CcpA

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  • Description: Carbon catabolite control protein A, involved in glucose regulation of many genes; represses catabolic genes and activates genes involved in excretion of excess carbon

Gene name ccpA
Synonyms graR, alsA, amyR
Essential no
Product transcriptional regulator (LacI family)
Function mediates carbon catabolite repression (CCR)
Gene expression levels in SubtiExpress: ccpA
Interactions involving this protein in SubtInteract: CcpA
Metabolic function and regulation of this protein in SubtiPathways:
Nucleoside catabolism, Nucleotides (regulation), Ile, Leu, Val,
His, Coenzyme A, Central C-metabolism
MW, pI 36,8 kDa, 5.06
Gene length, protein length 1002 bp, 334 amino acids
Immediate neighbours motP, aroA
Sequences Protein DNA DNA_with_flanks
Genetic context
CcpA context.gif
This image was kindly provided by SubtiList
Expression at a glance   PubMed
CcpA expression.png
















Categories containing this gene/protein

regulators of core metabolism

This gene is a member of the following regulons

The CcpA regulon

The gene

Basic information

  • Locus tag: BSU29740

Phenotypes of a mutant

Loss of carbon catabolite repression. Loss of PTS-dependent sugar transport due to excessive phosphorylation of HPr by HprK. The mutant is unable to grow on a minimal medium with glucose and ammonium as the only sources of carbon and nitrogen, respectively.

Database entries

  • DBTBS entry: [1]
  • SubtiList entry: [2]

Additional information

The protein

Basic information/ Evolution

  • Catalyzed reaction/ biological activity: transcriptional regulator of carbon catabolite repression (CCR)
  • Paralogous protein(s):

Extended information on the protein

  • Kinetic information:
  • Domains:
    • HTH LacI-type Domain (1 – 58)
    • DNA binding Domain (6 – 25)
  • Modification:
  • Cofactor(s): HPr-Ser46-P, Crh-Ser-46-P
  • Effectors of protein activity:glucose-6-phosphate, fructose-1,6-bisphosphate Pubmed

Database entries

  • Structure:
    • 2JCG (Apoprotein from Bacillus megaterium)
    • CcpA-Crh-DNA-complex NCBI
    • complex with P-Ser-HPr and sulphate ions NCBI
    • 3OQM (complex of B. subtilis CcpA with P-Ser-HPr and the ackA operator site)
    • 3OQN (complex of B. subtilis CcpA with P-Ser-HPr and the gntR operator site)
    • 3OQO (complex of B. subtilis CcpA with P-Ser-HPr and a optimal synthetic operator site)
  • KEGG entry: [3]

Additional information

Expression and regulation

  • Sigma factor:
  • Regulation: constitutively expressed PubMed
  • Additional information: there are about 3.000 molecules of CcpA per cell PubMed, this corresponds to a concentration of 3 myM (according to PubMed)

Biological materials

  • Expression vector:
  • Strep-tag construct: GP1303 ccpA-Strep (spc) in native locus, based on (pGP1389), available in Jörg Stülke's lab
  • lacZ fusion:
  • GFP fusion:

Labs working on this gene/protein

Your additional remarks

References

Reviews


General and physiological studies

Additional publications: PubMed

Frederik M Meyer, Matthieu Jules, Felix M P Mehne, Dominique Le Coq, Jens J Landmann, Boris Görke, Stéphane Aymerich, Jörg Stülke
Malate-mediated carbon catabolite repression in Bacillus subtilis involves the HPrK/CcpA pathway.
J Bacteriol: 2011, 193(24);6939-49
[PubMed:22001508] [WorldCat.org] [DOI] (I p)

Kalpana D Singh, Matthias H Schmalisch, Jörg Stülke, Boris Görke
Carbon catabolite repression in Bacillus subtilis: quantitative analysis of repression exerted by different carbon sources.
J Bacteriol: 2008, 190(21);7275-84
[PubMed:18757537] [WorldCat.org] [DOI] (I p)

