UniProtKB - Q9BXM7 (PINK1_HUMAN)
Serine/threonine-protein kinase PINK1, mitochondrial
PINK1
Functioni
Serine/threonine-protein kinase which protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins such as PRKN and DNM1L, to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:14607334, PubMed:18957282, PubMed:18443288, PubMed:15087508, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:22396657, PubMed:20798600, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24898855, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:25527291, PubMed:32484300, PubMed:20547144).
Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (PubMed:18443288, PubMed:23620051, PubMed:24898855, PubMed:20798600, PubMed:20404107, PubMed:19966284, PubMed:32484300, PubMed:22396657, PubMed:32047033, PubMed:15087508).
Mediates the translocation and activation of PRKN at the outer membrane (OMM) of dysfunctional/depolarized mitochondria (PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291).
At the OMM of damaged mitochondria, phosphorylates pre-existing polyubiquitin chains at 'Ser-65', the PINK1-phosphorylated polyubiquitin then recruits PRKN from the cytosol to the OMM where PRKN is fully activated by phosphorylation at 'Ser-65' by PINK1 (PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291).
In damaged mitochondria, mediates the decision between mitophagy or preventing apoptosis by promoting PRKN-dependent poly- or monoubiquitination of VDAC1; polyubiquitination of VDAC1 by PRKN promotes mitophagy, while monoubiquitination of VDAC1 by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033).
When cellular stress results in irreversible mitochondrial damage, functions with PRKN to promote clearance of damaged mitochondria via selective autophagy (mitophagy) (PubMed:14607334, PubMed:20798600, PubMed:20404107, PubMed:19966284, PubMed:23933751, PubMed:15087508).
The PINK1-PRKN pathway also promotes fission of damaged mitochondria by phosphorylating and thus promoting the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:18443288, PubMed:23620051, PubMed:24898855).
This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (PubMed:18443288, PubMed:23620051).
Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L (PubMed:18443288, PubMed:32484300).
Regulates motility of damaged mitochondria by promoting the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (PubMed:22396657).
Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10 (By similarity).
By similarity22 PublicationsCatalytic activityi
Cofactori
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
- C3HC4-type RING finger domain binding Source: BHF-UCL
- calcium-dependent protein kinase activity Source: BHF-UCL
- kinase activity Source: MGI
- magnesium ion binding Source: UniProtKB
- peptidase activator activity Source: ParkinsonsUK-UCL
- protease binding Source: ParkinsonsUK-UCL
- protein-containing complex binding Source: ParkinsonsUK-UCL
- protein kinase activity Source: UniProtKB
- protein kinase B binding Source: ParkinsonsUK-UCL
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: UniProtKB
- TORC2 complex binding Source: ParkinsonsUK-UCL
- ubiquitin protein ligase binding Source: UniProtKB
GO - Biological processi
- activation of protein kinase B activity Source: ParkinsonsUK-UCL
- autophagy of mitochondrion Source: UniProtKB
- cellular response to hydrogen sulfide Source: Ensembl
- 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: UniProtKB
- hemopoiesis Source: ARUK-UCL
- intracellular signal transduction Source: UniProtKB
- maintenance of protein location in mitochondrion Source: ParkinsonsUK-UCL
- mitochondrion organization Source: ParkinsonsUK-UCL
- mitochondrion to lysosome transport Source: ParkinsonsUK-UCL
- mitophagy Source: ARUK-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 Source: UniProtKB
- 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
- positive regulation of ATP biosynthetic process Source: ParkinsonsUK-UCL
- positive regulation of cristae formation Source: ParkinsonsUK-UCL
- 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
- 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 mitophagy in response to mitochondrial depolarization Source: ParkinsonsUK-UCL
- positive regulation of NMDA glutamate receptor activity Source: Ensembl
- 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 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 apoptotic process Source: GO_Central
- regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
- 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 oxidative phosphorylation Source: ParkinsonsUK-UCL
- regulation of proteasomal protein catabolic process Source: ParkinsonsUK-UCL
- regulation of protein-containing 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 ischemia Source: Ensembl
- response to oxidative stress Source: ParkinsonsUK-UCL
