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Description: two-component response regulator, regulation of degradative enzyme expression, genetic competence, biofilm formation, capsule biosynthesis (together with SwrAA), non-phosphorylated DegU is required for swarming motility

Name: degU
Locus: BSU35490BsubCyc
pI: 5.0
MW: 25.0 kDa
Protein length: 229 aaBLASTSequence
Gene length: 687 bpBLASTSequenceSequence + Flanks
Function: regulation of degradative enzymes, genetic competence,
Product: two-component response regulator
Essential: no
E.C. number:
Synonyms: sacU, iep
Databases: SubtiListKEGGUniProtExpression data browser

Categories containing this gene/protein


biofilm formation, transcription factors and their control, phosphoproteins

This gene is a member of the following regulons


CcpA regulon, DegU regulon, SinR regulon, TnrA regulon

The DegU regulon


Gene


  • Coordinates on the chromosome (coding sequence): 3,644,607 -> 3,645,296
  • Phenotypes of a mutant

  • defect in biofilm formation PubMed, this can be suppressed by DegU-independent expression of BslA PubMed
  • the mutation suppresses the mucoid phenotype of motA or motB mutants due to reduced expression of the capB-capC-capA-capE operon PubMed
  • The protein


    Catalyzed reaction/ biological activity

  • transcription activator and repressor (see DegU regulon)
  • DegU-P represses expression of the fla/che operon (flgB-flgC-fliE-fliF-fliG-fliH-fliI-fliJ-ylxF-fliK-flgD-flgE-fliL-fliM-fliY-cheY-fliZ-fliP-fliQ-fliR-flhB-flhA-flhF-flhG-cheB-cheA-cheW-cheC-cheD-sigD-swrB) in the absence of SwrA, and switches to an activator of the operon in the presence of SwrA PubMed
  • Protein family

    Paralogous protein(s)

    Kinetic information

    Domains

    Modification

  • phosphorylated by DegS on Asp-56 PubMed, this modulates DNA-binding activity
  • phosphorylation by DegS occurs in response to inhibition of flagellar rotation PubMed
  • Cofactors

    Effectors of protein activity

  • DNA-binding activity of DegU is inhibited by RapG PubMed
  • DegU-P is degraded by ClpC-ClpP PubMed
  • Structure

  • 4GVP (VraR from Staphylococcus aureus, 35% identity) PubMed
  • Localization

  • cytoplasm (according to Swiss-Prot)
  • Interactions

  • DegU-RapG PubMed
  • DegS-DegU
  • SwrA-DegU-P (N-terminal domain) PubMed
  • Additional information

  • DegU-P is degraded by ClpC-ClpP PubMed
  • accumulation of DegU-P results in decreased transcription of the epsA-epsO and tapA-sipW-tasA operons due to increased levels of Spo0A-P PubMed
  • Expression and Regulation


    Operon

  • degS-degU PubMed
  • degU PubMed
  • Sigma factor

  • degS: SigA PubMed
  • degU: SigA PubMed
  • Regulation

  • induced in the presence of ammonium (TnrA) PubMed
  • induced by glucose (CcpA) PubMed
  • Regulatory mechanism

  • DegU: positive autoregulation PubMed
  • TnrA: transcription repression PubMed
  • CcpA: transcription activation PubMed
  • SinR: transcription repression PubMed
  • Additional information

  • DegU-P is degraded by ClpC-ClpP PubMed
  • Biological materials


    Mutant

    Expression vector

    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

    Labs working on this gene/protein


    References


    Reviews

    Cairns LS, Hobley L, Stanley-Wall NR

    Biofilm formation by Bacillus subtilis: new insights into regulatory strategies and assembly mechanisms

    Mol Microbiol. 2014 Aug;93(4):587-98. doi: 10.1111/mmi.12697. Epub 2014 Jul 18. Review. PubMed PMID: 24988880; PubMed Central PMCID: PMC4238804.
    Belas R

    When the swimming gets tough, the tough form a biofilm

    Mol Microbiol. 2013 Oct;90(1):1-5. doi: 10.1111/mmi.12354. Epub 2013 Aug 16. PubMed PMID: 23927648.
    López D, Kolter R

    Extracellular signals that define distinct and coexisting cell fates in Bacillus subtilis

    FEMS Microbiol Rev. 2010 Mar;34(2):134-49. doi: 10.1111/j.1574-6976.2009.00199.x. Epub 2009 Nov 23. Review. PubMed PMID: 20030732.
    Murray EJ, Kiley TB, Stanley-Wall NR

    A pivotal role for the response regulator DegU in controlling multicellular behaviour

    Microbiology. 2009 Jan;155(Pt 1):1-8. doi: 10.1099/mic.0.023903-0. Review. PubMed PMID: 19118340.

