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Protein

Serine/threonine-protein kinase PINK1, mitochondrial

Gene

PINK1

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

Functioni

Protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins. Involved in the clearance of damaged mitochondria via selective autophagy (mitophagy) by mediating activation and translocation of PARK2. Targets PARK2 to dysfunctional depolarized mitochondria through the phosphorylation of MFN2. Activates PARK2 in 2 steps: (1) by mediating phosphorylation at 'Ser-65' of PARK2 and (2) mediating phosphorylation of ubiquitin, converting PARK2 to its fully-active form (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291).14 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.3 Publications

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei186ATPPROSITE-ProRule annotation1
Active sitei362Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi162 – 170ATPPROSITE-ProRule annotationBy similarity9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • C3HC4-type RING finger domain binding Source: BHF-UCL
  • calcium-dependent protein kinase activity Source: BHF-UCL
  • kinase activity Source: ParkinsonsUK-UCL
  • magnesium ion binding Source: UniProtKB
  • peptidase activator activity Source: ParkinsonsUK-UCL
  • protease binding Source: ParkinsonsUK-UCL
  • protein kinase activity Source: ParkinsonsUK-UCL
  • protein kinase B binding Source: ParkinsonsUK-UCL
  • protein serine/threonine kinase activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • activation of protein kinase B activity Source: ParkinsonsUK-UCL
  • cellular response to hypoxia Source: ParkinsonsUK-UCL
  • cellular response to oxidative stress Source: ParkinsonsUK-UCL
  • cellular response to toxic substance Source: ParkinsonsUK-UCL
  • establishment of protein localization to mitochondrion Source: ParkinsonsUK-UCL
  • intracellular signal transduction Source: UniProtKB
  • macroautophagy Source: Reactome
  • maintenance of protein location in mitochondrion Source: ParkinsonsUK-UCL
  • mitochondrion organization Source: ParkinsonsUK-UCL
  • mitochondrion to lysosome transport Source: ParkinsonsUK-UCL
  • mitophagy Source: UniProtKB
  • mitophagy in response to mitochondrial depolarization Source: ParkinsonsUK-UCL
  • negative regulation of autophagosome assembly Source: ParkinsonsUK-UCL
  • negative regulation of gene expression Source: ParkinsonsUK-UCL
  • negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway Source: ParkinsonsUK-UCL
  • negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway Source: Ensembl
  • negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide Source: ParkinsonsUK-UCL
  • negative regulation of JNK cascade Source: ParkinsonsUK-UCL
  • negative regulation of macroautophagy Source: ParkinsonsUK-UCL
  • negative regulation of mitochondrial fission Source: ParkinsonsUK-UCL
  • negative regulation of mitophagy Source: ParkinsonsUK-UCL
  • negative regulation of neuron apoptotic process Source: ParkinsonsUK-UCL
  • negative regulation of oxidative stress-induced cell death Source: ParkinsonsUK-UCL
  • negative regulation of oxidative stress-induced neuron death Source: ParkinsonsUK-UCL
  • negative regulation of reactive oxygen species metabolic process Source: ParkinsonsUK-UCL
  • peptidyl-serine autophosphorylation Source: ParkinsonsUK-UCL
  • peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of ATP biosynthetic process Source: ParkinsonsUK-UCL
  • positive regulation of cristae formation Source: ParkinsonsUK-UCL
  • positive regulation of dopamine secretion Source: Ensembl
  • positive regulation of free ubiquitin chain polymerization Source: ParkinsonsUK-UCL
  • positive regulation of histone deacetylase activity Source: Ensembl
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCL
  • positive regulation of macroautophagy Source: ParkinsonsUK-UCL
  • positive regulation of mitochondrial electron transport, NADH to ubiquinone Source: ParkinsonsUK-UCL
  • positive regulation of mitochondrial fission Source: GO_Central
  • positive regulation of peptidase activity Source: ParkinsonsUK-UCL
  • positive regulation of peptidyl-serine phosphorylation Source: ParkinsonsUK-UCL
  • positive regulation of protein dephosphorylation Source: Ensembl
  • positive regulation of protein kinase B signaling Source: ParkinsonsUK-UCL
  • positive regulation of protein phosphorylation Source: AgBase
  • positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
  • positive regulation of protein ubiquitination Source: ParkinsonsUK-UCL
  • positive regulation of release of cytochrome c from mitochondria Source: BHF-UCL
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  • positive regulation of synaptic transmission, dopaminergic Source: Ensembl
  • positive regulation of translation Source: Ensembl
  • positive regulation of ubiquitin-protein transferase activity Source: ParkinsonsUK-UCL
  • protein phosphorylation Source: UniProtKB
  • protein stabilization Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • regulation of cellular response to oxidative stress Source: ParkinsonsUK-UCL
  • regulation of hydrogen peroxide metabolic process Source: Ensembl
  • regulation of mitochondrial membrane potential Source: ParkinsonsUK-UCL
  • regulation of mitochondrion organization Source: ParkinsonsUK-UCL
  • regulation of mitophagy Source: ParkinsonsUK-UCL
  • regulation of oxidative phosphorylation Source: ParkinsonsUK-UCL
  • regulation of proteasomal protein catabolic process Source: ParkinsonsUK-UCL
  • regulation of protein complex assembly Source: BHF-UCL
  • regulation of protein targeting to mitochondrion Source: AgBase
  • regulation of protein ubiquitination Source: BHF-UCL
  • regulation of reactive oxygen species metabolic process Source: ParkinsonsUK-UCL
  • regulation of synaptic vesicle transport Source: ParkinsonsUK-UCL
  • respiratory electron transport chain Source: Ensembl
  • response to oxidative stress Source: ParkinsonsUK-UCL
  • response to stress Source: UniProtKB
  • TORC2 signaling Source: ParkinsonsUK-UCL
  • ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Autophagy

