CLPP_BACSU
ID CLPP_BACSU Reviewed; 197 AA.
AC P80244; O08433;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 3.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=ATP-dependent Clp protease proteolytic subunit {ECO:0000255|HAMAP-Rule:MF_00444};
DE EC=3.4.21.92 {ECO:0000255|HAMAP-Rule:MF_00444, ECO:0000269|PubMed:20305655};
DE AltName: Full=Caseinolytic protease;
DE AltName: Full=Endopeptidase Clp {ECO:0000255|HAMAP-Rule:MF_00444};
DE AltName: Full=Stress protein G7;
GN Name=clpP {ECO:0000255|HAMAP-Rule:MF_00444}; Synonyms=yvdN;
GN OrderedLocusNames=BSU34540;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION BY STRESS.
RX PubMed=9643546; DOI=10.1046/j.1365-2958.1998.00840.x;
RA Gerth U., Kruger E., Derre I., Msadek T., Hecker M.;
RT "Stress induction of the Bacillus subtilis clpP gene encoding a homologue
RT of the proteolytic component of the Clp protease and the involvement of
RT ClpP and ClpX in stress tolerance.";
RL Mol. Microbiol. 28:787-802(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RA Denizot F.;
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [4]
RP PROTEIN SEQUENCE OF 1-24, AND INDUCTION BY STRESS.
RC STRAIN=168 / IS58;
RX PubMed=8012595; DOI=10.1099/00221287-140-4-741;
RA Voelker U., Engelmann S., Maul B., Riethdorf S., Voelker A., Schmid R.,
RA Mach H., Hecker M.;
RT "Analysis of the induction of general stress proteins of Bacillus
RT subtilis.";
RL Microbiology 140:741-752(1994).
RN [5]
RP PROTEIN SEQUENCE OF 1-21, AND INDUCTION BY STRESS.
RC STRAIN=168 / IS58;
RX PubMed=1362210; DOI=10.1099/00221287-138-10-2125;
RA Voelker U., Mach H., Schmid R., Hecker M.;
RT "Stress proteins and cross-protection by heat shock and salt stress in
RT Bacillus subtilis.";
RL J. Gen. Microbiol. 138:2125-2135(1992).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=168 / Marburg / 1012;
RX PubMed=11395451; DOI=10.1128/jb.183.13.3885-3889.2001;
RA Wiegert T., Schumann W.;
RT "SsrA-mediated tagging in Bacillus subtilis.";
RL J. Bacteriol. 183:3885-3889(2001).
RN [7]
RP FUNCTION IN RSIW DEGRADATION.
RX PubMed=16899079; DOI=10.1111/j.1365-2958.2006.05323.x;
RA Zellmeier S., Schumann W., Wiegert T.;
RT "Involvement of Clp protease activity in modulating the Bacillus subtilis
RT sigma-W stress response.";
RL Mol. Microbiol. 61:1569-1582(2006).
RN [8]
RP FUNCTION, ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=168 / 1A700;
RX PubMed=31155236; DOI=10.1016/j.cell.2019.05.002;
RA Lytvynenko I., Paternoga H., Thrun A., Balke A., Mueller T.A., Chiang C.H.,
RA Nagler K., Tsaprailis G., Anders S., Bischofs I., Maupin-Furlow J.A.,
RA Spahn C.M.T., Joazeiro C.A.P.;
RT "Alanine Tails Signal Proteolysis in Bacterial Ribosome-Associated Quality
RT Control.";
RL Cell 0:0-0(2019).
RN [9] {ECO:0007744|PDB:3KTG, ECO:0007744|PDB:3KTH, ECO:0007744|PDB:3KTI, ECO:0007744|PDB:3KTJ, ECO:0007744|PDB:3KTK}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-197 ALONE AND IN COMPLEX WITH
RP ANTIBIOTICS, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF
RP ILE-20; LEU-25; SER-46; PHE-50; GLU-54; TYR-63 AND PHE-83.
