SubtiBank SubtiBank

Categories containing this gene/protein


phosphotransferase systems, transcription factors and their control, phosphoproteins, most abundant proteins

This gene is a member of the following regulons


GlcT regulon, stringent response

Gene


  • Coordinates on the chromosome (coding sequence): 1,459,384 -> 1,459,650
  • The protein


    Catalyzed reaction/ biological activity

  • Protein HPr N(pi)-phospho-L-histidine protein EIIA = protein HPr protein EIIA N(tau)-phospho-L-histidine (according to Swiss-Prot) Protein HPr N(pi)-phospho-L-histidine protein EIIA = protein HPr protein EIIA N(tau)-phospho-L-histidine
  • Protein family

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

  • Crh
  • Kinetic information

    Domains

  • HPr Domain (2–88)
  • Modification

  • transient phosphorylation by Enzyme I of the PTS on His-15
  • regulatory phosphorylation on Ser-46 by HprK PubMed
  • an extensive study on in vivo HPr phosphorylation can be found in Singh et al. (2008) PubMed
  • weak phosphorylation on Ser-12 PubMed
  • in vitro phosphorylated by PrkC on Ser-12 PubMed
  • Cofactors

    Effectors of protein activity

    Structure

  • 2HID (NMR) PubMed
  • 1KKM (complex of L. casei HprK with B. subtilis HPr-Ser-P)
  • 1KKL (complex of Lactobacillus casei HprK with B. subtilis HPr)
  • 3OQM (complex of B. subtilis CcpA with P-Ser-HPr and the ackA operator site)
  • 3OQN (complex of B. subtilis CcpA with P-Ser-HPr and the gntR operator site)
  • 3OQO (complex of B. subtilis CcpA with P-Ser-HPr and a optimal synthetic operator site)
  • Localization

  • cytoplasm PubMed
  • Interactions

  • HprK-HPr PubMed
  • Enzyme I-HPr
  • HPr-PtsG PubMed, PtsH-MtlF PubMed, ManP-HPr, GmuA-HPr
  • GamP-HPr, BglP-HPr, LicA-HPr, LevD-HPr
  • FruA-HPr, YpqE-HPr
  • HPr-LicT, HPr-SacY, HPr-SacT, HPr-GlcT
  • HPr-MtlR PubMed, HPr-LicR, HPr-LevR,HPr-ManR
  • HPr-GlpK
  • GapA-HPr PubMed
  • HPr(Ser-46)-P-CcpA PubMed
  • HPr-RbsR PubMed
  • HPr(His)-P-RhgR PubMed
  • Additional information

    Expression and Regulation


    Operon

  • ptsG-ptsH-ptsI PubMed
  • ptsH-ptsI PubMed
  • Sigma factor

  • ptsG: SigA PubMed
  • ptsH: SigA PubMed
  • Regulation

  • expression activated by glucose (2 fold) (GlcT) PubMed
  • the ptsH promoter is constitutive PubMed
  • subject to negative stringent control upon amino acid limitation (due to control of ptsG transcription initiation) PubMed
  • Regulatory mechanism

  • ptsG: transcriptional antitermination via the GlcT-dependent RNA switch PubMed
  • Additional information

  • belongs to the 100 most abundant proteins PubMed
  • Biological materials


    Mutant

  • available in Jörg Stülke's lab:
  • MZ303 (cat)
  • GP507 ptsH1 (S46A)
  • GP506 (ptsH-H15A)
  • GP778 (replacement of glcT and the ptsG-ptsH-ptsI operon by a spc cassette), PubMed
  • Expression vector

  • pGP438 (with N-terminal Strep-tag, in pGP172), available in Jörg Stülke's lab
  • pAG2 (His-tag) PubMed, available in Anne Galinier lab
  • pGP371(expression / purification of HPr-S46A, with His-tag from E. coli, in pWH844), available in Jörg Stülke's lab
  • pGP1415 (HPr, expression in B. subtilis, from pBQ200), available in Jörg Stülke's lab
  • pGP961 (HPr, expression in B. subtilis with N-terminal Strep-tag, for SPINE, available in Jörg Stülke's lab
  • pGP1416 (HPr-H15A, expression in B. subtilis, from pBQ200), available in Jörg Stülke's lab
  • pGP2431 (N-terminal Strep-tag, expression and purification from B. subtilis, in pGP380), for SPINE, 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 Jörg Stülke's lab
  • FLAG-tag construct

    Antibody

  • available in Jörg Stülke's lab
  • Labs working on this gene/protein


  • Josef Deutscher, Paris-Grignon, France
  • Jörg Stülke, University of Göttingen, Germany Homepage
  • Richard Brennan, Houston, Texas, USA Homepage
  • Boris Görke, University of Göttingen, Germany Homepage
  • Anne Galinier, University of Marseille, France
  • References