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS08335-MONOMER.
ReactomeiR-HSA-5205685. Pink/Parkin Mediated Mitophagy.
SignaLinkiQ9BXM7.
SIGNORiQ9BXM7.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase PINK1, mitochondrial (EC:2.7.11.13 Publications)
Alternative name(s):
BRPK
PTEN-induced putative kinase protein 1
Gene namesi
Name:PINK1
OrganismiHomo sapiens (Human)Imported
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:14581. PINK1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini78 – 93Mitochondrial intermembraneSequence analysisAdd BLAST16
Transmembranei94 – 110HelicalSequence analysisAdd BLAST17
Topological domaini111 – 581CytoplasmicSequence analysisAdd BLAST471

GO - Cellular componenti

  • astrocyte projection Source: ParkinsonsUK-UCL
  • axon Source: ParkinsonsUK-UCL
  • cell body Source: ParkinsonsUK-UCL
  • chromatin Source: ParkinsonsUK-UCL
  • cytoplasm Source: ParkinsonsUK-UCL
  • cytoskeleton Source: ParkinsonsUK-UCL
  • cytosol Source: UniProtKB
  • integral component of mitochondrial outer membrane Source: ParkinsonsUK-UCL
  • Lewy body Source: ParkinsonsUK-UCL
  • membrane Source: ParkinsonsUK-UCL
  • mitochondrial inner membrane Source: ParkinsonsUK-UCL
  • mitochondrial intermembrane space Source: ParkinsonsUK-UCL
  • mitochondrial outer membrane Source: ParkinsonsUK-UCL
  • mitochondrion Source: UniProtKB
  • nucleus Source: ParkinsonsUK-UCL
  • perinuclear region of cytoplasm Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Involvement in diseasei

