E0W1I1 · PINK1_PEDHC
- ProteinSerine/threonine-protein kinase Pink1, mitochondrial
- GenePink1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids575 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Acts as a serine/threonine-protein kinase (PubMed:22645651, PubMed:26161729, PubMed:29160309).
Exhibits a substrate preference for proline at position P+1 and a general preference at several residues for basic residues such as arginine (By similarity).
Also exhibits moderate preferences for a phosphotyrosine at position P-3 and a tryptophan at P-5 (By similarity).
Critical to mitochondrial homeostasis it mediates several pathways that maintain mitochondrial health and function (By similarity) Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins such as park and likely Drp1, to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:26161729).
Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (By similarity).
Appears to be particularly important in maintaining the physiology and function of cells with high energy demands that are undergoing stress or altered metabolic environment, including spermatids, muscle cells and neurons such as the dopaminergic (DA) neurons (By similarity).
Mediates the translocation and activation of park at the outer membrane (OMM) of dysfunctional/depolarized mitochondria (PubMed:26161729).
At the OMM of damaged mitochondria, phosphorylates pre-existing polyubiquitin chains, the Pink1-phosphorylated polyubiquitin then recruits park from the cytosol to the OMM where park is fully activated by phosphorylation at 'Ser-94' by Pink1 (By similarity).
When cellular stress results in irreversible mitochondrial damage, functions with park to promote the clearance of dysfunctional and/or depolarized mitochondria by selective autophagy (mitophagy) (By similarity).
The Pink1-park pathway also promotes fission and/or inhibits fusion of damaged mitochondria, by phosphorylating and thus promoting the park-dependent degradation of proteins involved in mitochondrial fusion/fission such as Marf, Opa1 and fzo (By similarity).
This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (By similarity).
Also likely to promote mitochondrial fission independently of park and Atg7-mediated mitophagy, via the phosphorylation and activation of Drp1 (By similarity).
Regulates motility of damaged mitochondria by phosphorylating Miro which likely promotes its park-dependent degradation by the proteasome; in motor neurons, this inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria being eliminated in the soma (By similarity).
The Pink1-park pathway is also involved in mitochondrial regeneration processes such as promoting mitochondrial biogenesis, activating localized mitochondrial repair, promoting selective turnover of mitochondrial proteins and initiating the mitochondrial import of endogenous proteins (By similarity).
Involved in mitochondrial biogenesis by promoting the park-dependent ubiquitination of transcriptional repressor Paris which leads to its subsequent proteasomal degradation and allows activation of the transcription factor srl (By similarity).
Functions with park to promote localized mitochondrial repair by activating the translation of specific nuclear-encoded mitochondrial RNAs (nc-mtRNAs) on the mitochondrial surface, including several key electron transport chain component nc-mtRNAs (By similarity).
During oogenesis, phosphorylates and inactivates larp on the membrane of defective mitochondria, thus impairing local translation and mtDNA replication and consequently, reducing transmission of deleterious mtDNA mutations to the mature oocyte (By similarity).
Phosphorylates the mitochondrial acyl-CoA dehydrogenase Mcad, and appears to be important for maintaining fatty acid and amino acid metabolism via a mechanism that is independent of it's role in maintaining production of ATP (By similarity).
Exhibits a substrate preference for proline at position P+1 and a general preference at several residues for basic residues such as arginine (By similarity).
Also exhibits moderate preferences for a phosphotyrosine at position P-3 and a tryptophan at P-5 (By similarity).
Critical to mitochondrial homeostasis it mediates several pathways that maintain mitochondrial health and function (By similarity) Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins such as park and likely Drp1, to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:26161729).
Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (By similarity).
Appears to be particularly important in maintaining the physiology and function of cells with high energy demands that are undergoing stress or altered metabolic environment, including spermatids, muscle cells and neurons such as the dopaminergic (DA) neurons (By similarity).
Mediates the translocation and activation of park at the outer membrane (OMM) of dysfunctional/depolarized mitochondria (PubMed:26161729).
At the OMM of damaged mitochondria, phosphorylates pre-existing polyubiquitin chains, the Pink1-phosphorylated polyubiquitin then recruits park from the cytosol to the OMM where park is fully activated by phosphorylation at 'Ser-94' by Pink1 (By similarity).
When cellular stress results in irreversible mitochondrial damage, functions with park to promote the clearance of dysfunctional and/or depolarized mitochondria by selective autophagy (mitophagy) (By similarity).
The Pink1-park pathway also promotes fission and/or inhibits fusion of damaged mitochondria, by phosphorylating and thus promoting the park-dependent degradation of proteins involved in mitochondrial fusion/fission such as Marf, Opa1 and fzo (By similarity).
