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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 CodY regulon


The CodY regulon


Gene


  • Coordinates on the chromosome (coding sequence): 1,690,119 -> 1,690,898
  • 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
  • The protein


    Catalyzed reaction/ biological activity

    Protein family

  • codY family (according to Swiss-Prot)
  • Paralogous protein(s)

    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
  • Structure

  • 5LOO (unliganded full-length protein) PubMed
  • 2B0L (C-terminal DNA-binding domain), 2GX5 (N-terminal Gaf domain)
  • Localization

  • cytoplasm (according to Swiss-Prot)
  • Interactions

  • active as dimer (according to PubMed)
  • CcpA-CodY PubMed
  • RpoA-CodY PubMed
  • Additional information

    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 Jörg Stülke's lab
  • a codY::erm mutant is available in Linc Sonenshein's lab
  • a codY::spc (BB1043) mutant is available in Linc Sonensheins, Fabian Commichaus and Jörg Stülke's labs
  • BKE16170 (codY::erm trpC2) is available from the Bacillus Genetic Stock Center
  • 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

  • B. pertussis adenylate cyclase-based bacterial two hybrid system (BACTH), available in Fabian Commichau's lab
  • FLAG-tag construct

    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

    Geiger T, Wolz C

    Intersection of the stringent response and the CodY regulon in low GC Gram-positive bacteria

    Int J Med Microbiol. 2014 Mar;304(2):150-5. doi: 10.1016/j.ijmm.2013.11.013. Epub 2013 Dec 1. Review. PubMed PMID: 24462007.
    Brantl S, Licht A

    Characterisation of Bacillus subtilis transcriptional regulators involved in metabolic processes

    Curr Protein Pept Sci. 2010 Jun;11(4):274-91. Review. PubMed PMID: 20408793.
    Sonenshein AL

    Control of key metabolic intersections in Bacillus subtilis

    Nat Rev Microbiol. 2007 Dec;5(12):917-27. Review. PubMed PMID: 17982469.
    Sonenshein AL

    CodY, a global regulator of stationary phase and virulence in Gram-positive bacteria

    Curr Opin Microbiol. 2005 Apr;8(2):203-7. Review. PubMed PMID: 15802253.

    The CodY regulon

    Brinsmade SR, Alexander EL, Livny J, Stettner AI, Segrè D, Rhee KY, Sonenshein AL

    Hierarchical expression of genes controlled by the Bacillus subtilis global regulatory protein CodY

    Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8227-32. doi: 10.1073/pnas.1321308111. Epub 2014 May 19. PubMed PMID: 24843172; PubMed Central PMCID: PMC4050614.
    Belitsky BR, Sonenshein AL

    Genome-wide identification of Bacillus subtilis CodY-binding sites at single-nucleotide resolution

    Proc Natl Acad Sci U S A. 2013 Apr 23;110(17):7026-31. doi: 10.1073/pnas.1300428110. Epub 2013 Apr 8. PubMed PMID: 23569278; PubMed Central PMCID: PMC3637721.
    Belitsky BR, Sonenshein AL

    Genetic and biochemical analysis of CodY-binding sites in Bacillus subtilis

    J Bacteriol. 2008 Feb;190(4):1224-36. Epub 2007 Dec 14. PubMed PMID: 18083814; PubMed Central PMCID: PMC2238193.
    Molle V, Nakaura Y, Shivers RP, Yamaguchi H, Losick R, Fujita Y, Sonenshein AL

    Additional targets of the Bacillus subtilis global regulator CodY identified by chromatin immunoprecipitation and genome-wide transcript analysis

    J Bacteriol. 2003 Mar;185(6):1911-22. PubMed PMID: 12618455; PubMed Central PMCID: PMC150151.

    Original Publications

    Levdikov VM, Blagova E, Young VL, Belitsky BR, Lebedev A, Sonenshein AL, Wilkinson AJ

    Structure of the Branched-chain Amino Acid and GTP-sensing Global Regulator, CodY, from Bacillus subtilis

    J Biol Chem. 2017 Feb 17;292(7):2714-2728. doi: 10.1074/jbc.M116.754309. Epub 2016 Dec 23. PubMed PMID: 28011634; PubMed Central PMCID: PMC5314169.
    Han AR, Kang HR, Son J, Kwon DH, Kim S, Lee WC, Song HK, Song MJ, Hwang KY

    The structure of the pleiotropic transcription regulator CodY provides insight into its GTP-sensing mechanism

    Nucleic Acids Res. 2016 Nov 2;44(19):9483-9493. Epub 2016 Sep 4. PubMed PMID: 27596595; PubMed Central PMCID: PMC5100569.
    Barbieri G, Albertini AM, Ferrari E, Sonenshein AL, Belitsky BR