Parkinson disease 6 (PARK6)17 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by parkinsonian signs such as rigidity, resting tremor and bradykinesia. A subset of patients manifest additional symptoms including hyperreflexia, autonomic instability, dementia and psychiatric disturbances. Symptoms show diurnal fluctuation and can improve after sleep.
See also OMIM:605909
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04656892C → F in PARK6. 1 Publication1
Natural variantiVAR_062773125C → G in PARK6. 1 Publication1
Natural variantiVAR_064344126Q → P in PARK6; strongly reduces interaction with PARK2. 2 Publications1
Natural variantiVAR_046574147R → H in PARK6; unknown pathological significance. 1 PublicationCorresponds to variant rs138050841dbSNPEnsembl.1
Natural variantiVAR_046575168A → P in PARK6; has reduced autophosphorylation activity compared to wild-type; localizes to the mitochondria and immunogold experiments reveal that both wild-type and mutant proteins face the mitochondrial intermembrane space. 4 PublicationsCorresponds to variant rs768091663dbSNPEnsembl.1
Natural variantiVAR_046577196P → L in PARK6. 1 PublicationCorresponds to variant rs138302371dbSNPEnsembl.1
Natural variantiVAR_046578217A → D in PARK6. 1 PublicationCorresponds to variant rs74315360dbSNPEnsembl.1
Natural variantiVAR_046581240E → K in PARK6. 2 PublicationsCorresponds to variant rs573931674dbSNPEnsembl.1
Natural variantiVAR_046584268L → V in PARK6. 2 PublicationsCorresponds to variant rs372280083dbSNPEnsembl.1
Natural variantiVAR_046585271H → Q in PARK6. 1 PublicationCorresponds to variant rs28940284dbSNPEnsembl.1
Natural variantiVAR_046587279R → H in PARK6. 1 PublicationCorresponds to variant rs74315358dbSNPEnsembl.1
Natural variantiVAR_062774280A → T in PARK6; early-onset. 1 PublicationCorresponds to variant rs772510148dbSNPEnsembl.1
Natural variantiVAR_018994309G → D in PARK6; fails to maintain mitochondrial membrane potential; has reduced autophosphorylation activity compared to wild-type; strongly reduces interaction with PARK2; decreases PARK2 and SNCAIP ubiquitination and degradation. 4 PublicationsCorresponds to variant rs74315355dbSNPEnsembl.1
Natural variantiVAR_046589313T → M in PARK6; decreases PARK2 and SNCAIP ubiquitination and degradation. 2 PublicationsCorresponds to variant rs74315359dbSNPEnsembl.1
Natural variantiVAR_046593347L → P in PARK6; strongly reduces interaction with PARK2. 4 PublicationsCorresponds to variant rs28940285dbSNPEnsembl.1
Natural variantiVAR_062775369L → P in PARK6. 1 Publication1
Natural variantiVAR_062776386G → A in PARK6; abolishes kinase activity. 2 Publications1
Natural variantiVAR_046596388C → R in PARK6. 1 Publication1
Natural variantiVAR_062778407R → Q in PARK6; early-onset. 1 PublicationCorresponds to variant rs556540177dbSNPEnsembl.1
Natural variantiVAR_062779409G → V in PARK6. 1 Publication1
Natural variantiVAR_046599417E → G in PARK6. 1 Publication1
Natural variantiVAR_046605464R → H in PARK6. 1 PublicationCorresponds to variant rs764328076dbSNPEnsembl.1
Natural variantiVAR_046607489L → P in PARK6. 1 Publication1
Natural variantiVAR_046610534Q → QQ in PARK6. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi219K → A: Abolishes MFN2 phosphorylation and interaction with PARK2; when associated with ALA-362 and ALA-384. 1 Publication1
Mutagenesisi362D → A: Abolishes MFN2 phosphorylation and interaction with PARK2; when associated with ALA-219 and ALA-384. 1 Publication1
Mutagenesisi384D → A: Abolishes MFN2 phosphorylation and interaction with PARK2; when associated with ALA-219 and ALA-362. 1 Publication1

Keywords - Diseasei

Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

DisGeNETi65018.
MalaCardsiPINK1.
MIMi168600. phenotype.
605909. phenotype.
OpenTargetsiENSG00000158828.
Orphaneti2828. Young adult-onset Parkinsonism.
PharmGKBiPA33325.

Chemistry databases

ChEMBLiCHEMBL3337330.

Polymorphism and mutation databases

BioMutaiPINK1.
DMDMi48428484.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 77MitochondrionSequence analysisAdd BLAST77
ChainiPRO_000002436978 – 581Serine/threonine-protein kinase PINK1, mitochondrialAdd BLAST504

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei228Phosphoserine; by autocatalysis1 Publication1
Modified residuei402Phosphoserine; by autocatalysis1 Publication1

Post-translational modificationi

Autophosphorylation at Ser-228 and Ser-402 is essential for Parkin/PARK2 recruitment to depolarized mitochondria.1 Publication
Two shorter forms of 55 kDa and 48 kDa seem to be produced by proteolytic cleavage and localize mainly in cytosol.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9BXM7.
PaxDbiQ9BXM7.
PeptideAtlasiQ9BXM7.
PRIDEiQ9BXM7.

