Protein

Serine/threonine-protein kinase PINK1, mitochondrial

Gene

PINK1

Organism

Homo sapiens (Human)

Status

Reviewed-Annotation score: -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 PRKN (PubMed:14607334, PubMed:15087508, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:25527291). Targets PRKN to dysfunctional depolarized mitochondria through the phosphorylation of MFN2 (PubMed:23620051). Activates PRKN in 2 steps: (1) by mediating phosphorylation at 'Ser-65' of PRKN and (2) mediating phosphorylation of ubiquitin, converting PRKN to its fully-active form (PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25527291). Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10 (By similarity).By similarity14 Publications

Catalytic activityⁱ

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

Cofactorⁱ

Mg²⁺

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	186	ATPPROSITE-ProRule annotation		1
Active siteⁱ	362	Proton acceptorPROSITE-ProRule annotation		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	162 – 170	ATPPROSITE-ProRule annotationBy similarity		9

GO - Molecular functionⁱ

ATP binding
Source: UniProtKB
Inferred from direct assayⁱ
- 14607334
C3HC4-type RING finger domain binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 19880420
calcium-dependent protein kinase activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 19880420
kinase activity
Source: MGI
Inferred from direct assayⁱ
- 15824318
magnesium ion binding
Source: UniProtKB
Inferred from direct assayⁱ
- 14607334
peptidase activator activity
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 24522549
protease binding
Source: ParkinsonsUK-UCL
Inferred from physical interactionⁱ
- 21138942
protein kinase activity
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 25527497
protein kinase B binding
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 21177249
protein serine/threonine kinase activity
Source: UniProtKB
Inferred from direct assayⁱ
ubiquitin protein ligase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 20798600

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

activation of protein kinase B activity
Source: ParkinsonsUK-UCL
Inferred by curatorⁱ
- 21177249
autophagy of mitochondrion
Source: UniProtKB
Inferred from mutant phenotypeⁱ
cellular response to hydrogen sulfide Source: Ensembl
cellular response to hypoxia
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 24553947
cellular response to oxidative stress
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 22764206
cellular response to toxic substance
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 18221368
establishment of protein localization to mitochondrion
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 25527497
intracellular signal transduction
Source: UniProtKB
Inferred from direct assayⁱ
- 14607334
macroautophagy Source: Reactome
maintenance of protein location in mitochondrion
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 25527497
mitochondrion organization
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 18560593
mitochondrion to lysosome transport
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 24446486
negative regulation of autophagosome assembly
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 19279012
negative regulation of autophagy of mitochondrion
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 19279012
negative regulation of gene expression
Source: ParkinsonsUK-UCL
Inferred from sequence or structural similarityⁱ
- 24475098
negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 21177249
negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway Source: Ensembl
negative regulation of intrinsic apoptotic signaling pathway
Source: UniProtKB
Inferred from direct assayⁱ
- 15087508
negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 17579517
negative regulation of JNK cascade
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 18221368
negative regulation of macroautophagy
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 19279012
negative regulation of mitochondrial fission
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 19279012
negative regulation of neuron apoptotic process
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 18560593
negative regulation of oxidative stress-induced cell death
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 16632486
negative regulation of oxidative stress-induced neuron death
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 24522549
negative regulation of reactive oxygen species metabolic process
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 18560593
peptidyl-serine autophosphorylation
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 25527497
peptidyl-serine phosphorylation
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 17579517
positive regulation of ATP biosynthetic process
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 20871098
positive regulation of cristae formation
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 19279012
positive regulation of DNA-binding transcription factor activity Source: Ensembl
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
Inferred from direct assayⁱ
- 19880420
positive regulation of macroautophagy
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 20871098
positive regulation of mitochondrial electron transport, NADH to ubiquinone
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 21138942
positive regulation of mitochondrial fission Source: GO_Central
positive regulation of mitophagy in response to mitochondrial depolarization
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 20871098
positive regulation of NMDA glutamate receptor activity Source: Ensembl
positive regulation of peptidase activity
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 24522549
positive regulation of peptidyl-serine phosphorylation
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 21177249
positive regulation of protein dephosphorylation Source: Ensembl
positive regulation of protein kinase B signaling
Source: ParkinsonsUK-UCL
Inferred by curatorⁱ
- 21177249
positive regulation of protein phosphorylation
Source: AgBase
Inferred from direct assayⁱ
- 25244949
positive regulation of protein targeting to mitochondrion
Source: ParkinsonsUK-UCL
Inferred from high throughput mutant phenotypeⁱ
- 24270810
positive regulation of protein ubiquitination Source: ParkinsonsUK-UCL
positive regulation of release of cytochrome c from mitochondria
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 19880420
positive regulation of synaptic transmission, dopaminergic Source: Ensembl
positive regulation of translation Source: Ensembl
positive regulation of ubiquitin-protein transferase activity
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 24522549
protein phosphorylation
Source: UniProtKB
Inferred from direct assayⁱ
- 14607334
- 25527291
protein stabilization
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 19229105
protein ubiquitination
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 23933751
regulation of autophagy of mitochondrion
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 21563316
regulation of cellular response to oxidative stress
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 24446486
regulation of hydrogen peroxide metabolic process Source: Ensembl
regulation of mitochondrial membrane potential
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 18560593
- 21138942
regulation of mitochondrion organization
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 21508222
regulation of oxidative phosphorylation
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 20871098
regulation of proteasomal protein catabolic process
Source: ParkinsonsUK-UCL
Non-traceable author statementⁱ
- 22078885
regulation of protein complex assembly
Source: BHF-UCL
Inferred from direct assayⁱ
- 19880420
regulation of protein targeting to mitochondrion
Source: AgBase
Inferred from direct assayⁱ
- 25244949
regulation of protein ubiquitination
Source: BHF-UCL
Inferred from direct assayⁱ
- 19880420
regulation of reactive oxygen species metabolic process
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 21138942
regulation of synaptic vesicle transport
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 21563316
respiratory electron transport chain Source: Ensembl
response to ischemia Source: Ensembl
response to oxidative stress
Source: ParkinsonsUK-UCL
Inferred from genetic interactionⁱ
- 24475098
TORC2 signaling
Source: ParkinsonsUK-UCL
Inferred by curatorⁱ
- 21177249
ubiquitin-dependent protein catabolic process
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 24522549

