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)
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
Get the DNA and protein sequences (Barbe et al., 2009)
Genetic context This image was kindly provided by SubtiList

Categories containing this gene/protein

regulators of core 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):

Genes controlled by CcpA

• Activation by CcpA: pta, ackA, ilvB-ilvH-ilvC-leuA-leuB-leuC-leuD

• Repression by CcpA: abbA, amyE, bglP-bglH, bglS, cccA, citZ-icd-mdh, levD-levE-levF-levG-sacC, licB-licC-licA-licH, phoP-phoR, xylA-xylB, xynP-xynB

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

• 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

• 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), GP302 (erm), GP300 (an in frame deletion of ccpA), available in Stülke lab

• Expression vector: pGP643 (N-terminal Strep-tag, purification from B. subtilis, for SPINE, in pGP380), available in Stülke lab

• lacZ fusion:

• GFP fusion:

• Antibody: available in Hillen and Stülke labs

Labs working on this gene/protein

• • Wolfgang Hillen, 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

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

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)

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)