CdaA

• Description: diadenylate cyclase, synthesis of c-di-AMP in vegetative cells
  
  

Gene name	cdaA
Synonyms	ybbP, ybbQ
Essential	no
Product	diadenylate cyclase
Function	synthesis of c-di-AMP
Gene expression levels in SubtiExpress: cdaA
Interactions involving this protein in SubtInteract: CdaA
Metabolic function and regulation of this protein in SubtiPathways: cdaA
MW, pI	30 kDa, 8.074
Gene length, protein length	819 bp, 273 aa
Immediate neighbours	rsiW, cdaR
Sequences	Protein DNA DNA_with_flanks
Genetic context This image was kindly provided by SubtiList
Expression at a glance   PubMed

Categories containing this gene/protein

membrane proteins, metabolism of signalling nucleotides

The gene

Basic information

• Locus tag: BSU01750

Phenotypes of a mutant

• inactivation of cdaA results in severe beta-lactam sensitivity PubMed

Database entries

• BsubCyc: BSU01750

• DBTBS entry: no entry

• SubtiList entry: [1]

The protein

Basic information/ Evolution

• Catalyzed reaction/ biological activity:
  • synthesis of c-di-AMP from two molecules of ATP PubMed

• Protein family:

• Paralogous protein(s): CdaS

Extended information on the protein

• Kinetic information:

• Domains:
  • contains a DAC domain involved in the synthesis of c-di-AMP PubMed

• Modification:

• Cofactors:

• Effectors of protein activity:
  • the interaction with CdaR stimulates the diadenylate cyclase activity of CdaA PubMed

• Interactions:
  • CdaA-CdaR, to stimulate CdaA activity PubMed

• Localization:
  • cell membrane (according to Swiss-Prot)

Database entries

• BsubCyc: BSU01750

• Structure: 4RV7 (the DAC domain and C-terminal domain of CdaA from Listeria monocytogenes (aa 101 - 273), 65% identity) PubMed

• UniProt: Q45589

• KEGG entry: [2]

• E.C. number:

Expression and regulation

• Operon: cdaA-cdaR-glmM-glmS PubMed

• Expression browser: cdaA PubMed

• Sigma factor: SigA PubMed

• Regulation:

• Regulatory mechanism:

• Additional information: the cdaA-cdaR part of the mRNA is very stable (half-life > 15 min) PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium): 60 PubMed
  • number of protein molecules per cell (complex medium with amino acids, without glucose): 239 PubMed

Biological materials

• Mutant:
  • GP94 (DcdaA::spc), available in Jörg Stülke's lab
  • GP997 (cdaA::cat), available in Jörg Stülke's lab
  • GP985 (cdaA-cdaR::cat), available in Jörg Stülke's lab

• Expression vector:
  • expression of native cdaA in B. subtilis: pGP1960 (in pBQ200), available in Jörg Stülke's lab
  • expression of cdaA-Strep in B. subtilis suitable for SPINE: pGP1986 (in pGP382), available in Jörg Stülke's lab
  • IPTG inducible expression of cdaA-Strep in E. coli: pGP2564 (in pGP574), available in Jörg Stülke's lab

• lacZ fusion: GP1339 (cat) based on pAC6, available in Jörg Stülke's lab

• GFP fusion:

• two-hybrid system: B. pertussis adenylate cyclase-based bacterial two hybrid system (BACTH), available in Jörg Stülke's lab. Respective plasmid: pGP1990.

• FLAG-tag construct:
  • GP1381 cdaA-3xFLAG ermC (based on pGP1087), available in Jörg Stülke's lab

• Antibody:

References

Reviews

Fabian M Commichau, Achim Dickmanns, Jan Gundlach, Ralf Ficner, Jörg Stülke
A jack of all trades: the multiple roles of the unique essential second messenger cyclic di-AMP.
Mol Microbiol: 2015, 97(2);189-204
[PubMed:25869574] [WorldCat.org] [DOI] (I p)

Ute Römling
Great times for small molecules: c-di-AMP, a second messenger candidate in Bacteria and Archaea.
Sci Signal: 2008, 1(33);pe39
[PubMed:18714086] [WorldCat.org] [DOI] (I e)

Original publications

Jan Gundlach, Felix M P Mehne, Christina Herzberg, Jan Kampf, Oliver Valerius, Volkhard Kaever, Jörg Stülke
An Essential Poison: Synthesis and Degradation of Cyclic Di-AMP in Bacillus subtilis.
J Bacteriol: 2015, 197(20);3265-74
[PubMed:26240071] [WorldCat.org] [DOI] (I p)

Carolina Gándara, Juan C Alonso
DisA and c-di-AMP act at the intersection between DNA-damage response and stress homeostasis in exponentially growing Bacillus subtilis cells.
DNA Repair (Amst): 2015, 27;1-8
[PubMed:25616256] [WorldCat.org] [DOI] (I p)

Jonathan Rosenberg, Achim Dickmanns, Piotr Neumann, Katrin Gunka, Johannes Arens, Volkhard Kaever, Jörg Stülke, Ralf Ficner, Fabian M Commichau
Structural and biochemical analysis of the essential diadenylate cyclase CdaA from Listeria monocytogenes.
J Biol Chem: 2015, 290(10);6596-606
[PubMed:25605729] [WorldCat.org] [DOI] (I p)

Felix M P Mehne, Katrin Gunka, Hinnerk Eilers, Christina Herzberg, Volkhard Kaever, Jörg Stülke
Cyclic di-AMP homeostasis in bacillus subtilis: both lack and high level accumulation of the nucleotide are detrimental for cell growth.
J Biol Chem: 2013, 288(3);2004-17
[PubMed:23192352] [WorldCat.org] [DOI] (I p)

Yun Luo, John D Helmann
Analysis of the role of Bacillus subtilis σ(M) in β-lactam resistance reveals an essential role for c-di-AMP in peptidoglycan homeostasis.
Mol Microbiol: 2012, 83(3);623-39
[PubMed:22211522] [WorldCat.org] [DOI] (I p)

Yaara Oppenheimer-Shaanan, Ezequiel Wexselblatt, Jehoshua Katzhendler, Eylon Yavin, Sigal Ben-Yehuda
c-di-AMP reports DNA integrity during sporulation in Bacillus subtilis.
EMBO Rep: 2011, 12(6);594-601
[PubMed:21566650] [WorldCat.org] [DOI] (I p)

G Hambraeus, C von Wachenfeldt, L Hederstedt
Genome-wide survey of mRNA half-lives in Bacillus subtilis identifies extremely stable mRNAs.
Mol Genet Genomics: 2003, 269(5);706-14
[PubMed:12884008] [WorldCat.org] [DOI] (P p)