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Kinase, Serine/threonine-protein kinase, Transferase
Biological process	Autophagy
Ligand	ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

Reactomeⁱ	R-HSA-5205685 Pink/Parkin Mediated Mitophagy
SignaLinkⁱ	Q9BXM7
SIGNORⁱ	Q9BXM7

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
Organismⁱ	Homo sapiens (Human)Imported
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 1

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000158828.5
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:14581 PINK1
MIMⁱ	608309 gene
neXtProtⁱ	NX_Q9BXM7

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	78 – 93	Mitochondrial intermembraneSequence analysisAdd BLAST	16
Transmembraneⁱ	94 – 110	HelicalSequence analysisAdd BLAST	17
Topological domainⁱ	111 – 581	CytoplasmicSequence analysisAdd BLAST	471

Keywords - Cellular componentⁱ

Cytoplasm, Membrane, Mitochondrion, Mitochondrion inner membrane, Mitochondrion outer membrane

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Parkinson disease 6 (PARK6)23 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn early-onset form of Parkinson disease, a 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. PARK6 pathogenesis involves respiratory complex I deficiency causing mitochondrial depolarization and dysfunction. Inheritance is autosomal recessive.

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_046568	92	C → F in PARK6. 1 Publication	1
Natural variantⁱVAR_062773	125	C → G in PARK6. 1 Publication	1
Natural variantⁱVAR_064344	126	Q → P in PARK6; strongly reduces interaction with PRKN. 2 Publications	1
Natural variantⁱVAR_046574	147	R → H in PARK6; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs138050841Ensembl.	1
Natural variantⁱVAR_046575	168	A → P in PARK6; no effect on autophosphorylation; localizes to the mitochondria and immunogold experiments reveal that both wild-type and mutant proteins face the mitochondrial intermembrane space. 4 PublicationsCorresponds to variant dbSNP:rs768091663EnsemblClinVar.	1
Natural variantⁱVAR_078934	170	V → G in PARK6. 1 Publication	1
Natural variantⁱVAR_046577	196	P → L in PARK6. 1 PublicationCorresponds to variant dbSNP:rs138302371EnsemblClinVar.	1
Natural variantⁱVAR_046578	217	A → D in PARK6. 1 PublicationCorresponds to variant dbSNP:rs74315360EnsemblClinVar.	1
Natural variantⁱVAR_046581	240	E → K in PARK6. 2 PublicationsCorresponds to variant dbSNP:rs573931674Ensembl.	1
Natural variantⁱVAR_046584	268	L → V in PARK6. 2 PublicationsCorresponds to variant dbSNP:rs372280083EnsemblClinVar.	1
Natural variantⁱVAR_046585	271	H → Q in PARK6. 1 PublicationCorresponds to variant dbSNP:rs28940284EnsemblClinVar.	1
Natural variantⁱVAR_046587	279	R → H in PARK6. 1 PublicationCorresponds to variant dbSNP:rs74315358EnsemblClinVar.	1
Natural variantⁱVAR_062774	280	A → T in PARK6; early-onset. 1 PublicationCorresponds to variant dbSNP:rs772510148Ensembl.	1
Natural variantⁱVAR_018994	309	G → D in PARK6; fails to maintain mitochondrial membrane potential; full-length mutant has no effect on autophosphorylation; strongly reduces interaction with PRKN; decreases PRKN and SNCAIP ubiquitination and degradation. 4 PublicationsCorresponds to variant dbSNP:rs74315355EnsemblClinVar.	1
Natural variantⁱVAR_046589	313	T → M in PARK6; decreases PRKN and SNCAIP ubiquitination and degradation. 2 PublicationsCorresponds to variant dbSNP:rs74315359EnsemblClinVar.	1
Natural variantⁱVAR_046593	347	L → P in PARK6; strongly reduces interaction with PRKN. 4 PublicationsCorresponds to variant dbSNP:rs28940285EnsemblClinVar.	1
Natural variantⁱVAR_062775	369	L → P in PARK6. 1 PublicationCorresponds to variant dbSNP:rs1195888869Ensembl.	1
Natural variantⁱVAR_062776	386	G → A in PARK6; abolishes kinase activity. 2 Publications	1
Natural variantⁱVAR_046596	388	C → R in PARK6. 1 Publication	1
Natural variantⁱVAR_062778	407	R → Q in PARK6; early-onset. 1 PublicationCorresponds to variant dbSNP:rs556540177Ensembl.	1
Natural variantⁱVAR_062779	409	G → V in PARK6. 1 Publication	1
Natural variantⁱVAR_046599	417	E → G in PARK6. 1 Publication	1
Natural variantⁱVAR_078935	456 – 581	Missing in PARK6. 1 PublicationAdd BLAST	126
Natural variantⁱVAR_046605	464	R → H in PARK6. 1 PublicationCorresponds to variant dbSNP:rs764328076Ensembl.	1
Natural variantⁱVAR_046607	489	L → P in PARK6. 1 Publication	1
Natural variantⁱVAR_046610	534	Q → QQ in PARK6. 1 Publication	1

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	219	K → A: Abolishes MFN2 phosphorylation and interaction with PRKN; when associated with ALA-362 and ALA-384. 1 Publication	1
Mutagenesisⁱ	362	D → A: Abolishes MFN2 phosphorylation and interaction with PRKN; when associated with ALA-219 and ALA-384. 1 Publication	1
Mutagenesisⁱ	384	D → A: Abolishes MFN2 phosphorylation and interaction with PRKN; when associated with ALA-219 and ALA-362. 1 Publication	1

Keywords - Diseaseⁱ

Disease mutation, Neurodegeneration, Parkinson disease, Parkinsonism, Primary mitochondrial disease