    Interplay of CodY and ScoC in the Regulation of Major Extracellular Protease Genes of Bacillus subtilis

    J Bacteriol. 2016 Jan 4;198(6):907-20. doi: 10.1128/JB.00894-15. PubMed PMID: 26728191; PubMed Central PMCID: PMC4772597.
    Belitsky BR, Brinsmade SR, Sonenshein AL

    Intermediate Levels of Bacillus subtilis CodY Activity Are Required for Derepression of the Branched-Chain Amino Acid Permease, BraB

    PLoS Genet. 2015 Oct 16;11(10):e1005600. doi: 10.1371/journal.pgen.1005600. eCollection 2015 Oct. PubMed PMID: 26473603; PubMed Central PMCID: PMC4608796.
    Coutte F, Niehren J, Dhali D, John M, Versari C, Jacques P

    Modeling leucine's metabolic pathway and knockout prediction improving the production of surfactin, a biosurfactant from Bacillus subtilis

    Biotechnol J. 2015 Aug;10(8):1216-34. doi: 10.1002/biot.201400541. PubMed PMID: 26220295.
    Ababneh QO, Herman JK

    CodY Regulates SigD Levels and Activity by Binding to Three Sites in the fla/che Operon

    J Bacteriol. 2015 Sep;197(18):2999-3006. doi: 10.1128/JB.00288-15. Epub 2015 Jul 13. PubMed PMID: 26170408; PubMed Central PMCID: PMC4542168.
    Belitsky BR, Barbieri G, Albertini AM, Ferrari E, Strauch MA, Sonenshein AL

    Interactive regulation by the Bacillus subtilis global regulators CodY and ScoC

    Mol Microbiol. 2015 Aug;97(4):698-716. doi: 10.1111/mmi.13056. Epub 2015 Jun 6. PubMed PMID: 25966844; PubMed Central PMCID: PMC4550321.
    Barbieri G, Voigt B, Albrecht D, Hecker M, Albertini AM, Sonenshein AL, Ferrari E, Belitsky BR

    CodY regulates expression of the Bacillus subtilis extracellular proteases Vpr and Mpr

    J Bacteriol. 2015 Apr;197(8):1423-32. doi: 10.1128/JB.02588-14. Epub 2015 Feb 9. PubMed PMID: 25666135; PubMed Central PMCID: PMC4372738.
    Belitsky BR

    Role of branched-chain amino acid transport in Bacillus subtilis CodY activity

    J Bacteriol. 2015 Apr;197(8):1330-8. doi: 10.1128/JB.02563-14. Epub 2015 Feb 2. PubMed PMID: 25645558; PubMed Central PMCID: PMC4372739.
    Fujita Y, Satomura T, Tojo S, Hirooka K

    CcpA-mediated catabolite activation of the Bacillus subtilis ilv-leu operon and its negation by either CodY- or TnrA-mediated negative regulation

    J Bacteriol. 2014 Nov;196(21):3793-806. doi: 10.1128/JB.02055-14. Epub 2014 Aug 25. PubMed PMID: 25157083; PubMed Central PMCID: PMC4248793.
    Bittner AN, Kriel A, Wang JD

    Lowering GTP level increases survival of amino acid starvation but slows growth rate for Bacillus subtilis cells lacking (p)ppGpp

    J Bacteriol. 2014 Jun;196(11):2067-76. doi: 10.1128/JB.01471-14. Epub 2014 Mar 28. PubMed PMID: 24682323; PubMed Central PMCID: PMC4010990.
    Chan JM, Guttenplan SB, Kearns DB

    Defects in the flagellar motor increase synthesis of poly-γ-glutamate in Bacillus subtilis

    J Bacteriol. 2014 Feb;196(4):740-53. doi: 10.1128/JB.01217-13. Epub 2013 Dec 2. PubMed PMID: 24296669; PubMed Central PMCID: PMC3911173.
    Kriel A, Brinsmade SR, Tse JL, Tehranchi AK, Bittner AN, Sonenshein AL, Wang JD

    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 Jan;196(1):189-201. doi: 10.1128/JB.00918-13. Epub 2013 Oct 25. PubMed PMID: 24163341; PubMed Central PMCID: PMC3911124.
    Ling B, Sun M, Bi S, Jing Z, Wang Z

    Molecular dynamics simulations of isoleucine-release pathway in GAF domain of N-CodY from Bacillus Subtilis

