CcpA

• 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: ccpA
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 This image was kindly provided by SubtiList
Expression at a glance   PubMed

Categories containing this gene/protein

• transcription factors and their control,

regulators of core metabolism

• see also: glutamate metabolism

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]

The protein

Basic information/ Evolution

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

• Protein family: LacI family

• 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

• Interactions:
  • CcpA-HPr PubMed
  • CcpA-Crh PubMed
  • CcpA-RpoA PubMed
  • CcpA-CodY PubMed

• Localization:

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)

• UniProt: P25144

• KEGG entry: [3]

Expression and regulation

• Operon: ccpA-motP-motS PubMed

• Expression browser: ccpA PubMed

• 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

• Mutant:
  • QB5407 (spc) PubMed, available in Jörg Stülke's lab
  • GP302 (erm) PubMed, available in Jörg Stülke's lab
  • GP300 (an in frame deletion of ccpA) PubMed, available in Jörg Stülke's lab
  • WH649 (aphA3), available in Gerald Seidel's lab

• Expression vector:
  • pGP643 (N-terminal Strep-tag, purification from B. subtilis, for SPINE, in pGP380), available in Jörg Stülke's lab
  • pWH940 (C-terminal Strep-tag, purification from B. subtilis, for SPINE, in pGP382), available in Gerald Seidel's lab

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

• lacZ fusion:

• GFP fusion:

• Antibody: available in Gerald Seidel's and in Jörg Stülke's lab

Labs working on this gene/protein

• Gerald Seidel, Erlangen University, Germany Homepage
• Richard Brennan, Houston, Texas, USA Homepage
• Milton H. Saier, University of California at San Diego, USA Homepage
• Yasutaro Fujita, University of Fukuyama, Japan
• Jörg Stülke, University of Göttingen, Germany Homepage
• Oscar Kuipers, University of Groningen, The Netherlands Homepage

References

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)

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)