Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
Symbol PINK1 contributors: shn - updated : 26-02-2016
HGNC name PTEN induced putative kinase 1
HGNC id 14581
Corresponding disease
PARK6 Parkinson disease 6
Location 1p36.12      Physical location : 20.959.947 - 20.978.003
Synonym name
  • protein kinase BRPK
  • serine/threonine-protein kinase PINK1, mitochondrial
  • Parkinson disease (autosomal recessive) 6
  • Synonym symbol(s) BRPK, FLJ27236, PARK6
    TYPE functioning gene
    STRUCTURE 18.06 kb     8 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D1S2732 - D1S3720 - PINK1 - D1S478 - D1S334 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 2680 66 581 mitochondrial 2008 18003639
  • A full-length pre-protein (66 kDa) and an N-terminally truncated mature form (55 kDa) have been described in human brain
  • full-length precursor protein has weak intrinsic kinase activity
  • accumulation of FL-PINK1 might have a dominant negative effect on PINK1 protein function
  • - - - 53 - - 2011 21138942
  • PINK1 is cleaved between Ala-103 and Phe-104 to generate the 53 kDa deltaN-PINK1 protein, and PARL is responsible for PINK1 cleavage at position A103
  • deltaN-PINK1 product is the functionally active form of the protein conferring cell protection against stress
    Rna function highest expressed in hippocampus, substantia nigra, cerebellar purkinge cells
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   highly
    Endocrinepancreas   highly
    Nervousbrain   highly
    Reproductivemale systemtestis  highly
    Urinarykidney   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cell lineage
    cell lines
    at STAGE
  • a N-terminal mitochondrial signal
  • a conserved kinase domain
  • a C-terminal domain that regulates autophosphorylation activity
    interspecies ortholog to Pink1, Mus musculus
    ortholog to Pink1, Rattus norvegicus
    ortholog to pink1, Danio rerio
    ortholog to PINK1, Pan troglodytes
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
  • precursor form of PINK1 translocates to the mitochondria and is processed into two cleaved forms of PINK1, which in turn localize more to the cytosolic than mitochondrial fraction
  • cytosolic and mitochondrially localized
  • with BECN1, localize to the mitochondrial compartment
  • localize to mitochondria, and upon entry into the organelle, is cleaved to produce a 53 kDa protein (deltaN-PINK1)
  • basic FUNCTION
  • acts with Parkin in a common pathway in maintaining mitochondrial integrity and function in both muscles and dopaminergic neurons
  • plays an essential role in maintaining neuronal survival by preventing neurons from undergoing oxidative stress
  • a possible regulatory role for the PINK1/Parkin pathway in mitochondrial fission
  • important for mitochondrial function and provides critical protection against both intrinsic and environmental stress
  • regulates calcium efflux from the mitochondria via the mitochondrial Na(+)/Ca(2+) exchanger
  • functional links between PINK1, Parkin and the selective autophagy of mitochondria
  • with PARK2 are intimately involved in preventing mitochondrial dysfunction
  • promotes proteasomal degradation of PARK2
  • PINK1 and HSPA9 accumulated in different cellular compartments, and these two proteins share, at least partially, the same pathway of mitochondrial import
  • PINK1 and HSPA9 are synthesized as a precursor protein which is cleaved into its mature form after import into mitochondria in a mitochondrial membrane potential-dependent manner
  • required for the recruitment of parkin to depolarize mitochondria prior to selective clearance of the functionally inactive organelles by autophagy
  • PINK1 and PARK2 are thus required for the removal of damaged mitochondria in dopaminergic cells, and inhibition of this pathway may lead to the accumulation of defective mitochondria which may contribute to Parkinson disease pathogenesis
  • restoration of autophagy in PINK1-silenced cells by PARK2 reverses ATP synthesis inhibition and the ubiquitination of MFN1 and MFN2 play a role in PINK1/PARK2-mediated mitophagy
  • PARK7 works in parallel to the PINK1/parkin pathway to maintain mitochondrial function in the presence of an oxidative environment
  • differential localization to the inner and outer mitochondrial membranes appears to regulate PINK1 stability and function
  • exerts its cytoprotective function not only in mitochondria but also in the cytoplasm through activation of CRTC2
  • key role for PINK1 in the regulation of mitochondrial homeostasis and energy metabolism under physiological conditions
  • PINK1 activity is crucial for postnatal myocardial development, through its role in maintaining mitochondrial function, and redox homeostasis in cardiomyocytes
  • crucial in the maintenance of mitochondrial function and redox homeostasis in cardiomyocytes
  • regulates histone methylation and gene expression through the polycomb repressor complex
  • importance of PINK1 as a mitochondrial protein functioning to regulate the complex interplay between mitochondrial function, ROS production, and hypertrophic signaling in the heart
  • because PINK1 acts via PARK2 in arresting mitochondria, PINK1 was predicted to require PARK2 to promote RHOT1, RHOT2 degradation
  • PRKN and PINK1 are regulated by neddylation and impaired NEDD8 modification of these proteins likely contributes to Parkinson disease pathogenesis
  • PINK1 is imported into mitochondria by a unique pathway that is independent of the TOM core complex but crucially depends on the import receptor TOMM70A
  • accumulates on depolarized mitochondria, where it recruits PARK2 to mainly induce K63-linked chain ubiquitination of outer membrane proteins and eventually mitophagy
  • its function is related to mitochondria homeostasis (
