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
Function	mediates carbon catabolite repression (CCR)
Metabolic function and regulation of this protein in SubtiPathways: 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	aroA, motP
Get the DNA and protein sequences (Barbe et al., 2009)
Genetic context This image was kindly provided by SubtiList

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: CcpA-Crh-DNA-complex NCBI, complex with P-Ser-HPr and sulphate ions NCBI

• Swiss prot entry: 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

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

General and physiological studies

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)

Repression of target genes by CcpA

Positive regulation of gene expression by CcpA

Control of CcpA activity

CcpA-DNA interaction

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