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Protein

ATP-dependent Clp protease proteolytic subunit, mitochondrial

Gene

CLPP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.2 Publications

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).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei153Nucleophile1 Publication1
Active sitei178By similarity1

GO - Molecular functioni

  • peptidase activity Source: ProtInc
  • serine-type endopeptidase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Enzyme and pathway databases

BioCyciZFISH:HS04911-MONOMER.
BRENDAi3.4.21.92. 2681.

Protein family/group databases

MEROPSiS14.003.

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-dependent Clp protease proteolytic subunit, mitochondrial (EC:3.4.21.92)
Alternative name(s):
Endopeptidase Clp
Gene namesi
Name:CLPP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:2084. CLPP.

Subcellular locationi

GO - Cellular componenti

  • endopeptidase Clp complex Source: UniProtKB
  • mitochondrial matrix Source: UniProtKB
  • mitochondrion Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Perrault syndrome 3 (PRLTS3)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile. A spectrum of additional clinical features, including cerebellar ataxia, learning disability, and peripheral neuropathy, have been described in some PRLTS3 affected individuals.
See also OMIM:614129
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070092145T → P in PRLTS3. 1 PublicationCorresponds to variant rs398123033dbSNPEnsembl.1
Natural variantiVAR_070093147C → S in PRLTS3. 1 PublicationCorresponds to variant rs398123034dbSNPEnsembl.1
Natural variantiVAR_074160229Y → D in PRLTS3. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi58 – 61Missing : Abolishes protease activity. 1 Publication4
Mutagenesisi153S → A or C: Abolishes protease activity. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation

Organism-specific databases

DisGeNETi8192.
MalaCardsiCLPP.
MIMi614129. phenotype.
OpenTargetsiENSG00000125656.
Orphaneti2855. Perrault syndrome.
PharmGKBiPA26610.

Polymorphism and mutation databases

BioMutaiCLPP.
DMDMi3023512.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 56MitochondrionCombined sources1 PublicationAdd BLAST56
ChainiPRO_000000551657 – 277ATP-dependent Clp protease proteolytic subunit, mitochondrialAdd BLAST221

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei200N6-succinyllysineBy similarity1
Modified residuei211N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ16740.
MaxQBiQ16740.
PaxDbiQ16740.
PeptideAtlasiQ16740.
PRIDEiQ16740.
TopDownProteomicsiQ16740.

PTM databases

iPTMnetiQ16740.
PhosphoSitePlusiQ16740.

Expressioni

Tissue specificityi

Detected in liver (at protein level). Predominantly expressed in skeletal muscle. Intermediate levels in heart, liver and pancreas. Low in brain, placenta, lung and kidney.2 Publications

Gene expression databases

BgeeiENSG00000125656.
CleanExiHS_CLPP.
ExpressionAtlasiQ16740. baseline and differential.
GenevisibleiQ16740. HS.

Organism-specific databases

HPAiHPA010649.

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 Publications

Protein-protein interaction databases

BioGridi113835. 21 interactors.
DIPiDIP-50384N.
IntActiQ16740. 50 interactors.
STRINGi9606.ENSP00000245816.

Structurei

Secondary structure

1277
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi75 – 80Combined sources6
Turni81 – 83Combined sources3
Beta strandi84 – 91Combined sources8
Helixi93 – 109Combined sources17
Beta strandi111 – 113Combined sources3
Beta strandi115 – 121Combined sources7
Helixi126 – 138Combined sources13
Beta strandi143 – 152Combined sources10
Helixi154 – 160Combined sources7
Beta strandi167 – 169Combined sources3
Beta strandi174 – 177Combined sources4
Helixi188 – 213Combined sources26
Helixi217 – 224Combined sources8
Beta strandi228 – 230Combined sources3
Helixi232 – 238Combined sources7
Beta strandi242 – 244Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TG6X-ray2.10A/B/C/D/E/F/G1-277[»]
ProteinModelPortaliQ16740.
SMRiQ16740.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16740.

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase S14 family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG0840. Eukaryota.
COG0740. LUCA.
GeneTreeiENSGT00390000005830.
HOGENOMiHOG000285833.
HOVERGENiHBG001689.
InParanoidiQ16740.
KOiK01358.
OMAiARMNELM.
OrthoDBiEOG091G0KCO.
PhylomeDBiQ16740.
TreeFamiTF105002.