Naoya Terahara, Makoto Fujisawa, Benjamin Powers, Tina M Henkin, Terry A Krulwich, Masahiro Ito
An intergenic stem-loop mutation in the Bacillus subtilis ccpA-motPS operon increases motPS transcription and the MotPS contribution to motility.
J Bacteriol: 2006, 188(7);2701-5
[PubMed:16547058] [WorldCat.org] [DOI] (P p)

Ingrid Wacker, Holger Ludwig, Irene Reif, Hans-Matti Blencke, Christian Detsch, Jörg Stülke
The regulatory link between carbon and nitrogen metabolism in Bacillus subtilis: regulation of the gltAB operon by the catabolite control protein CcpA.
Microbiology (Reading): 2003, 149(Pt 10);3001-3009
[PubMed:14523131] [WorldCat.org] [DOI] (P p)

Holger Ludwig, Nicole Rebhan, Hans-Matti Blencke, Matthias Merzbacher, Jörg Stülke
Control of the glycolytic gapA operon by the catabolite control protein A in Bacillus subtilis: a novel mechanism of CcpA-mediated regulation.
Mol Microbiol: 2002, 45(2);543-53
[PubMed:12123463] [WorldCat.org] [DOI] (P p)

N Faires, S Tobisch, S Bachem, I Martin-Verstraete, M Hecker, J Stülke
The catabolite control protein CcpA controls ammonium assimilation in Bacillus subtilis.
J Mol Microbiol Biotechnol: 1999, 1(1);141-8
[PubMed:10941796] [WorldCat.org] (P p)

Y Miwa, M Saikawa, Y Fujita
Possible function and some properties of the CcpA protein of Bacillus subtilis.
Microbiology (Reading): 1994, 140 ( Pt 10);2567-75
[PubMed:8000527] [WorldCat.org] [DOI] (P p)

T M Henkin, F J Grundy, W L Nicholson, G H Chambliss
Catabolite repression of alpha-amylase gene expression in Bacillus subtilis involves a trans-acting gene product homologous to the Escherichia coli lacl and galR repressors.
Mol Microbiol: 1991, 5(3);575-84
[PubMed:1904524] [WorldCat.org] [DOI] (P p)


Global analyses (proteome, transcriptome, ChIP-chip)

Additional publications: PubMed


Repression of target genes by CcpA

Additional publications: PubMed

José Manuel Inácio, Isabel de Sá-Nogueira
trans-Acting factors and cis elements involved in glucose repression of arabinan degradation in Bacillus subtilis.
J Bacteriol: 2007, 189(22);8371-6
[PubMed:17827291] [WorldCat.org] [DOI] (I p)

Soo-Keun Choi, Milton H Saier
Mechanism of CcpA-mediated glucose repression of the resABCDE operon of Bacillus subtilis.
J Mol Microbiol Biotechnol: 2006, 11(1-2);104-10
[PubMed:16825793] [WorldCat.org] [DOI] (P p)

Soo-Keun Choi, Milton H Saier
Regulation of pho regulon gene expression by the carbon control protein A, CcpA, in Bacillus subtilis.
J Mol Microbiol Biotechnol: 2005, 10(1);40-50
[PubMed:16491025] [WorldCat.org] [DOI] (P p)

Soo-Keun Choi, Milton H Saier
Regulation of sigL expression by the catabolite control protein CcpA involves a roadblock mechanism in Bacillus subtilis: potential connection between carbon and nitrogen metabolism.
J Bacteriol: 2005, 187(19);6856-61
[PubMed:16166551] [WorldCat.org] [DOI] (P p)

Boris R Belitsky, Hyun-Jin Kim, Abraham L Sonenshein
CcpA-dependent regulation of Bacillus subtilis glutamate dehydrogenase gene expression.
J Bacteriol: 2004, 186(11);3392-8
[PubMed:15150224] [WorldCat.org] [DOI] (P p)

Hyun-Jin Kim, Agnes Roux, Abraham L Sonenshein
Direct and indirect roles of CcpA in regulation of Bacillus subtilis Krebs cycle genes.
Mol Microbiol: 2002, 45(1);179-90
[PubMed:12100558] [WorldCat.org] [DOI] (P p)