PTM databases

iPTMnetiQ9BXM7.
PhosphoSitePlusiQ9BXM7.

Expressioni

Tissue specificityi

Highly expressed in heart, skeletal muscle and testis, and at lower levels in brain, placenta, liver, kidney, pancreas, prostate, ovary and small intestine. Present in the embryonic testis from an early stage of development.1 Publication

Gene expression databases

BgeeiENSG00000158828.
CleanExiHS_PINK1.
GenevisibleiQ9BXM7. HS.

Organism-specific databases

HPAiCAB026191.
HPA001931.

Interactioni

Subunit structurei

Interacts with PARK2. Interacts with FBXO7. Forms a complex with PARK2 and PARK7 (PubMed:19229105).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EEDO755306EBI-2846068,EBI-923794
FBXO7Q9Y3I18EBI-2846068,EBI-1161222
FBXO7Q9Y3I1-12EBI-2846068,EBI-9102965
MAP1LC3BQ9GZQ83EBI-2846068,EBI-373144
PARK2O602607EBI-2846068,EBI-716346
RHOT1Q8IXI23EBI-2846068,EBI-1396430
SOCS4Q8WXH53EBI-2846068,EBI-3942425

GO - Molecular functioni

  • C3HC4-type RING finger domain binding Source: BHF-UCL
  • protease binding Source: ParkinsonsUK-UCL
  • protein kinase B binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi122376. 61 interactors.
DIPiDIP-29427N.
IntActiQ9BXM7. 15 interactors.
MINTiMINT-6781189.
STRINGi9606.ENSP00000364204.

Structurei

3D structure databases

ProteinModelPortaliQ9BXM7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini156 – 511Protein kinasePROSITE-ProRule annotationCuratedAdd BLAST356

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4158. Eukaryota.
ENOG410YE6P. LUCA.
GeneTreeiENSGT00390000001206.
HOGENOMiHOG000231649.
HOVERGENiHBG053601.
InParanoidiQ9BXM7.
KOiK05688.
OMAiGPKQLAP.
OrthoDBiEOG091G03V6.
PhylomeDBiQ9BXM7.
TreeFamiTF313183.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 11 Publication (identifier: Q9BXM7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAVRQALGRG LQLGRALLLR FTGKPGRAYG LGRPGPAAGC VRGERPGWAA
60 70 80 90 100
GPGAEPRRVG LGLPNRLRFF RQSVAGLAAR LQRQFVVRAW GCAGPCGRAV
110 120 130 140 150
FLAFGLGLGL IEEKQAESRR AVSACQEIQA IFTQKSKPGP DPLDTRRLQG
160 170 180 190 200
FRLEEYLIGQ SIGKGCSAAV YEATMPTLPQ NLEVTKSTGL LPGRGPGTSA
210 220 230 240 250
PGEGQERAPG APAFPLAIKM MWNISAGSSS EAILNTMSQE LVPASRVALA
260 270 280 290 300
GEYGAVTYRK SKRGPKQLAP HPNIIRVLRA FTSSVPLLPG ALVDYPDVLP
310 320 330 340 350
SRLHPEGLGH GRTLFLVMKN YPCTLRQYLC VNTPSPRLAA MMLLQLLEGV
360 370 380 390 400
DHLVQQGIAH RDLKSDNILV ELDPDGCPWL VIADFGCCLA DESIGLQLPF
410 420 430 440 450
SSWYVDRGGN GCLMAPEVST ARPGPRAVID YSKADAWAVG AIAYEIFGLV
460 470 480 490 500
NPFYGQGKAH LESRSYQEAQ LPALPESVPP DVRQLVRALL QREASKRPSA
510 520 530 540 550
RVAANVLHLS LWGEHILALK NLKLDKMVGW LLQQSAATLL ANRLTEKCCV
560 570 580
ETKMKMLFLA NLECETLCQA ALLLCSWRAA L
Length:581
Mass (Da):62,769
Last modified:June 1, 2001 - v1
Checksum:i721FE01F63263A64
GO
Isoform 2Curated (identifier: Q9BXM7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-307: Missing.
     308-320: LGHGRTLFLVMKN → MCGSQRPSPLSTS