This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (By similarity).
Also likely to promote mitochondrial fission independently of park and Atg7-mediated mitophagy, via the phosphorylation and activation of Drp1 (By similarity).
Regulates motility of damaged mitochondria by phosphorylating Miro which likely promotes its park-dependent degradation by the proteasome; in motor neurons, this inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria being eliminated in the soma (By similarity).
The Pink1-park pathway is also involved in mitochondrial regeneration processes such as promoting mitochondrial biogenesis, activating localized mitochondrial repair, promoting selective turnover of mitochondrial proteins and initiating the mitochondrial import of endogenous proteins (By similarity).
Involved in mitochondrial biogenesis by promoting the park-dependent ubiquitination of transcriptional repressor Paris which leads to its subsequent proteasomal degradation and allows activation of the transcription factor srl (By similarity).
Functions with park to promote localized mitochondrial repair by activating the translation of specific nuclear-encoded mitochondrial RNAs (nc-mtRNAs) on the mitochondrial surface, including several key electron transport chain component nc-mtRNAs (By similarity).
During oogenesis, phosphorylates and inactivates larp on the membrane of defective mitochondria, thus impairing local translation and mtDNA replication and consequently, reducing transmission of deleterious mtDNA mutations to the mature oocyte (By similarity).
Phosphorylates the mitochondrial acyl-CoA dehydrogenase Mcad, and appears to be important for maintaining fatty acid and amino acid metabolism via a mechanism that is independent of it's role in maintaining production of ATP (By similarity).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Note: Binds 2 Mg2+ ions per subunit.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 193 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 214 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Active site | 334 | Proton acceptor | ||||
Sequence: D | ||||||
Binding site | 339 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 357 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 357 | Mg2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrial outer membrane | |
Molecular Function | ATP binding | |
Molecular Function | metal ion binding | |
Molecular Function | protein kinase activity | |
Molecular Function | protein serine/threonine kinase activity | |
Biological Process | autophagy of mitochondrion | |
Biological Process | positive regulation of mitochondrial fission | |
Biological Process | regulation of apoptotic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase Pink1, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Paraneoptera > Psocodea > Phthiraptera > Anoplura > Pediculidae > Pediculus
Accessions
- Primary accessionE0W1I1
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion outer membrane ; Single-pass membrane protein
Mitochondrion inner membrane ; Single-pass membrane protein
Note: Localizes mostly in mitochondrion, and the smaller proteolytic processed fragment localizes in the cytosol as well (By similarity).
When mitochondria are damaged, defective and/or enriched with deleterious mtDNA mutations, Pink1 import is arrested which induces its accumulation on the outer mitochondrial membrane where it acquires kinase activity (By similarity).
When mitochondria are damaged, defective and/or enriched with deleterious mtDNA mutations, Pink1 import is arrested which induces its accumulation on the outer mitochondrial membrane where it acquires kinase activity (By similarity).
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 52-94 | Mitochondrial intermembrane | ||||
Sequence: LSTGLNSVKNAVQLQARKLLINNVLERVTPTLNSDLKKKAAKR | ||||||
Transmembrane | 95-118 | Helical | ||||
Sequence: LFYGDSAPFFALVGVSLASGSGLL | ||||||
Topological domain | 119-575 | Cytoplasmic | ||||