  • could regulate the subcellular localization, phosphorylation, and stability of EED/WAIT1
  • acts as an upstream factor for PARK2 and is essential both for the activation of latent E3 PARK2 activity and for recruiting PARK2 onto depolarized mitochondria
  • PINK1 and PARK2, mediate local mitophagy of dysfunctional mitochondria in neuronal axons
  • is pivotal to maintain mitochondrial homeostasis in neural cells
    PHYSIOLOGICAL PROCESS mitochondrial transport
  • PINK1/Parkin pathway plays conserved roles in regulating neuronal mitochondrial dynamics and function
  • role of PARL-PINK1-PRKN pathway in adipocyte differentiation
  • by preventing mitochondrial movement, the PINK1/PARK2 pathway may quarantine damaged mitochondria prior to their clearance
  • TOMM machinery is a key molecular switch in the mitochondrial clearance program controlled by the PINK1-PARK2 pathway
  • PINK1-PARK2-mediated pathway is required for local mitophagy in distal axons in response to focal damage
  • a component
    small molecule
  • interaction between PINK1 and Mitofilin
  • regulates the E3 ubiquitin-protein ligase function of parkin through direct phosphorylation
  • interacts with the mitochondrial protease presenilin-associated rhomboid-like protein (PARL) and loss of PARL results in aberrant PINK1 cleavage in mammalian cells
  • normal PINK1 localization and stability requires PARL catalytic activity
  • PARL cleaves PINK1, which is implicated in Parkinson disease, within its conserved membrane anchor, to regulate PINK1 trafficking
  • phosphorylates Miro (RHOT1 and RHOT2), a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface
  • PRKN and PINK1 are NEDD8 conjugated
  • new role for PMPCB in PINK1 import and mitochondrial quality control via the PINK1–Parkin pathway
  • PINK1 autophosphorylation upon membrane potential dissipation is essential for PARK2 recruitment to damaged mitochondria
  • PARL mediates likely differential cleavage of PINK1 and PGAM5 depending on the health status of mitochondria
  • association of PINK1 with SARM1 and TRAF6 is an important step for mitophagy
  • TOMM70A is essential for PINK1 import
  • PINK1 associated with EED/WAIT1 in cells and relocated EED/WAIT1 to the mitochondria
  • functional cooperation at specific cell compartments between PINK1 and PRC2 may be relevant for the control of cell-death programs not only in neurons, but also in other cell types, with possible implications in oncogenesis
  • interaction of cytosolic PINK1 with PARK2 represses PARK2 translocation to the mitochondria and subsequent mitophagy
  • PINK1-dependent phosphorylation of both PARK2 and ubiquitin is sufficient for full activation of parkin E3 activity
  • PINK1 accumulation leads to PARK2 recruitment from the cytosol, which in turn promotes the degradation of the damaged mitochondria by autophagy (mitophagy)
  • different mitophagy effectors, including the mitophagy receptors BNIP3L, BNIP3 and FUNDC1 and the PINK1/Parkin pathway, have been identified to participate in the selective clearance of mitochondria
  • PGAM5 is indispensable for the process of PINK1 dependent mitophagy which antagonizes necroptosis
  • IMMT transiently interacts with PINK1, and IMMT downregulation leads to a reduction in PINK1 and mislocalization of PRKN
  • PGAM5 regulates PINK1-PRKN-mediated mitophagy, which can exert a neuroprotective effect against carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced apoptosis
  • cell & other
    induced by PTEN
    by FOXO3a is crucial for survival signals in lymphocytes, as depletion of PINK1 sensitizes these cells to death induced by deprivation of an essential growth factor
    corresponding disease(s) PARK6
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in ovarian tumor
    constitutional       loss of function
    elicits oxidative stress and mitochondrial turnover coordinated by the autophagic and fission/fusion machineries
    constitutional     --low  
    depletion of PINK1 induces moderate fragmentation of the mitochondrial network, mitochondrial membrane depolarization and increased production of reactive oxygen species
    constitutional     --low  
    markedly reduced in end-stage heart failure
    constitutional     --low  
    impairs mitochondrial fission, which causes defective assembly of the electron transport chain complexes, leading to abnormal bioenergetics
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • Drosophila with loss-of-function of PINK1 gene exhibit indirect flight muscle and dopaminergic neuronal degeneration accompanied by locomotive defects
  • removal of Drosophila PINK1 results in male sterility, apoptotic muscle degeneration, defects in mitochondrial morphology and increased sensitivity to multiple stresses including oxidative stress
  • inhibition of Drosophila Pink1 function results in energy depletion, shortened lifespan, and degeneration of select indirect flight muscles and dopaminergic neurons
  • inactivation of Drosophila PINK1 using RNAi results in progressive loss of dopaminergic neurons and in ommatidial degeneration of the compound eye
  • deletion of PINK1 gene in mice significantly impairs mitochondrial functions associated with impairment of mitochondrial respiration in the striatum and dopaminergic circuitry defects
  • transgenic expression of Parkin markedly ameliorated all PINK1 loss-of-function phenotypes in Drosophila PINK1 model
  • expression of human SOD1 suppresses neurodegeneration induced by drosophilia PINK1 inactivation
  • mdivi-1 (mitochondrial division inhibitor 1), a quinazolinone, rescue mitochondrial morphological and functional defects induced by mutations in PINK1
  • PINK1-/- mice have greater levels of oxidative stress and impaired mitochondrial function