CDAA_BACSU
ID CDAA_BACSU Reviewed; 273 AA.
AC Q45589; Q45590; Q7DL98;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 3.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Cyclic di-AMP synthase CdaA {ECO:0000303|PubMed:22211522, ECO:0000303|PubMed:23192352};
DE Short=c-di-AMP synthase;
DE EC=2.7.7.85 {ECO:0000255|HAMAP-Rule:MF_01499};
DE AltName: Full=Diadenylate cyclase;
DE Short=DAC {ECO:0000255|HAMAP-Rule:MF_01499};
GN Name=cdaA {ECO:0000303|PubMed:23192352}; Synonyms=ybbP;
GN OrderedLocusNames=BSU01750;
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;
RX PubMed=9274029; DOI=10.1099/00221287-143-8-2763;
RA Liu H., Haga K., Yasumoto K., Ohashi Y., Yoshikawa H., Takahashi H.;
RT "Sequence and analysis of a 31 kb segment of the Bacillus subtilis
RT chromosome in the area of the rrnH and rrnG operons.";
RL Microbiology 143:2763-2767(1997).
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 270.
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 FUNCTION, ACTIVITY REGULATION, INTERACTION WITH CDAR, INDUCTION, AND
RP DISRUPTION PHENOTYPE.
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 [6]
RP DISRUPTION PHENOTYPE.
RC STRAIN=168, and 168 / YB886 / BG214;
RX PubMed=25616256; DOI=10.1016/j.dnarep.2014.12.007;
RA Gandara C., Alonso J.C.;
RT "DisA and c-di-AMP act at the intersection between DNA-damage response and
RT stress homeostasis in exponentially growing Bacillus subtilis cells.";
RL DNA Repair 27:1-8(2015).
RN [7]
RP FUNCTION, SUBUNIT, INTERACTION WITH CDAR, AND SUBCELLULAR LOCATION.
RC STRAIN=168;
RX PubMed=26240071; DOI=10.1128/jb.00564-15;
RA Gundlach J., Mehne F.M., Herzberg C., Kampf J., Valerius O., Kaever V.,
RA Stuelke J.;
RT "An essential poison: synthesis and degradation of cyclic di-AMP in
RT Bacillus subtilis.";
RL J. Bacteriol. 197:3265-3274(2015).
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). Probably the main producer of c-di-AMP
CC for the cell; is probably implicated in control of peptidogylcan
CC synthesis (PubMed:22211522, PubMed:23192352, PubMed:26240071). 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 (PubMed:26240071). {ECO:0000269|PubMed:23192352,
CC ECO:0000269|PubMed:26240071, 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_01499};
CC -!- ACTIVITY REGULATION: DAC activity is stimulated about 20-fold in E.coli
CC by coexpression with CdaR (PubMed:23192352).
CC {ECO:0000269|PubMed:23192352}.
CC -!- SUBUNIT: Probably a homodimer (By similarity). Interacts with CdaR
CC (PubMed:23192352, PubMed:26240071). May interact with GlmM
CC (PubMed:26240071). {ECO:0000255|HAMAP-Rule:MF_01499,
CC ECO:0000269|PubMed:23192352, ECO:0000269|PubMed:26240071}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255|HAMAP-Rule:MF_01499,
CC ECO:0000269|PubMed:26240071}; Multi-pass membrane protein
CC {ECO:0000255|HAMAP-Rule:MF_01499}.
CC -!- INDUCTION: Constitutively expressed, part of the cdaA-cdaR-glmM-glmS
CC operon (PubMed:23192352). {ECO:0000269|PubMed:23192352}.
CC -!- DISRUPTION PHENOTYPE: Increased sensitivity to the beta-lactam
CC antibiotic cefuroxime (CEF), upon overexpression of the c-di-AMP
CC phosphodiesterase GdpP greatly increased sensitivity to CEF
CC (PubMed:22211522). Double disA-cdaA mutants cannot be made, suggesting
CC they are lethal, while double disA-cdaS and cdaA-cdaS mutants are
CC viable (PubMed:22211522, PubMed:23192352). Depletion of cdaA in double
CC disA-cdaA deletion cells leads to cell lysis (PubMed:22211522).
CC Exponentially growing cells are extremely sensitive to H(2)O(2), no
CC change in response to methyl methanesulfonate (PubMed:25616256).
CC {ECO:0000269|PubMed:22211522, ECO:0000269|PubMed:23192352,
CC ECO:0000269|PubMed:25616256}.
