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Protein

ATP-dependent Clp protease proteolytic subunit

Gene

clpP

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Cleaves peptides in various proteins in a process that requires ATP hydrolysis. Has a chymotrypsin-like activity. Plays a major role in the degradation of misfolded proteins. May play the role of a master protease which is attracted to different substrates by different specificity factors such as ClpA or ClpX. Participates in the final steps of RseA-sigma-E degradation, liberating sigma-E to induce the extracytoplasmic-stress response. Degrades antitoxin MazE (PubMed:24375411).UniRule annotation3 Publications

Miscellaneous

Acyldepsipeptide antibiotics bind in the ClpA or ClpX binding-sites, rendering the enzyme ATP-independent and indiscriminate, thus killing cells.1 Publication

Catalytic activityi

Hydrolysis of proteins to small peptides in the presence of ATP and magnesium. Alpha-casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolyzed (such as succinyl-Leu-Tyr-|-NHMec; and Leu-Tyr-Leu-|-Tyr-Trp, in which cleavage of the -Tyr-|-Leu- and -Tyr-|-Trp bonds also occurs).UniRule annotation

Enzyme regulationi

Inhibited by benzyloxycarbonyl leucyltyrosine chloromethylketone (Z-LY-CMK).1 Publication

Kineticsi

  1. KM=4.4 mM for N-succinyl-Leu-Tyr-7-amino-4-methyl-coumarin (N-succinyl-Leu-Tyr-AMC)2 Publications
  2. KM=1.0 mM for N-succinyl-Leu-Tyr-AMC2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei111NucleophileCurated1
    Active sitei136Curated1
    Active sitei185Curated1

    GO - Molecular functioni

    • ATPase binding Source: CAFA
    • ATP-dependent peptidase activity Source: CAFA
    • identical protein binding Source: IntAct
    • serine-type endopeptidase activity Source: InterPro
    • serine-type peptidase activity Source: EcoCyc

    GO - Biological processi

    • proteasomal protein catabolic process Source: CACAO
    • protein quality control for misfolded or incompletely synthesized proteins Source: MGI
    • proteolysis Source: CAFA
    • response to heat Source: EcoliWiki
    • response to radiation Source: EcoCyc
    • response to temperature stimulus Source: EcoCyc

    Keywordsi

    Molecular functionHydrolase, Protease, Serine protease
    Biological processStress response

    Enzyme and pathway databases

    BioCyciEcoCyc:EG10158-MONOMER
    MetaCyc:EG10158-MONOMER

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    ATP-dependent Clp protease proteolytic subunitUniRule annotation (EC:3.4.21.92UniRule annotation)
    Alternative name(s):
    Caseinolytic protease
    Endopeptidase ClpUniRule annotation
    Heat shock protein F21.5
    Protease Ti
    Gene namesi
    Name:clpPUniRule annotation
    Synonyms:lopP
    Ordered Locus Names:b0437, JW0427
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10158 clpP

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    • HslUV protease complex Source: CAFA
    • membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Cells undergo an apoptotic-like death upon DNA damage characterized by membrane depolarization (PubMed:22412352). Decreased persister cell formation upon antibotic challenge probably due to increased levels of MazF toxin (PubMed:24375411).2 Publications

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi17V → A: No ClpA-ClpP, little ClpX-ClpP complex forms. 1 Publication1
    Mutagenesisi18P → A: Reduced processing, no ClpA-ClpP complex forms. 1 Publication1
    Mutagenesisi19M → A: No ClpA-ClpP, little ClpX-ClpP complex forms. 1 Publication1
    Mutagenesisi20V → A: No ClpA-ClpP or ClpX-ClpP complex forms. 1 Publication1
    Mutagenesisi21I → A: No ClpA-ClpP or ClpX-ClpP complex forms. 1 Publication1
    Mutagenesisi24T → A: No ClpA-ClpP, little ClpX-ClpP complex forms. 1 Publication1
    Mutagenesisi27G → A: No ClpA-ClpP, little ClpX-ClpP complex forms. 1 Publication1
    Mutagenesisi32D → A: No ClpA-ClpP or ClpX-ClpP complex forms. 1 Publication1
    Mutagenesisi33I → A: No ClpA-ClpP or ClpX-ClpP complex forms. 1 Publication1
    Mutagenesisi34Y → A: No ClpA-ClpP or ClpX-ClpP complex forms. 1 Publication1
    Mutagenesisi126F → A: Little ClpA-ClpP or ClpX-ClpP complex forms. 1 Publication1
    Mutagenesisi185D → A: Loss of protease activity, forms ClpA-ClpP complex. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL3341578

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    PropeptideiPRO_00002680121 – 141 PublicationAdd BLAST14
    ChainiPRO_000017955115 – 207ATP-dependent Clp protease proteolytic subunitAdd BLAST193

    Keywords - PTMi

    Zymogen

    Proteomic databases

    EPDiP0A6G7
    PaxDbiP0A6G7
    PRIDEiP0A6G7

    2D gel databases

    SWISS-2DPAGEiP0A6G7

    Expressioni

    Inductioni

    By heat shock. Part of the clpP-clpX operon.1 Publication

    Interactioni

    Subunit structurei

    Fourteen ClpP subunits assemble into 2 heptameric rings which stack back to back to give a disk-like structure with a central cavity, resembling the structure of eukaryotic proteasomes. Component of the ClpAP and ClpXP complexes.UniRule annotation5 Publications

