CodY

• Description: regulation of a large regulon (more than 100 genes and operons) 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
Gene expression levels in SubtiExpress: codY
Interactions involving this protein in SubtInteract: CodY
Metabolic function and regulation of this protein in SubtiPathways: codY
MW, pI	28 kDa, 4.75
Gene length, protein length	777 bp, 259 aa
Immediate neighbours	clpY, flgB
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, phosphoproteins

This gene is a member of the following regulons

CodY regulon

The gene

Basic information

• Locus tag: BSU16170

Phenotypes of a mutant

• no swarming motility on B medium. PubMed
• the mutation suppresses the mucoid phenotype of motA or motB mutants due to loss of DegU phosphorylation and concomitant reduced expression of the capB-capC-capA-capE operon PubMed
• inactivation of codY suppresses the requirement of a relA sasA sasB triple mutant for branched chain amino acids, methionine and threonine PubMed

Database entries

• BsubCyc: BSU16170

• 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

• Cofactors:

• 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)
  • CcpA-CodY PubMed
  • RpoA-CodY PubMed

• Localization: cytoplasm (according to Swiss-Prot)

Database entries

• BsubCyc: BSU16170

• 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

• Expression browser: 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)
  • number of protein molecules per cell (minimal medium with glucose and ammonium): 955 PubMed
  • number of protein molecules per cell (complex medium with amino acids, without glucose): 3409 PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium, exponential phase): 350 PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium, early stationary phase after glucose exhaustion): 351 PubMed
  • number of protein molecules per cell (minimal medium with glucose and ammonium, late stationary phase after glucose exhaustion): 272 PubMed

Biological materials

• Mutant:
  • GP566, available in Jörg Stülke's lab
  • a codY::erm mutant is available in Linc Sonenshein's lab
  • a codY::spc (BB1043) mutant is available in Linc Sonenshein's, Fabian Commichau's and Jörg Stülke's labs

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

Tobias Geiger, Christiane Wolz
Intersection of the stringent response and the CodY regulon in low GC Gram-positive bacteria.
Int J Med Microbiol: 2014, 304(2);150-5
[PubMed:24462007] [WorldCat.org] [DOI] (I p)

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)

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)

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)

The CodY regulon

Shaun R Brinsmade, Elizabeth L Alexander, Jonathan Livny, Arion I Stettner, Daniel Segrè, Kyu Y Rhee, Abraham L Sonenshein
Hierarchical expression of genes controlled by the Bacillus subtilis global regulatory protein CodY.
Proc Natl Acad Sci U S A: 2014, 111(22);8227-32
[PubMed:24843172] [WorldCat.org] [DOI] (I p)

Boris R Belitsky, Abraham L Sonenshein
Genome-wide identification of Bacillus subtilis CodY-binding sites at single-nucleotide resolution.
Proc Natl Acad Sci U S A: 2013, 110(17);7026-31
[PubMed:23569278] [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)

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)