND PRO-201.
RC STRAIN=168;
RX PubMed=24939848; DOI=10.1074/jbc.m114.562066;
RA Mehne F.M., Schroeder-Tittmann K., Eijlander R.T., Herzberg C., Hewitt L.,
RA Kaever V., Lewis R.J., Kuipers O.P., Tittmann K., Stuelke J.;
RT "Control of the diadenylate cyclase CdaS in Bacillus subtilis: an
RT autoinhibitory domain limits cyclic di-AMP production.";
RL J. Biol. Chem. 289:21098-21107(2014).
CC -!- FUNCTION: One of 3 paralogous diadenylate cyclases (DAC) in this
CC bacteria, catalyzing the condensation of 2 ATP molecules into cyclic
CC di-AMP (c-di-AMP) (Probable). Upon expression in E.coli leads to c-di-
CC AMP synthesis (PubMed:23192352, PubMed:24939848). Overexpression of the
CC hyperactive mutant (L44F) in the absence of c-di-AMP phosphodiesterase
CC GdpP leads to growth defects in log phase (long curly cell filaments)
CC that disappear upon sporulation; spore formation is normal, showing
CC sporulation is insensitive to the excess c-di-AMP (PubMed:23192352). In
CC B.subtilis c-di-AMP is a second messenger that mediates growth, DNA
CC repair and cell wall homeostasis; it is toxic when present in excess.
CC {ECO:0000269|PubMed:23192352, ECO:0000269|PubMed:24939848, ECO:0000305,
CC ECO:0000305|PubMed:22211522}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 ATP = 3',3'-c-di-AMP + 2 diphosphate; Xref=Rhea:RHEA:35655,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:71500; EC=2.7.7.85;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00838};
CC -!- SUBUNIT: Forms dimers and probably also hexamers; the dimer may be
CC active while the hexamer may not be active.
CC {ECO:0000250|UniProtKB:Q812L9, ECO:0000269|PubMed:24939848}.
CC -!- DEVELOPMENTAL STAGE: Probably expressed only during sporulation in the
CC forespore. {ECO:0000305|PubMed:22383849}.
CC -!- INDUCTION: Expressed under control of the sigma-G factor in the
CC forespore. {ECO:0000269|PubMed:22383849}.
CC -!- DOMAIN: The N-terminus (residues 1-69) is thought to form 2 alpha-
CC helices that allow dimerization and probable hexamerization; this
CC region inhibits DAC activity of the rest of the protein
CC (PubMed:24939848). {ECO:0000269|PubMed:24939848}.
CC -!- DISRUPTION PHENOTYPE: No effect on antibiotic sensitivity to the beta-
CC lactam antibiotic cefuroxime (CEF), upon overexpression of the c-di-AMP
CC phosphodiesterase GdpP increased sensitivity to CEF (PubMed:22211522).
CC Double disA-cdaA mutants cannot be made, suggesting they are lethal,
CC while double disA-cdaS and cdaA-cdsS mutants are viable
CC (PubMed:22211522, PubMed:23192352). In single deletions of this gene,
CC germination efficiency is decreased (PubMed:24939848).
CC {ECO:0000269|PubMed:22211522, ECO:0000269|PubMed:23192352,
CC ECO:0000269|PubMed:24939848}.
CC -!- SIMILARITY: Belongs to the adenylate cyclase family. DacB/CdaS
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00838}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC17858.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC17858.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF026147; AAC17858.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL009126; CAB13835.3; -; Genomic_DNA.
DR RefSeq; NP_389825.3; NC_000964.3.
DR RefSeq; WP_010886531.1; NZ_JNCM01000036.1.
DR AlphaFoldDB; O31854; -.
DR SMR; O31854; -.
DR STRING; 224308.BSU19430; -.
DR PaxDb; O31854; -.
DR PRIDE; O31854; -.
DR EnsemblBacteria; CAB13835; CAB13835; BSU_19430.
DR GeneID; 939589; -.
DR KEGG; bsu:BSU19430; -.
DR PATRIC; fig|224308.43.peg.2059; -.
DR eggNOG; COG1624; Bacteria.