Organism-specific databases

DisGeNET More...DisGeNETⁱ	65018
GeneReviewsⁱ	PINK1
MalaCards human disease database More...MalaCardsⁱ	PINK1
MIMⁱ	168600 phenotype 605909 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000158828
Orphanetⁱ	2828 Young adult-onset Parkinsonism
PharmGKBⁱ	PA33325

Chemistry databases

ChEMBLⁱ	CHEMBL3337330

ChEMBLⁱ

CHEMBL3337330

Polymorphism and mutation databases

BioMutaⁱ	PINK1
DMDMⁱ	48428484

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Transit peptideⁱ	1 – 77	MitochondrionSequence analysisAdd BLAST		77
ChainⁱPRO_0000024369	78 – 581	Serine/threonine-protein kinase PINK1, mitochondrialAdd BLAST		504

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	228	Phosphoserine; by autocatalysis1 Publication		1
Modified residueⁱ	402	Phosphoserine; by autocatalysis1 Publication		1

Post-translational modificationⁱ

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

EPDⁱ	Q9BXM7
PaxDbⁱ	Q9BXM7
PeptideAtlas More...PeptideAtlasⁱ	Q9BXM7
PRIDEⁱ	Q9BXM7
ProteomicsDBⁱ	79455 79456 [Q9BXM7-2]

PTM databases

CarbonylDBⁱ	Q9BXM7
iPTMnetⁱ	Q9BXM7
PhosphoSitePlusⁱ	Q9BXM7

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

Bgeeⁱ	ENSG00000158828 Expressed in 236 organ(s), highest expression level in tendon
CleanExⁱ	HS_PINK1
Genevisibleⁱ	Q9BXM7 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB026191 HPA001931

HPAⁱ

CAB026191
HPA001931

Interactionⁱ

Subunit structureⁱ

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

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
FBXO7	Q9Y3I1	8	EBI-2846068,EBI-1161222
FBXO7	Q9Y3I1-1	2	EBI-2846068,EBI-9102965
MAP1LC3B	Q9GZQ8	3	EBI-2846068,EBI-373144
PRKN	O60260	7	EBI-2846068,EBI-716346
RHOT1	Q8IXI2	3	EBI-2846068,EBI-1396430
SOCS4	Q8WXH5	3	EBI-2846068,EBI-3942425
TRAP1	Q12931	4	EBI-15643376,EBI-1055869

GO - Molecular functionⁱ

C3HC4-type RING finger domain binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 19880420
protease binding
Source: ParkinsonsUK-UCL
Inferred from physical interactionⁱ
- 21138942
protein kinase B binding
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 21177249
ubiquitin protein ligase binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 20798600

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	122376, 63 interactors
CORUMⁱ	Q9BXM7
Database of interacting proteins More...DIPⁱ	DIP-29427N
IntActⁱ	Q9BXM7, 17 interactors
Molecular INTeraction database More...MINTⁱ	Q9BXM7
STRINGⁱ	9606.ENSP00000364204

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q9BXM7
SMRⁱ	Q9BXM7
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	156 – 511	Protein kinasePROSITE-ProRule annotationCuratedAdd BLAST		356

Sequence similaritiesⁱ

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

Keywords - Domainⁱ

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG4158 Eukaryota ENOG410YE6P LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000001206
HOGENOMⁱ	HOG000231649
HOVERGENⁱ	HBG053601
InParanoidⁱ	Q9BXM7
KEGG Orthology (KO) More...KOⁱ	K05688
OMAⁱ	FLVMKNY
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G03V6
PhylomeDBⁱ	Q9BXM7
TreeFamⁱ	TF313183

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR008271 Ser/Thr_kinase_AS
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 2 hits
PROSITEⁱ	View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit

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. Align Add to basket

Isoform 11 Publication (identifier: Q9BXM7-1) [UniParc]FASTA Add 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