    Rosenberg A, Soufi B, Ravikumar V, Soares NC, Krug K, Smith Y, Macek B, Ben-Yehuda S

    Phosphoproteome dynamics mediate revival of bacterial spores

    BMC Biol. 2015 Sep 17;13:76. doi: 10.1186/s12915-015-0184-7. PubMed PMID: 26381121; PubMed Central PMCID: PMC4574613.
    Garcia De Gonzalo CV, Denham EL, Mars RA, Stülke J, van der Donk WA, van Dijl JM

    The phosphoenolpyruvate:sugar phosphotransferase system is involved in sensitivity to the glucosylated bacteriocin sublancin

    Antimicrob Agents Chemother. 2015 Nov;59(11):6844-54. doi: 10.1128/AAC.01519-15. PubMed PMID: 26282429; PubMed Central PMCID: PMC4604375.
    Wenzel M, Altenbuchner J

    The Bacillus subtilis mannose regulator, ManR, a DNA-binding protein regulated by HPr and its cognate PTS transporter ManP

    Mol Microbiol. 2013 May;88(3):562-76. doi: 10.1111/mmi.12209. PubMed PMID: 23551403.
    Himmel S, Zschiedrich CP, Becker S, Hsiao HH, Wolff S, Diethmaier C, Urlaub H, Lee D, Griesinger C, Stülke J

    Determinants of interaction specificity of the Bacillus subtilis GlcT antitermination protein: functionality and phosphorylation specificity depend on the arrangement of the regulatory domains

    J Biol Chem. 2012 Aug 10;287(33):27731-42. doi: 10.1074/jbc.M112.388850. PubMed PMID: 22722928; PubMed Central PMCID: PMC3431645.
    Meyer FM, Jules M, Mehne FM, Le Coq D, Landmann JJ, Görke B, Aymerich S, Stülke J

    Malate-mediated carbon catabolite repression in Bacillus subtilis involves the HPrK/CcpA pathway

    J Bacteriol. 2011 Dec;193(24):6939-49. doi: 10.1128/JB.06197-11. PubMed PMID: 22001508; PubMed Central PMCID: PMC3232832.
    Joyet P, Derkaoui M, Poncet S, Deutscher J

    Control of Bacillus subtilis mtl operon expression by complex phosphorylation-dependent regulation of the transcriptional activator MtlR

    Mol Microbiol. 2010 Jun 1;76(5):1279-94. doi: 10.1111/j.1365-2958.2010.07175.x. PubMed PMID: 20444094.
    Pietack N, Becher D, Schmidl SR, Saier MH, Hecker M, Commichau FM, Stülke J

    In vitro phosphorylation of key metabolic enzymes from Bacillus subtilis: PrkC phosphorylates enzymes from different branches of basic metabolism

    J Mol Microbiol Biotechnol. 2010;18(3):129-40. doi: 10.1159/000308512. PubMed PMID: 20389117.
    Tojo S, Kumamoto K, Hirooka K, Fujita Y

    Heavy involvement of stringent transcription control depending on the adenine or guanine species of the transcription initiation site in glucose and pyruvate metabolism in Bacillus subtilis

    J Bacteriol. 2010 Mar;192(6):1573-85. doi: 10.1128/JB.01394-09. PubMed PMID: 20081037; PubMed Central PMCID: PMC2832531.
    Poncet S, Soret M, Mervelet P, Deutscher J, Noirot P

    Transcriptional activator YesS is stimulated by histidine-phosphorylated HPr of the Bacillus subtilis phosphotransferase system

    J Biol Chem. 2009 Oct 9;284(41):28188-97. doi: 10.1074/jbc.M109.046334. PubMed PMID: 19651770; PubMed Central PMCID: PMC2788870.
    Singh KD, Schmalisch MH, Stülke J, Görke B

    Carbon catabolite repression in Bacillus subtilis: quantitative analysis of repression exerted by different carbon sources

    J Bacteriol. 2008 Nov;190(21):7275-84. doi: 10.1128/JB.00848-08. PubMed PMID: 18757537; PubMed Central PMCID: PMC2580719.
    Singh KD, Halbedel S, Görke B, Stülke J

    Control of the phosphorylation state of the HPr protein of the phosphotransferase system in Bacillus subtilis: implication of the protein phosphatase PrpC

    J Mol Microbiol Biotechnol. 2007;13(1-3):165-71. PubMed PMID: 17693724.
    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. PubMed PMID: 17218307.
    Pompeo F, Luciano J, Galinier A

    Interaction of GapA with HPr and its homologue, Crh: Novel levels of regulation of a key step of glycolysis in Bacillus subtilis

    J Bacteriol. 2007 Feb;189(3):1154-7. PubMed PMID: 17142398; PubMed Central PMCID: PMC1797305.
    Müller W, Horstmann N, Hillen W, Sticht H