DR InParanoid; O31854; -.
DR OMA; YYLRHYL; -.
DR PhylomeDB; O31854; -.
DR BioCyc; BSUB:BSU19430-MON; -.
DR BRENDA; 2.7.7.85; 658.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0004016; F:adenylate cyclase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0106408; F:diadenylate cyclase activity; IEA:UniProtKB-EC.
DR GO; GO:0006171; P:cAMP biosynthetic process; IEA:InterPro.
DR GO; GO:0019932; P:second-messenger-mediated signaling; IEA:UniProtKB-UniRule.
DR Gene3D; 3.40.1700.10; -; 1.
DR HAMAP; MF_00838; DacB; 1.
DR InterPro; IPR014046; C-di-AMP_synthase.
DR InterPro; IPR034693; CdaS.
DR InterPro; IPR036888; DNA_integrity_DisA_N_sf.
DR InterPro; IPR003390; DNA_integrity_scan_DisA_N.
DR InterPro; IPR019457; Uncharacterised_YojJ_N.
DR Pfam; PF02457; DAC; 1.
DR Pfam; PF10372; YojJ; 1.
DR PIRSF; PIRSF004793; UCP004793; 1.
DR SUPFAM; SSF143597; SSF143597; 1.
DR PROSITE; PS51794; DAC; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Coiled coil; Nucleotide-binding; Nucleotidyltransferase;
KW Reference proteome; Transferase.
FT CHAIN 1..207
FT /note="Cyclic di-AMP synthase CdaS"
FT /id="PRO_0000389496"
FT DOMAIN 63..205
FT /note="DAC"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00838"
FT COILED 13..37
FT /evidence="ECO:0000305|PubMed:24939848"
FT MUTAGEN 1..69
FT /note="Missing: 17-fold increased production of c-di-AMP in
FT E.coli."
FT /evidence="ECO:0000269|PubMed:24939848"
FT MUTAGEN 1..39
FT /note="Missing: 20-fold increased production of c-di-AMP in
FT E.coli, forms only homodimers."
FT /evidence="ECO:0000269|PubMed:24939848"
FT MUTAGEN 41
FT /note="Q->K: Suppresses a triple DAC mutant."
FT /evidence="ECO:0000269|PubMed:24939848"
FT MUTAGEN 44
FT /note="L->F: Suppresses a triple DAC mutant, 90-fold
FT increased production of c-di-AMP in E.coli."
FT /evidence="ECO:0000269|PubMed:23192352,
FT ECO:0000269|PubMed:24939848"
FT MUTAGEN 46
FT /note="E->K: Suppresses a triple DAC mutant, 20-fold
FT increased production of c-di-AMP in E.coli."
FT /evidence="ECO:0000269|PubMed:24939848"
FT MUTAGEN 61
FT /note="A->V: Suppresses a triple DAC mutant, 10-fold
FT increased production of c-di-AMP in E.coli, forms
FT hexamers."
FT /evidence="ECO:0000269|PubMed:24939848"
FT MUTAGEN 76
FT /note="A->V: Suppresses a triple DAC mutant, 4-fold
FT increased production of c-di-AMP in E.coli."
FT /evidence="ECO:0000269|PubMed:24939848"
FT MUTAGEN 201
FT /note="P->Q: Suppresses a triple DAC mutant, 12-fold
FT increased production of c-di-AMP in E.coli."
FT /evidence="ECO:0000269|PubMed:24939848"
FT CONFLICT 149
FT /note="A -> S (in Ref. 1; AAC17858)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 207 AA; 22927 MW; 40B8F60A7B6A1A66 CRC64;
MKAMRYEQIS ENAFKGKIQV YLEQILGDAS LILKTLHEKD QCLLCELDDL GHVFQDMQGI
ASSFYLQSYI EEFTPAFIEL AKAIKALSEH KHGALIVIER ADPVERFIQK GTSLHAEISS
SLIESIFFPG NPLHDGALLV RENKLVSAAN VLPLTTKEVD IHLGTRHRAA LGMSGYTDAL
VLVVSEETGK MSFAKDGVLY PLISPRT
