PINK1_MOUSE
ID PINK1_MOUSE Reviewed; 580 AA.
AC Q99MQ3; A2AM77; Q7TMZ3; Q811I8; Q91XU5;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Serine/threonine-protein kinase PINK1, mitochondrial;
DE EC=2.7.11.1 {ECO:0000269|PubMed:24652937, ECO:0000269|PubMed:25474007, ECO:0000269|PubMed:32484300};
DE AltName: Full=BRPK;
DE AltName: Full=PTEN-induced putative kinase protein 1;
DE Flags: Precursor;
GN Name=Pink1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAK28061.1};
RN [1] {ECO:0000312|EMBL:BAB55651.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAB55651.1};
RC TISSUE=Lung {ECO:0000312|EMBL:BAB55651.1};
RX PubMed=11494141; DOI=10.1038/sj.onc.1204608;
RA Unoki M., Nakamura Y.;
RT "Growth-suppressive effects of BPOZ and EGR2, two genes involved in the
RT PTEN signaling pathway.";
RL Oncogene 20:4457-4465(2001).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=ICR {ECO:0000312|EMBL:AAK28061.1};
RC TISSUE=Testis {ECO:0000312|EMBL:AAK28061.1};
RX PubMed=14607334; DOI=10.1016/s0304-3835(03)00443-9;
RA Nakajima A., Kataoka K., Hong M., Sakaguchi M., Huh N.-H.;
RT "BRPK, a novel protein kinase showing increased expression in mouse cancer
RT cell lines with higher metastatic potential.";
RL Cancer Lett. 201:195-201(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH67066.1}, and
RC Czech II {ECO:0000312|EMBL:AAH44743.1};
RC TISSUE=Eye {ECO:0000312|EMBL:AAH67066.1}, and
RC Mammary gland {ECO:0000312|EMBL:AAH44743.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=18687901; DOI=10.1073/pnas.0802076105;
RA Gautier C.A., Kitada T., Shen J.;
RT "Loss of PINK1 causes mitochondrial functional defects and increased
RT sensitivity to oxidative stress.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:11364-11369(2008).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=20049710; DOI=10.1002/emmm.200900006;
RA Morais V.A., Verstreken P., Roethig A., Smet J., Snellinx A.,
RA Vanbrabant M., Haddad D., Frezza C., Mandemakers W., Vogt-Weisenhorn D.,
RA Van Coster R., Wurst W., Scorrano L., De Strooper B.;
RT "Parkinson's disease mutations in PINK1 result in decreased Complex I
RT activity and deficient synaptic function.";
RL EMBO Mol. Med. 1:99-111(2009).
RN [7]
RP SUBUNIT.
RX PubMed=19229105; DOI=10.1172/jci37617;
RA Xiong H., Wang D., Chen L., Choo Y.S., Ma H., Tang C., Xia K., Jiang W.,
RA Ronai Z., Zhuang X., Zhang Z.;
RT "Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting
RT unfolded protein degradation.";
RL J. Clin. Invest. 119:650-660(2009).
RN [8]
RP FUNCTION.
RX PubMed=24784582; DOI=10.1038/nature13392;
RA Koyano F., Okatsu K., Kosako H., Tamura Y., Go E., Kimura M., Kimura Y.,
RA Tsuchiya H., Yoshihara H., Hirokawa T., Endo T., Fon E.A., Trempe J.F.,
RA Saeki Y., Tanaka K., Matsuda N.;
RT "Ubiquitin is phosphorylated by PINK1 to activate parkin.";
RL Nature 510:162-166(2014).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION, AND MUTAGENESIS OF LYS-218;
RP ASP-361 AND ASP-383.
RX PubMed=25474007; DOI=10.1371/journal.pgen.1004861;
RA Shiba-Fukushima K., Arano T., Matsumoto G., Inoshita T., Yoshida S.,
RA Ishihama Y., Ryu K.Y., Nukina N., Hattori N., Imai Y.;
RT "Phosphorylation of mitochondrial polyubiquitin by PINK1 promotes Parkin
RT mitochondrial tethering.";
RL PLoS Genet. 10:e1004861-e1004861(2014).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=24652937; DOI=10.1126/science.1249161;
RA Morais V.A., Haddad D., Craessaerts K., De Bock P.J., Swerts J., Vilain S.,
RA Aerts L., Overbergh L., Gruenewald A., Seibler P., Klein C., Gevaert K.,
RA Verstreken P., De Strooper B.;
RT "PINK1 loss-of-function mutations affect mitochondrial complex I activity
RT via NdufA10 ubiquinone uncoupling.";
RL Science 344:203-207(2014).
