SubtiBank SubtiBank

Description: AAA unfoldase, ATPase subunit of the ClpC-ClpP protease, directs proteins phosphorylated on arginine residues to ClpP

Name: clpC
Locus: BSU00860BsubCyc
pI: 5.0
MW: 89.0 kDa
Protein length: 810 aaBLASTSequence
Gene length: 2430 bpBLASTSequenceSequence + Flanks
Function: protein degradation
positive regulator of autolysin (LytC and LytD) synthesis
Product: AAA unfoldase, ATPase subunit of the ClpC-ClpP protease
Essential: no
E.C. number:
Synonyms: mecB
Databases: SubtiListKEGGUniProtExpression data browser

Categories containing this gene/protein


proteolysis, sporulation proteins, general stress proteins (controlled by SigB), heat shock proteins, phosphoproteins

This gene is a member of the following regulons


CtsR regulon, SigB regulon, SigF regulon

Gene


  • Coordinates on the chromosome (coding sequence): 103,572 -> 106,004
  • Phenotypes of a mutant

  • inactivation of clpC reduces sporulation efficiency to 0.4% that of wild type cells; delayed entry into sporulation, defect in engulfment with reduced SigG activity, and production of small spores PubMed
  • The protein


    Catalyzed reaction/ biological activity

  • ATPase/chaperone
  • Protein family

  • mecA family (according to Swiss-Prot) clpA/clpB family. ClpC subfamily (according to Swiss-Prot), AAA -type ATPase (IPR013093) InterPro (PF07724) PFAM
  • Paralogous protein(s)

  • ClpE, ClpX
  • Kinetic information

    Domains

  • AAA-ATPase PFAM
  • Modification

  • phosphorylated on Arg-5 and Arg-254 PubMed
  • Cofactors

    Effectors of protein activity

    Structure

  • 2K77 (N-terminal domain)
  • 3PXG, 3J3U 3J3U (the MecA-ClpC complex) PubMed
  • Localization

  • cytoplasmic polar clusters, excluded from the nucleoid, induced clustering upon heatshock, colocalization with ClpP PubMed
  • forms foci coincident with nucleoid edges, usually near cell poles PubMed
  • [[File:ClpC.jpg‎ ]]

    Interactions

  • forms hexamers PubMed
  • the protease: ClpC-ClpP
  • interactions with adaptor proteins of ClpC-ClpP: YpbH-ClpC, McsB-ClpC, MecA-ClpC PubMed
  • CtsR-McsB-ClpC/ClpP (degradation of CtsR) PubMed
  • Additional information

  • subject to Clp-dependent proteolysis upon glucose starvation PubMed
  • Expression and Regulation


    Operon

  • ctsR-mcsA-mcsB-clpC-radA-disA PubMed
  • Sigma factor

  • SigA PubMed, SigB PubMed2, SigF PubMed
  • Regulation

  • expressed early during sporulation in the forespore (SigF) PubMed
  • induced by stress (SigB) PubMed
  • induced by heat (CtsR) PubMed
  • Regulatory mechanism

  • CtsR: transcription repression PubMed1, PubMed2, PubMed3, PubMed4
  • Additional information

  • subject to Clp-dependent proteolysis upon glucose starvation [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids= 17981983" target="_blank">PubMed
  • Biological materials


    Mutant

  • clpC::tet available from the Hamoen Lab
  • BP98 (clpC::spc), available in Fabian Commichau's lab PubMed
  • BKE00860 (clpC::erm trpC2) is available from the Bacillus Genetic Stock Center
  • Expression vector

    lacZ fusion

    GFP fusion

  • C-terminal GFP fusions (single copy, also as CFP and YFP variants) available from the Hamoen Lab
  • two-hybrid system

    FLAG-tag construct

    Antibody

  • available in Ulf Gerths and Jörg Stülkes labs
  • Labs working on this gene/protein


  • Leendert Hamoen, Newcastle University, UK homepage
  • Kürsad Turgay, Freie Universität Berlin, Germany homepage
  • References


    Reviews

    Olivares AO, Baker TA, Sauer RT

    Mechanistic insights into bacterial AAA+ proteases and protein-remodelling machines