    The DegU regulon

    Mäder U(1), Antelmann H, Buder T, Dahl MK, Hecker M, Homuth G.

    Bacillus subtilis functional genomics: genome-wide analysis of the DegS-DegU regulon by transcriptomics and proteomics.

    Mol Genet Genomics. 2002 Dec;268(4):455-67. Epub 2002 Nov 16.

    Original Publications

    1. Error occurred: cannot get document summary PMID: 122328658 Miras M, Dubnau D

    A DegU-P and DegQ-Dependent Regulatory Pathway for the K-state in Bacillus subtilis

    Front Microbiol. 2016 Nov 22;7:1868. eCollection 2016. PubMed PMID: 27920766; PubMed Central PMCID: PMC5118428.
    Ploss TN, Reilman E, Monteferrante CG, Denham EL, Piersma S, Lingner A, Vehmaanperä J, Lorenz P, van Dijl JM

    Homogeneity and heterogeneity in amylase production by Bacillus subtilis under different growth conditions

    Microb Cell Fact. 2016 Mar 29;15:57. doi: 10.1186/s12934-016-0455-1. PubMed PMID: 27026185; PubMed Central PMCID: PMC4812647.
    Ogura M

    Post-transcriptionally generated cell heterogeneity regulates biofilm formation in Bacillus subtilis

    Genes Cells. 2016 Apr;21(4):335-49. doi: 10.1111/gtc.12343. Epub 2016 Jan 28. PubMed PMID: 26819068.
    Cairns LS, Martyn JE, Bromley K, Stanley-Wall NR

    An alternate route to phosphorylating DegU of Bacillus subtilis using acetyl phosphate

    BMC Microbiol. 2015 Mar 31;15:78. doi: 10.1186/s12866-015-0410-z. PubMed PMID: 25887289; PubMed Central PMCID: PMC4404196.
    Tanaka K, Iwasaki K, Morimoto T, Matsuse T, Hasunuma T, Takenaka S, Chumsakul O, Ishikawa S, Ogasawara N, Yoshida K

    Hyperphosphorylation of DegU cancels CcpA-dependent catabolite repression of rocG in Bacillus subtilis

    BMC Microbiol. 2015 Feb 22;15:43. doi: 10.1186/s12866-015-0373-0. PubMed PMID: 25880922; PubMed Central PMCID: PMC4348106.
    7. Error occurred: cannot get document summary PMID: 25777015 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. Epub 2015 Mar 8. PubMed PMID: 25755103; PubMed Central PMCID: PMC4475385.
    Shiwa Y, Yoshikawa H, Tanaka T, Ogura M

    Bacillus subtilis degSU operon is regulated by the ClpXP-Spx regulated proteolysis system

    J Biochem. 2015 May;157(5):321-30. doi: 10.1093/jb/mvu076. Epub 2014 Nov 29. PubMed PMID: 25433860.
    Gupta M, Rao KK

    Phosphorylation of DegU is essential for activation of amyE expression in Bacillus subtilis

    J Biosci. 2014 Dec;39(5):747-52. PubMed PMID: 25431404.
    Mordini S, Osera C, Marini S, Scavone F, Bellazzi R, Galizzi A, Calvio C

    The role of SwrA, DegU and P(D3) in fla/che expression in B

    subtilis. PLoS One. 2013 Dec 27;8(12):e85065. doi: 10.1371/journal.pone.0085065. eCollection 2013. PubMed PMID: 24386445; PubMed Central PMCID: PMC3874003.
    Ogura M, Yoshikawa H, Chibazakura T

    Regulation of the response regulator gene degU through the binding of SinR/SlrR and exclusion of SinR/SlrR by DegU in Bacillus subtilis

