SubtiBank SubtiBank

Categories containing this gene/protein


biosynthesis/ acquisition of amino acids, glutamate metabolism, transcription factors and their control, regulators of core metabolism

This gene is a member of the following regulons


GlnR regulon, TnrA regulon

The TnrA regulon


Gene


  • Coordinates on the chromosome (coding sequence): 1,397,411 -> 1,397,743
  • The protein


    Catalyzed reaction/ biological activity

    Protein family

  • MerR family
  • Paralogous protein(s)

    Kinetic information

    Domains

    Modification

    Cofactors

    Effectors of protein activity

  • feedback-inhibited GlnA prevents TnrA from DNA binding
  • Structure

  • 4R22 (the TnrA-DNA complex) PubMed
  • 4S0R (the TnrA-GlnA complex) PubMed
  • Localization

  • membrane-associated via NrgA-NrgB under conditions of poor nitrogen supply PubMed
  • Interactions

  • TnrA-NrgB PubMed
  • TnrA-GlnA, this interaction results in loss of TnrA DNA-binding activity as well as in inhibition of GlnA PubMed
  • Additional information

    Expression and Regulation


    Operon

  • tnrA (according to DBTBS)
  • Sigma factor

    Regulation

  • expression is autocativated (TnrA) and repressed by GlnR PubMed
  • expressed in the absence of good nitrogen sources (glutamine or ammonium) (TnrA) PubMed
  • Regulatory mechanism

  • TnrA: transcription activation PubMed
  • Additional information

    Biological materials


    Mutant

  • GP252 (in frame deletion), available in the Stülke lab
  • BKE13310 (tnrA::ermC) (available at the BGSC and in Jörg Stülke's lab)
  • GP2262 (tnrA::ermC) (available in Jörg Stülke's lab)
  • 1A851 ( tnrA::erm), PubMed, available at BGSC
  • 1A851 ( tnrA::erm), PubMed, available at BGSC
  • Expression vector

  • for expression, purification in E. coli with N-terminal His-tag, in pWH844: pGP171 available in Stülke lab
  • pGP229 (N-terminal Strep-tag, for SPINE, expression in B. subtilis, in pGP380), available in Stülke lab
  • lacZ fusion

    GFP fusion

    two-hybrid system

    FLAG-tag construct

    Antibody

  • available in the Karl Forchhammer lab
  • Labs working on this gene/protein


  • Susan Fisher, Boston, USA homepage
  • Maria Schumacher, Durham, NC, USA homepage
  • References


    Reviews

    Gunka K, Commichau FM

    Control of glutamate homeostasis in Bacillus subtilis: a complex interplay between ammonium assimilation, glutamate biosynthesis and degradation

    Mol Microbiol. 2012 Jul;85(2):213-24. doi: 10.1111/j.1365-2958.2012.08105.x. Review. PubMed PMID: 22625175.
    Commichau FM, Stülke J

    Trigger enzymes: bifunctional proteins active in metabolism and in controlling gene expression

    Mol Microbiol. 2008 Feb;67(4):692-702. Review. PubMed PMID: 18086213.
    Fisher SH

    Regulation of nitrogen metabolism in Bacillus subtilis: vive la différence

    Mol Microbiol. 1999 Apr;32(2):223-32. Review. PubMed PMID: 10231480.

    The TnrA regulon

    Mirouze N, Bidnenko E, Noirot P, Auger S

    Genome-wide mapping of TnrA-binding sites provides new insights into the TnrA regulon in Bacillus subtilis

    Microbiologyopen. 2015 Jun;4(3):423-35. doi: 10.1002/mbo3.249. PubMed PMID: 25755103; PubMed Central PMCID: PMC4475385.
    Yoshida K, Yamaguchi H, Kinehara M, Ohki YH, Nakaura Y, Fujita Y

    Identification of additional TnrA-regulated genes of Bacillus subtilis associated with a TnrA box

    Mol Microbiol. 2003 Jul;49(1):157-65. PubMed PMID: 12823818.