Isoform 2Curated (identifier: Q9BXM7-2) [UniParc]FASTA Add to basket

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

« Hide

        10         20         30         40         50
MCGSQRPSPL STSYPCTLRQ YLCVNTPSPR LAAMMLLQLL EGVDHLVQQG 
        60         70         80         90        100
IAHRDLKSDN ILVELDPDGC PWLVIADFGC CLADESIGLQ LPFSSWYVDR 
       110        120        130        140        150
GGNGCLMAPE VSTARPGPRA VIDYSKADAW AVGAIAYEIF GLVNPFYGQG 
       160        170        180        190        200
KAHLESRSYQ EAQLPALPES VPPDVRQLVR ALLQREASKR PSARVAANVL 
       210        220        230        240        250
HLSLWGEHIL ALKNLKLDKM VGWLLQQSAA TLLANRLTEK CCVETKMKML 
       260        270 
FLANLECETL CQAALLLCSW RAAL

Note: No experimental confirmation available.Curated

Show »

Length:274

Mass (Da):30,104

Checksum:ⁱC54C628F879B4BED

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	209	P → A in AAH28215 (PubMed:15489334).Curated		1
Sequence conflictⁱ	419	S → P in BAC11484 (PubMed:14702039).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_046566	67	L → F1 PublicationCorresponds to variant dbSNP:rs763142730Ensembl.	1
Natural variantⁱVAR_046567	68	R → P1 PublicationCorresponds to variant dbSNP:rs1385309950Ensembl.	1
Natural variantⁱVAR_046568	92	C → F in PARK6. 1 Publication	1
Natural variantⁱVAR_046569	98	R → W1 PublicationCorresponds to variant dbSNP:rs575668171Ensembl.	1
Natural variantⁱVAR_046570	111	I → S1 Publication	1
Natural variantⁱVAR_046571	115	Q → L2 PublicationsCorresponds to variant dbSNP:rs148871409EnsemblClinVar.	1
Natural variantⁱVAR_046572	124	A → V1 Publication	1
Natural variantⁱVAR_062773	125	C → G in PARK6. 1 Publication	1
Natural variantⁱVAR_064344	126	Q → P in PARK6; strongly reduces interaction with PRKN. 2 Publications	1
Natural variantⁱVAR_046573	145	T → M1 PublicationCorresponds to variant dbSNP:rs45604240EnsemblClinVar.	1
Natural variantⁱVAR_046574	147	R → H in PARK6; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs138050841Ensembl.	1
Natural variantⁱVAR_041010	148	L → W1 PublicationCorresponds to variant dbSNP:rs56297806Ensembl.	1
Natural variantⁱVAR_046575	168	A → P in PARK6; no effect on autophosphorylation; localizes to the mitochondria and immunogold experiments reveal that both wild-type and mutant proteins face the mitochondrial intermembrane space. 4 PublicationsCorresponds to variant dbSNP:rs768091663EnsemblClinVar.	1
Natural variantⁱVAR_078934	170	V → G in PARK6. 1 Publication	1
Natural variantⁱVAR_046576	186	K → N1 PublicationCorresponds to variant dbSNP:rs143204084Ensembl.	1
Natural variantⁱVAR_046577	196	P → L in PARK6. 1 PublicationCorresponds to variant dbSNP:rs138302371EnsemblClinVar.	1
Natural variantⁱVAR_041011	196	P → S1 PublicationCorresponds to variant dbSNP:rs35802484Ensembl.	1
Natural variantⁱVAR_041012	209	P → L1 PublicationCorresponds to variant dbSNP:rs34677717Ensembl.	1
