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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei186 – 1861ATPPROSITE-ProRule annotation
Active sitei362 – 3621Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi162 – 1709ATPPROSITE-ProRule annotationBy similarity

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
  • 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 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 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

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini78 – 9316Mitochondrial intermembraneSequence analysisAdd
BLAST
Transmembranei94 – 11017HelicalSequence analysisAdd
BLAST
Topological domaini111 – 581471CytoplasmicSequence analysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti92 – 921C → F in PARK6. 1 Publication
VAR_046568
Natural varianti125 – 1251C → G in PARK6. 1 Publication
VAR_062773
Natural varianti126 – 1261Q → P in PARK6; strongly reduces interaction with PARK2. 2 Publications
VAR_064344
Natural varianti147 – 1471R → H in PARK6; unknown pathological significance. 1 Publication
Corresponds to variant rs138050841 [ dbSNP | Ensembl ].
VAR_046574
Natural varianti168 – 1681A → 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 Publications
Corresponds to variant rs768091663 [ dbSNP | Ensembl ].
VAR_046575
Natural varianti196 – 1961P → L in PARK6. 1 Publication
Corresponds to variant rs138302371 [ dbSNP | Ensembl ].
VAR_046577
Natural varianti217 – 2171A → D in PARK6. 1 Publication
Corresponds to variant rs74315360 [ dbSNP | Ensembl ].
VAR_046578
Natural varianti240 – 2401E → K in PARK6. 2 Publications
Corresponds to variant rs573931674 [ dbSNP | Ensembl ].
VAR_046581
Natural varianti268 – 2681L → V in PARK6. 2 Publications
Corresponds to variant rs372280083 [ dbSNP | Ensembl ].
VAR_046584
Natural varianti271 – 2711H → Q in PARK6. 1 Publication
Corresponds to variant rs28940284 [ dbSNP | Ensembl ].
VAR_046585
Natural varianti279 – 2791R → H in PARK6. 1 Publication
Corresponds to variant rs74315358 [ dbSNP | Ensembl ].
VAR_046587
Natural varianti280 – 2801A → T in PARK6; early-onset. 1 Publication
Corresponds to variant rs772510148 [ dbSNP | Ensembl ].
VAR_062774
Natural varianti309 – 3091G → 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 Publications
Corresponds to variant rs74315355 [ dbSNP | Ensembl ].
VAR_018994
Natural varianti313 – 3131T → M in PARK6; decreases PARK2 and SNCAIP ubiquitination and degradation. 2 Publications
Corresponds to variant rs74315359 [ dbSNP | Ensembl ].
VAR_046589
Natural varianti347 – 3471L → P in PARK6; strongly reduces interaction with PARK2. 4 Publications
Corresponds to variant rs28940285 [ dbSNP | Ensembl ].
VAR_046593
Natural varianti369 – 3691L → P in PARK6. 1 Publication
VAR_062775
Natural varianti386 – 3861G → A in PARK6; abolishes kinase activity. 2 Publications
VAR_062776
Natural varianti388 – 3881C → R in PARK6. 1 Publication
VAR_046596
Natural varianti407 – 4071R → Q in PARK6; early-onset. 1 Publication
Corresponds to variant rs556540177 [ dbSNP | Ensembl ].
VAR_062778
Natural varianti409 – 4091G → V in PARK6. 1 Publication
VAR_062779
Natural varianti417 – 4171E → G in PARK6. 1 Publication
VAR_046599
Natural varianti464 – 4641R → H in PARK6. 1 Publication
Corresponds to variant rs764328076 [ dbSNP | Ensembl ].
VAR_046605
Natural varianti489 – 4891L → P in PARK6. 1 Publication
VAR_046607
Natural varianti534 – 5341Q → QQ in PARK6. 1 Publication
VAR_046610

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi219 – 2191K → A: Abolishes MFN2 phosphorylation and interaction with PARK2; when associated with ALA-362 and ALA-384. 1 Publication
Mutagenesisi362 – 3621D → A: Abolishes MFN2 phosphorylation and interaction with PARK2; when associated with ALA-219 and ALA-384. 1 Publication
Mutagenesisi384 – 3841D → A: Abolishes MFN2 phosphorylation and interaction with PARK2; when associated with ALA-219 and ALA-362. 1 Publication

Keywords - Diseasei

Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism

Organism-specific databases

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

Chemistry

ChEMBLiCHEMBL3337330.

Polymorphism and mutation databases

BioMutaiPINK1.
DMDMi48428484.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 7777MitochondrionSequence analysisAdd
BLAST
Chaini78 – 581504Serine/threonine-protein kinase PINK1, mitochondrialPRO_0000024369Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei228 – 2281Phosphoserine; by autocatalysis1 Publication
Modified residuei402 – 4021Phosphoserine; by autocatalysis1 Publication

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.
PhosphoSiteiQ9BXM7.

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 interactions.
DIPiDIP-29427N.
IntActiQ9BXM7. 15 interactions.
MINTiMINT-6781189.
STRINGi9606.ENSP00000364204.