Sequence: TKDDELEGICWEIREAVSKGKWNDSESENVEQLQAANLDELDLGEPIAKGCNAVVYSAKLKNVQSNKLAHQLAVKMMFNYDVESNSTAILKAMYRETVPAMSYFFNQNLFNIENISDFKIRLPPHPNIVRMYSVFADRIPDLQCNKQLYPEALPPRINPEGSGRNMSLFLVMKRYDCTLKEYLRDKTPNMRSSILLLSQLLEAVAHMNIHNISHRDLKSDNILVDLSEGDAYPTIVITDFGCCLCDKQNGLVIPYRSEDQDKGGNRALMAPEIANAKPGTFSWLNYKKSDLWAVGAIAYEIFNIDNPFYDKTMKLLSKSYKEEDLPELPDTIPFIIRNLVSNMLSRSTNKRLDCDVAATVAQLYLWAPSSWLKENYTLPNSNEIIQWLLCLSSKVLCERDITARNKTNTMSESVSKAQYKGRRSLPEYELIASFLRRVRLHLVRKGLKWIQELHIYN |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 198 | Abolishes ubiquitin phosphorylation, but has no effect on autophosphorylation. | ||||
Sequence: Y → E | ||||||
Mutagenesis | 202-204 | Abolishes ubiquitin phosphorylation and displays reduced autophosphorylation. | ||||
Sequence: SNS → ANA | ||||||
Mutagenesis | 268 | Reduced phosphorylation of ubiquitin, but has no effect on autophosphorylation. | ||||
Sequence: P → L | ||||||
Mutagenesis | 281 | Abolishes ubiquitin phosphorylation and reduces autophosphorylation. | ||||
Sequence: G → D | ||||||
Mutagenesis | 282-283 | Abolishes ubiquitin phosphorylation and displays reduced autophosphorylation. | ||||
Sequence: RN → AA | ||||||
Mutagenesis | 357 | Loss of enzyme activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 379 | Reduced phosphorylation of ubiquitin, but has no effect on autophosphorylation. | ||||
Sequence: D → A | ||||||
Mutagenesis | 382 | Abolishes enzyme activity. Loss of ubiquitin phosphorylation and autophosphorylation. | ||||
Sequence: G → V |
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-51 | Mitochondrion | ||||
Sequence: MSLLAYTNLLLQNGRIFRYYKKANIKKFIKKIIKLDLKSTPSEASVSRQTF | ||||||
Chain | PRO_0000454927 | 52-575 | Serine/threonine-protein kinase Pink1, mitochondrial | |||
Sequence: LSTGLNSVKNAVQLQARKLLINNVLERVTPTLNSDLKKKAAKRLFYGDSAPFFALVGVSLASGSGLLTKDDELEGICWEIREAVSKGKWNDSESENVEQLQAANLDELDLGEPIAKGCNAVVYSAKLKNVQSNKLAHQLAVKMMFNYDVESNSTAILKAMYRETVPAMSYFFNQNLFNIENISDFKIRLPPHPNIVRMYSVFADRIPDLQCNKQLYPEALPPRINPEGSGRNMSLFLVMKRYDCTLKEYLRDKTPNMRSSILLLSQLLEAVAHMNIHNISHRDLKSDNILVDLSEGDAYPTIVITDFGCCLCDKQNGLVIPYRSEDQDKGGNRALMAPEIANAKPGTFSWLNYKKSDLWAVGAIAYEIFNIDNPFYDKTMKLLSKSYKEEDLPELPDTIPFIIRNLVSNMLSRSTNKRLDCDVAATVAQLYLWAPSSWLKENYTLPNSNEIIQWLLCLSSKVLCERDITARNKTNTMSESVSKAQYKGRRSLPEYELIASFLRRVRLHLVRKGLKWIQELHIYN | ||||||
Modified residue | 202 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 204 | Phosphoserine; by autocatalysis | ||||
Sequence: S | ||||||
Modified residue | 305 | Phosphothreonine; by autocatalysis | ||||
Sequence: T |
Post-translational modification
Proteolytically cleaved. In healthy cells, the precursor is continuously imported into mitochondria where it is proteolytically cleaved into its short form by the mitochondrial rhomboid protease rho-7 8231301. The short form is then released into the cytosol where it rapidly undergoes proteasome-dependent degradation. In unhealthy cells, when cellular stress conditions lead to the loss of mitochondrial membrane potential, mitochondrial import is impaired leading to the precursor accumulating on the outer mitochondrial membrane (OMM).
Autophosphorylated (PubMed:22645651, PubMed:29160309).
Autophosphorylated on Ser-202, which activates kinase activity (PubMed:29160309).
Loss of mitochondrial membrane potential results in the precursor accumulating on the outer mitochondrial membrane (OMM) where it is activated by autophosphorylation at Ser-202 (By similarity).
Autophosphorylation is sufficient and essential for selective recruitment of park to depolarized mitochondria, likely via Pink1-dependent phosphorylation of polyubiquitin chains (By similarity).
Also autophosphorylated at Ser-204 and Thr-305 (PubMed:29160309).
Autophosphorylated on Ser-202, which activates kinase activity (PubMed:29160309).
Loss of mitochondrial membrane potential results in the precursor accumulating on the outer mitochondrial membrane (OMM) where it is activated by autophosphorylation at Ser-202 (By similarity).
Autophosphorylation is sufficient and essential for selective recruitment of park to depolarized mitochondria, likely via Pink1-dependent phosphorylation of polyubiquitin chains (By similarity).
Also autophosphorylated at Ser-204 and Thr-305 (PubMed:29160309).
Keywords
- PTM
PTM databases
Interaction
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length575
- Mass (Da)65,446
- Last updated2010-11-02 v1
- Checksum6937F4BC747FF1BE
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AAZO01007021 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
DS235870 EMBL· GenBank· DDBJ | EEB19487.1 EMBL· GenBank· DDBJ | Genomic DNA |