    Nat Rev Microbiol. 2016 Jan;14(1):33-44. doi: 10.1038/nrmicro.2015.4. Review. PubMed PMID: 26639779.
    Molière N, Turgay K

    General and regulatory proteolysis in Bacillus subtilis

    Subcell Biochem. 2013;66:73-103. doi: 10.1007/978-94-007-5940-4_4. Review. PubMed PMID: 23479438.
    Battesti A, Gottesman S

    Roles of adaptor proteins in regulation of bacterial proteolysis

    Curr Opin Microbiol. 2013 Apr;16(2):140-7. doi: 10.1016/j.mib.2013.01.002. Review. PubMed PMID: 23375660; PubMed Central PMCID: PMC3646950.
    Molière N, Turgay K

    Chaperone-protease systems in regulation and protein quality control in Bacillus subtilis

    Res Microbiol. 2009 Nov;160(9):637-44. doi: 10.1016/j.resmic.2009.08.020. Review. PubMed PMID: 19781636.
    Kirstein J, Molière N, Dougan DA, Turgay K

    Adapting the machine: adaptor proteins for Hsp100/Clp and AAA+ proteases

    Nat Rev Microbiol. 2009 Aug;7(8):589-99. doi: 10.1038/nrmicro2185. Review. PubMed PMID: 19609260.
    Frees D, Savijoki K, Varmanen P, Ingmer H

    Clp ATPases and ClpP proteolytic complexes regulate vital biological processes in low GC, Gram-positive bacteria

    Mol Microbiol. 2007 Mar;63(5):1285-95. Review. PubMed PMID: 17302811.

    Original Publications

    Trentini DB, Suskiewicz MJ, Heuck A, Kurzbauer R, Deszcz L, Mechtler K, Clausen T

    Arginine phosphorylation marks proteins for degradation by a Clp protease

    Nature. 2016 Nov 3;539(7627):48-53. doi: 10.1038/nature20122. PubMed PMID: 27749819.
    Molière N, Hoßmann J, Schäfer H, Turgay K

    Role of Hsp100/Clp Protease Complexes in Controlling the Regulation of Motility in Bacillus subtilis

    Front Microbiol. 2016 Mar 16;7:315. doi: 10.3389/fmicb.2016.00315. PubMed PMID: 27014237; PubMed Central PMCID: PMC4793158.
    Meeske AJ, Rodrigues CD, Brady J, Lim HC, Bernhardt TG, Rudner DZ

    High-Throughput Genetic Screens Identify a Large and Diverse Collection of New Sporulation Genes in Bacillus subtilis

    PLoS Biol. 2016 Jan 6;14(1):e1002341. doi: 10.1371/journal.pbio.1002341. PubMed PMID: 26735940; PubMed Central PMCID: PMC4703394.
    Fuhrmann J, Subramanian V, Thompson PR

    Synthesis and Use of a Phosphonate Amidine to Generate an Anti-Phosphoarginine-Specific Antibody

    Angew Chem Int Ed Engl. 2015 Dec 1;54(49):14715-8. doi: 10.1002/anie.201506737. PubMed PMID: 26458230; PubMed Central PMCID: PMC4715515.
    Stannek L, Gunka K, Care RA, Gerth U, Commichau FM

    Factors that mediate and prevent degradation of the inactive and unstable GudB protein in Bacillus subtilis

    Front Microbiol. 2015 Jan 7;5:758. doi: 10.3389/fmicb.2014.00758. PubMed PMID: 25610436; PubMed Central PMCID: PMC4285742.
    Schmidt A, Trentini DB, Spiess S, Fuhrmann J, Ammerer G, Mechtler K, Clausen T

    Quantitative phosphoproteomics reveals the role of protein arginine phosphorylation in the bacterial stress response

    Mol Cell Proteomics. 2014 Feb;13(2):537-50. doi: 10.1074/mcp.M113.032292. PubMed PMID: 24263382; PubMed Central PMCID: PMC3916652.
    Liu J, Mei Z, Li N, Qi Y, Xu Y, Shi Y, Wang F, Lei J, Gao N

    Structural dynamics of the MecA-ClpC complex: a type II AAA+ protein unfolding machine