    J Bacteriol. 2014 Feb;196(4):873-81. doi: 10.1128/JB.01321-13. Epub 2013 Dec 6. PubMed PMID: 24317403; PubMed Central PMCID: PMC3911177.
    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.
    Marlow VL, Cianfanelli FR, Porter M, Cairns LS, Dale JK, Stanley-Wall NR

    The prevalence and origin of exoprotease-producing cells in the Bacillus subtilis biofilm

    Microbiology. 2014 Jan;160(Pt 1):56-66. doi: 10.1099/mic.0.072389-0. Epub 2013 Oct 22. PubMed PMID: 24149708; PubMed Central PMCID: PMC3917226.
    Marlow VL, Porter M, Hobley L, Kiley TB, Swedlow JR, Davidson FA, Stanley-Wall NR

    Phosphorylated DegU manipulates cell fate differentiation in the Bacillus subtilis biofilm

    J Bacteriol. 2014 Jan;196(1):16-27. doi: 10.1128/JB.00930-13. Epub 2013 Oct 11. PubMed PMID: 24123822; PubMed Central PMCID: PMC3911142.
    Cairns LS, Marlow VL, Bissett E, Ostrowski A, Stanley-Wall NR

    A mechanical signal transmitted by the flagellum controls signalling in Bacillus subtilis

    Mol Microbiol. 2013 Oct;90(1):6-21. doi: 10.1111/mmi.12342. Epub 2013 Aug 14. PubMed PMID: 23888912; PubMed Central PMCID: PMC3963450.
    Leonard PG, Golemi-Kotra D, Stock AM

    Phosphorylation-dependent conformational changes and domain rearrangements in Staphylococcus aureus VraR activation

    Proc Natl Acad Sci U S A. 2013 May 21;110(21):8525-30. doi: 10.1073/pnas.1302819110. Epub 2013 May 6. PubMed PMID: 23650349; PubMed Central PMCID: PMC3666669.
    Ishii H, Tanaka T, Ogura M

    The Bacillus subtilis response regulator gene degU is positively regulated by CcpA and by catabolite-repressed synthesis of ClpC

    J Bacteriol. 2013 Jan;195(2):193-201. doi: 10.1128/JB.01881-12. Epub 2012 Nov 2. PubMed PMID: 23123903; PubMed Central PMCID: PMC3553847.
    Davidson FA, Seon-Yi C, Stanley-Wall NR

    Selective heterogeneity in exoprotease production by Bacillus subtilis

    PLoS One. 2012;7(6):e38574. doi: 10.1371/journal.pone.0038574. Epub 2012 Jun 20. PubMed PMID: 22745669; PubMed Central PMCID: PMC3380070.
    Do TH, Suzuki Y, Abe N, Kaneko J, Itoh Y, Kimura K

    Mutations suppressing the loss of DegQ function in Bacillus subtilis (natto) poly-γ-glutamate synthesis

    Appl Environ Microbiol. 2011 Dec;77(23):8249-58. doi: 10.1128/AEM.05827-11. Epub 2011 Sep 30. PubMed PMID: 21965392; PubMed Central PMCID: PMC3233065.
    Ostrowski A, Mehert A, Prescott A, Kiley TB, Stanley-Wall NR

    YuaB functions synergistically with the exopolysaccharide and TasA amyloid fibers to allow biofilm formation by Bacillus subtilis

    J Bacteriol. 2011 Sep;193(18):4821-31. doi: 10.1128/JB.00223-11. Epub 2011 Jul 8. PubMed PMID: 21742882; PubMed Central PMCID: PMC3165672.
    Kiley TB, Stanley-Wall NR

    Post-translational control of Bacillus subtilis biofilm formation mediated by tyrosine phosphorylation

    Mol Microbiol. 2010 Nov;78(4):947-63. doi: 10.1111/j.1365-2958.2010.07382.x. Epub 2010 Sep 29. PubMed PMID: 20815827.
    Ogura M, Tsukahara K

    Autoregulation of the Bacillus subtilis response regulator gene degU is coupled with the proteolysis of DegU-P by ClpCP