    J Mol Graph Model. 2013 Jul;44:232-40. doi: 10.1016/j.jmgm.2013.07.002. Epub 2013 Jul 12. PubMed PMID: 23911932.
    Kriel A, Bittner AN, Kim SH, Liu K, Tehranchi AK, Zou WY, Rendon S, Chen R, Tu BP, Wang JD

    Direct regulation of GTP homeostasis by (p)ppGpp: a critical component of viability and stress resistance

    Mol Cell. 2012 Oct 26;48(2):231-41. doi: 10.1016/j.molcel.2012.08.009. Epub 2012 Sep 13. PubMed PMID: 22981860; PubMed Central PMCID: PMC3483369.
    Wünsche A, Hammer E, Bartholomae M, Völker U, Burkovski A, Seidel G, Hillen W

    CcpA forms complexes with CodY and RpoA in Bacillus subtilis

    FEBS J. 2012 Jun;279(12):2201-14. doi: 10.1111/j.1742-4658.2012.08604.x. Epub 2012 May 21. PubMed PMID: 22512862.
    Brinsmade SR, Sonenshein AL

    Dissecting complex metabolic integration provides direct genetic evidence for CodY activation by guanine nucleotides

    J Bacteriol. 2011 Oct;193(20):5637-48. doi: 10.1128/JB.05510-11. Epub 2011 Aug 19. PubMed PMID: 21856856; PubMed Central PMCID: PMC3187194.
    Wray LV Jr, Fisher SH

    Bacillus subtilis CodY operators contain overlapping CodY binding sites

    J Bacteriol. 2011 Sep;193(18):4841-8. doi: 10.1128/JB.05258-11. Epub 2011 Jul 15. PubMed PMID: 21764931; PubMed Central PMCID: PMC3165709.
    Belitsky BR, Sonenshein AL

    Roadblock repression of transcription by Bacillus subtilis CodY

    J Mol Biol. 2011 Aug 26;411(4):729-43. doi: 10.1016/j.jmb.2011.06.012. Epub 2011 Jun 15. PubMed PMID: 21699902; PubMed Central PMCID: PMC3156270.
    Brinsmade SR, Kleijn RJ, Sauer U, Sonenshein AL

    Regulation of CodY activity through modulation of intracellular branched-chain amino acid pools

    J Bacteriol. 2010 Dec;192(24):6357-68. doi: 10.1128/JB.00937-10. Epub 2010 Oct 8. PubMed PMID: 20935095; PubMed Central PMCID: PMC3008522.
    Villapakkam AC, Handke LD, Belitsky BR, Levdikov VM, Wilkinson AJ, Sonenshein AL

    Genetic and biochemical analysis of the interaction of Bacillus subtilis CodY with branched-chain amino acids

    J Bacteriol. 2009 Nov;191(22):6865-76. doi: 10.1128/JB.00818-09. Epub 2009 Sep 11. PubMed PMID: 19749041; PubMed Central PMCID: PMC2772489.
    Preis H, Eckart RA, Gudipati RK, Heidrich N, Brantl S

    CodY activates transcription of a small RNA in Bacillus subtilis

    J Bacteriol. 2009 Sep;191(17):5446-57. doi: 10.1128/JB.00602-09. Epub 2009 Jun 19. PubMed PMID: 19542274; PubMed Central PMCID: PMC2725614.
    Levdikov VM, Blagova E, Colledge VL, Lebedev AA, Williamson DC, Sonenshein AL, Wilkinson AJ

    Structural rearrangement accompanying ligand binding in the GAF domain of CodY from Bacillus subtilis

    J Mol Biol. 2009 Jul 31;390(5):1007-18. doi: 10.1016/j.jmb.2009.05.077. Epub 2009 Jun 3. PubMed PMID: 19500589; PubMed Central PMCID: PMC3128921.
    Hamze K, Julkowska D, Autret S, Hinc K, Nagorska K, Sekowska A, Holland IB, Séror SJ

    Identification of genes required for different stages of dendritic swarming in Bacillus subtilis, with a novel role for phrC

    Microbiology. 2009 Feb;155(Pt 2):398-412. doi: 10.1099/mic.0.021477-0. PubMed PMID: 19202088.
    Hamze K, Julkowska D, Autret S, Hinc K, Nagorska K, Sekowska A, Holland IB, Séror SJ

    Identification of genes required for different stages of dendritic swarming in Bacillus subtilis, with a novel role for phrC

    Microbiology. 2009 Feb;155(Pt 2):398-412. doi: 10.1099/mic.0.021477-0. PubMed PMID: 19202088.
    Tojo S, Satomura T, Kumamoto K, Hirooka K, Fujita Y

    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 Sep;190(18):6134-47. doi: 10.1128/JB.00606-08. Epub 2008 Jul 18. PubMed PMID: 18641142; PubMed Central PMCID: PMC2546780.
    Handke LD, Shivers RP, Sonenshein AL