Natural variantⁱVAR_041013	215	P → L in a glioblastoma multiforme sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs371854396EnsemblClinVar.	1
Natural variantⁱVAR_046578	217	A → D in PARK6. 1 PublicationCorresponds to variant dbSNP:rs74315360EnsemblClinVar.	1
Natural variantⁱVAR_046579	231	E → G1 Publication	1
Natural variantⁱVAR_046580	235	N → I1 Publication	1
Natural variantⁱVAR_046581	240	E → K in PARK6. 2 PublicationsCorresponds to variant dbSNP:rs573931674Ensembl.	1
Natural variantⁱVAR_046582	257	T → I. Corresponds to variant dbSNP:rs370906995EnsemblClinVar.	1
Natural variantⁱVAR_046583	263	R → G1 Publication	1
Natural variantⁱVAR_046584	268	L → V in PARK6. 2 PublicationsCorresponds to variant dbSNP:rs372280083EnsemblClinVar.	1
Natural variantⁱVAR_046585	271	H → Q in PARK6. 1 PublicationCorresponds to variant dbSNP:rs28940284EnsemblClinVar.	1
Natural variantⁱVAR_046586	276	R → Q1 PublicationCorresponds to variant dbSNP:rs548506734Ensembl.	1
Natural variantⁱVAR_046587	279	R → H in PARK6. 1 PublicationCorresponds to variant dbSNP:rs74315358EnsemblClinVar.	1
Natural variantⁱVAR_062774	280	A → T in PARK6; early-onset. 1 PublicationCorresponds to variant dbSNP:rs772510148Ensembl.	1
Natural variantⁱVAR_046588	296	P → L2 PublicationsCorresponds to variant dbSNP:rs779060308Ensembl.	1
Natural variantⁱVAR_018993	305	P → L. Corresponds to variant dbSNP:rs7349186Ensembl.	1
Natural variantⁱVAR_018994	309	G → D in PARK6; fails to maintain mitochondrial membrane potential; full-length mutant has no effect on autophosphorylation; strongly reduces interaction with PRKN; decreases PRKN and SNCAIP ubiquitination and degradation. 4 PublicationsCorresponds to variant dbSNP:rs74315355EnsemblClinVar.	1
Natural variantⁱVAR_046589	313	T → M in PARK6; decreases PRKN and SNCAIP ubiquitination and degradation. 2 PublicationsCorresponds to variant dbSNP:rs74315359EnsemblClinVar.	1
Natural variantⁱVAR_046590	317	V → I2 PublicationsCorresponds to variant dbSNP:rs200949139Ensembl.	1
Natural variantⁱVAR_046591	318	M → L1 PublicationCorresponds to variant dbSNP:rs139226733EnsemblClinVar.	1
Natural variantⁱVAR_046592	322	P → L1 PublicationCorresponds to variant dbSNP:rs768019187Ensembl.	1
Natural variantⁱVAR_041014	339	A → T4 PublicationsCorresponds to variant dbSNP:rs55831733EnsemblClinVar.	1
Natural variantⁱVAR_018995	340	A → T7 PublicationsCorresponds to variant dbSNP:rs3738136EnsemblClinVar.	1
Natural variantⁱVAR_041015	341	M → I1 PublicationCorresponds to variant dbSNP:rs35813094Ensembl.	1
Natural variantⁱVAR_046593	347	L → P in PARK6; strongly reduces interaction with PRKN. 4 PublicationsCorresponds to variant dbSNP:rs28940285EnsemblClinVar.	1
Natural variantⁱVAR_046594	362	D → H1 Publication	1
Natural variantⁱVAR_062775	369	L → P in PARK6. 1 PublicationCorresponds to variant dbSNP:rs1195888869Ensembl.	1
Natural variantⁱVAR_041016	377	C → F1 PublicationCorresponds to variant dbSNP:rs34203620Ensembl.	1