- TORC2 signaling Source: ParkinsonsUK-UCL
- ubiquitin-dependent protein catabolic process Source: ParkinsonsUK-UCL
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Autophagy |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q9BXM7 |
Reactomei | R-HSA-5205685, PINK1-PRKN Mediated Mitophagy R-HSA-9614657, FOXO-mediated transcription of cell death genes |
SignaLinki | Q9BXM7 |
SIGNORi | Q9BXM7 |
Names & Taxonomyi
Protein namesi | Recommended name: Serine/threonine-protein kinase PINK1, mitochondrial (EC:2.7.11.15 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 | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:14581, PINK1 |
MIMi | 608309, gene |
neXtProti | NX_Q9BXM7 |
VEuPathDBi | HostDB:ENSG00000158828 |
Subcellular locationi
Mitochondrion
- Mitochondrion outer membrane 8 Publications; Single-pass membrane protein Sequence analysis
- Mitochondrion inner membrane By similarity; Single-pass membrane protein Sequence analysis
Cytoplasm and Cytosol
- cytosol 4 Publications
Note: Localizes mostly in mitochondrion and the two smaller proteolytic processed fragments localize mainly in cytosol (PubMed:19229105). When mitochondria lose mitochondrial membrane potential following damage, PINK1 import is arrested, which induces its accumulation in the outer mitochondrial membrane, where it acquires kinase activity (PubMed:18957282).2 Publications
Cytoskeleton
- cytoskeleton Source: ParkinsonsUK-UCL
Cytosol
- cytosol Source: UniProtKB
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
Mitochondrion
- integral component of mitochondrial outer 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
- nucleus Source: ParkinsonsUK-UCL
Other locations
- astrocyte projection Source: ParkinsonsUK-UCL
- axon Source: ParkinsonsUK-UCL
- cell body Source: ParkinsonsUK-UCL
- chromatin Source: ParkinsonsUK-UCL
- cytoplasm Source: ParkinsonsUK-UCL
- growth cone Source: Ensembl
- Lewy body Source: ParkinsonsUK-UCL
- membrane Source: ParkinsonsUK-UCL
- perinuclear region of cytoplasm Source: ParkinsonsUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | 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 membranePathology & Biotechi
Involvement in diseasei
Parkinson disease 6 (PARK6)26 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_046568 | 92 | C → F in PARK6. 1 PublicationCorresponds to variant dbSNP:rs1553145550Ensembl. | 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 PublicationsCorresponds to variant dbSNP:rs775809722Ensembl. | 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 PublicationCorresponds to variant dbSNP:rs1553145929Ensembl. | 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:rs772510148EnsemblClinVar. | 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; decreases Drp1 phosphorylation. 5 PublicationsCorresponds to variant dbSNP:rs74315355EnsemblClinVar. | 1 | |
Natural variantiVAR_046589 | 313 | T → M in PARK6; decreases PRKN and SNCAIP ubiquitination and degradation; slightly decreases Drp1 phosphorylation. 4 PublicationsCorresponds to variant dbSNP:rs74315359EnsemblClinVar. | 1 | |
Natural variantiVAR_046593 | 347 | L → P in PARK6; strongly reduces interaction with PRKN; reduced ubiquitination of MIRO1. 5 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 PublicationCorresponds to variant dbSNP:rs1553146806EnsemblClinVar. | 1 | |
Natural variantiVAR_062778 | 407 | R → Q in PARK6; early-onset. 1 PublicationCorresponds to variant dbSNP:rs556540177EnsemblClinVar. | 1 | |
Natural variantiVAR_062779 | 409 | G → V in PARK6. 1 PublicationCorresponds to variant dbSNP:rs1553146818Ensembl. | 1 | |
Natural variantiVAR_046599 | 417 | E → G in PARK6. 1 PublicationCorresponds to variant dbSNP:rs1553146822Ensembl. | 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 PublicationCorresponds to variant dbSNP:rs1553146903Ensembl. | 1 | |
Natural variantiVAR_084338 | 492 – 581 | Missing in PARK6; mitochondria are deformed and dysfunctional with decreased mitochondrial membrane potential; shows increased apoptosis; increased oxidative stress; decreased phosphorylation of DNM1L and Drp1. 3 PublicationsCorresponds to variant dbSNP:rs34208370Add BLAST | 90 | |
Natural variantiVAR_046610 | 534 | Q → QQ in PARK6. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 112 – 117 | EEKQAE → AAKQAA in 3EA; impaired ability to localize to the outer mitochondrial membrane. 1 Publication | 6 | |
Mutagenesisi | 219 | K → A: Abolishes MFN2 phosphorylation and interaction with PRKN; when associated with ALA-362 and ALA-384. 1 Publication | 1 | |
Mutagenesisi | 219 | K → M: Loss of enzyme activity and impaired localization of PRKN to mitochondria; when associated with A-362 and A-384. 2 Publications | 1 | |
Mutagenesisi | 362 | D → A: Abolishes MFN2 phosphorylation and interaction with PRKN; when associated with A-219 and A-384. Loss of enzyme activity and impaired localization of PRKN to mitochondria; when associated with M-219 and A-384. 3 Publications | 1 | |