Hyun-Jin Kim, Cécile Jourlin-Castelli, Sam-In Kim, Abraham L Sonenshein
Regulation of the bacillus subtilis ccpC gene by ccpA and ccpC.
Mol Microbiol: 2002, 43(2);399-410
[PubMed:11985717] [WorldCat.org] [DOI] (P p)

Emmanuelle Darbon, Pascale Servant, Sandrine Poncet, Josef Deutscher
Antitermination by GlpP, catabolite repression via CcpA and inducer exclusion triggered by P-GlpK dephosphorylation control Bacillus subtilis glpFK expression.
Mol Microbiol: 2002, 43(4);1039-52
[PubMed:11929549] [WorldCat.org] [DOI] (P p)

I Martin-Verstraete, J Stülke, A Klier, G Rapoport
Two different mechanisms mediate catabolite repression of the Bacillus subtilis levanase operon.
J Bacteriol: 1995, 177(23);6919-27
[PubMed:7592486] [WorldCat.org] [DOI] (P p)

F J Grundy, A J Turinsky, T M Henkin
Catabolite regulation of Bacillus subtilis acetate and acetoin utilization genes by CcpA.
J Bacteriol: 1994, 176(15);4527-33
[PubMed:7913927] [WorldCat.org] [DOI] (P p)


Positive regulation of gene expression by CcpA

Robert P Shivers, Abraham L Sonenshein
Bacillus subtilis ilvB operon: an intersection of global regulons.
Mol Microbiol: 2005, 56(6);1549-59
[PubMed:15916605] [WorldCat.org] [DOI] (P p)

Holger Ludwig, Christoph Meinken, Anastasija Matin, Jörg Stülke
Insufficient expression of the ilv-leu operon encoding enzymes of branched-chain amino acid biosynthesis limits growth of a Bacillus subtilis ccpA mutant.
J Bacteriol: 2002, 184(18);5174-8
[PubMed:12193635] [WorldCat.org] [DOI] (P p)

A J Turinsky, T R Moir-Blais, F J Grundy, T M Henkin
Bacillus subtilis ccpA gene mutants specifically defective in activation of acetoin biosynthesis.
J Bacteriol: 2000, 182(19);5611-4
[PubMed:10986270] [WorldCat.org] [DOI] (P p)

E Presecan-Siedel, A Galinier, R Longin, J Deutscher, A Danchin, P Glaser, I Martin-Verstraete
Catabolite regulation of the pta gene as part of carbon flow pathways in Bacillus subtilis.
J Bacteriol: 1999, 181(22);6889-97
[PubMed:10559153] [WorldCat.org] [DOI] (P p)

A J Turinsky, F J Grundy, J H Kim, G H Chambliss, T M Henkin
Transcriptional activation of the Bacillus subtilis ackA gene requires sequences upstream of the promoter.
J Bacteriol: 1998, 180(22);5961-7
[PubMed:9811655] [WorldCat.org] [DOI] (P p)

F J Grundy, D A Waters, S H Allen, T M Henkin
Regulation of the Bacillus subtilis acetate kinase gene by CcpA.
J Bacteriol: 1993, 175(22);7348-55
[PubMed:8226682] [WorldCat.org] [DOI] (P p)

Control of CcpA activity

Lwin Mar Aung-Hilbrich, Gerald Seidel, Andrea Wagner, Wolfgang Hillen
Quantification of the influence of HPrSer46P on CcpA-cre interaction.
J Mol Biol: 2002, 319(1);77-85
[PubMed:12051938] [WorldCat.org] [DOI] (P p)

A Galinier, J Deutscher, I Martin-Verstraete
Phosphorylation of either crh or HPr mediates binding of CcpA to the bacillus subtilis xyn cre and catabolite repression of the xyn operon.
J Mol Biol: 1999, 286(2);307-14
[PubMed:9973552] [WorldCat.org] [DOI] (P p)

J H Kim, M I Voskuil, G H Chambliss
NADP, corepressor for the Bacillus catabolite control protein CcpA.
Proc Natl Acad Sci U S A: 1998, 95(16);9590-5
[PubMed:9689125] [WorldCat.org] [DOI] (P p)

