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

Sabine Brantl, Andreas Licht
Characterisation of Bacillus subtilis transcriptional regulators involved in metabolic processes.
Curr Protein Pept Sci: 2010, 11(4);274-91
[PubMed:20408793] [WorldCat.org] [DOI] (I p)

Yasutaro Fujita
Carbon catabolite control of the metabolic network in Bacillus subtilis.
Biosci Biotechnol Biochem: 2009, 73(2);245-59
[PubMed:19202299] [WorldCat.org] [DOI] (I p)

Boris Görke, Jörg Stülke
Carbon catabolite repression in bacteria: many ways to make the most out of nutrients.
Nat Rev Microbiol: 2008, 6(8);613-24
[PubMed:18628769] [WorldCat.org] [DOI] (I p)

Josef Deutscher
The mechanisms of carbon catabolite repression in bacteria.
Curr Opin Microbiol: 2008, 11(2);87-93
[PubMed:18359269] [WorldCat.org] [DOI] (P p)

Jessica B Warner, Juke S Lolkema
CcpA-dependent carbon catabolite repression in bacteria.
Microbiol Mol Biol Rev: 2003, 67(4);475-90
[PubMed:14665673] [WorldCat.org] [DOI] (P p)

T M Henkin
The role of CcpA transcriptional regulator in carbon metabolism in Bacillus subtilis.
FEMS Microbiol Lett: 1996, 135(1);9-15
[PubMed:8598282] [WorldCat.org] [DOI] (P p)


General and physiological studies

Andrea Wünsche, Elke Hammer, Maike Bartholomae, Uwe Völker, Andreas Burkovski, Gerald Seidel, Wolfgang Hillen
CcpA forms complexes with CodY and RpoA in Bacillus subtilis.
FEBS J: 2012, 279(12);2201-14
[PubMed:22512862] [WorldCat.org] [DOI] (I p)

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)

Bogumiła C Marciniak, Monika Pabijaniak, Anne de Jong, Robert Dűhring, Gerald Seidel, Wolfgang Hillen, Oscar P Kuipers
High- and low-affinity cre boxes for CcpA binding in Bacillus subtilis revealed by genome-wide analysis.
BMC Genomics: 2012, 13;401
[PubMed:22900538] [WorldCat.org] [DOI] (I e)

Joerg Martin Buescher, Wolfram Liebermeister, Matthieu Jules, Markus Uhr, Jan Muntel, Eric Botella, Bernd Hessling, Roelco Jacobus Kleijn, Ludovic Le Chat, François Lecointe, Ulrike Mäder, Pierre Nicolas, Sjouke Piersma, Frank Rügheimer, Dörte Becher, Philippe Bessieres, Elena Bidnenko, Emma L Denham, Etienne Dervyn, Kevin M Devine, Geoff Doherty, Samuel Drulhe, Liza Felicori, Mark J Fogg, Anne Goelzer, Annette Hansen, Colin R Harwood, Michael Hecker, Sebastian Hubner, Claus Hultschig, Hanne Jarmer, Edda Klipp, Aurélie Leduc, Peter Lewis, Frank Molina, Philippe Noirot, Sabine Peres, Nathalie Pigeonneau, Susanne Pohl, Simon Rasmussen, Bernd Rinn, Marc Schaffer, Julian Schnidder, Benno Schwikowski, Jan Maarten Van Dijl, Patrick Veiga, Sean Walsh, Anthony J Wilkinson, Jörg Stelling, Stéphane Aymerich, Uwe Sauer
Global network reorganization during dynamic adaptations of Bacillus subtilis metabolism.
Science: 2012, 335(6072);1099-103
[PubMed:22383848] [WorldCat.org] [DOI] (I p)

Andrzej T Lulko, Girbe Buist, Jan Kok, Oscar P Kuipers
Transcriptome analysis of temporal regulation of carbon metabolism by CcpA in Bacillus subtilis reveals additional target genes.
J Mol Microbiol Biotechnol: 2007, 12(1-2);82-95
[PubMed:17183215] [WorldCat.org] [DOI] (P p)

Hans-Matti Blencke, Georg Homuth, Holger Ludwig, Ulrike Mäder, Michael Hecker, Jörg Stülke
Transcriptional profiling of gene expression in response to glucose in Bacillus subtilis: regulation of the central metabolic pathways.
Metab Eng: 2003, 5(2);133-49
[PubMed:12850135] [WorldCat.org] [DOI] (P p)

M S Moreno, B L Schneider, R R Maile, W Weyler, M H Saier
Catabolite repression mediated by the CcpA protein in Bacillus subtilis: novel modes of regulation revealed by whole-genome analyses.
Mol Microbiol: 2001, 39(5);1366-81
[PubMed:11251851] [WorldCat.org] [DOI] (P p)

K Yoshida, K Kobayashi, Y Miwa, C M Kang, M Matsunaga, H Yamaguchi, S Tojo, M Yamamoto, R Nishi, N Ogasawara, T Nakayama, Y Fujita
Combined transcriptome and proteome analysis as a powerful approach to study genes under glucose repression in Bacillus subtilis.
Nucleic Acids Res: 2001, 29(3);683-92
[PubMed:11160890] [WorldCat.org] [DOI] (I p)

S Tobisch, D Zühlke, J Bernhardt, J Stülke, M Hecker
Role of CcpA in regulation of the central pathways of carbon catabolism in Bacillus subtilis.
J Bacteriol: 1999, 181(22);6996-7004
[PubMed:10559165] [WorldCat.org] [DOI] (P p)


Repression of target genes by CcpA


Positive regulation of gene expression by CcpA

Control of CcpA activity

CcpA-DNA interaction

Functional analysis of CcpA

Structural analyses

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