Family and domain databases

Gene3Di3.90.226.10. 1 hit.
HAMAPiMF_00444. ClpP. 1 hit.
InterProiIPR001907. ClpP.
IPR029045. ClpP/crotonase-like_dom.
IPR023562. ClpP/TepA.
IPR033135. ClpP_His_AS.
IPR018215. ClpP_Ser_AS.
[Graphical view]
PANTHERiPTHR10381. PTHR10381. 1 hit.
PfamiPF00574. CLP_protease. 1 hit.
[Graphical view]
PRINTSiPR00127. CLPPROTEASEP.
SUPFAMiSSF52096. SSF52096. 1 hit.
PROSITEiPS00382. CLP_PROTEASE_HIS. 1 hit.
PS00381. CLP_PROTEASE_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q16740-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:277
Mass (Da):30,180
Last modified:November 1, 1996 - v1
Checksum:iB03AAC5D50F7880E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti111N → S in BAG34912 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070092145T → P in PRLTS3. 1 PublicationCorresponds to variant rs398123033dbSNPEnsembl.1
Natural variantiVAR_070093147C → S in PRLTS3. 1 PublicationCorresponds to variant rs398123034dbSNPEnsembl.1
Natural variantiVAR_074160229Y → D in PRLTS3. 1 Publication1

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.
CCDSiCCDS12162.1.
PIRiS68421.
RefSeqiNP_006003.1. NM_006012.2.
UniGeneiHs.515092.

Genome annotation databases

EnsembliENST00000245816; ENSP00000245816; ENSG00000125656.
GeneIDi8192.
KEGGihsa:8192.
UCSCiuc002mem.2. human.

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.
CCDSiCCDS12162.1.
PIRiS68421.
RefSeqiNP_006003.1. NM_006012.2.
UniGeneiHs.515092.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TG6X-ray2.10A/B/C/D/E/F/G1-277[»]
ProteinModelPortaliQ16740.
SMRiQ16740.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113835. 21 interactors.
DIPiDIP-50384N.
IntActiQ16740. 50 interactors.
STRINGi9606.ENSP00000245816.

Protein family/group databases

MEROPSiS14.003.

PTM databases

iPTMnetiQ16740.
PhosphoSitePlusiQ16740.

Polymorphism and mutation databases

BioMutaiCLPP.
DMDMi3023512.

Proteomic databases

EPDiQ16740.
MaxQBiQ16740.
PaxDbiQ16740.
PeptideAtlasiQ16740.
PRIDEiQ16740.
TopDownProteomicsiQ16740.

Protocols and materials databases

DNASUi8192.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245816; ENSP00000245816; ENSG00000125656.
GeneIDi8192.
KEGGihsa:8192.
UCSCiuc002mem.2. human.

Organism-specific databases

CTDi8192.
DisGeNETi8192.
GeneCardsiCLPP.
HGNCiHGNC:2084. CLPP.
HPAiHPA010649.
MalaCardsiCLPP.
MIMi601119. gene.
614129. phenotype.
neXtProtiNX_Q16740.
OpenTargetsiENSG00000125656.
Orphaneti2855. Perrault syndrome.
PharmGKBiPA26610.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0840. Eukaryota.
COG0740. LUCA.
GeneTreeiENSGT00390000005830.
HOGENOMiHOG000285833.
HOVERGENiHBG001689.
InParanoidiQ16740.
KOiK01358.
OMAiARMNELM.
OrthoDBiEOG091G0KCO.
PhylomeDBiQ16740.
TreeFamiTF105002.

Enzyme and pathway databases

BioCyciZFISH:HS04911-MONOMER.
BRENDAi3.4.21.92. 2681.

Miscellaneous databases

EvolutionaryTraceiQ16740.
GeneWikiiCLPP.
GenomeRNAii8192.
PROiQ16740.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125656.
CleanExiHS_CLPP.
ExpressionAtlasiQ16740. baseline and differential.
GenevisibleiQ16740. HS.

Family and domain databases

Gene3Di3.90.226.10. 1 hit.
HAMAPiMF_00444. ClpP. 1 hit.
InterProiIPR001907. ClpP.
IPR029045. ClpP/crotonase-like_dom.
IPR023562. ClpP/TepA.
IPR033135. ClpP_His_AS.
IPR018215. ClpP_Ser_AS.
[Graphical view]
PANTHERiPTHR10381. PTHR10381. 1 hit.
PfamiPF00574. CLP_protease. 1 hit.
[Graphical view]
PRINTSiPR00127. CLPPROTEASEP.
SUPFAMiSSF52096. SSF52096. 1 hit.
PROSITEiPS00382. CLP_PROTEASE_HIS. 1 hit.
PS00381. CLP_PROTEASE_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCLPP_HUMAN
AccessioniPrimary (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: November 2, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.