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Information on EC 3.4.21.92 - Endopeptidase Clp
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3.4.21.92 Endopeptidase ClpSpecify your search results
Word Map
- 3.4.21.92
- proteases
- chloroplast
- adaptor
- tuberculosis
- mycobacterium
- plastid
- atpases
- sigma
-
ssra-tagged
-
hexamer
-
misfolded
- caulobacter
-
heptameric
-
machine
- apicoplasts
- dnak
- unfoldase
- crescentus
-
tetradecameric
- spx
-
plastid-encoded
-
self-compartmentalized
- medicine
- hsluv
-
n-degrons
-
chlorotic
- ctra
-
barrel-shaped
-
proteostasis
- drug development
- analysis
The enzyme appears in viruses and cellular organisms
Reaction Schemes
Hydrolysis of proteins to small peptides in the presence of ATP and Mg2+. alpha-Casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolysed (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)
Synonyms
clp protease, clpap, clpxp protease, clpc1, clpp1, clpp2, clpp protease, caseinolytic protease, clpp1p2, atp-dependent clp protease, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATP-dependent Clp protease proteolytic subunit 1
ATP-dependent Clp protease proteolytic subunit 2
Caseinolytic protease
CLP
Clp protease
Clp proteolytic subunit
ClpA
ClpAP
ClpC
ClpC1
ClpP
ClpP Peptidase
ClpP Protease
ClpP1
ClpP2
ClpP3
ClpS1
ClpX
ClpXP
CplC
endopeptidase Clp
ClpP
-
cyanobacteria have many ClpP paralogs plus a ClpP variant, ClpP1, ClpP2, ClpP3, ClpR, ClpX, ClpS1 and ClpS2
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Hydrolysis of proteins to small peptides in the presence of ATP and Mg2+. alpha-Casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolysed (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)
Hydrolysis of proteins to small peptides in the presence of ATP and Mg2+. alpha-Casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolysed (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)
in presence of ATP and Mg2+. In the absence of ATP only oligopeptides shorter than five residues are hydrolyzed
-
-
Hydrolysis of proteins to small peptides in the presence of ATP and Mg2+. alpha-Casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolysed (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)
dual mechanism in which translocation alternates with proteolysis, allowing peptides of more or less unifirm length to be cleaved processively from a translocating substrate
-
Hydrolysis of proteins to small peptides in the presence of ATP and Mg2+. alpha-Casein is the usual test substrate. In the absence of ATP, only oligopeptides shorter than five residues are hydrolysed (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)
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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CAS REGISTRY NUMBER
COMMENTARY
110910-59-3
-
131017-00-0
-
131017-01-1
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
31-knotted methyltransferase YbeA-ssrA + H2O
?
-
substrate contains a deep trefoil knot, with 70 and 34 residues lying to the N- and C-terminus of the knotted core, and is fused to the 11-amino acid ssrA degron
-
?
52-knotted ubiquitin C-terminal hydrolase L1-ssrA
?
-
substrate is fused to the 11-amino acid ssrA degron
-
?
alpha-casein + H2O
?
-
is completely degraded by ClpC and ClpP3/R within 20 min
-
?
antitoxin epsilon + H2O
?
-
Epsilon is an antitoxin of the Epsilon/Zeta toxin-antitoxin system family, purified Zeta toxin protects the Epsilon protein from rapid ClpXP-catalyzed degradation
-
?
Bacteriophage lambdaO-DNA replication protein + H2O
Hydrolyzed bacteriophage lambdaO-DNA replication protein
beta-Galactosidase fusion proteins + H2O
Hydrolyzed beta-galactosidase fusion protein
-
-
-
?
chlorophyllide a oxygenase + H2O
?
-
ClpC1 regulates the level of chlorophyllide a oxygenase, chloroplast ClpC1 regulates chlorophyll b biosynthesis
-
?
elongation factor Ts + H2O
?
-
clpP6 mutant have impaired photosynthesis and chloroplast development
-
?
fEGFP-ssrA + H2O
?
i.e. N-terminal His-tagged superfolder enhanced green fluorescent protein with the ssrA tag sequence at the C-terminus
-
?
FITC-casein + H2O
?
-
neither ClpC nor ClpP3/R alone degrade FITC-casein but they do when added together. No proteolytic activity when ClpP3 alone is combined with ClpC
-
?
FixK2 + H2O
?
substrate is a CRP-like transcription factor that controls the endosymbiotic lifestyle of Bradyrhizobium japonicum. Degradation occurs by the ClpAP1 chaperone-protease complex, but not by the ClpXP1 chaperone-protease complex, and is inhibited by the ClpS1 adaptor protein. The last 12 amino acids of FixK2 are recognized by ClpA
-
?
FR-GFP + H2O
?
-
ClpCP3/R with ClpS1 take over 20 min to completely degrade FR-GFP, whereas the ClpAP protease degrades all FR-GFP within 2 min
-
?
Gly-L-Arg-7-amido-4-methylcoumarin + H2O
Gly-L-Arg + 7-amino-4-methylcoumarin
substrate for the recombinant ClpP
-
?
Lambda O Arc + H2O
?
-
Arc repressor with a N-terminal lambda O degradation tag
-
?
Leu-Tyr-Leu-Tyr-Trp + H2O
Leu-Tyr-Leu + Tyr-Trp
-
cleavage occurs primarily at Leu3-Tyr4, but significant cleavage also at Tyr2-Leu3 and Leu4-Trp5 bond
-
?
Mutated repressor of Mu prophage + H2O
Hydrolyzed mutated repressor of Mu prophage
-
high susceptibility to the Clp-dependent degradation
-
?
N-succinyl-Ile-Ile-Trp-7-amido-4-methylcoumarin + H2O
N-succinyl-Ile-Ile-Trp + 7-amino-4-methylcoumarin
-
throughout the 5 min time course, ClpP readily degrades the dipeptide, whereas ClpP3/R does not. Prolonging the incubation time with ClpP3/R to 20 min does not result in any visible degradation. Addition of ClpC to the assays also fails to produce any degradation
-
?
N-succinyl-L-isoleucine-L-isoleucine-L-tryptophan-7-amido-4-methylcoumarin + H2O
?
-
-
?
N-succinyl-Leu-Tyr 4-methylcoumarin 7-amide + H2O
N-succinyl-Leu-Tyr + 7-amino-4-methylcoumarin
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin + H2O
N-succinyl-Leu-Tyr + 7-amino-4-methylcoumarin
N-succinyl-Val-Lys-Met-7-amido-4-methylcoumarin + H2O
N-succinyl-Val-Lys-Met + 7-amino-4-methylcoumarin
-
throughout the 5 min time course, ClpP readily degrades the dipeptide, whereas ClpP3/R does not. Prolonging the incubation time with ClpP3/R to 20 min does not result in any visible degradation. Addition of ClpC to the assays also fails to produce any degradation
-
?
ornithine decarboxylase CC030 + H2O
?
-
-
CC0360 is rapidly degraded by ClpP protease in vitro. CC0360 is exclusively degraded by the full-length ClpXP complex and not by a version of ClpX lacking the Nterminal domain
?
Oxidized insulin B-chain + H2O
Hydrolyzed insulin B-chain
-
cleavage at multiple sites
-
?