    J Biol Chem. 2013 Jun 14;288(24):17597-608. doi: 10.1074/jbc.M113.458752. PubMed PMID: 23595989; PubMed Central PMCID: PMC3682559.
    Elsholz AK, Turgay K, Michalik S, Hessling B, Gronau K, Oertel D, Mäder U, Bernhardt J, Becher D, Hecker M, Gerth U

    Global impact of protein arginine phosphorylation on the physiology of Bacillus subtilis

    Proc Natl Acad Sci U S A. 2012 May 8;109(19):7451-6. doi: 10.1073/pnas.1117483109. PubMed PMID: 22517742; PubMed Central PMCID: PMC3358850.
    Brown CT, Fishwick LK, Chokshi BM, Cuff MA, Jackson JM 4th, Oglesby T, Rioux AT, Rodriguez E, Stupp GS, Trupp AH, Woollcombe-Clarke JS, Wright TN, Zaragoza WJ, Drew JC, Triplett EW, Nicholson WL

    Whole-genome sequencing and phenotypic analysis of Bacillus subtilis mutants following evolution under conditions of relaxed selection for sporulation

    Appl Environ Microbiol. 2011 Oct;77(19):6867-77. doi: 10.1128/AEM.05272-11. PubMed PMID: 21821766; PubMed Central PMCID: PMC3187084.
    Elsholz AK, Hempel K, Michalik S, Gronau K, Becher D, Hecker M, Gerth U

    Activity control of the ClpC adaptor McsB in Bacillus subtilis

    J Bacteriol. 2011 Aug;193(15):3887-93. doi: 10.1128/JB.00079-11. PubMed PMID: 21622759; PubMed Central PMCID: PMC3147538.
    Wang F, Mei Z, Qi Y, Yan C, Hu Q, Wang J, Shi Y

    Structure and mechanism of the hexameric MecA-ClpC molecular machine

    Nature. 2011 Mar 17;471(7338):331-5. doi: 10.1038/nature09780. PubMed PMID: 21368759.
    Chai Y, Kolter R, Losick R

    Reversal of an epigenetic switch governing cell chaining in Bacillus subtilis by protein instability

    Mol Microbiol. 2010 Oct;78(1):218-29. doi: 10.1111/j.1365-2958.2010.07335.x. PubMed PMID: 20923420; PubMed Central PMCID: PMC2998389.
    Elsholz AK, Michalik S, Zühlke D, Hecker M, Gerth U

    CtsR, the Gram-positive master regulator of protein quality control, feels the heat

    EMBO J. 2010 Nov 3;29(21):3621-9. doi: 10.1038/emboj.2010.228. PubMed PMID: 20852588; PubMed Central PMCID: PMC2982754.
    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. PubMed PMID: 20070525.
    Mei Z, Wang F, Qi Y, Zhou Z, Hu Q, Li H, Wu J, Shi Y

    Molecular determinants of MecA as a degradation tag for the ClpCP protease

    J Biol Chem. 2009 Dec 4;284(49):34366-75. doi: 10.1074/jbc.M109.053017. PubMed PMID: 19767395; PubMed Central PMCID: PMC2797204.
    Kojetin DJ, McLaughlin PD, Thompson RJ, Dubnau D, Prepiak P, Rance M, Cavanagh J

    Structural and motional contributions of the Bacillus subtilis ClpC N-domain to adaptor protein interactions

    J Mol Biol. 2009 Apr 3;387(3):639-52. doi: 10.1016/j.jmb.2009.01.046. PubMed PMID: 19361434; PubMed Central PMCID: PMC2692191.
    Kojetin DJ, McLaughlin PD, Thompson RJ, Dubnau D, Prepiak P, Rance M, Cavanagh J

    Structural and motional contributions of the Bacillus subtilis ClpC N-domain to adaptor protein interactions

    J Mol Biol. 2009 Apr 3;387(3):639-52. doi: 10.1016/j.jmb.2009.01.046. PubMed PMID: 19361434; PubMed Central PMCID: PMC2692191.
    Hahn J, Kramer N, Briley K Jr, Dubnau D

    McsA and B mediate the delocalization of competence proteins from the cell poles of Bacillus subtilis

    Mol Microbiol. 2009 Apr;72(1):202-15. doi: 10.1111/j.1365-2958.2009.06636.x. PubMed PMID: 19226326; PubMed Central PMCID: PMC4429805.
    Kirstein J, Strahl H, Molière N, Hamoen LW, Turgay K