RX PubMed=20305655; DOI=10.1038/nsmb.1787;
RA Lee B.G., Park E.Y., Lee K.E., Jeon H., Sung K.H., Paulsen H.,
RA Rubsamen-Schaeff H., Brotz-Oesterhelt H., Song H.K.;
RT "Structures of ClpP in complex with acyldepsipeptide antibiotics reveal its
RT activation mechanism.";
RL Nat. Struct. Mol. Biol. 17:471-478(2010).
RN [10] {ECO:0007744|PDB:3TT6, ECO:0007744|PDB:3TT7}
RP X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS) IN COMPRESSED FORM AND IN COMPLEX
RP WITH ANTIBIOTIC, ACTIVITY REGULATION, ACTIVE SITE, SUBUNIT, AND DOMAIN.
RX PubMed=22080375; DOI=10.1007/s10059-011-0197-1;
RA Lee B.G., Kim M.K., Song H.K.;
RT "Structural insights into the conformational diversity of ClpP from
RT Bacillus subtilis.";
RL Mol. Cells 32:589-595(2011).
CC -!- FUNCTION: Cleaves peptides in various proteins in a process that
CC requires ATP hydrolysis. Has a limited peptidase activity in the
CC absence of ATP-binding subunits ClpC, ClpE or ClpX (PubMed:20305655).
CC Has a chymotrypsin-like activity. Plays a major role in the degradation
CC of misfolded proteins (By similarity). ClpXP is involved in the
CC complete degradation of the site-2 clipped anti-sigma-W factor RsiW.
CC This results in the release of SigW and the transcriptional activation
CC of genes under the control of the sigma-W factor (PubMed:16899079).
CC Probably the major protease that degrades proteins tagged by trans-
CC translation (PubMed:11395451, PubMed:31155236). {ECO:0000255|HAMAP-
CC Rule:MF_00444, ECO:0000269|PubMed:11395451,
CC ECO:0000269|PubMed:16899079, ECO:0000269|PubMed:20305655,
CC ECO:0000269|PubMed:31155236}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins to small peptides in the presence of
CC ATP and magnesium. alpha-casein is the usual test substrate. In the
CC absence of ATP, only oligopeptides shorter than five residues are
CC hydrolyzed (such as succinyl-Leu-Tyr-|-NHMec, and Leu-Tyr-Leu-|-Tyr-
CC Trp, in which cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp bonds also
CC occurs).; EC=3.4.21.92; Evidence={ECO:0000255|HAMAP-Rule:MF_00444,
CC ECO:0000269|PubMed:20305655};
CC -!- ACTIVITY REGULATION: Low intrinsic peptidase activity is stimulated by
CC ATP-binding subunits ClpC, ClpE and ClpX. Activity is disregulated by
CC acyldepsipeptides (ADEP) antibiotics, which negate the need for ATP-
CC binding subunits for activation and which makes it into an unregulated
CC protease. Each ClpP subunit binds 1 ADEP molecule, which prevents
CC binding of ClpX. ADEP binding causes conformational shifts that open
CC the gated pore of the ring (PubMed:20305655). Protease activity is
CC inhibited by diisopropylfluoro-phosphate (PubMed:22080375). Protease
CC activity is inhibited by bortezomib, an oncology drug originally
CC designed to work on the human proteasome (PubMed:31155236).
CC {ECO:0000269|PubMed:20305655, ECO:0000269|PubMed:22080375,
CC ECO:0000269|PubMed:31155236}.
CC -!- SUBUNIT: Fourteen ClpP subunits assemble into 2 heptameric rings which
CC stack back to back to give a disk-like structure with a central cavity,
CC resembling the structure of eukaryotic proteasomes (PubMed:20305655,
CC PubMed:22080375). Forms large heterooligomeric complexes consisting of
CC an ATPase component (ClpX, ClpC or ClpE) and a proteolytic component
CC (ClpP)(PubMed:20305655). {ECO:0000255|HAMAP-Rule:MF_00444,
CC ECO:0000269|PubMed:20305655, ECO:0000269|PubMed:22080375}.
CC -!- INTERACTION:
CC P80244; P80244: clpP; NbExp=4; IntAct=EBI-8165631, EBI-8165631;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00444}.