Phe-Ala-Pro-His-Met-Ala-Leu-Val-Pro-Val + H2O
?
-
synthetic polypeptide that corresponds to the 10 amino acids surrounding the in vivo processing site in ClpP subunit
-
?
RpoS sigma factor + H2O
?
-
with the assistance of recognition factor RssB, ClpXP degrades the RpoS sigma factor
-
?
SpollAB + H2O
?
-
ClpCP, LCN at C-terminal as degradation tag, MecA not required, production of ClpP is strongly increased in response to heat shock or other stress signals, ClpP removes heat damaged proteins
-
?
SsrA tagged proteins + H2O
?
-
ClpXP, AA at C-terminal as degradation tag
-
?
ssrA-dabsyl + H2O
?
-
initial rate of degradation of this intermediate-sized substrate is 3fold faster with ClpAP as compared to wild-type Clp and 5fold faster with ClpPDELTAN as compared to wild-type ClpP
-
?
stalk synthesis transcription factor TacA + H2O
?
-
TacA degradation is controlled during the cell cycle dependent on the ClpXP regulator CpdR and stabilization of TacA increases degradation of another ClpXP substrate, CtrA, while restoring deficiencies associated with prolific CpdR activity
-
?
Starvation proteins + H2O
?
-
the ClpP proteolytic subunit plays a subtle but important role when cells are recovering from starvation. This enzyme is important in the selective degradation of starvation proteins when growth resumes
-
?
Succinyl-Ala-Ala-Phe 4-methylcoumarin 7-amide + H2O
Succinyl-Ala-Ala + Phe 4-methylcoumarin 7-amide
succinyl-L-Leu-L-Lys-7-amido-4-methylcoumarin + H2O
?
recombinant mature ClpP is most active against succinyl-L-Leu-L-Lys-7-amido-4-methylcoumarin
-
?
succinyl-L-Leu-L-Tyr-7-amido-4-methylcoumarin + H2O
succinyl-L-Leu-L-Tyr + 7-amino-4-methylcoumarin
recombinant ClpP does not cleave the known ClpP substrate succinyl-L-Leu-L-Tyr-7-amido-4-methylcoumarin
-
?
Succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide + H2O
Succinyl-Leu + Leu + Val-Tyr 4-methylcoumarin 7-amide
Succinyl-Leu-Tyr 4-methylcoumarin 7-amide + H2O
Succinyl-Leu-Tyr + 7-amino-4-methylcoumarin
-
ClpP subunit alone
-
?
succinyl-LLVY-7-amido-4-methylcoumarin + H2O
succinyl-LLVY + 7-amino-4-methylcoumarin
-
-
?
Bacteriophage lambdaO-DNA replication protein + H2O
Hydrolyzed bacteriophage lambdaO-DNA replication protein
-
degraded by ClpXP
-
?
Bacteriophage lambdaO-DNA replication protein + H2O
Hydrolyzed bacteriophage lambdaO-DNA replication protein
-
degraded by ClpXP
-
?
casein + H2O
small peptides derived from casein
-
-
-
?
central competence regulator sigmax + H2O
?
adaptor protein MecA ultimately targets sigmaX for its degradation by the ClpCP protease in an ATP-dependent manner
-
?
central competence regulator sigmax + H2O
?
adaptor protein MecA ultimately targets sigmaX for its degradation by the ClpCP protease in an ATP-dependent manner
-
?
FlhC subunit + H2O + ATP
?
subunit of the flagellar master transcriptional regulator complex, FlhD4C2. Flagellum-related protein FliT selectively increases ClpXP-dependent proteolysis of the FlhC subunit in the FlhD4C2 complex. FliT promotes the affinity of ClpX against FlhD4C2 complex, whereas FliT does not directly interact with ClpX. FliT interacts with the FlhC in FlhD4C2 complex and increases the presentation of the FlhC recognition region to ClpX. The DNA-bound form of FlhD4C2 complex is resistant to ClpXP proteolysis
-
?
FlhC subunit + H2O + ATP
?
subunit of the flagellar master transcriptional regulator complex, FlhD4C2. Flagellum-related protein FliT selectively increases ClpXP-dependent proteolysis of the FlhC subunit in the FlhD4C2 complex. FliT promotes the affinity of ClpX against FlhD4C2 complex, whereas FliT does not directly interact with ClpX. FliT interacts with the FlhC in FlhD4C2 complex and increases the presentation of the FlhC recognition region to ClpX. The DNA-bound form of FlhD4C2 complex is resistant to ClpXP proteolysis
-
?
Glucagon + H2O
Hydrolyzed glucagon
-
cleavage at multiple sites
-
?
LacZ + H2O
?
-
proteolytic subunit ClpP2 over-expression induces degradation of untagged LacZ
?
LacZ + H2O
?
-
proteolytic subunit ClpP2 over-expression induces degradation of untagged LacZ
?
N-succinyl-Leu-Tyr 4-methylcoumarin 7-amide + H2O
N-succinyl-Leu-Tyr + 7-amino-4-methylcoumarin
-
-
-
?
N-succinyl-Leu-Tyr 4-methylcoumarin 7-amide + H2O
N-succinyl-Leu-Tyr + 7-amino-4-methylcoumarin
-
-
-
?
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin + H2O
?
-
initial degradation rate is the same within error for wild-type ClpP, ClpAP, and ClpPDELTAN
-
?
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin + H2O
N-succinyl-Leu-Tyr + 7-amino-4-methylcoumarin
-
-
-
?
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin + H2O
N-succinyl-Leu-Tyr + 7-amino-4-methylcoumarin
-
-
-
?
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin + H2O
N-succinyl-Leu-Tyr + 7-amino-4-methylcoumarin
-
throughout the 5 min time course, ClpP readily degrades the dipeptide, whereas ClpP3/R does not. Prolonging the incubation time with ClpP3/R to 20 min does not result in any visible degradation. Addition of ClpC to the assays also fails to produce any degradation
-
?
Spx + H2O
?
-
ClpXP, LAN at C-terminal as degradation tag, MecA not required
-
?
SsrA-tagged LacZ + H2O
?
both proteolytic subunits ClpP1 and ClpP2 degrade SsrA-tagged LacZ
-
?
SsrA-tagged LacZ + H2O
?
both proteolytic subunits ClpP1 and ClpP2 degrade SsrA-tagged LacZ
-
?
Succinyl-Ala-Ala-Phe 4-methylcoumarin 7-amide + H2O
Succinyl-Ala-Ala + Phe 4-methylcoumarin 7-amide
-
ClpP subunit alone
-
?
Succinyl-Ala-Ala-Phe 4-methylcoumarin 7-amide + H2O
Succinyl-Ala-Ala + Phe 4-methylcoumarin 7-amide
-
ClpP subunit alone
-
?
Succinyl-Ala-Ala-Phe 4-methylcoumarin 7-amide + H2O
Succinyl-Ala-Ala + Phe 4-methylcoumarin 7-amide
-
ClpP subunit alone
-
?
Succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide + H2O
Succinyl-Leu + Leu + Val-Tyr 4-methylcoumarin 7-amide
-
ClpP subunit alone
-
?
Succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide + H2O
Succinyl-Leu + Leu + Val-Tyr 4-methylcoumarin 7-amide
-
ClpP subunit alone
-
?
Succinyl-Leu-Leu-Val-Tyr 4-methylcoumarin 7-amide + H2O
Succinyl-Leu + Leu + Val-Tyr 4-methylcoumarin 7-amide
-
ClpP subunit alone
-
?
additional information
?
-
-
enzyme complex ClpPRS consisting of five ClpP protease molecules, four nonproteolytic ClpR molecules, and two associated ClpS molecules, is central to chloroplast biogenesis, thylakoid protein homeostasis, and plant development
-
?
additional information
?
-
ClpP linked to many activities, including sporulation, cell competence, stress tolerance and regulation of gene expression
-
?
additional information
?
-
-
stress- and starvation-induced bulk protein turnover depends virtually exclusively on enzyme, which is also essential for intracellular protein quality control
-
?
additional information
?
-
-
degradation of anchor proteins by the McsA-McsB-(ClpC or ClpE)-ClpP protease in an ATP-dependent process that involves the autophosphorylation of McsB. ClpC, ClpE and ClpP contribute to delocalization
-
?
additional information
?
-
ClpP requires association with ClpA or ClpX to unfold and thread protein substrates through the axial pore into the inner chamber where degradation occurs
-
?
additional information
?
-
after phosphorylation by the McsB arginine kinase, phosphoarginine-tagged proteins are targeted to the ClpCP protease. Binding of phophoarginine proteins to one of the 12 N-terminal domain binding pockets stimulates the ATPase activity of ClpC, leading to the translocation of the captured substrate into the ClpP protease cage and to protein degradation
-
?
additional information
?
-
-
after phosphorylation by the McsB arginine kinase, phosphoarginine-tagged proteins are targeted to the ClpCP protease. Binding of phophoarginine proteins to one of the 12 N-terminal domain binding pockets stimulates the ATPase activity of ClpC, leading to the translocation of the captured substrate into the ClpP protease cage and to protein degradation
-
?
additional information
?
-
after phosphorylation by the McsB arginine kinase, phosphoarginine-tagged proteins are targeted to the ClpCP protease. Binding of phophoarginine proteins to one of the 12 N-terminal domain binding pockets stimulates the ATPase activity of ClpC, leading to the translocation of the captured substrate into the ClpP protease cage and to protein degradation
-
?
additional information
?
-
-
one ClpP recognition motif is the presence of Ala-Ala at the extreme C-terminus of substrates. Mutating the C-terminal residues of substrates flagellar regulator FlaF and IbpA to Asp-Asp eliminates recognition
-
?
additional information
?
-
-
role for the Clp protease in activating Mu-mediated DNA rearrangements
-
?
additional information
?
-
-
ClpP subunit has peptidase activity against very short peptides, with fewer than five amino acid residues in the absence of ClpA and nucleotide
-
?
additional information
?
-
-
when activated by ClpA subunit, ClpP can degrade longer polypeptides and proteins
-
?
additional information
?
-
-
physiological activation of Mu-dependent DNA rearrangements requires Clp functions. Clp plays a role in monitoring the physiological status of the cell
-
?
additional information
?
-
-
ClpXP appears to be involved in plasmid maintenance and in phage Mu virulence
-
?
additional information
?
-
-
the high degree of similarity among the ClpA-like proteins suggests that Clp-like proteases are likely to be important participants in energy-dependent proteolysis in prokaryotic and eukaryotic cells
-
?
additional information
?
-
-
selectivity of degradation by ClpP in vivo is determined by interaction of ClpP with different regulatory ATPase subunits
-
?
additional information
?
-
-
ClpP is present in a wide range of prokaryotic and eukaryotic cells and is highly conserved in plant chloroplasts
-
?
additional information
?
-
-
removing of irreversibly damaged polypeptides
-
?
additional information
?
-
-
the ClpP N-terminus acts as a gate controlling substrate access to the active sites, binding of ClpA opens this gate, allowing substrate entry and formation of the acyl-enzyme intermediate, and closing of the N-terminal gate stimulates acyl-enzyme hydrolysis
-
?
additional information
?
-
-
ClpP associates with ClpX or ClpA to form the AAA+ ClpXP or ClpAP proteases
-
?
additional information
?
-
-
ClpP binds to AAA+ ATPase/unfoldase, ClpA or ClpX
-
?
additional information
?
-
-
phosphate release is the force-generating step of the ATPase cycle. Protease ClpXP translocates substrate polypeptides by highly coordinated conformational changes in up to four ATPase subunits. To unfold stable substrates like GFP, ClpXP must use this maximum successive firing capacity. The dwell duration between individual bursts of translocation is constant and governed by an internal clock, regardless of the number of translocating subunits
-
?
additional information
?
-
protease ClpXP unfolds most domains by a single pathway, with kinetics that depend on the native fold and structural stability. Subsequent translocation or pausing occurs at rates that vary with the sequence of the unfolded substrate. During translocation, ClpXP does not exhibit a sequential pattern of step sizes, supporting a fundamentally stochastic reaction, but a mechanism of enzymatic memory results in short physical steps being more probable after short steps and longer physical steps being more likely after longer steps, allowing the enzyme to run at different speeds. Two ATP-hydrolysis events can drive more than two power strokes. Solution proteolysis is many times slower than predicted from single-molecule results
-
?
additional information
?
-
ClpP requires association with ClpA or ClpX to unfold and thread protein substrates through the axial pore into the inner chamber where degradation occurs
-
?
additional information
?
-
-
ClpXP can easily degrade a deeply 31-knotted protein and is able to degrade 52-knotted proteins. The degradation depends critically on the location of the degradation tag and the local stability near the tag
-
?
additional information
?
-
-
ClpP subunit has peptidase activity against very short peptides, with fewer than five amino acid residues in the absence of ClpA and nucleotide
-
?
additional information
?
-
-
when activated by ClpA subunit, ClpP can degrade longer polypeptides and proteins
-
?
additional information
?
-
-
ClpXP appears to be involved in plasmid maintenance and in phage Mu virulence
-
?
additional information
?
-
-
the high degree of similarity among the ClpA-like proteins suggests that Clp-like proteases are likely to be important participants in energy-dependent proteolysis in prokaryotic and eukaryotic cells
-
?
additional information
?
-
the SsrA tag directs proteins to degradation by both ClpP1 and ClpP2. The terminal three residues of the ssrA-tag sequence are LAA. A LAA-tag is sufficient to direct proteins into the degradation pathway
-
?
additional information
?
-
the SsrA tag directs proteins to degradation by both ClpP1 and ClpP2. The terminal three residues of the ssrA-tag sequence are LAA. A LAA-tag is sufficient to direct proteins into the degradation pathway
-
?
additional information
?
-
-
the SsrA tag directs proteins to degradation by both ClpP1 and ClpP2. The terminal three residues of the ssrA-tag sequence are LAA. A LAA-tag is sufficient to direct proteins into the degradation pathway
-
?
additional information
?
-
the SsrA tag directs proteins to degradation by both ClpP1 and ClpP2. The terminal three residues of the ssrA-tag sequence are LAA. A LAA-tag is sufficient to direct proteins into the degradation pathway
-
?
additional information
?