    Localization of general and regulatory proteolysis in Bacillus subtilis cells

    Mol Microbiol. 2008 Nov;70(3):682-94. doi: 10.1111/j.1365-2958.2008.06438.x. PubMed PMID: 18786145; PubMed Central PMCID: PMC2628427.
    Simmons LA, Grossman AD, Walker GC

    Clp and Lon proteases occupy distinct subcellular positions in Bacillus subtilis

    J Bacteriol. 2008 Oct;190(20):6758-68. doi: 10.1128/JB.00590-08. PubMed PMID: 18689473; PubMed Central PMCID: PMC2566193.
    Gerth U, Kock H, Kusters I, Michalik S, Switzer RL, Hecker M

    Clp-dependent proteolysis down-regulates central metabolic pathways in glucose-starved Bacillus subtilis

    J Bacteriol. 2008 Jan;190(1):321-31. PubMed PMID: 17981983; PubMed Central PMCID: PMC2223743.
    Prepiak P, Dubnau D

    A peptide signal for adapter protein-mediated degradation by the AAA+ protease ClpCP

    Mol Cell. 2007 Jun 8;26(5):639-47. PubMed PMID: 17560370; PubMed Central PMCID: PMC2041856.
    Kirstein J, Dougan DA, Gerth U, Hecker M, Turgay K

    The tyrosine kinase McsB is a regulated adaptor protein for ClpCP

    EMBO J. 2007 Apr 18;26(8):2061-70. PubMed PMID: 17380125; PubMed Central PMCID: PMC1852781.
    Kirstein J, Schlothauer T, Dougan DA, Lilie H, Tischendorf G, Mogk A, Bukau B, Turgay K

    Adaptor protein controlled oligomerization activates the AAA+ protein ClpC

    EMBO J. 2006 Apr 5;25(7):1481-91. PubMed PMID: 16525504; PubMed Central PMCID: PMC1440321.
    Wang ST, Setlow B, Conlon EM, Lyon JL, Imamura D, Sato T, Setlow P, Losick R, Eichenberger P

    The forespore line of gene expression in Bacillus subtilis

    J Mol Biol. 2006 Apr 21;358(1):16-37. PubMed PMID: 16497325.
    Kirstein J, Zühlke D, Gerth U, Turgay K, Hecker M

    A tyrosine kinase and its activator control the activity of the CtsR heat shock repressor in B

    subtilis. EMBO J. 2005 Oct 5;24(19):3435-45. PubMed PMID: 16163393; PubMed Central PMCID: PMC1276163.
    Kock H, Gerth U, Hecker M

    MurAA, catalysing the first committed step in peptidoglycan biosynthesis, is a target of Clp-dependent proteolysis in Bacillus subtilis

    Mol Microbiol. 2004 Feb;51(4):1087-102. PubMed PMID: 14763982.
    Gerth U, Kirstein J, Mostertz J, Waldminghaus T, Miethke M, Kock H, Hecker M

    Fine-tuning in regulation of Clp protein content in Bacillus subtilis

    J Bacteriol. 2004 Jan;186(1):179-91. PubMed PMID: 14679237; PubMed Central PMCID: PMC303445.
    Pan Q, Losick R

    Unique degradation signal for ClpCP in Bacillus subtilis

    J Bacteriol. 2003 Sep;185(17):5275-8. PubMed PMID: 12923101; PubMed Central PMCID: PMC181016.
    Schlothauer T, Mogk A, Dougan DA, Bukau B, Turgay K

    MecA, an adaptor protein necessary for ClpC chaperone activity

    Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2306-11. PubMed PMID: 12598648; PubMed Central PMCID: PMC151336.
    Nakano MM, Nakano S, Zuber P

    Spx (YjbD), a negative effector of competence in Bacillus subtilis, enhances ClpC-MecA-ComK interaction

    Mol Microbiol. 2002 Jun;44(5):1341-9. PubMed PMID: 12028382.
    Persuh M, Mandic-Mulec I, Dubnau D