CC -!- INDUCTION: By heat shock, salt stress, ethanol stress, oxidative
CC stress, glucose limitation and oxygen limitation.
CC {ECO:0000269|PubMed:1362210, ECO:0000269|PubMed:8012595,
CC ECO:0000269|PubMed:9643546}.
CC -!- DOMAIN: Peptide exit pores open in the compressed state; in this
CC conformation the active site residues move apart and the protease
CC cannot be active. {ECO:0000269|PubMed:22080375}.
CC -!- DISRUPTION PHENOTYPE: No degradation of trans-translationally tagged-
CC peptides (PubMed:11395451, PubMed:31155236). Triple rqcH clpP ssrA
CC mutants cannot be generated (ssrA, or tmRNA, encodes the SsrA tag added
CC to nascent proteins in stalled ribosomes by trans-translation,
CC targeting the nascent protein for degradation) (PubMed:31155236).
CC {ECO:0000269|PubMed:11395451, ECO:0000269|PubMed:31155236}.
CC -!- SIMILARITY: Belongs to the peptidase S14 family. {ECO:0000255|HAMAP-
CC Rule:MF_00444}.
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DR EMBL; U59754; AAC46381.1; -; Genomic_DNA.
DR EMBL; Z94043; CAB08043.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB15459.1; -; Genomic_DNA.
DR PIR; B69601; B69601.
DR RefSeq; NP_391334.1; NC_000964.3.
DR RefSeq; WP_003228214.1; NZ_JNCM01000033.1.
DR PDB; 3KTG; X-ray; 2.40 A; A/B/C/D/E/F/G=2-197.
DR PDB; 3KTH; X-ray; 3.00 A; A/B/C/D/E/F/G=2-197.
DR PDB; 3KTI; X-ray; 2.00 A; A/B/C/D/E/F/G=2-197.
DR PDB; 3KTJ; X-ray; 2.60 A; A/B/C/D/E/F/G=2-197.
DR PDB; 3KTK; X-ray; 2.60 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N=2-197.
DR PDB; 3TT6; X-ray; 2.59 A; A/B/C/D/E/F/G=2-197.
DR PDB; 3TT7; X-ray; 2.56 A; A/B/C/D/E/F/G=1-197.
DR PDBsum; 3KTG; -.
DR PDBsum; 3KTH; -.
DR PDBsum; 3KTI; -.
DR PDBsum; 3KTJ; -.
DR PDBsum; 3KTK; -.
DR PDBsum; 3TT6; -.
DR PDBsum; 3TT7; -.
DR AlphaFoldDB; P80244; -.
DR SMR; P80244; -.
DR DIP; DIP-43711N; -.
DR IntAct; P80244; 1.
DR MINT; P80244; -.
DR STRING; 224308.BSU34540; -.
DR ChEMBL; CHEMBL2146309; -.
DR MEROPS; S14.001; -.
DR jPOST; P80244; -.
DR PaxDb; P80244; -.
DR PRIDE; P80244; -.
DR EnsemblBacteria; CAB15459; CAB15459; BSU_34540.
DR GeneID; 938625; -.
DR KEGG; bsu:BSU34540; -.
DR PATRIC; fig|224308.179.peg.3741; -.
DR eggNOG; COG0740; Bacteria.
DR InParanoid; P80244; -.
DR OMA; GIFDTMQ; -.
DR PhylomeDB; P80244; -.
DR BioCyc; BSUB:BSU34540-MON; -.
DR BRENDA; 3.4.21.92; 658.
DR EvolutionaryTrace; P80244; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0009368; C:endopeptidase Clp complex; IBA:GO_Central.
DR GO; GO:0004176; F:ATP-dependent peptidase activity; IMP:CACAO.
DR GO; GO:0051117; F:ATPase binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IBA:GO_Central.
DR CDD; cd07017; S14_ClpP_2; 1.
DR HAMAP; MF_00444; ClpP; 1.
DR InterPro; IPR001907; ClpP.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR023562; ClpP/TepA.
DR InterPro; IPR033135; ClpP_His_AS.
DR InterPro; IPR018215; ClpP_Ser_AS.