    Mol Microbiol. 2010 Mar;75(5):1244-59. doi: 10.1111/j.1365-2958.2010.07047.x. Epub 2010 Jan 12. PubMed PMID: 20070525.
    Ohsawa T, Tsukahara K, Ogura M

    Bacillus subtilis response regulator DegU is a direct activator of pgsB transcription involved in gamma-poly-glutamic acid synthesis

    Biosci Biotechnol Biochem. 2009 Sep;73(9):2096-102. Epub 2009 Sep 7. PubMed PMID: 19734658.
    Kimura K, Tran LS, Do TH, Itoh Y

    Expression of the pgsB encoding the poly-gamma-DL-glutamate synthetase of Bacillus subtilis (natto)

    Biosci Biotechnol Biochem. 2009 May;73(5):1149-55. Epub 2009 May 7. PubMed PMID: 19420703.
    Gupta M, Rao KK

    Epr plays a key role in DegU-mediated swarming motility of Bacillus subtilis

    FEMS Microbiol Lett. 2009 Jun;295(2):187-94. doi: 10.1111/j.1574-6968.2009.01596.x. Epub 2009 Apr 16. PubMed PMID: 19416356.
    Osera C, Amati G, Calvio C, Galizzi A

    SwrAA activates poly-gamma-glutamate synthesis in addition to swarming in Bacillus subtilis

    Microbiology. 2009 Jul;155(Pt 7):2282-7. doi: 10.1099/mic.0.026435-0. Epub 2009 Apr 23. PubMed PMID: 19389763.
    Osera C, Amati G, Calvio C, Galizzi A

    SwrAA activates poly-gamma-glutamate synthesis in addition to swarming in Bacillus subtilis

    Microbiology. 2009 Jul;155(Pt 7):2282-7. doi: 10.1099/mic.0.026435-0. Epub 2009 Apr 23. PubMed PMID: 19389763.
    Verhamme DT, Murray EJ, Stanley-Wall NR

    DegU and Spo0A jointly control transcription of two loci required for complex colony development by Bacillus subtilis

    J Bacteriol. 2009 Jan;191(1):100-8. doi: 10.1128/JB.01236-08. Epub 2008 Oct 31. PubMed PMID: 18978066; PubMed Central PMCID: PMC2612447.
    Yasumura A, Abe S, Tanaka T

    Involvement of nitrogen regulation in Bacillus subtilis degU expression

    J Bacteriol. 2008 Aug;190(15):5162-71. doi: 10.1128/JB.00368-08. Epub 2008 May 23. PubMed PMID: 18502860; PubMed Central PMCID: PMC2493268.
    Yasumura A, Abe S, Tanaka T

    Involvement of nitrogen regulation in Bacillus subtilis degU expression

    J Bacteriol. 2008 Aug;190(15):5162-71. doi: 10.1128/JB.00368-08. Epub 2008 May 23. PubMed PMID: 18502860; PubMed Central PMCID: PMC2493268.
    Veening JW, Igoshin OA, Eijlander RT, Nijland R, Hamoen LW, Kuipers OP

    Transient heterogeneity in extracellular protease production by Bacillus subtilis

    Mol Syst Biol. 2008;4:184. doi: 10.1038/msb.2008.18. Epub 2008 Apr 15. PubMed PMID: 18414485; PubMed Central PMCID: PMC2387230.
    Tsukahara K, Ogura M

    Promoter selectivity of the Bacillus subtilis response regulator DegU, a positive regulator of the fla/che operon and sacB

    BMC Microbiol. 2008 Jan 15;8:8. doi: 10.1186/1471-2180-8-8. PubMed PMID: 18197985; PubMed Central PMCID: PMC2245950.
    Tsukahara K, Ogura M

    Characterization of DegU-dependent expression of bpr in Bacillus subtilis

    FEMS Microbiol Lett. 2008 Mar;280(1):8-13. doi: 10.1111/j.1574-6968.2007.01019.x. Epub 2008 Jan 7. PubMed PMID: 18194340.
    Kobayashi K

    Gradual activation of the response regulator DegU controls serial expression of genes for flagellum formation and biofilm formation in Bacillus subtilis

    Mol Microbiol. 2007 Oct;66(2):395-409. Epub 2007 Sep 10. PubMed PMID: 17850253.
    Verhamme DT, Kiley TB, Stanley-Wall NR