RN [11]
RP INTERACTION WITH NENF, AND SUBCELLULAR LOCATION.
RX PubMed=31536960; DOI=10.1016/j.isci.2019.08.057;
RA Moutaoufik M.T., Malty R., Amin S., Zhang Q., Phanse S., Gagarinova A.,
RA Zilocchi M., Hoell L., Minic Z., Gagarinova M., Aoki H., Stockwell J.,
RA Jessulat M., Goebels F., Broderick K., Scott N.E., Vlasblom J., Musso G.,
RA Prasad B., Lamantea E., Garavaglia B., Rajput A., Murayama K., Okazaki Y.,
RA Foster L.J., Bader G.D., Cayabyab F.S., Babu M.;
RT "Rewiring of the Human Mitochondrial Interactome during Neuronal
RT Reprogramming Reveals Regulators of the Respirasome and Neurogenesis.";
RL IScience 19:1114-1132(2019).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=32484300; DOI=10.15252/embr.201948686;
RA Han H., Tan J., Wang R., Wan H., He Y., Yan X., Guo J., Gao Q., Li J.,
RA Shang S., Chen F., Tian R., Liu W., Liao L., Tang B., Zhang Z.;
RT "PINK1 phosphorylates Drp1S616 to regulate mitophagy-independent
RT mitochondrial dynamics.";
RL EMBO Rep. 21:48686-48686(2020).
CC -!- FUNCTION: Serine/threonine-protein kinase which protects against
CC mitochondrial dysfunction during cellular stress by phosphorylating
CC mitochondrial proteins such as PRKN and DNM1L, to coordinate
CC mitochondrial quality control mechanisms that remove and replace
CC dysfunctional mitochondrial components (PubMed:24652937,
CC PubMed:24784582, PubMed:25474007, PubMed:32484300). Depending on the
CC severity of mitochondrial damage and/or dysfunction, activity ranges
CC from preventing apoptosis and stimulating mitochondrial biogenesis to
CC regulating mitochondrial dynamics and eliminating severely damaged
CC mitochondria via mitophagy (By similarity). Mediates the translocation
CC and activation of PRKN at the outer membrane (OMM) of
CC dysfunctional/depolarized mitochondria (PubMed:24652937,
CC PubMed:24784582, PubMed:25474007, PubMed:32484300). At the OMM of
CC damaged mitochondria, phosphorylates pre-existing polyubiquitin chains
CC at 'Ser-65', the PINK1-phosphorylated polyubiquitin then recruits PRKN
CC from the cytosol to the OMM where PRKN is fully activated by
CC phosphorylation at 'Ser-65' by PINK1 (PubMed:24652937, PubMed:24784582,
CC PubMed:25474007, PubMed:32484300). In damaged mitochondria, mediates
CC the decision between mitophagy or preventing apoptosis by promoting
CC PRKN-dependent poly- or monoubiquitination of VDAC1; polyubiquitination
CC of VDAC1 by PRKN promotes mitophagy, while monoubiquitination of VDAC1
CC by PRKN decreases mitochondrial calcium influx which ultimately
CC inhibits apoptosis (By similarity). When cellular stress results in
CC irreversible mitochondrial damage, functions with PRKN to promote
CC clearance of damaged mitochondria via selective autophagy (mitophagy)
CC (PubMed:24784582, PubMed:25474007). The PINK1-PRKN pathway also
CC promotes fission of damaged mitochondria by phosphorylating and thus
CC promoting the PRKN-dependent degradation of mitochondrial proteins
CC involved in fission such as MFN2 (By similarity). This prevents the
CC refusion of unhealthy mitochondria with the mitochondrial network or
CC initiates mitochondrial fragmentation facilitating their later
CC engulfment by autophagosomes (By similarity). Also promotes
CC mitochondrial fission independently of PRKN and ATG7-mediated
CC mitophagy, via the phosphorylation and activation of DNM1L
CC (PubMed:32484300). Regulates motility of damaged mitochondria by
CC promoting the ubiquitination and subsequent degradation of MIRO1 and
CC MIRO2; in motor neurons, this likely inhibits mitochondrial
CC intracellular anterograde transport along the axons which probably
CC increases the chance of the mitochondria undergoing mitophagy in the
CC soma (By similarity). Required for ubiquinone reduction by
CC mitochondrial complex I by mediating phosphorylation of complex I
CC subunit NDUFA10 (PubMed:24652937). {ECO:0000250|UniProtKB:Q9BXM7,
CC ECO:0000269|PubMed:24652937, ECO:0000269|PubMed:24784582,
CC ECO:0000269|PubMed:25474007, ECO:0000269|PubMed:32484300}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:24652937, ECO:0000269|PubMed:25474007,
CC ECO:0000269|PubMed:32484300};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:24652937,
CC ECO:0000269|PubMed:25474007, ECO:0000269|PubMed:32484300};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Interacts with PRKN (By similarity). Interacts with FBXO7 (By
CC similarity). Forms a complex with PRKN and PARK7 (PubMed:19229105).