    Control of TnrA activity by the trigger enzyme GlnA

    Hauf K, Kayumov A, Gloge F, Forchhammer K

    The Molecular Basis of TnrA Control by Glutamine Synthetase in Bacillus subtilis

    J Biol Chem. 2016 Feb 12;291(7):3483-95. doi: 10.1074/jbc.M115.680991. PubMed PMID: 26635369; PubMed Central PMCID: PMC4751389.
    Fisher SH, Wray LV Jr

    Novel trans-Acting Bacillus subtilis glnA mutations that derepress glnRA expression

    J Bacteriol. 2009 Apr;191(8):2485-92. doi: 10.1128/JB.01734-08. PubMed PMID: 19233925; PubMed Central PMCID: PMC2668423.
    Wray LV Jr, Fisher SH

    Functional analysis of the carboxy-terminal region of Bacillus subtilis TnrA, a MerR family protein

    J Bacteriol. 2007 Jan;189(1):20-7. PubMed PMID: 17085574; PubMed Central PMCID: PMC1797213.
    Fisher SH, Wray LV Jr

    Feedback-resistant mutations in Bacillus subtilis glutamine synthetase are clustered in the active site

    J Bacteriol. 2006 Aug;188(16):5966-74. PubMed PMID: 16885465; PubMed Central PMCID: PMC1540052.
    Fisher SH, Brandenburg JL, Wray LV Jr

    Mutations in Bacillus subtilis glutamine synthetase that block its interaction with transcription factor TnrA

    Mol Microbiol. 2002 Aug;45(3):627-35. PubMed PMID: 12139611.
    Wray LV Jr, Zalieckas JM, Fisher SH

    Bacillus subtilis glutamine synthetase controls gene expression through a protein-protein interaction with transcription factor TnrA

    Cell. 2001 Nov 16;107(4):427-35. PubMed PMID: 11719184.

    Other original publications

    Schumacher MA, Chinnam NB, Cuthbert B, Tonthat NK, Whitfill T

    Structures of regulatory machinery reveal novel molecular mechanisms controlling B

    subtilis nitrogen homeostasis. Genes Dev. 2015 Feb 15;29(4):451-64. doi: 10.1101/gad.254714.114. PubMed PMID: 25691471; PubMed Central PMCID: PMC4335299.
    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. PubMed PMID: 25157083; PubMed Central PMCID: PMC4248793.
    Fedorova KP, Sharafutdinov IS, Turbina EIu, Bogachev MI, Il'inskaia ON, Kaiumov AR

    [The C-terminus of transcription factor TnrA from Bacillus subtilis controls DNA-binding domain activity but is not required for dimerization]

    Mol Biol (Mosk). 2013 Mar-Apr;47(2):331-7. Russian. PubMed PMID: 23808168.
    Fedorova K, Kayumov A, Woyda K, Ilinskaja O, Forchhammer K

    Transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in Bacillus subtilis

    FEBS Lett. 2013 May 2;587(9):1293-8. doi: 10.1016/j.febslet.2013.03.015. PubMed PMID: 23535029.
    Kayumov A, Heinrich A, Fedorova K, Ilinskaya O, Forchhammer K

    Interaction of the general transcription factor TnrA with the PII-like protein GlnK and glutamine synthetase in Bacillus subtilis

    FEBS J. 2011 May;278(10):1779-89. doi: 10.1111/j.1742-4658.2011.08102.x. PubMed PMID: 21435182.
    Kayumov A, Heinrich A, Sharipova M, Iljinskaya O, Forchhammer K

    Inactivation of the general transcription factor TnrA in Bacillus subtilis by proteolysis

    Microbiology. 2008 Aug;154(Pt 8):2348-55. doi: 10.1099/mic.0.2008/019802-0. PubMed PMID: 18667567.
    Heinrich A, Woyda K, Brauburger K, Meiss G, Detsch C, Stülke J, Forchhammer K

    Interaction of the membrane-bound GlnK-AmtB complex with the master regulator of nitrogen metabolism TnrA in Bacillus subtilis

    J Biol Chem. 2006 Nov 17;281(46):34909-17. PubMed PMID: 17001076.
    Zalieckas JM, Wray LV Jr, Fisher SH