Note: No experimental confirmation available.Curated
Show »
Length:274
Mass (Da):30,104
Checksum:iC54C628F879B4BED
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti209P → A in AAH28215 (PubMed:15489334).Curated1
Sequence conflicti419S → P in BAC11484 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04656667L → F.1 PublicationCorresponds to variant rs763142730dbSNPEnsembl.1
Natural variantiVAR_04656768R → P.1 Publication1
Natural variantiVAR_04656892C → F in PARK6. 1 Publication1
Natural variantiVAR_04656998R → W.1 PublicationCorresponds to variant rs575668171dbSNPEnsembl.1
Natural variantiVAR_046570111I → S.1 Publication1
Natural variantiVAR_046571115Q → L.2 PublicationsCorresponds to variant rs148871409dbSNPEnsembl.1
Natural variantiVAR_046572124A → V.1 Publication1
Natural variantiVAR_062773125C → G in PARK6. 1 Publication1
Natural variantiVAR_064344126Q → P in PARK6; strongly reduces interaction with PARK2. 2 Publications1
Natural variantiVAR_046573145T → M.1 PublicationCorresponds to variant rs45604240dbSNPEnsembl.1
Natural variantiVAR_046574147R → H in PARK6; unknown pathological significance. 1 PublicationCorresponds to variant rs138050841dbSNPEnsembl.1
Natural variantiVAR_041010148L → W.1 PublicationCorresponds to variant rs56297806dbSNPEnsembl.1
Natural variantiVAR_046575168A → P in PARK6; has reduced autophosphorylation activity compared to wild-type; localizes to the mitochondria and immunogold experiments reveal that both wild-type and mutant proteins face the mitochondrial intermembrane space. 4 PublicationsCorresponds to variant rs768091663dbSNPEnsembl.1
Natural variantiVAR_046576186K → N.1 PublicationCorresponds to variant rs143204084dbSNPEnsembl.1
Natural variantiVAR_046577196P → L in PARK6. 1 PublicationCorresponds to variant rs138302371dbSNPEnsembl.1
Natural variantiVAR_041011196P → S.1 PublicationCorresponds to variant rs35802484dbSNPEnsembl.1
Natural variantiVAR_041012209P → L.1 PublicationCorresponds to variant rs34677717dbSNPEnsembl.1
Natural variantiVAR_041013215P → L in a glioblastoma multiforme sample; somatic mutation. 1 PublicationCorresponds to variant rs371854396dbSNPEnsembl.1
Natural variantiVAR_046578217A → D in PARK6. 1 PublicationCorresponds to variant rs74315360dbSNPEnsembl.1
Natural variantiVAR_046579231E → G.1 Publication1
Natural variantiVAR_046580235N → I.1 Publication1
Natural variantiVAR_046581240E → K in PARK6. 2 PublicationsCorresponds to variant rs573931674dbSNPEnsembl.1
Natural variantiVAR_046582257T → I.Corresponds to variant rs370906995dbSNPEnsembl.1
Natural variantiVAR_046583263R → G.1 Publication1
Natural variantiVAR_046584268L → V in PARK6. 2 PublicationsCorresponds to variant rs372280083dbSNPEnsembl.1
Natural variantiVAR_046585271H → Q in PARK6. 1 PublicationCorresponds to variant rs28940284dbSNPEnsembl.1
Natural variantiVAR_046586276R → Q.1 PublicationCorresponds to variant rs548506734dbSNPEnsembl.1
Natural variantiVAR_046587279R → H in PARK6. 1 PublicationCorresponds to variant rs74315358dbSNPEnsembl.1
Natural variantiVAR_062774280A → T in PARK6; early-onset. 1 PublicationCorresponds to variant rs772510148dbSNPEnsembl.1
Natural variantiVAR_046588296P → L.2 PublicationsCorresponds to variant rs779060308dbSNPEnsembl.1
Natural variantiVAR_018993305P → L.Corresponds to variant rs7349186dbSNPEnsembl.1
Natural variantiVAR_018994309G → D in PARK6; fails to maintain mitochondrial membrane potential; has reduced autophosphorylation activity compared to wild-type; strongly reduces interaction with PARK2; decreases PARK2 and SNCAIP ubiquitination and degradation. 4 PublicationsCorresponds to variant rs74315355dbSNPEnsembl.1
Natural variantiVAR_046589313T → M in PARK6; decreases PARK2 and SNCAIP ubiquitination and degradation. 2 PublicationsCorresponds to variant rs74315359dbSNPEnsembl.1