    A MecA paralog, YpbH, binds ClpC, affecting both competence and sporulation

    J Bacteriol. 2002 Apr;184(8):2310-3. PubMed PMID: 11914365; PubMed Central PMCID: PMC134970.
    Turgay K, Persuh M, Hahn J, Dubnau D

    Roles of the two ClpC ATP binding sites in the regulation of competence and the stress response

    Mol Microbiol. 2001 Nov;42(3):717-27. PubMed PMID: 11722737.
    Pan Q, Garsin DA, Losick R

    Self-reinforcing activation of a cell-specific transcription factor by proteolysis of an anti-sigma factor in B

    subtilis. Mol Cell. 2001 Oct;8(4):873-83. PubMed PMID: 11684022.
    Petersohn A, Brigulla M, Haas S, Hoheisel JD, Völker U, Hecker M

    Global analysis of the general stress response of Bacillus subtilis

    J Bacteriol. 2001 Oct;183(19):5617-31. PubMed PMID: 11544224; PubMed Central PMCID: PMC95453.
    Krüger E, Witt E, Ohlmeier S, Hanschke R, Hecker M

    The clp proteases of Bacillus subtilis are directly involved in degradation of misfolded proteins

    J Bacteriol. 2000 Jun;182(11):3259-65. PubMed PMID: 10809708; PubMed Central PMCID: PMC94515.
    Persuh M, Turgay K, Mandic-Mulec I, Dubnau D

    The N- and C-terminal domains of MecA recognize different partners in the competence molecular switch

    Mol Microbiol. 1999 Aug;33(4):886-94. PubMed PMID: 10447896.
    Derré I, Rapoport G, Msadek T

    CtsR, a novel regulator of stress and heat shock response, controls clp and molecular chaperone gene expression in gram-positive bacteria

    Mol Microbiol. 1999 Jan;31(1):117-31. PubMed PMID: 9987115.
    Derré I, Rapoport G, Msadek T

    CtsR, a novel regulator of stress and heat shock response, controls clp and molecular chaperone gene expression in gram-positive bacteria

    Mol Microbiol. 1999 Jan;31(1):117-31. PubMed PMID: 9987115.
    Turgay K, Hahn J, Burghoorn J, Dubnau D

    Competence in Bacillus subtilis is controlled by regulated proteolysis of a transcription factor

    EMBO J. 1998 Nov 16;17(22):6730-8. PubMed PMID: 9890793; PubMed Central PMCID: PMC1171018.
    Krüger E, Msadek T, Ohlmeier S, Hecker M

    The Bacillus subtilis clpC operon encodes DNA repair and competence proteins

    Microbiology. 1997 Apr;143 ( Pt 4):1309-16. PubMed PMID: 9141693.
    Turgay K, Hamoen LW, Venema G, Dubnau D

    Biochemical characterization of a molecular switch involving the heat shock protein ClpC, which controls the activity of ComK, the competence transcription factor of Bacillus subtilis

    Genes Dev. 1997 Jan 1;11(1):119-28. PubMed PMID: 9000055.
    Krüger E, Msadek T, Hecker M

    Alternate promoters direct stress-induced transcription of the Bacillus subtilis clpC operon

    Mol Microbiol. 1996 May;20(4):713-23. PubMed PMID: 8793870.
    Krüger E, Völker U, Hecker M

    Stress induction of clpC in Bacillus subtilis and its involvement in stress tolerance

    J Bacteriol. 1994 Jun;176(11):3360-7. PubMed PMID: 8195092; PubMed Central PMCID: PMC205508.
    Kong L, Dubnau D

    Regulation of competence-specific gene expression by Mec-mediated protein-protein interaction in Bacillus subtilis

    Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5793-7. PubMed PMID: 8016067; PubMed Central PMCID: PMC44083.
    Msadek T, Kunst F, Rapoport G

    MecB of Bacillus subtilis, a member of the ClpC ATPase family, is a pleiotropic regulator controlling competence gene expression and growth at high temperature

    Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5788-92. PubMed PMID: 8016066; PubMed Central PMCID: PMC44082.
    Roggiani M, Hahn J, Dubnau D

    Suppression of early competence mutations in Bacillus subtilis by mec mutations

    J Bacteriol. 1990 Jul;172(7):4056-63. PubMed PMID: 2113920; PubMed Central PMCID: PMC213392.
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