UniProtKB - Q16740 (CLPP_HUMAN)
ATP-dependent Clp protease proteolytic subunit, mitochondrial
CLPP
Functioni
Protease component of the Clp complex that cleaves peptides and various proteins in an ATP-dependent process. Has low peptidase activity in the absence of CLPX. The Clp complex can degrade CSN1S1, CSN2 and CSN3, as well as synthetic peptides (in vitro) and may be responsible for a fairly general and central housekeeping function rather than for the degradation of specific substrates (PubMed:11923310, PubMed:15522782).
Cleaves PINK1 in the mitochondrion (PubMed:22354088).
3 PublicationsCatalytic 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).3 Publications EC:3.4.21.92
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 153 | Nucleophile1 Publication | 1 | |
Active sitei | 178 | By similarity | 1 |
GO - Molecular functioni
- ATPase binding Source: GO_Central
- ATP-dependent peptidase activity Source: GO_Central
- endopeptidase activity Source: UniProtKB
- identical protein binding Source: Ensembl
- peptidase activity Source: ProtInc
- serine-type endopeptidase activity Source: UniProtKB
GO - Biological processi
- membrane protein proteolysis Source: UniProtKB
- protein quality control for misfolded or incompletely synthesized proteins Source: GO_Central
- proteolysis Source: ComplexPortal
- proteolysis involved in cellular protein catabolic process Source: UniProtKB
Keywordsi
Molecular function | Hydrolase, Protease, Serine protease |
Enzyme and pathway databases
BRENDAi | 3.4.21.92, 2681 |
PathwayCommonsi | Q16740 |
SignaLinki | Q16740 |
Protein family/group databases
MEROPSi | S14.003 |
Names & Taxonomyi
Protein namesi | Recommended name: ATP-dependent Clp protease proteolytic subunit, mitochondrial (EC:3.4.21.923 Publications)Alternative name(s): Endopeptidase Clp |
Gene namesi | Name:CLPP |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:2084, CLPP |
MIMi | 601119, gene |
neXtProti | NX_Q16740 |
VEuPathDBi | HostDB:ENSG00000125656 |
Subcellular locationi
Mitochondrion
- Mitochondrion matrix 2 Publications
Mitochondrion
- mitochondrial matrix Source: UniProtKB
- mitochondrion Source: UniProtKB
Other locations
- endopeptidase Clp complex Source: UniProtKB
Keywords - Cellular componenti
MitochondrionPathology & Biotechi
Involvement in diseasei
Perrault syndrome 3 (PRLTS3)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070092 | 145 | T → P in PRLTS3. 1 PublicationCorresponds to variant dbSNP:rs398123033EnsemblClinVar. | 1 | |
Natural variantiVAR_070093 | 147 | C → S in PRLTS3. 1 PublicationCorresponds to variant dbSNP:rs398123034EnsemblClinVar. | 1 | |
Natural variantiVAR_074160 | 229 | Y → D in PRLTS3. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 58 – 61 | Missing : Abolishes protease activity. 1 Publication | 4 | |
Mutagenesisi | 153 | S → A or C: Abolishes protease activity. 1 Publication | 1 |
Keywords - Diseasei
Deafness, Disease variantOrganism-specific databases
DisGeNETi | 8192 |
GeneReviewsi | CLPP |
MalaCardsi | CLPP |
MIMi | 614129, phenotype |
OpenTargetsi | ENSG00000125656 |
Orphaneti | 2855, Perrault syndrome |
PharmGKBi | PA26610 |
Miscellaneous databases
Pharosi | Q16740, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4523305 |
DrugBanki | DB04464, N-Formylmethionine |
Genetic variation databases
BioMutai | CLPP |
DMDMi | 3023512 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 56 | MitochondrionCombined sources1 PublicationAdd BLAST | 56 | |
ChainiPRO_0000005516 | 57 – 277 | ATP-dependent Clp protease proteolytic subunit, mitochondrialAdd BLAST | 221 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 200 | N6-succinyllysineBy similarity | 1 | |
Modified residuei | 211 | N6-acetyllysineCombined sources | 1 |
Keywords - PTMi
AcetylationProteomic databases
EPDi | Q16740 |
jPOSTi | Q16740 |
MassIVEi | Q16740 |
MaxQBi | Q16740 |
PaxDbi | Q16740 |
PeptideAtlasi | Q16740 |
PRIDEi | Q16740 |
ProteomicsDBi | 61051 |
TopDownProteomicsi | Q16740 |
PTM databases
iPTMneti | Q16740 |
MetOSitei | Q16740 |
PhosphoSitePlusi | Q16740 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000125656, Expressed in gastrocnemius and 241 other tissues |
ExpressionAtlasi | Q16740, baseline and differential |
Genevisiblei | Q16740, HS |
Organism-specific databases
HPAi | ENSG00000125656, Low tissue specificity |
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.