Structurei

3D structure databases

ProteinModelPortaliQ9BXM7.
SMRiQ9BXM7. Positions 246-545.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini156 – 511356Protein kinasePROSITE-ProRule annotationCuratedAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti209 – 2091P → A in AAH28215 (PubMed:15489334).Curated
Sequence conflicti419 – 4191S → P in BAC11484 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti67 – 671L → F.1 Publication
Corresponds to variant rs763142730 [ dbSNP | Ensembl ].
VAR_046566
Natural varianti68 – 681R → P.1 Publication
VAR_046567
Natural varianti92 – 921C → F in PARK6. 1 Publication
VAR_046568
Natural varianti98 – 981R → W.1 Publication
Corresponds to variant rs575668171 [ dbSNP | Ensembl ].
VAR_046569
Natural varianti111 – 1111I → S.1 Publication
VAR_046570
Natural varianti115 – 1151Q → L.2 Publications
Corresponds to variant rs148871409 [ dbSNP | Ensembl ].
VAR_046571
Natural varianti124 – 1241A → V.1 Publication
VAR_046572
Natural varianti125 – 1251C → G in PARK6. 1 Publication
VAR_062773
Natural varianti126 – 1261Q → P in PARK6; strongly reduces interaction with PARK2. 2 Publications
VAR_064344
Natural varianti145 – 1451T → M.1 Publication
Corresponds to variant rs45604240 [ dbSNP | Ensembl ].
VAR_046573
Natural varianti147 – 1471R → H in PARK6; unknown pathological significance. 1 Publication
Corresponds to variant rs138050841 [ dbSNP | Ensembl ].
VAR_046574
Natural varianti148 – 1481L → W.1 Publication
Corresponds to variant rs56297806 [ dbSNP | Ensembl ].
VAR_041010
Natural varianti168 – 1681A → 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 Publications
Corresponds to variant rs768091663 [ dbSNP | Ensembl ].
VAR_046575
Natural varianti186 – 1861K → N.1 Publication
Corresponds to variant rs143204084 [ dbSNP | Ensembl ].
VAR_046576
Natural varianti196 – 1961P → L in PARK6. 1 Publication
Corresponds to variant rs138302371 [ dbSNP | Ensembl ].
VAR_046577
Natural varianti196 – 1961P → S.1 Publication
Corresponds to variant rs35802484 [ dbSNP | Ensembl ].
VAR_041011
Natural varianti209 – 2091P → L.1 Publication
Corresponds to variant rs34677717 [ dbSNP | Ensembl ].
VAR_041012
Natural varianti215 – 2151P → L in a glioblastoma multiforme sample; somatic mutation. 1 Publication
Corresponds to variant rs371854396 [ dbSNP | Ensembl ].
VAR_041013
Natural varianti217 – 2171A → D in PARK6. 1 Publication
Corresponds to variant rs74315360 [ dbSNP | Ensembl ].
VAR_046578
Natural varianti231 – 2311E → G.1 Publication
VAR_046579
Natural varianti235 – 2351N → I.1 Publication
VAR_046580
Natural varianti240 – 2401E → K in PARK6. 2 Publications
Corresponds to variant rs573931674 [ dbSNP | Ensembl ].
VAR_046581
Natural varianti257 – 2571T → I.
Corresponds to variant rs370906995 [ dbSNP | Ensembl ].
VAR_046582
Natural varianti263 – 2631R → G.1 Publication
VAR_046583
Natural varianti268 – 2681L → V in PARK6. 2 Publications
Corresponds to variant rs372280083 [ dbSNP | Ensembl ].
VAR_046584
Natural varianti271 – 2711H → Q in PARK6. 1 Publication
Corresponds to variant rs28940284 [ dbSNP | Ensembl ].
VAR_046585
Natural varianti276 – 2761R → Q.1 Publication
Corresponds to variant rs548506734 [ dbSNP | Ensembl ].
VAR_046586
Natural varianti279 – 2791R → H in PARK6. 1 Publication
Corresponds to variant rs74315358 [ dbSNP | Ensembl ].
VAR_046587
Natural varianti280 – 2801A → T in PARK6; early-onset. 1 Publication
Corresponds to variant rs772510148 [ dbSNP | Ensembl ].
VAR_062774
Natural varianti296 – 2961P → L.2 Publications
Corresponds to variant rs779060308 [ dbSNP | Ensembl ].
VAR_046588
Natural varianti305 – 3051P → L.
Corresponds to variant rs7349186 [ dbSNP | Ensembl ].
VAR_018993
Natural varianti309 – 3091G → 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 Publications
Corresponds to variant rs74315355 [ dbSNP | Ensembl ].
VAR_018994
Natural varianti313 – 3131T → M in PARK6; decreases PARK2 and SNCAIP ubiquitination and degradation. 2 Publications
Corresponds to variant rs74315359 [ dbSNP | Ensembl ].
VAR_046589
Natural varianti317 – 3171V → I.2 Publications
Corresponds to variant rs200949139 [ dbSNP | Ensembl ].
VAR_046590
Natural varianti318 – 3181M → L.1 Publication
Corresponds to variant rs139226733 [ dbSNP | Ensembl ].
VAR_046591