-
the SsrA tag directs proteins to degradation by both ClpP1 and ClpP2. The terminal three residues of the ssrA-tag sequence are LAA. A LAA-tag is sufficient to direct proteins into the degradation pathway
-
?
additional information
?
-
recombinant mature ClpP is not capable of hydrolyzing Gly-L-Arg-7-amido-4-methylcoumarin, Gly–L-Phe-7-amido-4-methylcoumarin, and benzyloxycarbonyl-L-Gln-L-Arg-L-Arg-7-amido-4-methylcoumarin. Mature ClpP protein does not cleave N-succinyl-L-leucine-L-tyrosine-7-amido-4-methylcoumarin and N-succinyl-L-isoleucine-L-isoleucine-L-tryptophan-7-amido-4-methylcoumarin
-
?
additional information
?
-
-
recombinant mature ClpP is not capable of hydrolyzing Gly-L-Arg-7-amido-4-methylcoumarin, Gly–L-Phe-7-amido-4-methylcoumarin, and benzyloxycarbonyl-L-Gln-L-Arg-L-Arg-7-amido-4-methylcoumarin. Mature ClpP protein does not cleave N-succinyl-L-leucine-L-tyrosine-7-amido-4-methylcoumarin and N-succinyl-L-isoleucine-L-isoleucine-L-tryptophan-7-amido-4-methylcoumarin
-
?
additional information
?
-
ClpP affects the expression of luxR(mA), the transcriptional regulator of the massetolide biosynthesis genes massABC, thereby regulating biofilm formation and swarming motility of Pseudomonas fluorescens SS101. At the transcriptional level, ClpP-mediated regulation of massetolide biosynthesis operates independently of regulation by the GacA/GacS two-component system
-
?
additional information
?
-
-
ClpP affects the expression of luxR(mA), the transcriptional regulator of the massetolide biosynthesis genes massABC, thereby regulating biofilm formation and swarming motility of Pseudomonas fluorescens SS101. At the transcriptional level, ClpP-mediated regulation of massetolide biosynthesis operates independently of regulation by the GacA/GacS two-component system
-
?
additional information
?
-
ClpP affects the expression of luxR(mA), the transcriptional regulator of the massetolide biosynthesis genes massABC, thereby regulating biofilm formation and swarming motility of Pseudomonas fluorescens SS101. At the transcriptional level, ClpP-mediated regulation of massetolide biosynthesis operates independently of regulation by the GacA/GacS two-component system
-
?
additional information
?
-
-
ClpP affects the expression of luxR(mA), the transcriptional regulator of the massetolide biosynthesis genes massABC, thereby regulating biofilm formation and swarming motility of Pseudomonas fluorescens SS101. At the transcriptional level, ClpP-mediated regulation of massetolide biosynthesis operates independently of regulation by the GacA/GacS two-component system
-
?
additional information
?
-
-
enzyme is required for release of autolysin A and pneumolysin. In vivo, it is required for growth of pneumococcus in the lungs and blood in a murine model of disease
-
?
additional information
?
-
-
enzyme is required for the growth at elevated temperature and for virulence
-
?
additional information
?
-
-
mucosal immunization with ClpP antigen induces both systemic and mucosal antibodies, and in this way reduces lung colonization in an invasive pneumococcal pneumonia model and also protects mice against death in an intraperitoneal-sepsis model. Intraperitoneal immunization of BALB/c mice with recombinant ClpP protein. ClpP protein is immunogenic in healthy children and is expressed during disease based on the elevated antibody levels in infected individuals. In vitro functional anti-ClpP antibody can kill streptococcus pneumoniae by polymorphonuclear leukocytes in a complement-dependent assay
-
?
additional information
?
-
nasal immunizations with ClpP and CbpA are efficient for induction of systemic and mucosal antibodies
-
?
additional information
?
-
-
ClpR subunit is proteolytically inactive, thus ClpR subunit does not contribute to the proteolytic activity of the ClpP3/R core. Inclusion of ClpR is not rate-limiting for the ClpCP3/R protease. ClpC is not affected by auto-degradation as is ClpA. ClpS1 alters the substrate specificity of the ClpCP3/R protease
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
antitoxin epsilon + H2O
?
-
Epsilon is an antitoxin of the Epsilon/Zeta toxin-antitoxin system family, purified Zeta toxin protects the Epsilon protein from rapid ClpXP-catalyzed degradation
-
-
?
FixK2 + H2O
?
substrate is a CRP-like transcription factor that controls the endosymbiotic lifestyle of Bradyrhizobium japonicum. Degradation occurs by the ClpAP1 chaperone-protease complex, but not by the ClpXP1 chaperone-protease complex, and is inhibited by the ClpS1 adaptor protein. The last 12 amino acids of FixK2 are recognized by ClpA
-
-
?
Starvation proteins + H2O
?
-
the ClpP proteolytic subunit plays a subtle but important role when cells are recovering from starvation. This enzyme is important in the selective degradation of starvation proteins when growth resumes
-
-
?
central competence regulator sigmax + H2O
?
adaptor protein MecA ultimately targets sigmaX for its degradation by the ClpCP protease in an ATP-dependent manner
-
-
?
central competence regulator sigmax + H2O
?
adaptor protein MecA ultimately targets sigmaX for its degradation by the ClpCP protease in an ATP-dependent manner
-
-
?
FlhC subunit + H2O + ATP
?
subunit of the flagellar master transcriptional regulator complex, FlhD4C2. Flagellum-related protein FliT selectively increases ClpXP-dependent proteolysis of the FlhC subunit in the FlhD4C2 complex. FliT promotes the affinity of ClpX against FlhD4C2 complex, whereas FliT does not directly interact with ClpX. FliT interacts with the FlhC in FlhD4C2 complex and increases the presentation of the FlhC recognition region to ClpX. The DNA-bound form of FlhD4C2 complex is resistant to ClpXP proteolysis
-
-
?
FlhC subunit + H2O + ATP
?
subunit of the flagellar master transcriptional regulator complex, FlhD4C2. Flagellum-related protein FliT selectively increases ClpXP-dependent proteolysis of the FlhC subunit in the FlhD4C2 complex. FliT promotes the affinity of ClpX against FlhD4C2 complex, whereas FliT does not directly interact with ClpX. FliT interacts with the FlhC in FlhD4C2 complex and increases the presentation of the FlhC recognition region to ClpX. The DNA-bound form of FlhD4C2 complex is resistant to ClpXP proteolysis
-
-
?
additional information
?
-
-
enzyme complex ClpPRS consisting of five ClpP protease molecules, four nonproteolytic ClpR molecules, and two associated ClpS molecules, is central to chloroplast biogenesis, thylakoid protein homeostasis, and plant development
-
-
?
additional information
?
-
ClpP linked to many activities, including sporulation, cell competence, stress tolerance and regulation of gene expression
-
?
additional information
?
-
-
stress- and starvation-induced bulk protein turnover depends virtually exclusively on enzyme, which is also essential for intracellular protein quality control
-
-
?
additional information
?
-
ClpP requires association with ClpA or ClpX to unfold and thread protein substrates through the axial pore into the inner chamber where degradation occurs
-
-
?
additional information
?
