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 Stülke 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)

Original Publications

Jia Mun Chan, Sarah B Guttenplan, Daniel B Kearns
Defects in the flagellar motor increase synthesis of poly-γ-glutamate in Bacillus subtilis.
J Bacteriol: 2014, 196(4);740-53
[PubMed:24296669] [WorldCat.org] [DOI] (I p)

Allison Kriel, Shaun R Brinsmade, Jessica L Tse, Ashley K Tehranchi, Alycia N Bittner, Abraham L Sonenshein, Jue D Wang
GTP dysregulation in Bacillus subtilis cells lacking (p)ppGpp results in phenotypic amino acid auxotrophy and failure to adapt to nutrient downshift and regulate biosynthesis genes.
J Bacteriol: 2014, 196(1);189-201
[PubMed:24163341] [WorldCat.org] [DOI] (I p)

Baoping Ling, Min Sun, Siwei Bi, Zhihong Jing, Zhiguo Wang
Molecular dynamics simulations of isoleucine-release pathway in GAF domain of N-CodY from Bacillus Subtilis.
J Mol Graph Model: 2013, 44;232-40
[PubMed:23911932] [WorldCat.org] [DOI] (I p)

Allison Kriel, Alycia N Bittner, Sok Ho Kim, Kuanqing Liu, Ashley K Tehranchi, Winnie Y Zou, Samantha Rendon, Rui Chen, Benjamin P Tu, Jue D Wang
Direct regulation of GTP homeostasis by (p)ppGpp: a critical component of viability and stress resistance.
Mol Cell: 2012, 48(2);231-41
[PubMed:22981860] [WorldCat.org] [DOI] (I p)

Andrea Wünsche, Elke Hammer, Maike Bartholomae, Uwe Völker, Andreas Burkovski, Gerald Seidel, Wolfgang Hillen
CcpA forms complexes with CodY and RpoA in Bacillus subtilis.
FEBS J: 2012, 279(12);2201-14
[PubMed:22512862] [WorldCat.org] [DOI] (I p)

Shaun R Brinsmade, Abraham L Sonenshein
Dissecting complex metabolic integration provides direct genetic evidence for CodY activation by guanine nucleotides.
J Bacteriol: 2011, 193(20);5637-48
[PubMed:21856856] [WorldCat.org] [DOI] (I p)

Lewis V Wray, Susan H Fisher
Bacillus subtilis CodY operators contain overlapping CodY binding sites.
J Bacteriol: 2011, 193(18);4841-8
[PubMed:21764931] [WorldCat.org] [DOI] (I p)

Boris R Belitsky, Abraham L Sonenshein
Roadblock repression of transcription by Bacillus subtilis CodY.
J Mol Biol: 2011, 411(4);729-43
[PubMed:21699902] [WorldCat.org] [DOI] (I p)

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)

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)

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)

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)

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)