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Categories containing this gene/protein

utilization of specific carbon sources, transcription factors and their control, phosphoproteins

This gene is a member of the following regulons

CcpA regulon

The MtlR regulon


  • Coordinates on the chromosome (coding sequence): 467,130 -> 469,214
  • The protein

    Catalyzed reaction/ biological activity

    Protein family

    Paralogous protein(s)

    Kinetic information


  • N-terminal DNA-binding domains, two PTS-regulation domains (PRD1 and PRD2), EIIB (Gat)-like domain, EIIA (Mtl)-like domain
  • Modification

  • phosphorylated on His-342 and/or His-399 by PtsH PubMed
  • phosphorylation on His-599 by MtlA PubMed
  • phosphorylation on Cys-419 by MtlF PubMed
  • Cofactors

    Effectors of protein activity

  • activity is stimulated by PtsH-dependent phosphorylation in PRD2 (mechnism of carbon catabolite repression) PubMed
  • activity is inhibited by MtlF-dependent phosphorylation in the EIIB(Gat)-like domain on Cys-419 (this prevents activity in the absence of mannitol and allows induction in presence of mannitol) PubMed
  • Structure


  • upon interaction with non-phosphorylated MtlA, the active MtlR localizes to the membrane PubMed
  • Interactions

  • PtsH-MtlR PubMed
  • MtlA-MtlR PubMed (the non-phosphorylated IIB domain of MtlA interacts with the two C-terminal EIIB (Gat)-like and EIIA (Mtl)-like domains of MtlR) PubMed
  • MtlF-MtlR PubMed
  • Additional information

    Expression and Regulation


  • mtlR PubMed
  • Sigma factor

  • SigA PubMed
  • Regulation

  • repressed by glucose (CcpA) PubMed
  • Regulatory mechanism

  • CcpA: transcription repression PubMed
  • Additional information

    Biological materials


    Expression vector

    lacZ fusion

    GFP fusion

    two-hybrid system

    FLAG-tag construct


    Labs working on this gene/protein



    Joyet P, Bouraoui H, Aké FM, Derkaoui M, Zébré AC, Cao TN, Ventroux M, Nessler S, Noirot-Gros MF, Deutscher J, Milohanic E

    Transcription regulators controlled by interaction with enzyme IIB components of the phosphoenolpyruvate: sugar phosphotransferase system

    Biochim Biophys Acta. 2013 Jul;1834(7):1415-24. doi: 10.1016/j.bbapap.2013.01.004. Epub 2013 Jan 11. Review. PubMed PMID: 23318733.
    Stülke J, Arnaud M, Rapoport G, Martin-Verstraete I

    PRD--a protein domain involved in PTS-dependent induction and carbon catabolite repression of catabolic operons in bacteria

    Mol Microbiol. 1998 Jun;28(5):865-74. Review. PubMed PMID: 9663674.

    Original publications

    Joyet P, Derkaoui M, Bouraoui H, Deutscher J

    PTS-Mediated Regulation of the Transcription Activator MtlR from Different Species: Surprising Differences despite Strong Sequence Conservation

    J Mol Microbiol Biotechnol. 2015;25(2-3):94-105. doi: 10.1159/000369619. Epub 2015 Jul 9. PubMed PMID: 26159071.
    Bouraoui H, Ventroux M, Noirot-Gros MF, Deutscher J, Joyet P

    Membrane sequestration by the EIIB domain of the mannitol permease MtlA activates the Bacillus subtilis mtl operon regulator MtlR

    Mol Microbiol. 2013 Feb;87(4):789-801. doi: 10.1111/mmi.12131. Epub 2013 Jan 7. PubMed PMID: 23279188.
    Marciniak BC, Pabijaniak M, de Jong A, Dűhring R, Seidel G, Hillen W, Kuipers OP

    High- and low-affinity cre boxes for CcpA binding in Bacillus subtilis revealed by genome-wide analysis

    BMC Genomics. 2012 Aug 17;13:401. doi: 10.1186/1471-2164-13-401. PubMed PMID: 22900538; PubMed Central PMCID: PMC3463425.
    Heravi KM, Wenzel M, Altenbuchner J

    Regulation of mtl operon promoter of Bacillus subtilis: requirements of its use in expression vectors

    Microb Cell Fact. 2011 Oct 20;10:83. doi: 10.1186/1475-2859-10-83. PubMed PMID: 22014119; PubMed Central PMCID: PMC3217849.
    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. Epub 2010 May 4. PubMed PMID: 20444094.
    Watanabe S, Hamano M, Kakeshita H, Bunai K, Tojo S, Yamaguchi H, Fujita Y, Wong SL, Yamane K

    Mannitol-1-phosphate dehydrogenase (MtlD) is required for mannitol and glucitol assimilation in Bacillus subtilis: possible cooperation of mtl and gut operons

    J Bacteriol. 2003 Aug;185(16):4816-24. PubMed PMID: 12897001; PubMed Central PMCID: PMC166460.
    Henstra SA, Duurkens RH, Robillard GT

    Multiple phosphorylation events regulate the activity of the mannitol transcriptional regulator MtlR of the Bacillus stearothermophilus phosphoenolpyruvate-dependent mannitol phosphotransferase system

    J Biol Chem. 2000 Mar 10;275(10):7037-44. PubMed PMID: 10702268.
    Reizer J, Bachem S, Reizer A, Arnaud M, Saier MH Jr, Stülke J

    Novel phosphotransferase system genes revealed by genome analysis - the complete complement of PTS proteins encoded within the genome of Bacillus subtilis

    Microbiology. 1999 Dec;145 ( Pt 12):3419-29. PubMed PMID: 10627040.
    Henstra SA, Tuinhof M, Duurkens RH, Robillard GT

    The Bacillus stearothermophilus mannitol regulator, MtlR, of the phosphotransferase system

    A DNA-binding protein, regulated by HPr and iicbmtl-dependent phosphorylation. J Biol Chem. 1999 Feb 19;274(8):4754-63. PubMed PMID: 9988713.
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