E0W1I1 · PINK1_PEDHC

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).

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Note: Binds 2 Mg2+ ions per subunit.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site193ATP (UniProtKB | ChEBI)
Binding site214Mg2+ 1 (UniProtKB | ChEBI)
Active site334Proton acceptor
Binding site339Mg2+ 2 (UniProtKB | ChEBI)
Binding site357Mg2+ 1 (UniProtKB | ChEBI)
Binding site357Mg2+ 2 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytosol
Cellular Componentmitochondrial inner membrane
Cellular Componentmitochondrial outer membrane
Molecular FunctionATP binding
Molecular Functionmetal ion binding
Molecular Functionprotein kinase activity
Molecular Functionprotein serine/threonine kinase activity
Biological Processautophagy of mitochondrion
Biological Processpositive regulation of mitochondrial fission
Biological Processregulation of apoptotic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Serine/threonine-protein kinase Pink1, mitochondrial
  • EC number
  • Alternative names
    • PTEN-induced putative kinase 1

Gene names

    • Name
      Pink1
    • ORF names
      Phum_PHUM577390

Organism names

  • Taxonomic identifier
  • Strain
    • USDA
  • Taxonomic lineage
    Eukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Paraneoptera > Psocodea > Phthiraptera > Anoplura > Pediculidae > Pediculus

Accessions

  • Primary accession
    E0W1I1

Proteomes

Organism-specific databases

Subcellular Location

Mitochondrion outer membrane
; Single-pass membrane protein
Mitochondrion inner membrane
; Single-pass membrane protein
Cytoplasm, cytosol
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).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain52-94Mitochondrial intermembrane
Transmembrane95-118Helical
Topological domain119-575Cytoplasmic

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis198Abolishes ubiquitin phosphorylation, but has no effect on autophosphorylation.
Mutagenesis202-204Abolishes ubiquitin phosphorylation and displays reduced autophosphorylation.
Mutagenesis268Reduced phosphorylation of ubiquitin, but has no effect on autophosphorylation.
Mutagenesis281Abolishes ubiquitin phosphorylation and reduces autophosphorylation.
Mutagenesis282-283Abolishes ubiquitin phosphorylation and displays reduced autophosphorylation.
Mutagenesis357Loss of enzyme activity.
Mutagenesis379Reduced phosphorylation of ubiquitin, but has no effect on autophosphorylation.
Mutagenesis382Abolishes enzyme activity. Loss of ubiquitin phosphorylation and autophosphorylation.

PTM/Processing

Features

Showing features for transit peptide, chain, modified residue.

TypeIDPosition(s)Description
Transit peptide1-51Mitochondrion
ChainPRO_000045492752-575Serine/threonine-protein kinase Pink1, mitochondrial
Modified residue202Phosphoserine; by autocatalysis
Modified residue204Phosphoserine; by autocatalysis
Modified residue305Phosphothreonine; by autocatalysis

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).

Keywords

PTM databases

Interaction

Protein-protein interaction databases

Family & Domains

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    575
  • Mass (Da)
    65,446
  • Last updated
    2010-11-02 v1
  • Checksum
    6937F4BC747FF1BE
MSLLAYTNLLLQNGRIFRYYKKANIKKFIKKIIKLDLKSTPSEASVSRQTFLSTGLNSVKNAVQLQARKLLINNVLERVTPTLNSDLKKKAAKRLFYGDSAPFFALVGVSLASGSGLLTKDDELEGICWEIREAVSKGKWNDSESENVEQLQAANLDELDLGEPIAKGCNAVVYSAKLKNVQSNKLAHQLAVKMMFNYDVESNSTAILKAMYRETVPAMSYFFNQNLFNIENISDFKIRLPPHPNIVRMYSVFADRIPDLQCNKQLYPEALPPRINPEGSGRNMSLFLVMKRYDCTLKEYLRDKTPNMRSSILLLSQLLEAVAHMNIHNISHRDLKSDNILVDLSEGDAYPTIVITDFGCCLCDKQNGLVIPYRSEDQDKGGNRALMAPEIANAKPGTFSWLNYKKSDLWAVGAIAYEIFNIDNPFYDKTMKLLSKSYKEEDLPELPDTIPFIIRNLVSNMLSRSTNKRLDCDVAATVAQLYLWAPSSWLKENYTLPNSNEIIQWLLCLSSKVLCERDITARNKTNTMSESVSKAQYKGRRSLPEYELIASFLRRVRLHLVRKGLKWIQELHIYN

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AAZO01007021
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
DS235870
EMBL· GenBank· DDBJ
EEB19487.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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