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diadenylate cyclase, synthesis of c-di-AMP in vegetative cells
function
synthesis of c-di-AMP
product
diadenylate cyclase
Genomic Context
categories
[category|SW 2|Metabolism] → [category|SW 2.5|Nucleotide metabolism] → [category|SW 2.5.3|Metabolism of signalling nucleotides][category|SW 6|Groups of genes] → [category|SW 6.2|Membrane proteins]Gene
Coordinates
196,213 → 197,034
Phenotypes of a mutant
inactivation of ''[gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA]'' results in severe beta-lactam sensitivity [Pubmed|22211522]a [gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA] [gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA] double mutant or [gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA] [gene|92EF98B872C1AD729B0BFAD46D3FA572E9C2AA32|cdaS] [gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA] triple mutant is not viable on complex medium; however, the mutant grows at low potassium concentration (0.1 mM) [pubmed|28420751]The protein
Catalyzed reaction/ biological activity
synthesis of c-di-AMP from two molecules of ATP [Pubmed|23192352]2 ATP --> c-di-AMP + 2 diphosphate (according to UniProt)Protein family
adenylate cyclase family (with [protein|92EF98B872C1AD729B0BFAD46D3FA572E9C2AA32|CdaS], according to UniProt)Paralogous protein(s)
[protein|92EF98B872C1AD729B0BFAD46D3FA572E9C2AA32|CdaS] [SW|Domains]
contains a [SW|DAC domain] involved in the synthesis of c-di-AMP [Pubmed|21566650][SW|DAC domain] (aa 82-242) (according to UniProt)[SW|Cofactors]
Mn2+ [pubmed|31118276,25605729]Effectors of protein activity
the interaction with [protein|FB23F2AB0E2A82658009D115E5876E7AF1BDE5FD|CdaR] controls the diadenylate cyclase activity of [protein|AFE2A9998219162FE32E95628B3CA9071099B61A|CdaA] [Pubmed|23192352]the interaction with [protein|FB23F2AB0E2A82658009D115E5876E7AF1BDE5FD|CdaR] inhibits the diadenylate cyclase activity of [protein|AFE2A9998219162FE32E95628B3CA9071099B61A|CdaA] (shown in S. aureus) [pubmed|30668586]the interaction with [protein|F022ACB2CBB8DA46B392CE1D26474093645F26DA|GlmM] inhibits the diadenylate cyclase activity of [protein|AFE2A9998219162FE32E95628B3CA9071099B61A|CdaA] under conditions of osmotic stress (shown in L. monocytogenes) [pubmed|32250026]Structure
[PDB|6HUW][PDB|4RV7] (the [SW|DAC domain] and C-terminal domain of CdaA from ''Listeria monocytogenes'' (aa 101 - 273), 65% identity) [Pubmed|25605729][PDB|6HVL] (the [SW|DAC domain] and C-terminal domain of CdaA from ''Listeria monocytogenes'' (aa 101 - 273) in complex with c-di-AMP, 65% identity) [Pubmed|31118276][SW|Localization]
cell membrane [Pubmed|26240071]Expression and Regulation
Operons
genes
[gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA]-[gene|FB23F2AB0E2A82658009D115E5876E7AF1BDE5FD|cdaR]-[gene|F022ACB2CBB8DA46B392CE1D26474093645F26DA|glmM]-[gene|4E23D2043D51C587027ABBF6335F148295E90B8F|glmS]
description
[Pubmed|23192352]
sigma factors
[protein|360F48D576DE950DF79C1A2677B7A35A8D8CC30C|SigA]: sigma factor, [Pubmed|22211522], in [regulon|360F48D576DE950DF79C1A2677B7A35A8D8CC30C|SigA regulon]view in new tabadditional information
CdaA levels are increased at increased potassium concentrations [pubmed|28420751]the mRNA is very stable (> 15 min) [pubmed|12884008]Biological materials
Mutant
GP94 Δ[gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA]::spec, available in [SW|Jörg Stülke]'s lab [pubmed|28420751]GP997 Δ[gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA]::cat, available in [SW|Jörg Stülke]'s lab [pubmed|23192352]GP2790 Δ[gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA]::aphA3, available in [SW|Jörg Stülke]'s labGP985 (''[gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA]''-''[gene|FB23F2AB0E2A82658009D115E5876E7AF1BDE5FD|cdaR]''::''cat''), available in [SW|Jörg Stülke]'s labGP2222 ([gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA]::cat [gene|92EF98B872C1AD729B0BFAD46D3FA572E9C2AA32|cdaS]::ermC ''[gene|2B091CCEE9E34D659771E39B1FC9050A145048AB|disA]''::''tet''), available in [SW|Jörg Stülke]'s lab, the mutant is only viable on minimal medium at low potassium concentration [pubmed|28420751]BKE01750 (Δ[gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA]::erm trpC2) available at [http://www.bgsc.org/getdetail.php?bgscid=BKE01750 BGSC], [Pubmed|28189581], upstream reverse: _UP1_CATTTCCTCGTCCTCCAAGA, downstream forward: _UP4_CGCTGGTATTGGAGGGGCAABKK01750 (Δ[gene|AFE2A9998219162FE32E95628B3CA9071099B61A|cdaA]::kan trpC2) available at [http://www.bgsc.org/getdetail.php?bgscid=BKK01750 BGSC], [Pubmed|28189581], upstream reverse: _UP1_CATTTCCTCGTCCTCCAAGA, downstream forward: _UP4_CGCTGGTATTGGAGGGGCAAExpression vectors
expression of native ''cdaA'' in ''B. subtilis'': pGP1960 (in [SW|pBQ200]), available in [SW|Jörg Stülke]'s labexpression of ''cdaA''-Strep in ''B. subtilis'' suitable for [SW|SPINE]: pGP1986 (in [SW|pGP382]), available in [SW|Jörg Stülke]'s labIPTG inducible expression of ''cdaA''-Strep in ''E. coli'': pGP2564 (in [SW|pGP574]), available in [SW|Jörg Stülke]'s lablacZ fusion
GP1339 (cat) based on [SW|pAC6], available in [SW|Jörg Stülke]'s labtwo-hybrid system
B. pertussis adenylate cyclase-based bacterial two hybrid system ([SW|BACTH]), available in [SW|Jörg Stülke]'s lab. Respective plasmid: pGP1990.FLAG-tag construct
GP1381 ''cdaA-3xFLAG ermC'' (based on [SW|pGP1087]), available in [SW|Jörg Stülke]'s lab [pubmed|28420751]labs
[SW|Jörg Stülke], University of Göttingen, Germany [http://genmibio.uni-goettingen.de Homepage]References
Reviews
18714086,25869574,23812326,30224435,32472931,32603625 Original publications
32250026,12884008,21566650,23192352,22211522,25605729,25616256,26240071,26527648,26585449,28420751,30668586,31118276,32250026