CodY

• Description: regulation of a large regulon in response to branched-chain amino acid limitation
  
  

Gene name	codY
Synonyms
Essential	no
Product	transcriptional pleiotropic repressor
Function	regulation of a large regulon in response to branched-chain amino acid limitation to the presence of branched-chain amino acids
Metabolic function and regulation of this protein in SubtiPathways: Lipid synthesis
MW, pI	28 kDa, 4.75
Gene length, protein length	777 bp, 259 aa
Immediate neighbours	clpY, flgB
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: BSU16170

Phenotypes of a mutant

No swarming motility on B medium. PubMed

Database entries

• DBTBS entry: [1]

• SubtiList entry: [2]

The protein

Basic information/ Evolution

• Catalyzed reaction/ biological activity:

• Protein family: codY family (according to Swiss-Prot)

• Paralogous protein(s):

Extended information on the protein

• Kinetic information:

• Domains: contains a GAF domain (ligand binding domain)

• Modification: phosphorylation on Ser-215 PubMed

• Cofactor(s):

• Effectors of protein activity: GTP and branched chained amino acids (BCAA) increase the affinity of CodY for its DNA target sequences PubMed

• Interactions: active as dimer (according to PubMed)

• Localization: cytoplasm (according to Swiss-Prot)

Database entries

• Structure: 2B0L (C-terminal DNA-binding domain), 2GX5 (N-terminal Gaf domain)

• UniProt: P39779

• KEGG entry: [3]

• E.C. number:

Expression and regulation

• Operon: codV-clpQ-clpY-codY PubMed

• Sigma factor: SigA PubMed

• Regulation:
  • repressed during growth in the presence of branched chain amino acids (CodY) PubMed

• Regulatory mechanism:
  • CodY: transcription repression PubMed

• Additional information:
  • the intracellular concentration of CodY is about 2.5 myM (according to PubMed)

Biological materials

• Mutant: GP566, available in Stülke lab

• Expression vector:
  • for expression, purification in E. coli with N-terminal His-tag, in pWH844: pGP245, available in Stülke lab

• lacZ fusion:

• GFP fusion:

• two-hybrid system:

• Antibody:

Labs working on this gene/protein

Linc Sonenshein, Tufts University, Boston, MA, USA Homepage

Tony Wilkinson, York University, U.K. 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)

Original Publications

Boris R Belitsky, Abraham L Sonenshein
Contributions of multiple binding sites and effector-independent binding to CodY-mediated regulation in Bacillus subtilis.
J Bacteriol: 2011, 193(2);473-84
[PubMed:21097623] [WorldCat.org] [DOI] (I p)

Shaun R Brinsmade, Roelco J Kleijn, Uwe Sauer, Abraham L Sonenshein
Regulation of CodY activity through modulation of intracellular branched-chain amino acid pools.
J Bacteriol: 2010, 192(24);6357-68
[PubMed:20935095] [WorldCat.org] [DOI] (I p)

Anuradha C Villapakkam, Luke D Handke, Boris R Belitsky, Vladimir M Levdikov, Anthony J Wilkinson, Abraham L Sonenshein
Genetic and biochemical analysis of the interaction of Bacillus subtilis CodY with branched-chain amino acids.
J Bacteriol: 2009, 191(22);6865-76
[PubMed:19749041] [WorldCat.org] [DOI] (I p)

Heike Preis, Rita A Eckart, Rajani K Gudipati, Nadja Heidrich, Sabine Brantl
CodY activates transcription of a small RNA in Bacillus subtilis.
J Bacteriol: 2009, 191(17);5446-57
[PubMed:19542274] [WorldCat.org] [DOI] (I p)

Vladimir M Levdikov, Elena Blagova, Vicki L Colledge, Andrey A Lebedev, David C Williamson, Abraham L Sonenshein, Anthony J Wilkinson
Structural rearrangement accompanying ligand binding in the GAF domain of CodY from Bacillus subtilis.
J Mol Biol: 2009, 390(5);1007-18
[PubMed:19500589] [WorldCat.org] [DOI] (I p)

Kassem Hamze, Daria Julkowska, Sabine Autret, Krzysztof Hinc, Krzysztofa Nagorska, Agnieszka Sekowska, I Barry Holland, Simone J Séror
Identification of genes required for different stages of dendritic swarming in Bacillus subtilis, with a novel role for phrC.
Microbiology (Reading): 2009, 155(Pt 2);398-412
[PubMed:19202088] [WorldCat.org] [DOI] (P p)

Shigeo Tojo, Takenori Satomura, Kanako Kumamoto, Kazutake Hirooka, Yasutaro Fujita
Molecular mechanisms underlying the positive stringent response of the Bacillus subtilis ilv-leu operon, involved in the biosynthesis of branched-chain amino acids.
J Bacteriol: 2008, 190(18);6134-47
[PubMed:18641142] [WorldCat.org] [DOI] (I p)