-
-
physiological activation of Mu-dependent DNA rearrangements requires Clp functions. Clp plays a role in monitoring the physiological status of the cell
-
-
?
additional information
?
-
-
ClpXP appears to be involved in plasmid maintenance and in phage Mu virulence
-
-
?
additional information
?
-
-
the high degree of similarity among the ClpA-like proteins suggests that Clp-like proteases are likely to be important participants in energy-dependent proteolysis in prokaryotic and eukaryotic cells
-
-
?
additional information
?
-
-
selectivity of degradation by ClpP in vivo is determined by interaction of ClpP with different regulatory ATPase subunits
-
-
?
additional information
?
-
-
ClpP is present in a wide range of prokaryotic and eukaryotic cells and is highly conserved in plant chloroplasts
-
-
?
additional information
?
-
-
removing of irreversibly damaged polypeptides
-
?
additional information
?
-
-
ClpP associates with ClpX or ClpA to form the AAA+ ClpXP or ClpAP proteases
-
-
?
additional information
?
-
-
ClpP binds to AAA+ ATPase/unfoldase, ClpA or ClpX
-
-
?
additional information
?
-
ClpP requires association with ClpA or ClpX to unfold and thread protein substrates through the axial pore into the inner chamber where degradation occurs
-
-
?
additional information
?
-
-
ClpXP appears to be involved in plasmid maintenance and in phage Mu virulence
-
-
?
additional information
?
-
-
the high degree of similarity among the ClpA-like proteins suggests that Clp-like proteases are likely to be important participants in energy-dependent proteolysis in prokaryotic and eukaryotic cells
-
-
?
additional information
?
-
-
enzyme is required for release of autolysin A and pneumolysin. In vivo, it is required for growth of pneumococcus in the lungs and blood in a murine model of disease
-
-
?
additional information
?
-
-
enzyme is required for the growth at elevated temperature and for virulence
-
-
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ATP
-
cleavage of peptides of more than five amino acids residues by ClpP requires activation by ClpA and either ATP or a nonhydrolyzable analog of ATP such as ATPgammaS or 5'-adenylyl imidodiphosphate
ATP
-
ATP hydrolysis is required for protein breakdown but not for hydrolysis of small peptides
ATP
-
ATP has two functions in activating Clp protease: an allosteric role in promoting association between the subunits and a mechanistically undefined role in promoting continuous rounds of peptide bond cleavage. The functions may be separately fulfilled by the two ATP-binding sites identified by sequence analysis on each ClpA subunit
ATP
-
ATP dependent, for full proteolytic activity ClpP must associate with one of two related ATPase subunits, ClpA or ClpX, other nucleoside triphosphates cannot substitute for ATP
ATP
ATP dependent, for full proteolytic activity ClpP must associate with one of two related ATPase subunits, ClpA or ClpX, other nucleoside triphosphates cannot substitute for ATP
ATP
ATP dependent, for full proteolytic activity ClpP must associate with one of two related ATPase subunits, ClpA or ClpX, other nucleoside triphosphates cannot substitute for ATP
additional information
-
degradation of GFP-K17 is MecA dependent and prevented in the presence of ComS, MecA and ComS can be degraded by ClpCP. ComS competes with ComK for MecA binding and protects MecA from degradation by ClpP. The degradation of ComS requires the presence of MecA, which acts as an adapter for both ComS and ComK. MecA knockout strain fails to target ComK for degradation by ClpCP
-
additional information
-
MecA facilitates ClpC oligomerization into a complex containing both ClpC and MecA. Formation of this complex is a prerequisite for all ClpC mediated activities, including ATPase activity, substrate recognition and interaction with ClpP
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
-
proteolytic activity of ClpAP is dependent on, concentrations higher than about 30 mM are inhibitory
Mg2+
-
ClpA degrades large proteins down to short peptides of 7 to 10 amino acids, the process requires both Mg2+ and ATP hydrolysis
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(4R)-3-(4-methoxyphenyl)-4-(pent-4-yn-1-yl)oxetan-2-one
-
inhibitor efficiently alters the oligomerization of the enzyme to smaller species, almost quantitative shift from the tetradecamer to the heptamer with modification of 35% of the active sites
1-(1,1-dioxido-1,2-thiazetidin-2-yl)hexan-1-one
-
alkyne-free beta-sultam analogue. Treatment leads to dehydroalanine formation of the active site serine. The reaction proceeds through sulfonylation and subsequent elimination, thereby obliterating the catalytic charge relay system
1-(4-benzoyl-1,1-dioxido-1,2-thiazetidin-2-yl)ethanone
-
alkyne-free beta-sultam analogue. Treatment leads to dehydroalanine formation of the active site serine. The reaction proceeds through sulfonylation and subsequent elimination, thereby obliterating the catalytic charge relay system
1-[4-(4-ethynylbenzoyl)-1,1-dioxido-1,2-thiazetidin-2-yl]ethanone
-
treatment results in almost instant covalent modification of all 14 active sites and complete inhibition of peptidase activity
1-[4-(4-ethynylbenzoyl)-1,1-dioxido-1,2-thiazetidin-2-yl]undec-10-en-1-one
-
inhibitor efficiently alters the oligomerization of the enzyme to smaller species, almost quantitative shift from the tetradecamer to the heptamer with modification of 63% of the active sites
1-[4-benzoyl-1,1-dioxido-1,2-thiazetidin-2-yl]undec-10-en-1-one
-
alkyne-free beta-sultam analogue. Treatment leads to dehydroalanine formation of the active site serine. The reaction proceeds through sulfonylation and subsequent elimination, thereby obliterating the catalytic charge relay system
3-(4-methoxyphenyl)-4-(pent-4-ynyl)oxetan-2-one
-
shows stronger inhibitory effect
3-(non-8-ynyl)-4-(pent-4-ynyl)oxetan-2-one
-
exerts the weakest effect on peptidase activity
ClpS
adaptor protein ClpS is inhibitory to ClpC1. the unfolding rate of substrates shows a a nearly three-fold for conditions lacking ClpS relative to conditions with ClpS in excess
-
cyclomarin
-
cyclomarin binding to subunit ClpC1 N-terminal domain specifically blockes the N-terminal dynamics induced by arginine-phosphate binding. Cyclomarin-induced restriction of ClpC1 dynamics may modulate the chaperone enzymatic activity leading eventually to cell death
High salt concentrations
-
chloride is much more inhibitory than acetate, divalent anions are also very inhibitory
-
Mg2+
-
proteolytic activity of ClpAP is dependent on, but concentrations higher than about 30 mM are inhibitory
rufomycin I
cyclic peptide with potent and selective in vitro activity against Mycobacterium tuberculosis and Mycobacterium abscessus. Compound significantly decreases the proteolytic capabilities of the ClpC1/P1/P2 complex to degrade casein, while having no significant effect on the ATPase activity of ClpC1
Succinyl-Leu-Tyr 4-methylcoumarin 7-amide
-
at high concentrations complete inhibition of casein breakdown
Xaa-Tyr-Leu-Tyr-Trp
-
competitive to succinyl-Leu-Tyr 4-methylcoumarin 7-amide degradation
diisopropyl fluorophosphate
-
inhibits both oligopeptidase activity of ClpP and proteinase activity of ClpAP
diisopropyl fluorophosphate
-
blocks similarly the hydrolysis of both protein and peptide substrates
diisopropyl fluorophosphate
-
inhibitor efficiently alters the oligomerization of the enzyme to smaller species, almost quantitative shift from the tetradecamer to the heptamer with modification of 57% of the active sites