Natural variantⁱVAR_046595	383	A → T2 PublicationsCorresponds to variant dbSNP:rs45515602Ensembl.	1
Natural variantⁱVAR_062776	386	G → A in PARK6; abolishes kinase activity. 2 Publications	1
Natural variantⁱVAR_046596	388	C → R in PARK6. 1 Publication	1
Natural variantⁱVAR_046597	395	G → V1 PublicationCorresponds to variant dbSNP:rs1035071310Ensembl.	1
Natural variantⁱVAR_062777	399	P → L Probable disease-associated mutation found in early-onset Parkinson disease with digenic inheritance; found in a patient also carrying mutation S-39 in PARK7; decreases PRKN and SNCAIP ubiquitination and degradation. 2 PublicationsCorresponds to variant dbSNP:rs119451946EnsemblClinVar.	1
Natural variantⁱVAR_062778	407	R → Q in PARK6; early-onset. 1 PublicationCorresponds to variant dbSNP:rs556540177Ensembl.	1
Natural variantⁱVAR_062779	409	G → V in PARK6. 1 Publication	1
Natural variantⁱVAR_046598	411	G → S1 PublicationCorresponds to variant dbSNP:rs45478900Ensembl.	1
Natural variantⁱVAR_046599	417	E → G in PARK6. 1 Publication	1
Natural variantⁱVAR_046600	425	P → S1 PublicationCorresponds to variant dbSNP:rs554114655Ensembl.	1
Natural variantⁱVAR_046601	431	Y → H May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 PublicationCorresponds to variant dbSNP:rs74315361EnsemblClinVar.	1
Natural variantⁱVAR_046602	442	I → T2 Publications	1
Natural variantⁱVAR_046603	451	N → S May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 PublicationCorresponds to variant dbSNP:rs747400197Ensembl.	1
Natural variantⁱVAR_078935	456 – 581	Missing in PARK6. 1 PublicationAdd BLAST	126
Natural variantⁱVAR_046604	461	L → S1 Publication	1
Natural variantⁱVAR_046605	464	R → H in PARK6. 1 PublicationCorresponds to variant dbSNP:rs764328076Ensembl.	1
Natural variantⁱVAR_046606	476	E → K May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 5 PublicationsCorresponds to variant dbSNP:rs115477764EnsemblClinVar.	1
Natural variantⁱVAR_041017	477	S → T1 PublicationCorresponds to variant dbSNP:rs34416410Ensembl.	1
Natural variantⁱVAR_046607	489	L → P in PARK6. 1 Publication	1
Natural variantⁱVAR_046608	501	R → P May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 Publication	1
Natural variantⁱVAR_018996	521	N → T7 PublicationsCorresponds to variant dbSNP:rs1043424EnsemblClinVar.	1
Natural variantⁱVAR_046609	525	D → N2 PublicationsCorresponds to variant dbSNP:rs531477772Ensembl.	1
Natural variantⁱVAR_046610	534	Q → QQ in PARK6. 1 Publication	1
Natural variantⁱVAR_046611	537	A → T1 PublicationCorresponds to variant dbSNP:rs771032673Ensembl.	1
Natural variantⁱVAR_046612	575	C → R May predispose to Parkinson disease development; shows decreased mitochondrial membrane potential under stress conditions. 1 Publication	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_050754	1 – 307	Missing in isoform 2. 1 PublicationAdd BLAST		307
Alternative sequenceⁱVSP_050755	308 – 320	LGHGR…LVMKN → MCGSQRPSPLSTS in isoform 2. 1 PublicationAdd BLAST		13