    The transcription regulator RbsR represents a novel interaction partner of the phosphoprotein HPr-Ser46-P in Bacillus subtilis

    FEBS J. 2006 Mar;273(6):1251-61. PubMed PMID: 16519689.
    Müller W, Horstmann N, Hillen W, Sticht H

    The transcription regulator RbsR represents a novel interaction partner of the phosphoprotein HPr-Ser46-P in Bacillus subtilis

    FEBS J. 2006 Mar;273(6):1251-61. PubMed PMID: 16519689.
    Eymann C, Dreisbach A, Albrecht D, Bernhardt J, Becher D, Gentner S, Tam le T, Büttner K, Buurman G, Scharf C, Venz S, Völker U, Hecker M

    A comprehensive proteome map of growing Bacillus subtilis cells

    Proteomics. 2004 Oct;4(10):2849-76. PubMed PMID: 15378759.
    Schumacher MA, Allen GS, Diel M, Seidel G, Hillen W, Brennan RG

    Structural basis for allosteric control of the transcription regulator CcpA by the phosphoprotein HPr-Ser46-P

    Cell. 2004 Sep 17;118(6):731-41. PubMed PMID: 15369672.
    Görke B, Fraysse L, Galinier A

    Drastic differences in Crh and HPr synthesis levels reflect their different impacts on catabolite repression in Bacillus subtilis

    J Bacteriol. 2004 May;186(10):2992-5. PubMed PMID: 15126459; PubMed Central PMCID: PMC400640.
    Schmalisch MH, Bachem S, Stülke J

    Control of the Bacillus subtilis antiterminator protein GlcT by phosphorylation

    Elucidation of the phosphorylation chain leading to inactivation of GlcT. J Biol Chem. 2003 Dec 19;278(51):51108-15. PubMed PMID: 14527945.
    Fieulaine S, Morera S, Poncet S, Mijakovic I, Galinier A, Janin J, Deutscher J, Nessler S

    X-ray structure of a bifunctional protein kinase in complex with its protein substrate HPr

    Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13437-41. PubMed PMID: 12359875; PubMed Central PMCID: PMC129691.
    Lindner C, Hecker M, Le Coq D, Deutscher J

    Bacillus subtilis mutant LicT antiterminators exhibiting enzyme I- and HPr-independent antitermination affect catabolite repression of the bglPH operon

    J Bacteriol. 2002 Sep;184(17):4819-28. PubMed PMID: 12169607; PubMed Central PMCID: PMC135283.
    Darbon E, Servant P, Poncet S, Deutscher J

    Antitermination by GlpP, catabolite repression via CcpA and inducer exclusion triggered by P-GlpK dephosphorylation control Bacillus subtilis glpFK expression

    Mol Microbiol. 2002 Feb;43(4):1039-52. PubMed PMID: 11929549.
    Martin-Verstraete I, Deutscher J, Galinier A

    Phosphorylation of HPr and Crh by HprK, early steps in the catabolite repression signalling pathway for the Bacillus subtilis levanase operon

    J Bacteriol. 1999 May;181(9):2966-9. PubMed PMID: 10217795; PubMed Central PMCID: PMC93746.
    Lindner C, Galinier A, Hecker M, Deutscher J

    Regulation of the activity of the Bacillus subtilis antiterminator LicT by multiple PEP-dependent, enzyme I- and HPr-catalysed phosphorylation

    Mol Microbiol. 1999 Feb;31(3):995-1006. PubMed PMID: 10048041.
    Galinier A, Deutscher J, Martin-Verstraete I

    Phosphorylation of either crh or HPr mediates binding of CcpA to the bacillus subtilis xyn cre and catabolite repression of the xyn operon

    J Mol Biol. 1999 Feb 19;286(2):307-14. PubMed PMID: 9973552.
    Martin-Verstraete I, Charrier V, Stülke J, Galinier A, Erni B, Rapoport G, Deutscher J

    Antagonistic effects of dual PTS-catalysed phosphorylation on the Bacillus subtilis transcriptional activator LevR

    Mol Microbiol. 1998 Apr;28(2):293-303. PubMed PMID: 9622354.
    Jones BE, Rajagopal P, Klevit RE

    Phosphorylation on histidine is accompanied by localized structural changes in the phosphocarrier protein, HPr from Bacillus subtilis

    Protein Sci. 1997 Oct;6(10):2107-19. PubMed PMID: 9336834; PubMed Central PMCID: PMC2143559.
    Jones BE, Rajagopal P, Klevit RE

    Phosphorylation on histidine is accompanied by localized structural changes in the phosphocarrier protein, HPr from Bacillus subtilis