additional information
-
ClpP of E. coli has a serine and a histidine that are necessary for activity and probably represent two elements of the active site triad found in most serine proteases
-
additional information
-
not inhibitory: 4-(2-aminoethyl) benzenesulfonyl fluoride, phenylmethylsulfonyl fluoride as well as Z-L-CMK and N-p-tosylphenylalanyl chloromethyl ketone
-
additional information
anti-infection activity and production of hyperimmune antibodies induced by mucosal immunization with ClpP and CbpA can be abrogated by the depletion of CD4+ T lymphocytes. Hyperimmune mouse sera against ClpP and CbpA can inhibit pneumococcus adhesion to cultured A549 epithelial cells and are efficiently opsonic for uptake and killing of pneumococcus by human polymorphonuclear leukocytes in a complement-dependent assay
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acyldepsipeptides
-
ADEP series 2, 3, 4 as well as two other synthesized derivatives, IDR-10001 and IDR-10011, which incorporate N-methylalanine instead of the more rigid homoproline in the depsipeptide core structure. All five compound are active against Mycobacterium tuberculosis, ADEP2 is the most active
-
ATP
stimulates proteolytic activity of ClpP in heart mitochondria of muscle creatine kinase mutants
ClpX
-
ClpX binding stimulates ClpP cleavage of peptides larger than a few amino acids and enhances ClpP active-site modification. Stimulation requires ATP binding but not hydrolysis by ClpX
-
acyldepsipeptide
-
allow the protease to degrade folded native proteins in the absence of its cognate chaperones
acyldepsipeptide
acyldepsipeptides in addition to opening the axial pore directly stimulate ClpP activity through cooperative binding
additional information
-
carbonyl cyanide m-chloro phenylhydrazone and 2,4-dinitrophenol induce the heat-shock-like response, cellular level of the heat shock regulator protein sigma-32 also increases
-
additional information
frataxin deficiency causes significant upregulation of both mitochondrial Lon and ClpP proteases in the cardiac mouse model for Friedreich ataxia. ClpP protein level is progressively enhanced, with ca. 3fold, 3.5fold and 4.5fold increases at 5, 7 and 10 weeks of age in muscle creatine kinase mutants, respectively, despite no change in mRNA levels
-
additional information
-
ClpP3/R complex stimulates the steady-state ATPase activity of ClpC
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.52
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
mutant L144M, pH and temperature not specified in the publication
0.58
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
wild-type, pH and temperature not specified in the publication
0.8
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
wild-type, non-reducing conditions, 4°C, pH not specified in the publication
1
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
wild-type, reducing conditions, 4°C, pH not specified in the publication
1.1
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
mutant A153C, reducing conditions, 4°C, pH not specified in the publication
0.065
Suc-LLVY-4-methylcoumarin-7-amide
succinyl-LLVY-7-amido-4-methylcoumarin
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000036
succinyl-LLVY-7-amido-4-methylcoumarin
30°C, pH 7.0, PfClpP is a very weak peptidase on its own
0.003
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
mutant L144M, pH and temperature not specified in the publication
0.093
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
wild-type, pH and temperature not specified in the publication
0.5
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
mutant A153C, reducing conditions, 4°C, pH not specified in the publication
9.6
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
wild-type, non-reducing conditions, 4°C, pH not specified in the publication
15.8
N-succinyl-Leu-Tyr-7-amido-4-methylcoumarin
-
wild-type, reducing conditions, 4°C, pH not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
98
1-[4-(4-ethynylbenzoyl)-1,1-dioxido-1,2-thiazetidin-2-yl]ethanone
Staphylococcus aureus
-
pH not specified in the publication, temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
42
-
active in degrading alpha-casein up to 42°C, no proteinase activity at 55°C
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain NCTC11168, mutants are constructed by replacing the central parts of the C. jejuni clpP genes with a cat gene
-
-
brenda
strain NCTC11168, mutants are constructed by replacing the central parts of the C. jejuni clpP genes with a cat gene
-
-
brenda
mutant overexpressing chlorophyllide a oxygenase and mutant in the ClpC1 gene
-
-
brenda
wild type and mutant transfected with an antisense clpP6 plasmid
-
-
brenda
-
29856, 29857, 29859, 29862, 29863, 29866, 29867, 29868, 29869, 29870, 653260, 653631, 653668, 667634, 669410, 683473, 683865, 696224, 717472, 717708, 717731, 717787, 717989, 717999, 718406, 731636
-
-
brenda
wild-type cells K12 and mutants in which the gene for the ATP-dependent Lon protease is deleted
-
-
brenda
wild-type Escherichia coli cells transformed with the multicopy plasmid pWPC9 (ClpP)
-
-
brenda
P9WPC5 i.e. subunit P1, P9WPC3 i.e. subunit P2
SwissProt
brenda
P9WPC5 i.e. subunit P1, P9WPC3 i.e. subunit P2
SwissProt
brenda
parasite contains four Clp ATPases, one protease subunit ClpP and one inactive protease ClpR
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
reduced level of the Lon and ClpP proteins in SPG13 patient cells as compared with controls
brenda
reduced level of the Lon and ClpP proteins in SPG13 patient cells as compared with controls
brenda
additional information
decreased expression of the mitochondrial protein quality control proteases Lon and ClpP, both at the RNA and protein level, in patients with an autosomal dominant form of hereditary spastic paraplegia (SPG13)
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
-
ClpC and ClpP localize to the cell poles of competent cells
-
brenda
additional information
-
no protein detected in the thylakoid fraction
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
-
a point mutation from G to A at nucleotide 2317 of ClpC1 on chromosome V of Arabidopsis is responsible for the irm1 phenotype (typical Fe-deficiency chlorosis)
malfunction
-
both FlhD and FlhC regulator proteins accumulate markedly following ClpXP depletion, and their half-lives are significantly longer in the mutant cells
malfunction
-
ClpP1 is essential for viability. The gene can only be deleted from the chromosome when a second functional copy is provided. Over-expression of clpP1 has no effect on growth in aerobic culture or viability under anaerobic conditions or during nutrient starvation
malfunction
-
deletion of clpX and clpP suppresses temperature-sensitive filamentation of cells carrying the ftsZ84 allele and reduces FtsZ84 degradation, consistent with ClpXP (two-component protease composed of ClpX and ClpP) playing a role in modulating the level of FtsZ (a tubulin-like protein)
malfunction
-
in a DELTAclpP strain, 288 genes show significant changes in relative transcript amounts as compared with the parent. Similarly, 242 genes are differentially expressed by a DELTAclpX strain. Several genes associated with cell growth are down-regulated in both mutants, consistent with the slow-growth phenotype of the DELTAclp strains. Among the up-regulated genes are those encoding enzymes required for the biosynthesis of intracellular polysaccharides and malolactic fermentation. Expression of several genes known or predicted to be involved in competence and mutacin production are down-regulated in the DELTAclp strains