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 No translation available. BC009534 mRNA Translation: AAH09534.1 BC028215 mRNA Translation: AAH28215.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS211.1 [Q9BXM7-1]
NCBI Reference Sequences More...RefSeqⁱ	NP_115785.1, NM_032409.2 [Q9BXM7-1]
UniGeneⁱ	Hs.389171

Genome annotation databases

Ensemblⁱ	ENST00000321556; ENSP00000364204; ENSG00000158828 [Q9BXM7-1]
GeneIDⁱ	65018
KEGGⁱ	hsa:65018
UCSC genome browser More...UCSCⁱ	uc001bdm.3 human [Q9BXM7-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q9BXM7	PINK1 isoform 1		PONAB		581	UniRef90_Q9BXM7
Uncharacterized protein		MACFA		581
PTEN induced putative kinase 1		MACMU		581
Uncharacterized protein		MACNE		581
Uncharacterized protein		PAPAN		581
+12

Protein	Similar proteins		Species	Score	Length	Source
Q9BXM7	Serine/threonine-protein kinase PINK1, mitochondrial		MOUSE		580	UniRef50_Q9BXM7
PTEN induced putative kinase 1		GORGO		581
Uncharacterized protein		CHLSB		581
Uncharacterized protein		MACFA		581
PTEN induced putative kinase 1		MACMU		581
+171
Q9BXM7-2	Serine/threonine-protein kinase PINK1, mitochondrial (Fragment)		ESCRO		237	UniRef50_Q9BXM7-2