CC Interacts with NENF (PubMed:31536960). {ECO:0000250|UniProtKB:Q9BXM7,
CC ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:31536960}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q9BXM7}; Single-pass membrane protein
CC {ECO:0000255}. Mitochondrion inner membrane
CC {ECO:0000269|PubMed:24652937}; Single-pass membrane protein
CC {ECO:0000255}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9BXM7}.
CC Note=Localizes mostly in mitochondrion and the two smaller proteolytic
CC processed fragments localize mainly in cytosol. When mitochondria lose
CC mitochondrial membrane potential following damage, PINK1 import is
CC arrested, which induces its accumulation in the outer mitochondrial
CC membrane, where it acquires kinase activity.
CC {ECO:0000250|UniProtKB:Q9BXM7}.
CC -!- TISSUE SPECIFICITY: High levels expressed in testis, lower levels in
CC brain, heart, lung, liver and kidney. {ECO:0000269|PubMed:14607334}.
CC -!- PTM: Proteolytically cleaved. In healthy cells, the precursor is
CC continuously imported into the inner mitochondrial membrane (IMM),
CC where it is proteolytically cleaved by mitochondrial-processing
CC peptidase (MPP) and then undergoes further proteolytic cleavage by PARL
CC or AFG3L2 to give rise to the 52 kDa short form. The 52 kDa short form
CC is then released into the cytosol where it rapidly undergoes
CC proteasome-dependent degradation. In unhealthy cells, when cellular
CC stress conditions lead to the loss of mitochondrial membrane potential,
CC mitochondrial import is impaired leading to the precursor accumulating
CC on the outer mitochondrial membrane (OMM). If accumulation at the OMM
CC fails and it is imported into the depolarized mitochondria, it
CC undergoes cleavage by the IMM protease OMA1, promoting its subsequent
CC degradation by the proteasome. {ECO:0000250|UniProtKB:Q9BXM7}.
CC -!- PTM: Autophosphorylated (PubMed:25474007). Loss of mitochondrial
CC membrane potential results in the precursor accumulating on the outer
CC mitochondrial membrane (OMM) where it is activated by
CC autophosphorylation (By similarity). Autophosphorylation at Ser-227 and
CC Ser-401 is essential for selective recruitment of PRKN to depolarized
CC mitochondria, via PINK1-dependent phosphorylation of ubiquitin and PRKN
CC (By similarity). {ECO:0000250|UniProtKB:Q9BXM7,
CC ECO:0000269|PubMed:25474007}.
CC -!- DISRUPTION PHENOTYPE: Mitochondrial dysfunction (PubMed:18687901,
CC PubMed:20049710, PubMed:32484300). Mice do not show gross structural
CC defects in mitochondria, although the number of larger mitochondria is
CC selectively increased (PubMed:18687901, PubMed:32484300). Mitochondrial
CC respiration is impaired in the striatum, which is rich in dopaminergic
CC terminals, but not in the cerebral cortex in young mice
CC (PubMed:18687901). Mitochondrial respiration activities in the cerebral
CC cortex are decreased in 2 years old mice (PubMed:18687901). Mice show
CC defects in mitochondrial complex I and a decrease in mitochondrial
CC membrane potential (PubMed:20049710). Decreased phosphorylation of
CC Dnm1l in embryonic fibroblasts and in the substantial nigra of 18 month
CC old mice (PubMed:32484300). {ECO:0000269|PubMed:18687901,
CC ECO:0000269|PubMed:20049710, ECO:0000269|PubMed:32484300}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AB053476; BAB55651.1; -; mRNA.
DR EMBL; AF316872; AAK28061.1; -; mRNA.
DR EMBL; AL807249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC044743; AAH44743.1; -; mRNA.
DR EMBL; BC054349; AAH54349.1; -; mRNA.