Natural variantiVAR_046590317V → I.2 PublicationsCorresponds to variant rs200949139dbSNPEnsembl.1
Natural variantiVAR_046591318M → L.1 PublicationCorresponds to variant rs139226733dbSNPEnsembl.1
Natural variantiVAR_046592322P → L.1 PublicationCorresponds to variant rs768019187dbSNPEnsembl.1
Natural variantiVAR_041014339A → T.4 PublicationsCorresponds to variant rs55831733dbSNPEnsembl.1
Natural variantiVAR_018995340A → T.7 PublicationsCorresponds to variant rs3738136dbSNPEnsembl.1
Natural variantiVAR_041015341M → I.1 PublicationCorresponds to variant rs35813094dbSNPEnsembl.1
Natural variantiVAR_046593347L → P in PARK6; strongly reduces interaction with PARK2. 4 PublicationsCorresponds to variant rs28940285dbSNPEnsembl.1
Natural variantiVAR_046594362D → H.1 Publication1
Natural variantiVAR_062775369L → P in PARK6. 1 Publication1
Natural variantiVAR_041016377C → F.1 PublicationCorresponds to variant rs34203620dbSNPEnsembl.1
Natural variantiVAR_046595383A → T.2 PublicationsCorresponds to variant rs45515602dbSNPEnsembl.1
Natural variantiVAR_062776386G → A in PARK6; abolishes kinase activity. 2 Publications1
Natural variantiVAR_046596388C → R in PARK6. 1 Publication1
Natural variantiVAR_046597395G → V.1 Publication1
Natural variantiVAR_062777399P → L Probable disease-associated mutation found in early-onset Parkinson disease with digenic inheritance; associated with Ser-39 mutation in PARK7 gene; decreases PARK2 and SNCAIP ubiquitination and degradation. 2 PublicationsCorresponds to variant rs119451946dbSNPEnsembl.1
Natural variantiVAR_062778407R → Q in PARK6; early-onset. 1 PublicationCorresponds to variant rs556540177dbSNPEnsembl.1
Natural variantiVAR_062779409G → V in PARK6. 1 Publication1
Natural variantiVAR_046598411G → S.1 PublicationCorresponds to variant rs45478900dbSNPEnsembl.1
Natural variantiVAR_046599417E → G in PARK6. 1 Publication1
Natural variantiVAR_046600425P → S.1 PublicationCorresponds to variant rs554114655dbSNPEnsembl.1
Natural variantiVAR_046601431Y → H May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 PublicationCorresponds to variant rs74315361dbSNPEnsembl.1
Natural variantiVAR_046602442I → T.2 Publications1
Natural variantiVAR_046603451N → S May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 PublicationCorresponds to variant rs747400197dbSNPEnsembl.1
Natural variantiVAR_046604461L → S.1 Publication1
Natural variantiVAR_046605464R → H in PARK6. 1 PublicationCorresponds to variant rs764328076dbSNPEnsembl.1
Natural variantiVAR_046606476E → K May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 5 PublicationsCorresponds to variant rs115477764dbSNPEnsembl.1
Natural variantiVAR_041017477S → T.1 PublicationCorresponds to variant rs34416410dbSNPEnsembl.1
Natural variantiVAR_046607489L → P in PARK6. 1 Publication1
Natural variantiVAR_046608501R → P May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 Publication1
Natural variantiVAR_018996521N → T.7 PublicationsCorresponds to variant rs1043424dbSNPEnsembl.1
Natural variantiVAR_046609525D → N.2 PublicationsCorresponds to variant rs531477772dbSNPEnsembl.1
Natural variantiVAR_046610534Q → QQ in PARK6. 1 Publication1
Natural variantiVAR_046611537A → T.1 PublicationCorresponds to variant rs771032673dbSNPEnsembl.1
Natural variantiVAR_046612575C → R May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0507541 – 307Missing in isoform 2. 1 PublicationAdd BLAST307
Alternative sequenceiVSP_050755308 – 320LGHGR…LVMKN → MCGSQRPSPLSTS in isoform 2. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB053323 mRNA. Translation: BAB55647.1.
AF316873 mRNA. Translation: AAK28062.1.
AK075225 mRNA. Translation: BAC11484.1.
AL391357 Genomic DNA. Translation: CAH73475.1.
BC009534 mRNA. Translation: AAH09534.1.
BC028215 mRNA. Translation: AAH28215.1.
CCDSiCCDS211.1. [Q9BXM7-1]
RefSeqiNP_115785.1. NM_032409.2. [Q9BXM7-1]
UniGeneiHs.389171.