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 No translation available. BC009534 mRNA Translation: AAH09534.1 BC028215 mRNA Translation: AAH28215.1
CCDSⁱ	CCDS211.1 [Q9BXM7-1]
RefSeqⁱ	NP_115785.1, NM_032409.2 [Q9BXM7-1]
UniGeneⁱ	Hs.389171

3D structure databases

ProteinModelPortalⁱ	Q9BXM7
SMRⁱ	Q9BXM7
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	122376, 63 interactors
CORUMⁱ	Q9BXM7
DIPⁱ	DIP-29427N
IntActⁱ	Q9BXM7, 17 interactors
MINTⁱ	Q9BXM7
STRINGⁱ	9606.ENSP00000364204

Chemistry databases

ChEMBLⁱ	CHEMBL3337330

ChEMBLⁱ

CHEMBL3337330

PTM databases

CarbonylDBⁱ	Q9BXM7
iPTMnetⁱ	Q9BXM7
PhosphoSitePlusⁱ	Q9BXM7

Polymorphism and mutation databases

BioMutaⁱ	PINK1
DMDMⁱ	48428484

Proteomic databases

EPDⁱ	Q9BXM7
PaxDbⁱ	Q9BXM7
PeptideAtlasⁱ	Q9BXM7
PRIDEⁱ	Q9BXM7
ProteomicsDBⁱ	79455 79456 [Q9BXM7-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	65018
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000321556; ENSP00000364204; ENSG00000158828 [Q9BXM7-1]
GeneIDⁱ	65018
KEGGⁱ	hsa:65018
UCSCⁱ	uc001bdm.3 human [Q9BXM7-1]

Organism-specific databases

CTDⁱ	65018
DisGeNETⁱ	65018
EuPathDBⁱ	HostDB:ENSG00000158828.5
GeneCardsⁱ	PINK1
GeneReviewsⁱ	PINK1
HGNCⁱ	HGNC:14581 PINK1
HPAⁱ	CAB026191 HPA001931
MalaCardsⁱ	PINK1
MIMⁱ	168600 phenotype 605909 phenotype 608309 gene
neXtProtⁱ	NX_Q9BXM7
OpenTargetsⁱ	ENSG00000158828
Orphanetⁱ	2828 Young adult-onset Parkinsonism
PharmGKBⁱ	PA33325
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG4158 Eukaryota ENOG410YE6P LUCA
GeneTreeⁱ	ENSGT00390000001206
HOGENOMⁱ	HOG000231649
HOVERGENⁱ	HBG053601
InParanoidⁱ	Q9BXM7
KOⁱ	K05688
OMAⁱ	FLVMKNY
OrthoDBⁱ	EOG091G03V6
PhylomeDBⁱ	Q9BXM7
TreeFamⁱ	TF313183

Enzyme and pathway databases

Reactomeⁱ	R-HSA-5205685 Pink/Parkin Mediated Mitophagy
SignaLinkⁱ	Q9BXM7
SIGNORⁱ	Q9BXM7

Miscellaneous databases

ChiTaRSⁱ	PINK1 human
GeneWikiⁱ	PINK1
GenomeRNAiⁱ	65018
Protein Ontology More...PROⁱ	PR:Q9BXM7
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000158828 Expressed in 236 organ(s), highest expression level in tendon
CleanExⁱ	HS_PINK1
Genevisibleⁱ	Q9BXM7 HS

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR008271 Ser/Thr_kinase_AS
Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 2 hits
PROSITEⁱ	View protein in PROSITE PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	PINK1_HUMAN
Accessionⁱ	Q9BXM7Primary (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:	October 10, 2018
	This is version 171 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human and mouse protein kinases
Human and mouse protein kinases: classification and index
SIMILARITY comments
Index of protein domains and families
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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UniProtKB - Q9BXM7 (PINK1_HUMAN)

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Serine/threonine-protein kinase PINK1, mitochondrial

PINK1

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

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Keywords - Cellular componenti

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Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

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<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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Experimental Info

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Alternative sequence

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Keywords - Coding sequence diversityi

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Chemistry databases

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Proteomic databases

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