CC -!- SIMILARITY: Belongs to the adenylate cyclase family. DacA/CdaA
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_01499}.
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DR EMBL; AB002150; BAA19509.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB11951.2; -; Genomic_DNA.
DR PIR; H69744; H69744.
DR RefSeq; NP_388056.2; NC_000964.3.
DR RefSeq; WP_003223651.1; NZ_JNCM01000030.1.
DR PDB; 6HUW; X-ray; 2.80 A; A/B=97-273.
DR PDB; 7OJS; X-ray; 4.20 A; D/E/H/I/K/L=107-273.
DR PDB; 7OLH; X-ray; 3.65 A; G/H/I/J/K/L=107-273.
DR PDBsum; 6HUW; -.
DR PDBsum; 7OJS; -.
DR PDBsum; 7OLH; -.
DR AlphaFoldDB; Q45589; -.
DR SASBDB; Q45589; -.
DR SMR; Q45589; -.
DR STRING; 224308.BSU01750; -.
DR PaxDb; Q45589; -.
DR PRIDE; Q45589; -.
DR EnsemblBacteria; CAB11951; CAB11951; BSU_01750.
DR GeneID; 64302034; -.
DR GeneID; 938735; -.
DR KEGG; bsu:BSU01750; -.
DR PATRIC; fig|224308.179.peg.181; -.
DR eggNOG; COG1624; Bacteria.
DR InParanoid; Q45589; -.
DR OMA; ILWQGEL; -.
DR PhylomeDB; Q45589; -.
DR BioCyc; BSUB:BSU01750-MON; -.
DR BRENDA; 2.7.7.85; 658.
DR PRO; PR:Q45589; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
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_01499; DacA; 1.
DR InterPro; IPR014046; C-di-AMP_synthase.
DR InterPro; IPR034701; CdaA.
DR InterPro; IPR045585; CdaA_N.
DR InterPro; IPR036888; DNA_integrity_DisA_N_sf.
DR InterPro; IPR003390; DNA_integrity_scan_DisA_N.
DR Pfam; PF19293; CdaA_N; 1.
DR Pfam; PF02457; DAC; 1.
DR PIRSF; PIRSF004793; UCP004793; 1.
DR SUPFAM; SSF143597; SSF143597; 1.
DR TIGRFAMs; TIGR00159; TIGR00159; 1.
DR PROSITE; PS51794; DAC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell membrane; Membrane; Nucleotide-binding;
KW Nucleotidyltransferase; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..273
FT /note="Cyclic di-AMP synthase CdaA"
FT /id="PRO_0000360441"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01499"
FT TRANSMEM 40..60
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01499"
FT TRANSMEM 61..81
FT /note="Helical"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01499"
FT DOMAIN 82..242
FT /note="DAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01130"
FT CONFLICT 270
FT /note="K -> R (in Ref. 1; BAA19509)"
FT /evidence="ECO:0000305"
FT TURN 108..113
FT /evidence="ECO:0007829|PDB:6HUW"
FT HELIX 114..126
FT /evidence="ECO:0007829|PDB:6HUW"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:6HUW"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:6HUW"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:6HUW"
FT HELIX 156..162
FT /evidence="ECO:0007829|PDB:6HUW"
FT STRAND 171..177
FT /evidence="ECO:0007829|PDB:6HUW"
FT STRAND 180..186
FT /evidence="ECO:0007829|PDB:6HUW"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:6HUW"
FT HELIX 203..213
FT /evidence="ECO:0007829|PDB:6HUW"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:6HUW"
FT TURN 223..225
FT /evidence="ECO:0007829|PDB:6HUW"
FT STRAND 228..232
FT /evidence="ECO:0007829|PDB:6HUW"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:6HUW"
FT HELIX 242..251
FT /evidence="ECO:0007829|PDB:6HUW"
SQ SEQUENCE 273 AA; 30547 MW; 29F2984C5F90007C CRC64;
MAFEDIPFLQ YLGNAVDILL VWYVIYKLIM VIRGTKAVQL LKGIVVIVLV RMASQYLGLS
TLQWLMDQAI TWGFLAIIII FQPELRRALE QLGRGRFFSR SGTPVEEAQQ KTIEAITKAI
NYMAKRRIGA LLTIERDTGM GDYIETGIPL NAKVSSELLI NIFIPNTPLH DGAVIMKNNE
IAAAACYLPL SESPFISKEL GTRHRAAVGI SEVTDSLTII VSEETGGVSV AKNGDLHREL
TEEALKEMLE AEFKKNTRDT SSNRWYWRGK KNG