DR PANTHER; PTHR10381; PTHR10381; 1.
DR Pfam; PF00574; CLP_protease; 1.
DR PRINTS; PR00127; CLPPROTEASEP.
DR SUPFAM; SSF52096; SSF52096; 1.
DR TIGRFAMs; TIGR00493; clpP; 1.
DR PROSITE; PS00382; CLP_PROTEASE_HIS; 1.
DR PROSITE; PS00381; CLP_PROTEASE_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Hydrolase; Protease;
KW Reference proteome; Serine protease; Stress response.
FT CHAIN 1..197
FT /note="ATP-dependent Clp protease proteolytic subunit"
FT /id="PRO_0000179501"
FT ACT_SITE 98
FT /note="Nucleophile"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00444,
FT ECO:0000305|PubMed:22080375"
FT ACT_SITE 123
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00444,
FT ECO:0000305|PubMed:22080375"
FT MUTAGEN 20
FT /note="I->C,S: Protein no longer oligomerizes, loss of
FT protease activity."
FT /evidence="ECO:0000269|PubMed:20305655"
FT MUTAGEN 25
FT /note="L->S: Protein no longer oligomerizes, loss of
FT protease activity."
FT /evidence="ECO:0000269|PubMed:20305655"
FT MUTAGEN 46
FT /note="S->C: Has peptidase but not protease activity,
FT activated by ADEP antibiotics."
FT /evidence="ECO:0000269|PubMed:20305655"
FT MUTAGEN 50
FT /note="F->S: Protein no longer oligomerizes, loss of
FT protease activity, activated by ADEP antibiotics."
FT /evidence="ECO:0000269|PubMed:20305655"
FT MUTAGEN 54
FT /note="E->R: Has peptidase but not protease activity,
FT activated by ADEP antibiotics."
FT /evidence="ECO:0000269|PubMed:20305655"
FT MUTAGEN 63
FT /note="Y->A: Has peptidase but not protease activity,
FT partially activated by ADEP antibiotics."
FT /evidence="ECO:0000269|PubMed:20305655"
FT MUTAGEN 63
FT /note="Y->W: Has peptidase but not protease activity."
FT /evidence="ECO:0000269|PubMed:20305655"
FT MUTAGEN 83
FT /note="F->A: Has peptidase but not protease activity."
FT /evidence="ECO:0000269|PubMed:20305655"
FT HELIX 20..26
FT /evidence="ECO:0007829|PDB:3KTI"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:3KTI"
FT HELIX 38..54
FT /evidence="ECO:0007829|PDB:3KTI"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:3KTI"
FT STRAND 60..66
FT /evidence="ECO:0007829|PDB:3KTI"
FT HELIX 71..83
FT /evidence="ECO:0007829|PDB:3KTI"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:3KTI"
FT STRAND 88..97
FT /evidence="ECO:0007829|PDB:3KTI"
FT HELIX 99..105
FT /evidence="ECO:0007829|PDB:3KTI"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:3KTI"
FT STRAND 119..122
FT /evidence="ECO:0007829|PDB:3KTI"
FT STRAND 126..132
FT /evidence="ECO:0007829|PDB:3KTK"
FT HELIX 133..158
FT /evidence="ECO:0007829|PDB:3KTI"
FT HELIX 162..168
FT /evidence="ECO:0007829|PDB:3KTI"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:3KTI"
FT HELIX 177..183
FT /evidence="ECO:0007829|PDB:3KTI"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:3KTI"
SQ SEQUENCE 197 AA; 21682 MW; 5D4D4BD548DC45A0 CRC64;
MNLIPTVIEQ TNRGERAYDI YSRLLKDRII MLGSAIDDNV ANSIVSQLLF LAAEDPEKEI
SLYINSPGGS ITAGMAIYDT MQFIKPKVST ICIGMAASMG AFLLAAGEKG KRYALPNSEV
MIHQPLGGAQ GQATEIEIAA KRILLLRDKL NKVLAERTGQ PLEVIERDTD RDNFKSAEEA
LEYGLIDKIL THTEDKK