DR EMBL; BC067066; AAH67066.1; -; mRNA.
DR CCDS; CCDS18825.1; -.
DR RefSeq; NP_081156.2; NM_026880.2.
DR AlphaFoldDB; Q99MQ3; -.
DR SMR; Q99MQ3; -.
DR BioGRID; 213129; 2.
DR IntAct; Q99MQ3; 5.
DR MINT; Q99MQ3; -.
DR STRING; 10090.ENSMUSP00000030536; -.
DR iPTMnet; Q99MQ3; -.
DR PhosphoSitePlus; Q99MQ3; -.
DR PaxDb; Q99MQ3; -.
DR PRIDE; Q99MQ3; -.
DR ProteomicsDB; 287733; -.
DR ABCD; Q99MQ3; 4 sequenced antibodies.
DR Antibodypedia; 1105; 831 antibodies from 49 providers.
DR DNASU; 68943; -.
DR Ensembl; ENSMUST00000030536; ENSMUSP00000030536; ENSMUSG00000028756.
DR GeneID; 68943; -.
DR KEGG; mmu:68943; -.
DR UCSC; uc008vku.1; mouse.
DR CTD; 65018; -.
DR MGI; MGI:1916193; Pink1.
DR VEuPathDB; HostDB:ENSMUSG00000028756; -.
DR eggNOG; KOG4158; Eukaryota.
DR GeneTree; ENSGT00390000001206; -.
DR InParanoid; Q99MQ3; -.
DR OMA; MMILQLL; -.
DR OrthoDB; 314975at2759; -.
DR PhylomeDB; Q99MQ3; -.
DR TreeFam; TF313183; -.
DR Reactome; R-MMU-5205685; PINK1-PRKN Mediated Mitophagy.
DR BioGRID-ORCS; 68943; 7 hits in 75 CRISPR screens.
DR ChiTaRS; Pink1; mouse.
DR PRO; PR:Q99MQ3; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q99MQ3; protein.
DR Bgee; ENSMUSG00000028756; Expressed in hindlimb stylopod muscle and 249 other tissues.
DR ExpressionAtlas; Q99MQ3; baseline and differential.
DR Genevisible; Q99MQ3; MM.
DR GO; GO:0097449; C:astrocyte projection; ISO:MGI.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0044297; C:cell body; ISO:MGI.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0030426; C:growth cone; IEA:Ensembl.
DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:MGI.
DR GO; GO:0005758; C:mitochondrial intermembrane space; ISO:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0055131; F:C3HC4-type RING finger domain binding; ISO:MGI.
DR GO; GO:0010857; F:calcium-dependent protein kinase activity; ISO:MGI.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0043422; F:protein kinase B binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IMP:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:1904841; F:TORC2 complex binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0000422; P:autophagy of mitochondrion; ISS:UniProtKB.
DR GO; GO:0050432; P:catecholamine secretion; IMP:MGI.
DR GO; GO:1904881; P:cellular response to hydrogen sulfide; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IMP:ParkinsonsUK-UCL.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0097237; P:cellular response to toxic substance; IMP:BHF-UCL.
DR GO; GO:0014046; P:dopamine secretion; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; ISO:MGI.
DR GO; GO:0030097; P:hemopoiesis; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0072656; P:maintenance of protein location in mitochondrion; ISO:MGI.
DR GO; GO:0007005; P:mitochondrion organization; ISO:MGI.
DR GO; GO:0099074; P:mitochondrion to lysosome transport; ISO:MGI.
DR GO; GO:0000423; P:mitophagy; ISO:MGI.
DR GO; GO:1902902; P:negative regulation of autophagosome assembly; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903384; P:negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:1903298; P:negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:1903751; P:negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0016242; P:negative regulation of macroautophagy; ISO:MGI.
DR GO; GO:0090258; P:negative regulation of mitochondrial fission; ISO:MGI.
DR GO; GO:1901525; P:negative regulation of mitophagy; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903202; P:negative regulation of oxidative stress-induced cell death; ISO:MGI.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0036289; P:peptidyl-serine autophosphorylation; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0033605; P:positive regulation of catecholamine secretion; IMP:MGI.
DR GO; GO:1903852; P:positive regulation of cristae formation; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0033603; P:positive regulation of dopamine secretion; IMP:MGI.
DR GO; GO:1901727; P:positive regulation of histone deacetylase activity; IMP:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISO:MGI.
DR GO; GO:1902958; P:positive regulation of mitochondrial electron transport, NADH to ubiquinone; IMP:MGI.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IBA:GO_Central.