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    • ATPase binding Source: CAFA
    • identical protein binding Source: IntAct

    Protein-protein interaction databases

    BioGridi4260736, 465 interactors
    DIPiDIP-31838N
    IntActiP0A6G7, 68 interactors
    STRINGi316385.ECDH10B_0393

    Chemistry databases

    BindingDBiP0A6G7

    Structurei

    Secondary structure

    1207
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi19 – 21Combined sources3
    Beta strandi22 – 24Combined sources3
    Beta strandi27 – 29Combined sources3
    Beta strandi30 – 32Combined sources3
    Helixi33 – 38Combined sources6
    Turni39 – 41Combined sources3
    Beta strandi42 – 49Combined sources8
    Helixi51 – 67Combined sources17
    Beta strandi69 – 71Combined sources3
    Beta strandi73 – 79Combined sources7
    Helixi84 – 96Combined sources13
    Beta strandi97 – 99Combined sources3
    Beta strandi101 – 110Combined sources10
    Helixi112 – 118Combined sources7
    Beta strandi125 – 127Combined sources3
    Beta strandi132 – 135Combined sources4
    Beta strandi139 – 145Combined sources7
    Helixi146 – 171Combined sources26
    Helixi175 – 181Combined sources7
    Turni182 – 185Combined sources4
    Beta strandi186 – 189Combined sources4
    Helixi190 – 195Combined sources6
    Beta strandi198 – 202Combined sources5

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1TYFX-ray2.30A/B/C/D/E/F/G/H/I/J/K/L/M/N15-207[»]
    1YG6X-ray1.90A/B/C/D/E/F/G/H/I/J/K/L/M/N15-207[»]
    1YG8X-ray2.60A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b18-207[»]
    2FZSX-ray1.90A/B/C/D/E/F/G/H/I/J/K/L/M/N15-207[»]
    3HLNX-ray3.201/2/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z15-207[»]
    3MT6X-ray1.90A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b1-207[»]
    ProteinModelPortaliP0A6G7
    SMRiP0A6G7
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0A6G7

    Family & Domainsi

    Domaini

    The N-terminus (residues 17-34) interact with ClpA and ClpX.1 Publication

    Sequence similaritiesi

    Belongs to the peptidase S14 family.UniRule annotation

    Phylogenomic databases

    eggNOGiENOG4105CCQ Bacteria
    COG0740 LUCA
    HOGENOMiHOG000285833
    InParanoidiP0A6G7
    KOiK01358
    OMAiLFLQSEN
    PhylomeDBiP0A6G7

    Family and domain databases

    CDDicd07017 S14_ClpP_2, 1 hit
    HAMAPiMF_00444 ClpP, 1 hit
    InterProiView protein in InterPro
    IPR001907 ClpP
    IPR029045 ClpP/crotonase-like_dom_sf
    IPR023562 ClpP/TepA
    IPR033135 ClpP_His_AS
    IPR018215 ClpP_Ser_AS
    PANTHERiPTHR10381 PTHR10381, 1 hit
    PfamiView protein in Pfam
    PF00574 CLP_protease, 1 hit
    PRINTSiPR00127 CLPPROTEASEP
    SUPFAMiSSF52096 SSF52096, 1 hit
    TIGRFAMsiTIGR00493 clpP, 1 hit
    PROSITEiView protein in PROSITE
    PS00382 CLP_PROTEASE_HIS, 1 hit
    PS00381 CLP_PROTEASE_SER, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P0A6G7-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSYSGERDNF APHMALVPMV IEQTSRGERS FDIYSRLLKE RVIFLTGQVE
    60 70 80 90 100
    DHMANLIVAQ MLFLEAENPE KDIYLYINSP GGVITAGMSI YDTMQFIKPD
    110 120 130 140 150
    VSTICMGQAA SMGAFLLTAG AKGKRFCLPN SRVMIHQPLG GYQGQATDIE
    160 170 180 190 200
    IHAREILKVK GRMNELMALH TGQSLEQIER DTERDRFLSA PEAVEYGLVD

    SILTHRN
    Length:207
    Mass (Da):23,187
    Last modified:March 29, 2005 - v1
    Checksum:iA7843D036C8CB3C2
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    J05534 Genomic DNA Translation: AAA23588.1
    U82664 Genomic DNA Translation: AAB40193.1
    U00096 Genomic DNA Translation: AAC73540.1
    AP009048 Genomic DNA Translation: BAE76217.1
    PIRiB36575
    RefSeqiNP_414971.1, NC_000913.3
    WP_000122253.1, NZ_LN832404.1

    Genome annotation databases

    EnsemblBacteriaiAAC73540; AAC73540; b0437
    BAE76217; BAE76217; BAE76217
    GeneIDi945082
    KEGGiecj:JW0427
    eco:b0437
    PATRICifig|1411691.4.peg.1839

    Similar proteinsi

    Entry informationi

    Entry nameiCLPP_ECOLI
    AccessioniPrimary (citable) accession number: P0A6G7
    Secondary accession number(s): P19245, Q2MBY9
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 29, 2005
    Last sequence update: March 29, 2005
    Last modified: March 28, 2018
    This is version 122 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health