Natural varianti322 – 3221P → L.1 Publication
Corresponds to variant rs768019187 [ dbSNP | Ensembl ].
VAR_046592
Natural varianti339 – 3391A → T.4 Publications
Corresponds to variant rs55831733 [ dbSNP | Ensembl ].
VAR_041014
Natural varianti340 – 3401A → T.7 Publications
Corresponds to variant rs3738136 [ dbSNP | Ensembl ].
VAR_018995
Natural varianti341 – 3411M → I.1 Publication
Corresponds to variant rs35813094 [ dbSNP | Ensembl ].
VAR_041015
Natural varianti347 – 3471L → P in PARK6; strongly reduces interaction with PARK2. 4 Publications
Corresponds to variant rs28940285 [ dbSNP | Ensembl ].
VAR_046593
Natural varianti362 – 3621D → H.1 Publication
VAR_046594
Natural varianti369 – 3691L → P in PARK6. 1 Publication
VAR_062775
Natural varianti377 – 3771C → F.1 Publication
Corresponds to variant rs34203620 [ dbSNP | Ensembl ].
VAR_041016
Natural varianti383 – 3831A → T.2 Publications
Corresponds to variant rs45515602 [ dbSNP | Ensembl ].
VAR_046595
Natural varianti386 – 3861G → A in PARK6; abolishes kinase activity. 2 Publications
VAR_062776
Natural varianti388 – 3881C → R in PARK6. 1 Publication
VAR_046596
Natural varianti395 – 3951G → V.1 Publication
VAR_046597
Natural varianti399 – 3991P → 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 Publications
Corresponds to variant rs119451946 [ dbSNP | Ensembl ].
VAR_062777
Natural varianti407 – 4071R → Q in PARK6; early-onset. 1 Publication
Corresponds to variant rs556540177 [ dbSNP | Ensembl ].
VAR_062778
Natural varianti409 – 4091G → V in PARK6. 1 Publication
VAR_062779
Natural varianti411 – 4111G → S.1 Publication
Corresponds to variant rs45478900 [ dbSNP | Ensembl ].
VAR_046598
Natural varianti417 – 4171E → G in PARK6. 1 Publication
VAR_046599
Natural varianti425 – 4251P → S.1 Publication
Corresponds to variant rs554114655 [ dbSNP | Ensembl ].
VAR_046600
Natural varianti431 – 4311Y → H May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 Publication
Corresponds to variant rs74315361 [ dbSNP | Ensembl ].
VAR_046601
Natural varianti442 – 4421I → T.2 Publications
VAR_046602
Natural varianti451 – 4511N → S May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 Publication
Corresponds to variant rs747400197 [ dbSNP | Ensembl ].
VAR_046603
Natural varianti461 – 4611L → S.1 Publication
VAR_046604
Natural varianti464 – 4641R → H in PARK6. 1 Publication
Corresponds to variant rs764328076 [ dbSNP | Ensembl ].
VAR_046605
Natural varianti476 – 4761E → K May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 5 Publications
Corresponds to variant rs115477764 [ dbSNP | Ensembl ].
VAR_046606
Natural varianti477 – 4771S → T.1 Publication
Corresponds to variant rs34416410 [ dbSNP | Ensembl ].
VAR_041017
Natural varianti489 – 4891L → P in PARK6. 1 Publication
VAR_046607
Natural varianti501 – 5011R → P May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 Publication
VAR_046608
Natural varianti521 – 5211N → T.7 Publications
Corresponds to variant rs1043424 [ dbSNP | Ensembl ].
VAR_018996
Natural varianti525 – 5251D → N.2 Publications
Corresponds to variant rs531477772 [ dbSNP | Ensembl ].
VAR_046609
Natural varianti534 – 5341Q → QQ in PARK6. 1 Publication
VAR_046610
Natural varianti537 – 5371A → T.1 Publication
Corresponds to variant rs771032673 [ dbSNP | Ensembl ].
VAR_046611
Natural varianti575 – 5751C → R May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 Publication
VAR_046612

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 307307Missing in isoform 2. 1 PublicationVSP_050754Add
BLAST
Alternative sequencei308 – 32013LGHGR…LVMKN → MCGSQRPSPLSTS in isoform 2. 1 PublicationVSP_050755Add
BLAST

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.
SMRiQ9BXM7. Positions 246-545.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry

ChEMBLiCHEMBL3337330.

PTM databases

iPTMnetiQ9BXM7.
PhosphoSiteiQ9BXM7.

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.
GeneCardsiPINK1.
GeneReviewsiPINK1.
HGNCiHGNC:14581. PINK1.
HPAiCAB026191.
HPA001931.
MalaCardsiPINK1.
MIMi168600. phenotype.
605909. phenotype.
608309. gene.
neXtProtiNX_Q9BXM7.
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

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: September 7, 2016
This is version 152 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.