    Cross-regulation of the Bacillus subtilis glnRA and tnrA genes provides evidence for DNA binding site discrimination by GlnR and TnrA

    J Bacteriol. 2006 Apr;188(7):2578-85. PubMed PMID: 16547045; PubMed Central PMCID: PMC1428417.
    Lévine A, Vannier F, Absalon C, Kuhn L, Jackson P, Scrivener E, Labas V, Vinh J, Courtney P, Garin J, Séror SJ

    Analysis of the dynamic Bacillus subtilis Ser/Thr/Tyr phosphoproteome implicated in a wide variety of cellular processes

    Proteomics. 2006 Apr;6(7):2157-73. PubMed PMID: 16493705.
    Tojo S, Satomura T, Morisaki K, Yoshida K, Hirooka K, Fujita Y

    Negative transcriptional regulation of the ilv-leu operon for biosynthesis of branched-chain amino acids through the Bacillus subtilis global regulator TnrA

    J Bacteriol. 2004 Dec;186(23):7971-9. PubMed PMID: 15547269; PubMed Central PMCID: PMC529080.
    Belitsky BR, Sonenshein AL

    Modulation of activity of Bacillus subtilis regulatory proteins GltC and TnrA by glutamate dehydrogenase

    J Bacteriol. 2004 Jun;186(11):3399-407. PubMed PMID: 15150225; PubMed Central PMCID: PMC415766.
    Guedon E, Moore CM, Que Q, Wang T, Ye RW, Helmann JD

    The global transcriptional response of Bacillus subtilis to manganese involves the MntR, Fur, TnrA and sigmaB regulons

    Mol Microbiol. 2003 Sep;49(6):1477-91. PubMed PMID: 12950915.
    Brandenburg JL, Wray LV Jr, Beier L, Jarmer H, Saxild HH, Fisher SH

    Roles of PucR, GlnR, and TnrA in regulating expression of the Bacillus subtilis ure P3 promoter

    J Bacteriol. 2002 Nov;184(21):6060-4. PubMed PMID: 12374841; PubMed Central PMCID: PMC135401.
    Belitsky BR, Wray LV Jr, Fisher SH, Bohannon DE, Sonenshein AL

    Role of TnrA in nitrogen source-dependent repression of Bacillus subtilis glutamate synthase gene expression

    J Bacteriol. 2000 Nov;182(21):5939-47. PubMed PMID: 11029411; PubMed Central PMCID: PMC94725.
    Robichon D, Arnaud M, Gardan R, Pragai Z, O'Reilly M, Rapoport G, Débarbouillé M

    Expression of a new operon from Bacillus subtilis, ykzB-ykoL, under the control of the TnrA and PhoP-phoR global regulators

    J Bacteriol. 2000 Mar;182(5):1226-31. PubMed PMID: 10671441; PubMed Central PMCID: PMC94406.
    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.
    Wray LV Jr, Ferson AE, Rohrer K, Fisher SH

    TnrA, a transcription factor required for global nitrogen regulation in Bacillus subtilis

    Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):8841-5. PubMed PMID: 8799114; PubMed Central PMCID: PMC38555.
    Brown SW, Sonenshein AL

    Autogenous regulation of the Bacillus subtilis glnRA operon

    J Bacteriol. 1996 Apr;178(8):2450-4. PubMed PMID: 8636055; PubMed Central PMCID: PMC177962.
    Fisher SH, Sonenshein AL

    Bacillus subtilis glutamine synthetase mutants pleiotropically altered in glucose catabolite repression

    J Bacteriol. 1984 Feb;157(2):612-21. PubMed PMID: 6141156; PubMed Central PMCID: PMC215290.
    Schreier HJ, Brown SW, Hirschi KD, Nomellini JF, Sonenshein AL

    Regulation of Bacillus subtilis glutamine synthetase gene expression by the product of the glnR gene

    J Mol Biol. 1989 Nov 5;210(1):51-63. Erratum in: J Mol Biol 1992 Jul 20;226(2):571. PubMed PMID: 2573733.
    PubMed
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