Component of the Clp complex formed by the assembly of two CLPP heptameric rings with two CLPX hexameric rings, giving rise to a symmetrical structure with two central CLPP rings flanked by a CLPX ring at either end of the complex.
4 PublicationsBinary interactionsi
Q16740
ATP-dependent Clp protease proteolytic subunit, mitochondrial (PRO_0000005516)
With | #Exp. | IntAct |
---|---|---|
CLPX [O76031] | 2 | EBI-25815820,EBI-1052667 |
GO - Molecular functioni
- ATPase binding Source: GO_Central
- identical protein binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 113835, 344 interactors |
ComplexPortali | CPX-6177, Mitochondrial endopeptidase ClpXP complex |
CORUMi | Q16740 |
DIPi | DIP-50384N |
IntActi | Q16740, 108 interactors |
MINTi | Q16740 |
STRINGi | 9606.ENSP00000245816 |
Chemistry databases
BindingDBi | Q16740 |
Miscellaneous databases
RNActi | Q16740, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q16740 |
SMRi | Q16740 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q16740 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 246 – 277 | DisorderedSequence analysisAdd BLAST | 32 |
Sequence similaritiesi
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG0840, Eukaryota |
GeneTreei | ENSGT00390000005830 |
InParanoidi | Q16740 |
OMAi | RDYWMKA |
OrthoDBi | 1274502at2759 |
PhylomeDBi | Q16740 |
TreeFami | TF105002 |
Family and domain databases
CDDi | cd07017, S14_ClpP_2, 1 hit |
HAMAPi | MF_00444, ClpP, 1 hit |
InterProi | View protein in InterPro IPR001907, ClpP IPR029045, ClpP/crotonase-like_dom_sf IPR023562, ClpP/TepA IPR033135, ClpP_His_AS IPR018215, ClpP_Ser_AS |
PANTHERi | PTHR10381, PTHR10381, 1 hit |
Pfami | View protein in Pfam PF00574, CLP_protease, 1 hit |
PRINTSi | PR00127, CLPPROTEASEP |
SUPFAMi | SSF52096, SSF52096, 1 hit |
PROSITEi | View protein in PROSITE PS00382, CLP_PROTEASE_HIS, 1 hit PS00381, CLP_PROTEASE_SER, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MWPGILVGGA RVASCRYPAL GPRLAAHFPA QRPPQRTLQN GLALQRCLHA
60 70 80 90 100
TATRALPLIP IVVEQTGRGE RAYDIYSRLL RERIVCVMGP IDDSVASLVI
110 120 130 140 150
AQLLFLQSES NKKPIHMYIN SPGGVVTAGL AIYDTMQYIL NPICTWCVGQ
160 170 180 190 200
AASMGSLLLA AGTPGMRHSL PNSRIMIHQP SGGARGQATD IAIQAEEIMK
210 220 230 240 250
LKKQLYNIYA KHTKQSLQVI ESAMERDRYM SPMEAQEFGI LDKVLVHPPQ
260 270
DGEDEPTLVQ KEPVEAAPAA EPVPAST
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketM0R208 | M0R208_HUMAN | ATP-dependent Clp protease proteoly... | CLPP | 190 | Annotation score: | ||
A0A2R8YEF5 | A0A2R8YEF5_HUMAN | Endopeptidase Clp | CLPP | 33 | Annotation score: | ||
M0QXE9 | M0QXE9_HUMAN | ATP-dependent Clp protease proteoly... | CLPP | 71 | Annotation score: | ||
M0QYV5 | M0QYV5_HUMAN | ATP-dependent Clp protease proteoly... | CLPP | 143 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 111 | N → S in BAG34912 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070092 | 145 | T → P in PRLTS3. 1 PublicationCorresponds to variant dbSNP:rs398123033EnsemblClinVar. | 1 | |
Natural variantiVAR_070093 | 147 | C → S in PRLTS3. 1 PublicationCorresponds to variant dbSNP:rs398123034EnsemblClinVar. | 1 | |
Natural variantiVAR_074160 | 229 | Y → D in PRLTS3. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Z50853 mRNA Translation: CAA90705.1 AK311973 mRNA Translation: BAG34912.1 BC002956 mRNA Translation: AAH02956.1 |
CCDSi | CCDS12162.1 |
PIRi | S68421 |
RefSeqi | NP_006003.1, NM_006012.2 |
Genome annotation databases
Ensembli | ENST00000245816.11; ENSP00000245816.3; ENSG00000125656.11 |
GeneIDi | 8192 |
KEGGi | hsa:8192 |
MANE-Selecti | ENST00000245816.11; ENSP00000245816.3; NM_006012.4; NP_006003.1 |
