Q16740 · CLPP_HUMAN
- ProteinATP-dependent Clp protease proteolytic subunit, mitochondrial
- GeneCLPP
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids277 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Cleaves PINK1 in the mitochondrion (PubMed:22354088).
Catalytic activity
- 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).
Features
Showing features for active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 153 | Nucleophile | ||||
Sequence: S | ||||||
Active site | 178 | |||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endopeptidase Clp complex | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrion | |
Molecular Function | ATP-dependent peptidase activity | |
Molecular Function | ATPase binding | |
Molecular Function | endopeptidase activity | |
Molecular Function | identical protein binding | |
Molecular Function | peptidase activity | |
Molecular Function | serine-type endopeptidase activity | |
Biological Process | membrane protein proteolysis | |
Biological Process | mitochondrial protein catabolic process | |
Biological Process | protein quality control for misfolded or incompletely synthesized proteins | |
Biological Process | proteolysis | |
Biological Process | proteolysis involved in protein catabolic process |
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameATP-dependent Clp protease proteolytic subunit, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ16740
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Perrault syndrome 3 (PRLTS3)
- Note
- 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 alsoMIM:614129
Natural variants in PRLTS3
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_070092 | 145 | T>P | in PRLTS3; dbSNP:rs398123033 | |
VAR_070093 | 147 | C>S | in PRLTS3; dbSNP:rs398123034 | |
VAR_074160 | 229 | Y>D | in PRLTS3 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 58-61 | Abolishes protease activity. | ||||
Sequence: Missing | ||||||
Natural variant | VAR_070092 | 145 | in PRLTS3; dbSNP:rs398123033 | |||
Sequence: T → P | ||||||
Natural variant | VAR_070093 | 147 | in PRLTS3; dbSNP:rs398123034 | |||
Sequence: C → S | ||||||
Mutagenesis | 153 | Abolishes protease activity. | ||||
Sequence: S → A or C | ||||||
Natural variant | VAR_074160 | 229 | in PRLTS3 | |||
Sequence: Y → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 320 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Transit peptide | 1-56 | UniProt | Mitochondrion | ||||
Sequence: MWPGILVGGARVASCRYPALGPRLAAHFPAQRPPQRTLQNGLALQRCLHATATRAL | |||||||
Chain | PRO_0000005516 | 57-277 | UniProt | ATP-dependent Clp protease proteolytic subunit, mitochondrial | |||
Sequence: PLIPIVVEQTGRGERAYDIYSRLLRERIVCVMGPIDDSVASLVIAQLLFLQSESNKKPIHMYINSPGGVVTAGLAIYDTMQYILNPICTWCVGQAASMGSLLLAAGTPGMRHSLPNSRIMIHQPSGGARGQATDIAIQAEEIMKLKKQLYNIYAKHTKQSLQVIESAMERDRYMSPMEAQEFGILDKVLVHPPQDGEDEPTLVQKEPVEAAPAAEPVPAST | |||||||
Modified residue | 200 | UniProt | N6-succinyllysine | ||||
Sequence: K | |||||||
Modified residue | 211 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 277 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
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.
Gene expression databases
Organism-specific databases
Interaction
Subunit
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.
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 246-277 | Disordered | ||||
Sequence: VHPPQDGEDEPTLVQKEPVEAAPAAEPVPAST |
Sequence similarities
Belongs to the peptidase S14 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length277
- Mass (Da)30,180
- Last updated1996-11-01 v1
- ChecksumB03AAC5D50F7880E
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A2R8YEF5 | A0A2R8YEF5_HUMAN | CLPP | 33 | ||
M0R208 | M0R208_HUMAN | CLPP | 190 | ||
M0QXE9 | M0QXE9_HUMAN | CLPP | 71 | ||
M0QYV5 | M0QYV5_HUMAN | CLPP | 143 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 111 | in Ref. 2; BAG34912 | ||||
Sequence: N → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Z50853 EMBL· GenBank· DDBJ | CAA90705.1 EMBL· GenBank· DDBJ | mRNA | ||
AK311973 EMBL· GenBank· DDBJ | BAG34912.1 EMBL· GenBank· DDBJ | mRNA | ||
BC002956 EMBL· GenBank· DDBJ | AAH02956.1 EMBL· GenBank· DDBJ | mRNA |