Boris R Belitsky, Abraham L Sonenshein
Genetic and biochemical analysis of CodY-binding sites in Bacillus subtilis.
J Bacteriol: 2008, 190(4);1224-36
[PubMed:18083814] [WorldCat.org] [DOI] (I p)

Luke D Handke, Robert P Shivers, Abraham L Sonenshein
Interaction of Bacillus subtilis CodY with GTP.
J Bacteriol: 2008, 190(3);798-806
[PubMed:17993518] [WorldCat.org] [DOI] (I p)

Abraham L Sonenshein
Control of key metabolic intersections in Bacillus subtilis.
Nat Rev Microbiol: 2007, 5(12);917-27
[PubMed:17982469] [WorldCat.org] [DOI] (I p)

Wiep Klaas Smits, Tran Thu Hoa, Leendert W Hamoen, Oscar P Kuipers, David Dubnau
Antirepression as a second mechanism of transcriptional activation by a minor groove binding protein.
Mol Microbiol: 2007, 64(2);368-81
[PubMed:17493123] [WorldCat.org] [DOI] (P p)

Boris Macek, Ivan Mijakovic, Jesper V Olsen, Florian Gnad, Chanchal Kumar, Peter R Jensen, Matthias Mann
The serine/threonine/tyrosine phosphoproteome of the model bacterium Bacillus subtilis.
Mol Cell Proteomics: 2007, 6(4);697-707
[PubMed:17218307] [WorldCat.org] [DOI] (P p)

Robert P Shivers, Sean S Dineen, Abraham L Sonenshein
Positive regulation of Bacillus subtilis ackA by CodY and CcpA: establishing a potential hierarchy in carbon flow.
Mol Microbiol: 2006, 62(3);811-22
[PubMed:16995897] [WorldCat.org] [DOI] (P p)

Pascale Joseph, Manoja Ratnayake-Lecamwasam, Abraham L Sonenshein
A region of Bacillus subtilis CodY protein required for interaction with DNA.
J Bacteriol: 2005, 187(12);4127-39
[PubMed:15937175] [WorldCat.org] [DOI] (P p)

Shigeo Tojo, Takenori Satomura, Kaori Morisaki, Josef Deutscher, Kazutake Hirooka, Yasutaro Fujita
Elaborate transcription regulation of the Bacillus subtilis ilv-leu operon involved in the biosynthesis of branched-chain amino acids through global regulators of CcpA, CodY and TnrA.
Mol Microbiol: 2005, 56(6);1560-73
[PubMed:15916606] [WorldCat.org] [DOI] (P p)

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)

Abraham L Sonenshein
CodY, a global regulator of stationary phase and virulence in Gram-positive bacteria.
Curr Opin Microbiol: 2005, 8(2);203-7
[PubMed:15802253] [WorldCat.org] [DOI] (P p)

Robert P Shivers, Abraham L Sonenshein
Activation of the Bacillus subtilis global regulator CodY by direct interaction with branched-chain amino acids.
Mol Microbiol: 2004, 53(2);599-611
[PubMed:15228537] [WorldCat.org] [DOI] (P p)

Virginie Molle, Yoshiko Nakaura, Robert P Shivers, Hirotake Yamaguchi, Richard Losick, Yasutaro Fujita, Abraham L Sonenshein
Additional targets of the Bacillus subtilis global regulator CodY identified by chromatin immunoprecipitation and genome-wide transcript analysis.
J Bacteriol: 2003, 185(6);1911-22
[PubMed:12618455] [WorldCat.org] [DOI] (P p)

Hyun-Jin Kim, Sam-In Kim, Manoja Ratnayake-Lecamwasam, Kiyoshi Tachikawa, Abraham L Sonenshein, Mark Strauch
Complex regulation of the Bacillus subtilis aconitase gene.
J Bacteriol: 2003, 185(5);1672-80
[PubMed:12591885] [WorldCat.org] [DOI] (P p)

M Ratnayake-Lecamwasam, P Serror, K W Wong, A L Sonenshein
Bacillus subtilis CodY represses early-stationary-phase genes by sensing GTP levels.
Genes Dev: 2001, 15(9);1093-103
[PubMed:11331605] [WorldCat.org] [DOI] (P p)

L V Wray, A E Ferson, S H Fisher
Expression of the Bacillus subtilis ureABC operon is controlled by multiple regulatory factors including CodY, GlnR, TnrA, and Spo0H.
J Bacteriol: 1997, 179(17);5494-501
[PubMed:9287005] [WorldCat.org] [DOI] (P p)

P Serror, A L Sonenshein
Interaction of CodY, a novel Bacillus subtilis DNA-binding protein, with the dpp promoter region.
Mol Microbiol: 1996, 20(4);843-52
[PubMed:8793880] [WorldCat.org] [DOI] (P p)

F J Slack, P Serror, E Joyce, A L Sonenshein
A gene required for nutritional repression of the Bacillus subtilis dipeptide permease operon.
Mol Microbiol: 1995, 15(4);689-702
[PubMed:7783641] [WorldCat.org] [DOI] (P p)