    Interaction of Bacillus subtilis CodY with GTP

    J Bacteriol. 2008 Feb;190(3):798-806. Epub 2007 Nov 9. PubMed PMID: 17993518; PubMed Central PMCID: PMC2223590.
    Smits WK, Hoa TT, Hamoen LW, Kuipers OP, Dubnau D

    Antirepression as a second mechanism of transcriptional activation by a minor groove binding protein

    Mol Microbiol. 2007 Apr;64(2):368-81. PubMed PMID: 17493123; PubMed Central PMCID: PMC3831528.
    Macek B, Mijakovic I, Olsen JV, Gnad F, Kumar C, Jensen PR, Mann M

    The serine/threonine/tyrosine phosphoproteome of the model bacterium Bacillus subtilis

    Mol Cell Proteomics. 2007 Apr;6(4):697-707. Epub 2007 Jan 10. PubMed PMID: 17218307.
    Shivers RP, Dineen SS, Sonenshein AL

    Positive regulation of Bacillus subtilis ackA by CodY and CcpA: establishing a potential hierarchy in carbon flow

    Mol Microbiol. 2006 Nov;62(3):811-22. Epub 2006 Sep 21. PubMed PMID: 16995897.
    Joseph P, Ratnayake-Lecamwasam M, Sonenshein AL

    A region of Bacillus subtilis CodY protein required for interaction with DNA

    J Bacteriol. 2005 Jun;187(12):4127-39. PubMed PMID: 15937175; PubMed Central PMCID: PMC1151725.
    Tojo S, Satomura T, Morisaki K, Deutscher J, Hirooka K, Fujita Y

    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 Jun;56(6):1560-73. PubMed PMID: 15916606.
    Shivers RP, Sonenshein AL

    Bacillus subtilis ilvB operon: an intersection of global regulons

    Mol Microbiol. 2005 Jun;56(6):1549-59. PubMed PMID: 15916605.
    Shivers RP, Sonenshein AL

    Activation of the Bacillus subtilis global regulator CodY by direct interaction with branched-chain amino acids

    Mol Microbiol. 2004 Jul;53(2):599-611. PubMed PMID: 15228537.
    Shivers RP, Sonenshein AL

    Activation of the Bacillus subtilis global regulator CodY by direct interaction with branched-chain amino acids

    Mol Microbiol. 2004 Jul;53(2):599-611. PubMed PMID: 15228537.
    Kim HJ, Kim SI, Ratnayake-Lecamwasam M, Tachikawa K, Sonenshein AL, Strauch M

    Complex regulation of the Bacillus subtilis aconitase gene

    J Bacteriol. 2003 Mar;185(5):1672-80. PubMed PMID: 12591885; PubMed Central PMCID: PMC148081.
    Ratnayake-Lecamwasam M, Serror P, Wong KW, Sonenshein AL

    Bacillus subtilis CodY represses early-stationary-phase genes by sensing GTP levels

    Genes Dev. 2001 May 1;15(9):1093-103. PubMed PMID: 11331605; PubMed Central PMCID: PMC312684.
    Ratnayake-Lecamwasam M, Serror P, Wong KW, Sonenshein AL

    Bacillus subtilis CodY represses early-stationary-phase genes by sensing GTP levels

    Genes Dev. 2001 May 1;15(9):1093-103. PubMed PMID: 11331605; PubMed Central PMCID: PMC312684.
    Ratnayake-Lecamwasam M, Serror P, Wong KW, Sonenshein AL

    Bacillus subtilis CodY represses early-stationary-phase genes by sensing GTP levels

    Genes Dev. 2001 May 1;15(9):1093-103. PubMed PMID: 11331605; PubMed Central PMCID: PMC312684.
    Wray LV Jr, Ferson AE, Fisher SH

    Expression of the Bacillus subtilis ureABC operon is controlled by multiple regulatory factors including CodY, GlnR, TnrA, and Spo0H

    J Bacteriol. 1997 Sep;179(17):5494-501. PubMed PMID: 9287005; PubMed Central PMCID: PMC179421.
    Serror P, Sonenshein AL

    Interaction of CodY, a novel Bacillus subtilis DNA-binding protein, with the dpp promoter region

    Mol Microbiol. 1996 May;20(4):843-52. PubMed PMID: 8793880.
    Slack FJ, Serror P, Joyce E, Sonenshein AL

    A gene required for nutritional repression of the Bacillus subtilis dipeptide permease operon

    Mol Microbiol. 1995 Feb;15(4):689-702. PubMed PMID: 7783641.
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