malfunction
-
in a division-defective strain, DELTAminC, the additional deletion of clpX or clpP delays cell division and exacerbates filamentation
metabolism
-
presence of ATP favours assembly and ADP dissociation of the hexameric assembly. Subunit exchange kinetics is at least one order of magnitude slower than the ATP hydrolysis rate, and ClpB dynamics and activity are related processe. DnaK and substrate proteins regulate the ATPase activity and dynamics of ClpB
metabolism
Escherichia coli BB4561
-
presence of ATP favours assembly and ADP dissociation of the hexameric assembly. Subunit exchange kinetics is at least one order of magnitude slower than the ATP hydrolysis rate, and ClpB dynamics and activity are related processe. DnaK and substrate proteins regulate the ATPase activity and dynamics of ClpB
physiological function
-
accessory proteins ClpT1 and ClpT2 regulate the assembly of the Clp proteolytic core in vascular plants
physiological function
-
Azotobacter vinelandii carries a duplicated copy of the ATPase component of the ubiquitous ClpXP protease (ClpX2), which is induced under nitrogen fixing conditions. Inactivation of clpX2 results in the accumulation of NifB and NifEN and a defect in diazotrophic growth, especially when iron is in short supply
physiological function
-
ClpXP positively regulates T3SS through RpoS degradation. In addition to the regulation of T3SS, ClpXP protease, RssB, and RpoS play a role in pectinolytic enzyme production and virulence of Dickeya dadantii
physiological function
-
ClpXP protease of Escherichia coli consists of the AAA+ ClpX unfoldase and the associated ClpP compartmental peptidase. Once the substrate is unfolded, ClpX translocates the unfolded polypeptide into the degradation chamber of ClpP in steps of five to eight amino acids per power stroke
physiological function
-
ClpXP protease tightly regulates the flagellar expression by degrading the FlhD/FlhC master regulator in EHEC. The flagellar regulon in EHEC might be controlled by ClpXP protease through two pathways, namely post-translational control of the FlhD/FlhC master regulator by degrading them and transcriptional control of the flhDC operon through the locus of enterocyte effacement (LEE)-encoded GrlR-GrlA regulatory system
physiological function
-
proteolysis of the LexA N-terminal domain is dependent on ClpP. In the absence of the proteolytic subunit ClpP, or one or both of the Clp ATPases, ClpX and ClpC, the LexA domains are stabilized after autocleavage
physiological function
-
a mutant strain lacking the N-terminal domain of ClpX is not viable
physiological function
adaptor protein MecA specifically interacts with both central competence regulator sigmax and protease ClpC, suggesting the formation of a ternary sigmaX-MecA-ClpC complex. MecA ultimately targets sigmaX for its degradation by the ClpCP protease in an ATP-dependent manner. A short sequence of 18 amino acids in the N-terminal domain of sigmaX is essential for the interaction with MecA and subsequent sigmaX degradation. Increased transformability of a MecA-deficient strain in the presence of subinducing SigX-inducing peptide concentrations suggests that the MecA-ClpCP proteolytic complex acts as an additional locking device to prevent competence under inappropriate conditions
physiological function
both protein and small-molecule activators of ClpP allosterically control the ClpP barrel conformation. Acyldepsipeptides in addition to opening the axial pore directly stimulate ClpP activity through cooperative binding. ClpP activation thus reaches beyond active site accessibility and also involves conformational control of the catalytic residues. Substoichiometric amounts of acyldepsipeptide potently prevent binding of ClpX to ClpP and, at the same time, partially inhibit ClpP through conformational perturbance. The hydrophobic binding pocket is a major conformational regulatory site with implications for both ClpXP proteolysis and acyldepsipeptide -based anti-bacterial activity
physiological function
-
deletion of the clpP gene results in a mutant strain displaying reduced growth at high temperatures and under several other stress conditions. The mutant exhibits an increased ability to take up iron in vitro compared to the wild-type strain and displays rough and irregular surfaces and increased cell volume relative to the wild-type strain. The mutant shows decreased biofilm formation. The expression of 16 genes is changed by the deletion of the clpP gene
physiological function
highly specific association between HSP100 chaperone ClpC and the ClpP3/R core. Two conserved sequences in the N-terminus of ClpR and one in the N-terminus of ClpP3 are crucial for the ClpC-ClpP3/R sdubunit association. These N-terminal domains also influence the stability of the ClpP3/R core complex itself. A unique C-terminal sequence just downstream of the P-loop region previously in ClpC confers specificity for the ClpP3/R core and prevents association with Escherichia coli ClpP
physiological function
-
arginine-phosphate and arginine-phosphorylated proteins bind to subunit ClpC1 N-terminal domain and induce millisecond dynamics. These dynamics are caused by conformational changes and do not result from unfolding or oligomerization of this domain
physiological function
Clp chaperones ClpX and ClpC1 require the intact interaction face of subunit ClpP2 to support degradation. Binding results in an asymmetric complex where chaperones only bind to the ClpP2 side of the proteolytic core
physiological function
ClpC1-catalyzed unfolding of an SsrA-tagged protein is negatively impacted by association with the ClpS adaptor protein. ClpS-dependent inhibition of ClpC1-catalyzed SsrA-dependent protein unfolding does not require the ClpC1 N-terminal domain but instead requires the presence of an interaction surface located in the ClpC1 middle domain
physiological function
ClpXP protease consists of the ClpX hexamer and the ClpP peptidase. Small-molecule acyldepsipeptides such as ADEP-2B compete with the IGF loops of ClpX for ClpP-cleft binding and cause exceptionally rapid dissociation of otherwise stable ClpXP complexes, suggesting that the IGF-loop interactions with ClpP must be highly dynamic
physiological function
-
plants defective in the chloroplast caseinolytic protease Clp system are specifically impaired in copper transporter PAA2/HMA8 protein turnover on media containing elevated copper concentrations
physiological function
proteins phosphorylated on arginine residues are selectively targeted to ClpC-ClpP. Arginine phosphorylation by the McsB kinase is required and sufficient for the degradation of substrate proteins. The ClpCP protease complex alone is not active. The docking site for phosphoarginine is located in the amino-terminal domain of the ClpC ATPase
physiological function
purified ClpXP added to a cell-free transcription-translation system that uses Escherichia coli S30 cell extract, has very low proteolytic activity. Addition of exogenous ATP and an energy regeneration system improves activity
physiological function