    Protein Sci. 1997 Oct;6(10):2107-19. PubMed PMID: 9336834; PubMed Central PMCID: PMC2143559.
    Tortosa P, Aymerich S, Lindner C, Saier MH Jr, Reizer J, Le Coq D

    Multiple phosphorylation of SacY, a Bacillus subtilis transcriptional antiterminator negatively controlled by the phosphotransferase system

    J Biol Chem. 1997 Jul 4;272(27):17230-7. PubMed PMID: 9202047.
    Charrier V, Buckley E, Parsonage D, Galinier A, Darbon E, Jaquinod M, Forest E, Deutscher J, Claiborne A

    Cloning and sequencing of two enterococcal glpK genes and regulation of the encoded glycerol kinases by phosphoenolpyruvate-dependent, phosphotransferase system-catalyzed phosphorylation of a single histidyl residue

    J Biol Chem. 1997 May 30;272(22):14166-74. PubMed PMID: 9162046.
    Pullen K, Rajagopal P, Branchini BR, Huffine ME, Reizer J, Saier MH Jr, Scholtz JM, Klevit RE

    Phosphorylation of serine-46 in HPr, a key regulatory protein in bacteria, results in stabilization of its solution structure

    Protein Sci. 1995 Dec;4(12):2478-86. PubMed PMID: 8580838; PubMed Central PMCID: PMC2143046.
    Chen Y, Reizer J, Saier MH Jr, Fairbrother WJ, Wright PE

    Mapping of the binding interfaces of the proteins of the bacterial phosphotransferase system, HPr and IIAglc

    Biochemistry. 1993 Jan 12;32(1):32-7. PubMed PMID: 8418852.
    Frisby D, Zuber P

    Mutations in pts cause catabolite-resistant sporulation and altered regulation of spo0H in Bacillus subtilis

    J Bacteriol. 1994 May;176(9):2587-95. PubMed PMID: 8169206; PubMed Central PMCID: PMC205396.
    Rajagopal P, Waygood EB, Klevit RE

    Structural consequences of histidine phosphorylation: NMR characterization of the phosphohistidine form of histidine-containing protein from Bacillus subtilis and Escherichia coli

    Biochemistry. 1994 Dec 27;33(51):15271-82. PubMed PMID: 7803390.
    Deutscher J, Küster E, Bergstedt U, Charrier V, Hillen W

    Protein kinase-dependent HPr/CcpA interaction links glycolytic activity to carbon catabolite repression in gram-positive bacteria

    Mol Microbiol. 1995 Mar;15(6):1049-53. PubMed PMID: 7623661.
    Stülke J, Martin-Verstraete I, Charrier V, Klier A, Deutscher J, Rapoport G

    The HPr protein of the phosphotransferase system links induction and catabolite repression of the Bacillus subtilis levanase operon

    J Bacteriol. 1995 Dec;177(23):6928-36. PubMed PMID: 7592487; PubMed Central PMCID: PMC177562.
    Eisermann R, Deutscher J, Gonzy-Treboul G, Hengstenberg W

    Site-directed mutagenesis with the ptsH gene of Bacillus subtilis

    Isolation and characterization of heat-stable proteins altered at the ATP-dependent regulatory phosphorylation site. J Biol Chem. 1988 Nov 15;263(32):17050-4. PubMed PMID: 2846556.
    Reizer J, Sutrina SL, Saier MH, Stewart GC, Peterkofsky A, Reddy P

    Mechanistic and physiological consequences of HPr(ser) phosphorylation on the activities of the phosphoenolpyruvate:sugar phosphotransferase system in gram-positive bacteria: studies with site-specific mutants of HPr

    EMBO J. 1989 Jul;8(7):2111-20. PubMed PMID: 2507315; PubMed Central PMCID: PMC401104.
    Arnaud M, Vary P, Zagorec M, Klier A, Debarbouille M, Postma P, Rapoport G

    Regulation of the sacPA operon of Bacillus subtilis: identification of phosphotransferase system components involved in SacT activity

    J Bacteriol. 1992 May;174(10):3161-70. PubMed PMID: 1577686; PubMed Central PMCID: PMC205982.
    Herzberg O, Reddy P, Sutrina S, Saier MH Jr, Reizer J, Kapadia G

    Structure of the histidine-containing phosphocarrier protein HPr from Bacillus subtilis at 2

    0-A resolution. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2499-503. PubMed PMID: 1549615; PubMed Central PMCID: PMC48686.
    Wittekind M, Rajagopal P, Branchini BR, Reizer J, Saier MH Jr, Klevit RE

    Solution structure of the phosphocarrier protein HPr from Bacillus subtilis by two-dimensional NMR spectroscopy

    Protein Sci. 1992 Oct;1(10):1363-76. PubMed PMID: 1303754; PubMed Central PMCID: PMC2142093.
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