Genome annotation databases

EnsembliENST00000321556; ENSP00000364204; ENSG00000158828. [Q9BXM7-1]
GeneIDi65018.
KEGGihsa:65018.
UCSCiuc001bdm.3. human. [Q9BXM7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB053323 mRNA. Translation: BAB55647.1.
AF316873 mRNA. Translation: AAK28062.1.
AK075225 mRNA. Translation: BAC11484.1.
AL391357 Genomic DNA. Translation: CAH73475.1.
BC009534 mRNA. Translation: AAH09534.1.
BC028215 mRNA. Translation: AAH28215.1.
CCDSiCCDS211.1. [Q9BXM7-1]
RefSeqiNP_115785.1. NM_032409.2. [Q9BXM7-1]
UniGeneiHs.389171.

3D structure databases

ProteinModelPortaliQ9BXM7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122376. 61 interactors.
DIPiDIP-29427N.
IntActiQ9BXM7. 15 interactors.
MINTiMINT-6781189.
STRINGi9606.ENSP00000364204.

Chemistry databases

ChEMBLiCHEMBL3337330.

PTM databases

iPTMnetiQ9BXM7.
PhosphoSitePlusiQ9BXM7.

Polymorphism and mutation databases

BioMutaiPINK1.
DMDMi48428484.

Proteomic databases

EPDiQ9BXM7.
PaxDbiQ9BXM7.
PeptideAtlasiQ9BXM7.
PRIDEiQ9BXM7.

Protocols and materials databases

DNASUi65018.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321556; ENSP00000364204; ENSG00000158828. [Q9BXM7-1]
GeneIDi65018.
KEGGihsa:65018.
UCSCiuc001bdm.3. human. [Q9BXM7-1]

Organism-specific databases

CTDi65018.
DisGeNETi65018.
GeneCardsiPINK1.
GeneReviewsiPINK1.
HGNCiHGNC:14581. PINK1.
HPAiCAB026191.
HPA001931.
MalaCardsiPINK1.
MIMi168600. phenotype.
605909. phenotype.
608309. gene.
neXtProtiNX_Q9BXM7.
OpenTargetsiENSG00000158828.
Orphaneti2828. Young adult-onset Parkinsonism.
PharmGKBiPA33325.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4158. Eukaryota.
ENOG410YE6P. LUCA.
GeneTreeiENSGT00390000001206.
HOGENOMiHOG000231649.
HOVERGENiHBG053601.
InParanoidiQ9BXM7.
KOiK05688.
OMAiGPKQLAP.
OrthoDBiEOG091G03V6.
PhylomeDBiQ9BXM7.
TreeFamiTF313183.

Enzyme and pathway databases

BioCyciZFISH:HS08335-MONOMER.
ReactomeiR-HSA-5205685. Pink/Parkin Mediated Mitophagy.
SignaLinkiQ9BXM7.
SIGNORiQ9BXM7.

Miscellaneous databases

ChiTaRSiPINK1. human.
GeneWikiiPINK1.
GenomeRNAii65018.
PROiQ9BXM7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000158828.
CleanExiHS_PINK1.
GenevisibleiQ9BXM7. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPINK1_HUMAN
AccessioniPrimary (citable) accession number: Q9BXM7
Secondary accession number(s): Q8N6T9, Q8NBU3, Q96DE4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 1, 2001
Last modified: November 30, 2016
This is version 155 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. 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.