reducing the levels of mitochondrial ClpP or ClpX renders human cancer cells more sensitive to cisplatin. Overexpression of ClpP desensitizes cells to cisplatin. Cisplatin resistance correlates with decreased cellular accumulation of cisplatin and decreased levels of diguanosine-cisplatin adducts in both mitochondrial and genomic DNA. Higher levels of cisplatin-DNA adducts are found in cells in which ClpP has been depleted. Changes in the levels of ClpP have no effect on the levels of copper transporter CTR1. The levels of copper efflux pumps ATP7A and ATP7B are increased when ClpPwas overexpressed
physiological function
-
both protein and small-molecule activators of ClpP allosterically control the ClpP barrel conformation. Acyldepsipeptides in addition to opening the axial pore directly stimulate ClpP activity through cooperative binding. ClpP activation thus reaches beyond active site accessibility and also involves conformational control of the catalytic residues. Substoichiometric amounts of acyldepsipeptide potently prevent binding of ClpX to ClpP and, at the same time, partially inhibit ClpP through conformational perturbance. The hydrophobic binding pocket is a major conformational regulatory site with implications for both ClpXP proteolysis and acyldepsipeptide -based anti-bacterial activity
physiological function
-
proteins phosphorylated on arginine residues are selectively targeted to ClpC-ClpP. Arginine phosphorylation by the McsB kinase is required and sufficient for the degradation of substrate proteins. The ClpCP protease complex alone is not active. The docking site for phosphoarginine is located in the amino-terminal domain of the ClpC ATPase
physiological function
-
plants defective in the chloroplast caseinolytic protease Clp system are specifically impaired in copper transporter PAA2/HMA8 protein turnover on media containing elevated copper concentrations
physiological function
-
ClpC1-catalyzed unfolding of an SsrA-tagged protein is negatively impacted by association with the ClpS adaptor protein. ClpS-dependent inhibition of ClpC1-catalyzed SsrA-dependent protein unfolding does not require the ClpC1 N-terminal domain but instead requires the presence of an interaction surface located in the ClpC1 middle domain
physiological function
-
adaptor protein MecA specifically interacts with both central competence regulator sigmax and protease ClpC, suggesting the formation of a ternary sigmaX-MecA-ClpC complex. MecA ultimately targets sigmaX for its degradation by the ClpCP protease in an ATP-dependent manner. A short sequence of 18 amino acids in the N-terminal domain of sigmaX is essential for the interaction with MecA and subsequent sigmaX degradation. Increased transformability of a MecA-deficient strain in the presence of subinducing SigX-inducing peptide concentrations suggests that the MecA-ClpCP proteolytic complex acts as an additional locking device to prevent competence under inappropriate conditions
physiological function
-
highly specific association between HSP100 chaperone ClpC and the ClpP3/R core. Two conserved sequences in the N-terminus of ClpR and one in the N-terminus of ClpP3 are crucial for the ClpC-ClpP3/R sdubunit association. These N-terminal domains also influence the stability of the ClpP3/R core complex itself. A unique C-terminal sequence just downstream of the P-loop region previously in ClpC confers specificity for the ClpP3/R core and prevents association with Escherichia coli ClpP
Show AA Sequence and Transmembrane Helices (56134 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
Bacillus subtilis (strain 168)
Coxiella burnetii (strain RSA 493 / Nine Mile phase I)
Enterococcus faecium (strain ATCC BAA-472 / TX0016 / DO)
Escherichia coli (strain K12)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Helicobacter pylori (strain ATCC 700392 / 26695)
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh)
Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155)
Neisseria meningitidis serogroup B (strain MC58)
Staphylococcus aureus (strain NCTC 8325)
Thermus thermophilus (strain HB27 / ATCC BAA-163 / DSM 7039)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Helicobacter pylori (strain ATCC 700392 / 26695)
Helicobacter pylori (strain ATCC 700392 / 26695)
Helicobacter pylori (strain ATCC 700392 / 26695)
Helicobacter pylori (strain ATCC 700392 / 26695)
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Neisseria meningitidis serogroup B (strain MC58)
Neisseria meningitidis serogroup B (strain MC58)
Neisseria meningitidis serogroup B (strain MC58)
Neisseria meningitidis serogroup B (strain MC58)
Neisseria meningitidis serogroup B (strain MC58)
Thermus thermophilus (strain HB27 / ATCC BAA-163 / DSM 7039)
Thermus thermophilus (strain HB27 / ATCC BAA-163 / DSM 7039)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
140000
150000
-
gel filtration, enzyme treated with inhibitor diisopropyl fluorophosphate, 1-[4-(4-ethynylbenzoyl)-1,1-dioxido-1,2-thiazetidin-2-yl]undec-10-en-1-one, or beta-lactone (4R)-3-(4-methoxyphenyl)-4-(pent-4-yn-1-yl)oxetan-2-one
180000
-
n * 230000, n * 180000, ClpP1, ClpP3, clpP4, ClpP5, clpP6, clpR1, clpR2, ClpR3, cClR4, ClpS1
21000
-
1 * 230000, subunit ClpP (12 * 21000, amino acid sequence, subunit of ClpP)
22000
-
ClpP1(pClpP), MALDI-TOF, ClpS1(nClpC like), MALDI-TOF, ClpP5 (nClpP1), MALDI-TOF, ClpP6 (nClpP6), MALDI-TOF
23000
230000
240000
-
240000 (ClpP with the subunit structure 12 * 23000, SDS-PAGE), gel filtration in presence of more than or at 0.1 M KCl, in absence of KCl, native ClpP appears to dimerize giving a structure with a MW of 500000
26000 - 29000
-
2 isoenzymes, immunoblot analysis, antibody against plastid-encoded rice ClpP
270000
300000
335000
-
wild type, native Page, decreased by 80% in clpP6 antisense mutants, ClpP6 is necessary for the formation of the Clp proteolytic core complex
346000
-
sedimentation velocity analytical ultracentrifugation, tetradecamer
80000
-
x * 80000 (ClpA, SDS-PAGE, behaves as a dimer of MW 140000 Da on gel filtration) + x * 23000 (ClpP, SDS-PAGE, behaves as a complex of 10-12 subunits, MW 260000 Da)
83000
-
x * 120000-140000, subunit ClpA, gel filtration, x * 83000, subunit ClpA, amino acid sequence
23000
-
x * 80000 (ClpA, SDS-PAGE, behaves as a dimer of MW 140000 Da on gel filtration) + x * 23000 (ClpP, SDS-PAGE, behaves as a complex of 10-12 subunits, MW 260000 Da)
23000
-
240000 (ClpP with the subunit structure 12 * 23000, SDS-PAGE), gel filtration in presence of more than or at 0.1 M KCl, in absence of KCl, native ClpP appears to dimerize giving a structure with a MW of 500000
230000
-
1 * 230000, subunit ClpP (12 * 21000, amino acid sequence, subunit of ClpP)
230000
-
n * 230000, n * 180000, ClpP1, ClpP3, clpP4, ClpP5, clpP6, clpR1, clpR2, ClpR3, cClR4, ClpS1
300000
gel filtration, assembled double-ring complex
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
heptamer
multimer
-
n * 230000, n * 180000, ClpP1, ClpP3, clpP4, ClpP5, clpP6, clpR1, clpR2, ClpR3, cClR4, ClpS1
oligomer
tetradecamer
additional information
?
-
1 * 230000, subunit ClpP (12 * 21000, amino acid sequence, subunit of ClpP)
?
-
x * 120000-140000, subunit ClpA, gel filtration, x * 83000, subunit ClpA, amino acid sequence
?
-
ClpP is composed of two superimposed rings of six subunits each, ClpA and ClpP form a tight complex in the presence of MgCl2 and ATP, the ClpAP complex is composed of a dodecamer of ClpP and a hexamer of ClpA
?
-
x * 80000 (ClpA, SDS-PAGE, behaves as a dimer of MW 140000 Da on gel filtration) + x * 23000 (ClpP, SDS-PAGE, behaves as a complex of 10-12 subunits, MW 260000 Da)
?