Mutagenesisi | 384 | D → A: Abolishes MFN2 phosphorylation and interaction with PRKN; when associated with A-219 and A-362. Loss of enzyme activity and impaired localization of PRKN to mitochondria; when associated with M-219 and A-362. 3 Publications | 1 | |
Mutagenesisi | 384 | D → N: Loss of activity. Abolishes Drp1 phosphorylation. No effect on localization to mitochondria. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Neurodegeneration, Parkinson disease, Parkinsonism, Primary mitochondrial diseaseOrganism-specific databases
DisGeNETi | 65018 |
GeneReviewsi | PINK1 |
MalaCardsi | PINK1 |
MIMi | 168600, phenotype 605909, phenotype |
OpenTargetsi | ENSG00000158828 |
Orphaneti | 2828, Young-onset Parkinson disease |
PharmGKBi | PA33325 |
Miscellaneous databases
Pharosi | Q9BXM7, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3337330 |
Genetic variation 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
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9BXM7 |
MassIVEi | Q9BXM7 |
PaxDbi | Q9BXM7 |
PeptideAtlasi | Q9BXM7 |
PRIDEi | Q9BXM7 |
ProteomicsDBi | 79455 [Q9BXM7-1] 79456 [Q9BXM7-2] |
PTM databases
CarbonylDBi | Q9BXM7 |
iPTMneti | Q9BXM7 |
PhosphoSitePlusi | Q9BXM7 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000158828, Expressed in tendon and 249 other tissues |
Genevisiblei | Q9BXM7, HS |
Organism-specific databases
HPAi | ENSG00000158828, Tissue enhanced (skeletal muscle, tongue) |
Interactioni
Subunit structurei
Binary interactionsi
Q9BXM7
Isoform 1 [Q9BXM7-1]
With | #Exp. | IntAct |
---|---|---|
PRKN [O60260] | 2 | EBI-15643376,EBI-716346 |
TRAP1 [Q12931] | 4 | EBI-15643376,EBI-1055869 |
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
BioGRIDi | 122376, 683 interactors |
CORUMi | Q9BXM7 |
DIPi | DIP-29427N |
IntActi | Q9BXM7, 38 interactors |
MINTi | Q9BXM7 |
STRINGi | 9606.ENSP00000364204 |
Miscellaneous databases
RNActi | Q9BXM7, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 156 – 511 | Protein kinasePROSITE-ProRule annotationCuratedAdd BLAST | 356 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 111 – 117 | Required for outer membrane localization1 Publication | 7 | |
Regioni | 189 – 208 | DisorderedSequence analysisAdd BLAST | 20 |
Sequence similaritiesi
Keywords - Domaini
Transit peptide, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4158, Eukaryota |
GeneTreei | ENSGT00390000001206 |
HOGENOMi | CLU_022208_1_0_1 |
InParanoidi | Q9BXM7 |
OMAi | MMILQLL |
OrthoDBi | 314975at2759 |
PhylomeDBi | Q9BXM7 |
TreeFami | TF313183 |
Family and domain databases
CDDi | cd14018, STKc_PINK1, 1 hit |
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR040110, PINK1_STKc 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, 1 hit |
PROSITEi | View protein in PROSITE PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
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 | Graphical view | 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 PublicationCorresponds to variant dbSNP:rs1553145550Ensembl. | 1 | |
Natural variantiVAR_046569 | 98 | R → W1 PublicationCorresponds to variant dbSNP:rs575668171Ensembl. | 1 | |
Natural variantiVAR_046570 | 111 | I → S1 PublicationCorresponds to variant dbSNP:rs1553145560Ensembl. | 1 | |
Natural variantiVAR_046571 | 115 | Q → L2 PublicationsCorresponds to variant dbSNP:rs148871409EnsemblClinVar. | 1 | |
Natural variantiVAR_046572 | 124 | A → V1 PublicationCorresponds to variant dbSNP:rs1274588239Ensembl. | 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 PublicationsCorresponds to variant dbSNP:rs775809722Ensembl. | 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 PublicationCorresponds to variant dbSNP:rs1553145929Ensembl. | 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:rs34677717EnsemblClinVar. | 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 PublicationCorresponds to variant dbSNP:rs1303935100Ensembl. | 1 | |
Natural variantiVAR_046580 | 235 | N → I1 PublicationCorresponds to variant dbSNP:rs1557562082Ensembl. | 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 PublicationCorresponds to variant dbSNP:rs1553146419Ensembl. | 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:rs548506734EnsemblClinVar. | 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:rs772510148EnsemblClinVar. | 1 | |
Natural variantiVAR_046588 | 296 | P → L2 PublicationsCorresponds to variant dbSNP:rs779060308EnsemblClinVar. | 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; decreases Drp1 phosphorylation. 5 PublicationsCorresponds to variant dbSNP:rs74315355EnsemblClinVar. | 1 | |
Natural variantiVAR_046589 | 313 | T → M in PARK6; decreases PRKN and SNCAIP ubiquitination and degradation; slightly decreases Drp1 phosphorylation. 4 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 Publications |