DR GO; GO:0098779; P:positive regulation of mitophagy in response to mitochondrial depolarization; ISO:MGI.
DR GO; GO:1904783; P:positive regulation of NMDA glutamate receptor activity; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:0032226; P:positive regulation of synaptic transmission, dopaminergic; IMP:MGI.
DR GO; GO:0045727; P:positive regulation of translation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; ISO:MGI.
DR GO; GO:0010310; P:regulation of hydrogen peroxide metabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; ISO:MGI.
DR GO; GO:0010821; P:regulation of mitochondrion organization; ISO:MGI.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IMP:BHF-UCL.
DR GO; GO:0002082; P:regulation of oxidative phosphorylation; ISO:MGI.
DR GO; GO:1903214; P:regulation of protein targeting to mitochondrion; ISO:MGI.
DR GO; GO:0031396; P:regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0043254; P:regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0022904; P:respiratory electron transport chain; IMP:ParkinsonsUK-UCL.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
DR CDD; cd14018; STKc_PINK1; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR040110; PINK1_STKc.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Autophagy; Cytoplasm; Kinase; Magnesium; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion inner membrane;
KW Mitochondrion outer membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Transit peptide; Transmembrane; Transmembrane helix.
FT TRANSIT 1..77
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 78..580
FT /note="Serine/threonine-protein kinase PINK1,
FT mitochondrial"
FT /id="PRO_0000024370"
FT TOPO_DOM 78..93
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT TRANSMEM 94..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..580
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 156..510
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305"
FT REGION 111..117
FT /note="Required for outer membrane localization"
FT /evidence="ECO:0000250|UniProtKB:Q9BXM7"
FT ACT_SITE 361
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 162..170
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q02750,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 186
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 227
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9BXM7"
FT MOD_RES 401
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9BXM7"
FT MUTAGEN 218
FT /note="K->A: Abolishes ubiquitin phosphorylation; when
FT associated with A-361 and A-383."
FT /evidence="ECO:0000269|PubMed:25474007"
FT MUTAGEN 361
FT /note="D->A: Abolishes ubiquitin phosphorylation; when
FT associated with A-218 and A-383."
FT /evidence="ECO:0000269|PubMed:25474007"
FT MUTAGEN 383
FT /note="D->A: Abolishes ubiquitin phosphorylation; when
FT associated with A-218 and A-361."
FT /evidence="ECO:0000269|PubMed:25474007"
FT CONFLICT 9
FT /note="R -> P (in Ref. 1; BAB55651)"
FT /evidence="ECO:0000305"
FT CONFLICT 48
FT /note="Q -> R (in Ref. 2; AAK28061)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="A -> D (in Ref. 2; AAK28061)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="S -> G (in Ref. 4; AAH54349)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="E -> K (in Ref. 2; AAK28061)"
FT /evidence="ECO:0000305"
FT CONFLICT 476
FT /note="S -> L (in Ref. 4; AAH54349)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 580 AA; 63181 MW; 8AB6994B8B4E443E CRC64;
MAVRQALGRG LQLGRALLLR FAPKPGPLFG WGKPGPAAAW GRGERPGQVV SPGAQPRPVG
LPLPDRYRFF RQSVAGLAAR IQRQFMVRAR GGAGPCGRAV FLAFGLGLGL IEEKQAEGRR
AASACQEIQA IFTQKTKRVS DPLDTRCWQG FRLEDYLIGQ AIGKGCNAAV YEATMPTLPQ
HLEKAKHLGL IGKGPDVVLK GADGEQAPGT PTFPFAIKMM WNISAGSSSE AILSKMSQEL
VPASRVALAG EYGAVTYRRS RDGPKQLAPH PNIIRVFRAF TSSVPLLPGA LADYPDMLPP
HYYPEGLGHG RTLFLVMKNY PCTLRQYLEE QTPSSRLATM MTLQLLEGVD HLVQQGIAHR
DLKSDNILVE WDSDGCPWLV ISDFGCCLAD QHVGLRLPFN SSSVERGGNG SLMAPEVSTA
HSGPSAVIDY SKADTWAVGA IAYEIFGLAN PFYGQGSAHL ESRSYQEAQL PEMPESVPPE
ARRLVRSLLQ REASKRPSAR LAANVLHLSL WGEHLLALKN LKLDKMIAWL LQQSAATLLA
DRLREKSCVE TKLQMLFLAN LECEALCQAA LLLSSWRAAP