    DegU co-ordinates multicellular behaviour exhibited by Bacillus subtilis

    Mol Microbiol. 2007 Jul;65(2):554-68. Epub 2007 Jun 21. PubMed PMID: 17590234.
    Shimane K, Ogura M

    Mutational analysis of the helix-turn-helix region of Bacillus subtilis response regulator DegU, and identification of cis-acting sequences for DegU in the aprE and comK promoters

    J Biochem. 2004 Sep;136(3):387-97. PubMed PMID: 15598897.
    Steil L, Hoffmann T, Budde I, Völker U, Bremer E

    Genome-wide transcriptional profiling analysis of adaptation of Bacillus subtilis to high salinity

    J Bacteriol. 2003 Nov;185(21):6358-70. PubMed PMID: 14563871; PubMed Central PMCID: PMC219388.
    Ogura M, Shimane K, Asai K, Ogasawara N, Tanaka T

    Binding of response regulator DegU to the aprE promoter is inhibited by RapG, which is counteracted by extracellular PhrG in Bacillus subtilis

    Mol Microbiol. 2003 Sep;49(6):1685-97. PubMed PMID: 12950930.
    Hamoen LW, Van Werkhoven AF, Venema G, Dubnau D

    The pleiotropic response regulator DegU functions as a priming protein in competence development in Bacillus subtilis

    Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9246-51. PubMed PMID: 10908654; PubMed Central PMCID: PMC16853.
    Fabret C, Feher VA, Hoch JA

    Two-component signal transduction in Bacillus subtilis: how one organism sees its world

    J Bacteriol. 1999 Apr;181(7):1975-83. Review. PubMed PMID: 10094672; PubMed Central PMCID: PMC93607.
    Ogura M, Tanaka T

    Bacillus subtilis DegU acts as a positive regulator for comK expression

    FEBS Lett. 1996 Nov 18;397(2-3):173-6. PubMed PMID: 8955341.
    Hahn J, Luttinger A, Dubnau D

    Regulatory inputs for the synthesis of ComK, the competence transcription factor of Bacillus subtilis

    Mol Microbiol. 1996 Aug;21(4):763-75. PubMed PMID: 8878039.
    Haijema BJ, Hamoen LW, Kooistra J, Venema G, van Sinderen D

    Expression of the ATP-dependent deoxyribonuclease of Bacillus subtilis is under competence-mediated control

    Mol Microbiol. 1995 Jan;15(2):203-11. PubMed PMID: 7746142.
    Shimotsu H, Henner DJ

    Modulation of Bacillus subtilis levansucrase gene expression by sucrose and regulation of the steady-state mRNA level by sacU and sacQ genes

    J Bacteriol. 1986 Oct;168(1):380-8. PubMed PMID: 2428811; PubMed Central PMCID: PMC213462.
    Dahl MK, Msadek T, Kunst F, Rapoport G

    Mutational analysis of the Bacillus subtilis DegU regulator and its phosphorylation by the DegS protein kinase

    J Bacteriol. 1991 Apr;173(8):2539-47. PubMed PMID: 1901568; PubMed Central PMCID: PMC207818.
    Msadek T, Kunst F, Henner D, Klier A, Rapoport G, Dedonder R

    Signal transduction pathway controlling synthesis of a class of degradative enzymes in Bacillus subtilis: expression of the regulatory genes and analysis of mutations in degS and degU

    J Bacteriol. 1990 Feb;172(2):824-34. PubMed PMID: 1688843; PubMed Central PMCID: PMC208512.
    Mukai K, Kawata-Mukai M, Tanaka T

    Stabilization of phosphorylated Bacillus subtilis DegU by DegR

    J Bacteriol. 1992 Dec;174(24):7954-62. PubMed PMID: 1459944; PubMed Central PMCID: PMC207531.
    Dahl MK, Msadek T, Kunst F, Rapoport G

    The phosphorylation state of the DegU response regulator acts as a molecular switch allowing either degradative enzyme synthesis or expression of genetic competence in Bacillus subtilis

    J Biol Chem. 1992 Jul 15;267(20):14509-14. PubMed PMID: 1321152.
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