B E Jones, V Dossonnet, E Küster, W Hillen, J Deutscher, R E Klevit
Binding of the catabolite repressor protein CcpA to its DNA target is regulated by phosphorylation of its corepressor HPr.
J Biol Chem: 1997, 272(42);26530-5
[PubMed:9334231] [WorldCat.org] [DOI] (P p)

J Deutscher, E Küster, U Bergstedt, V Charrier, W Hillen
Protein kinase-dependent HPr/CcpA interaction links glycolytic activity to carbon catabolite repression in gram-positive bacteria.
Mol Microbiol: 1995, 15(6);1049-53
[PubMed:7623661] [WorldCat.org] [DOI] (P p)

CcpA-DNA interaction

Maria A Schumacher, Mareen Sprehe, Maike Bartholomae, Wolfgang Hillen, Richard G Brennan
Structures of carbon catabolite protein A-(HPr-Ser46-P) bound to diverse catabolite response element sites reveal the basis for high-affinity binding to degenerate DNA operators.
Nucleic Acids Res: 2011, 39(7);2931-42
[PubMed:21106498] [WorldCat.org] [DOI] (I p)

Gerald Seidel, Marco Diel, Norbert Fuchsbauer, Wolfgang Hillen
Quantitative interdependence of coeffectors, CcpA and cre in carbon catabolite regulation of Bacillus subtilis.
FEBS J: 2005, 272(10);2566-77
[PubMed:15885105] [WorldCat.org] [DOI] (P p)

Y Miwa, A Nakata, A Ogiwara, M Yamamoto, Y Fujita
Evaluation and characterization of catabolite-responsive elements (cre) of Bacillus subtilis.
Nucleic Acids Res: 2000, 28(5);1206-10
[PubMed:10666464] [WorldCat.org] [DOI] (I p)

J H Kim, G H Chambliss
Contacts between Bacillus subtilis catabolite regulatory protein CcpA and amyO target site.
Nucleic Acids Res: 1997, 25(17);3490-6
[PubMed:9254709] [WorldCat.org] [DOI] (P p)

Y Fujita, Y Miwa, A Galinier, J Deutscher
Specific recognition of the Bacillus subtilis gnt cis-acting catabolite-responsive element by a protein complex formed between CcpA and seryl-phosphorylated HPr.
Mol Microbiol: 1995, 17(5);953-60
[PubMed:8596444] [WorldCat.org] [DOI] (P p)

J H Kim, Z T Guvener, J Y Cho, K C Chung, G H Chambliss
Specificity of DNA binding activity of the Bacillus subtilis catabolite control protein CcpA.
J Bacteriol: 1995, 177(17);5129-34
[PubMed:7665492] [WorldCat.org] [DOI] (P p)

Functional analysis of CcpA

H Ludwig, J Stülke
The Bacillus subtilis catabolite control protein CcpA exerts all its regulatory functions by DNA-binding.
FEMS Microbiol Lett: 2001, 203(1);125-9
[PubMed:11557150] [WorldCat.org] [DOI] (P p)

E Küster-Schöck, A Wagner, U Völker, W Hillen
Mutations in catabolite control protein CcpA showing glucose-independent regulation in Bacillus megaterium.
J Bacteriol: 1999, 181(24);7634-8
[PubMed:10601226] [WorldCat.org] [DOI] (P p)

E Küster, T Hilbich, M K Dahl, W Hillen
Mutations in catabolite control protein CcpA separating growth effects from catabolite repression.
J Bacteriol: 1999, 181(13);4125-8
[PubMed:10383986] [WorldCat.org] [DOI] (P p)

A Kraus, E Küster, A Wagner, K Hoffmann, W Hillen
Identification of a co-repressor binding site in catabolite control protein CcpA.
Mol Microbiol: 1998, 30(5);955-63
[PubMed:9988473] [WorldCat.org] [DOI] (P p)

A Kraus, W Hillen
Analysis of CcpA mutations defective in carbon catabolite repression in Bacillus megaterium.
FEMS Microbiol Lett: 1997, 153(1);221-6
[PubMed:9252590] [WorldCat.org] [DOI] (P p)

Structural analyses

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