UCSCi | uc002mem.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Z50853 mRNA Translation: CAA90705.1 AK311973 mRNA Translation: BAG34912.1 BC002956 mRNA Translation: AAH02956.1 |
CCDSi | CCDS12162.1 |
PIRi | S68421 |
RefSeqi | NP_006003.1, NM_006012.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1TG6 | X-ray | 2.10 | A/B/C/D/E/F/G | 1-277 | [»] | |
6BBA | X-ray | 2.80 | A/B/C/D/E/F/G | 58-277 | [»] | |
6DL7 | X-ray | 2.00 | A/B/C/D/E/F/G | 58-277 | [»] | |
6H23 | X-ray | 3.09 | A/B/C/D/E/F/G/H/I/J/K/L/M/N | 57-277 | [»] | |
AlphaFoldDBi | Q16740 | |||||
SMRi | Q16740 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 113835, 344 interactors |
ComplexPortali | CPX-6177, Mitochondrial endopeptidase ClpXP complex |
CORUMi | Q16740 |
DIPi | DIP-50384N |
IntActi | Q16740, 108 interactors |
MINTi | Q16740 |
STRINGi | 9606.ENSP00000245816 |
Chemistry databases
BindingDBi | Q16740 |
ChEMBLi | CHEMBL4523305 |
DrugBanki | DB04464, N-Formylmethionine |
Protein family/group databases
MEROPSi | S14.003 |
PTM databases
iPTMneti | Q16740 |
MetOSitei | Q16740 |
PhosphoSitePlusi | Q16740 |
Genetic variation databases
BioMutai | CLPP |
DMDMi | 3023512 |
Proteomic databases
EPDi | Q16740 |
jPOSTi | Q16740 |
MassIVEi | Q16740 |
MaxQBi | Q16740 |
PaxDbi | Q16740 |
PeptideAtlasi | Q16740 |
PRIDEi | Q16740 |
ProteomicsDBi | 61051 |
TopDownProteomicsi | Q16740 |
Protocols and materials databases
Antibodypediai | 1703, 350 antibodies from 35 providers |
DNASUi | 8192 |
Genome annotation databases
Ensembli | ENST00000245816.11; ENSP00000245816.3; ENSG00000125656.11 |
GeneIDi | 8192 |
KEGGi | hsa:8192 |
MANE-Selecti | ENST00000245816.11; ENSP00000245816.3; NM_006012.4; NP_006003.1 |
UCSCi | uc002mem.2, human |
Organism-specific databases
CTDi | 8192 |
DisGeNETi | 8192 |
GeneCardsi | CLPP |
GeneReviewsi | CLPP |
HGNCi | HGNC:2084, CLPP |
HPAi | ENSG00000125656, Low tissue specificity |
MalaCardsi | CLPP |
MIMi | 601119, gene 614129, phenotype |
neXtProti | NX_Q16740 |
OpenTargetsi | ENSG00000125656 |
Orphaneti | 2855, Perrault syndrome |
PharmGKBi | PA26610 |
VEuPathDBi | HostDB:ENSG00000125656 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0840, Eukaryota |
GeneTreei | ENSGT00390000005830 |
InParanoidi | Q16740 |
OMAi | RDYWMKA |
OrthoDBi | 1274502at2759 |
PhylomeDBi | Q16740 |
TreeFami | TF105002 |
Enzyme and pathway databases
BRENDAi | 3.4.21.92, 2681 |
PathwayCommonsi | Q16740 |
SignaLinki | Q16740 |
Miscellaneous databases
BioGRID-ORCSi | 8192, 38 hits in 1076 CRISPR screens |
ChiTaRSi | CLPP, human |
EvolutionaryTracei | Q16740 |
GeneWikii | CLPP |
GenomeRNAii | 8192 |
Pharosi | Q16740, Tchem |
PROi | PR:Q16740 |
RNActi | Q16740, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000125656, Expressed in gastrocnemius and 241 other tissues |
ExpressionAtlasi | Q16740, baseline and differential |
Genevisiblei | Q16740, HS |
Family and domain databases
CDDi | cd07017, S14_ClpP_2, 1 hit |
HAMAPi | MF_00444, ClpP, 1 hit |
InterProi | View protein in InterPro IPR001907, ClpP IPR029045, ClpP/crotonase-like_dom_sf IPR023562, ClpP/TepA IPR033135, ClpP_His_AS IPR018215, ClpP_Ser_AS |
PANTHERi | PTHR10381, PTHR10381, 1 hit |
Pfami | View protein in Pfam PF00574, CLP_protease, 1 hit |
PRINTSi | PR00127, CLPPROTEASEP |
SUPFAMi | SSF52096, SSF52096, 1 hit |
PROSITEi | View protein in PROSITE PS00382, CLP_PROTEASE_HIS, 1 hit PS00381, CLP_PROTEASE_SER, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CLPP_HUMAN | |
Accessioni | Q16740Primary (citable) accession number: Q16740 Secondary accession number(s): B2R4W5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1998 |
Last sequence update: | November 1, 1996 | |
Last modified: | May 25, 2022 | |
This is version 188 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families