ID PINK1_HUMAN Reviewed; 581 AA. AC Q9BXM7; Q8N6T9; Q8NBU3; Q96DE4; DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 28-JAN-2026, entry version 212. DE RecName: Full=Serine/threonine-protein kinase PINK1, mitochondrial; DE EC=2.7.11.1 {ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:24660806, ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:32484300}; DE AltName: Full=BRPK; DE AltName: Full=PTEN-induced putative kinase protein 1; DE Flags: Precursor; GN Name=PINK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606 {ECO:0000312|EMBL:AAK28062.1}; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Endometrium {ECO:0000269|PubMed:11494141}; 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] (ISOFORM 1), FUNCTION, AND AUTOPHOSPHORYLATION. RC TISSUE=Placenta {ECO:0000312|EMBL:AAK28062.1}; 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] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS THR-340 RP AND THR-521. RC TISSUE=Placenta {ECO:0000312|EMBL:BAC11484.1}; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Leukocyte {ECO:0000312|EMBL:AAH28215.1}, and RC Lung {ECO:0000312|EMBL:AAH09534.1}; 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 [6] RP SUBCELLULAR LOCATION. RX PubMed=16672980; DOI=10.1038/nature04788; RA Park J., Lee S.B., Lee S., Kim Y., Song S., Kim S., Bae E., Kim J., RA Shong M., Kim J.M., Chung J.; RT "Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by RT parkin."; RL Nature 441:1157-1161(2006). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND RP MUTAGENESIS OF LYS-219; ASP-362 AND ASP-384. RX PubMed=18957282; DOI=10.1016/j.bbrc.2008.10.104; RA Kim Y., Park J., Kim S., Song S., Kwon S.K., Lee S.H., Kitada T., Kim J.M., RA Chung J.; RT "PINK1 controls mitochondrial localization of Parkin through direct RT phosphorylation."; RL Biochem. Biophys. Res. Commun. 377:975-980(2008). RN [8] RP FUNCTION. RX PubMed=18443288; DOI=10.1073/pnas.0711845105; RA Yang Y., Ouyang Y., Yang L., Beal M.F., McQuibban A., Vogel H., Lu B.; RT "Pink1 regulates mitochondrial dynamics through interaction with the RT fission/fusion machinery."; RL Proc. Natl. Acad. Sci. U.S.A. 105:7070-7075(2008). RN [9] RP ERRATUM OF PUBMED:18443288. RA Yang Y., Ouyang Y., Yang L., Beal M.F., McQuibban A., Vogel H., Lu B.; RT "Pink1 regulates mitochondrial dynamics through interaction with the RT fission/fusion machinery."; RL Proc. Natl. Acad. Sci. U.S.A. 105:17585-17585(2008). RN [10] RP SUBCELLULAR LOCATION, AND MEMBRANE TOPOLOGY. RX PubMed=18687899; DOI=10.1073/pnas.0802814105; RA Zhou C., Huang Y., Shao Y., May J., Prou D., Perier C., Dauer W., RA Schon E.A., Przedborski S.; RT "The kinase domain of mitochondrial PINK1 faces the cytoplasm."; RL Proc. Natl. Acad. Sci. U.S.A. 105:12022-12027(2008). RN [11] RP FUNCTION, COMPONENT OF A COMPLEX COMPOSED OF PRKN; PARK7 AND PINK1, RP SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, CHARACTERIZATION OF VARIANTS RP PARK6 ASP-309 AND MET-313, AND CHARACTERIZATION OF VARIANT LEU-399. 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 [12] RP FUNCTION IN MITOCHONDRIAL AUTOPHAGY, SUBCELLULAR LOCATION, INTERACTION WITH RP PRKN, AND CHARACTERIZATION OF VARIANTS PARK6 PRO-126; ASP-309 AND PRO-347. RX PubMed=20798600; DOI=10.4161/auto.6.7.13286; RA Geisler S., Holmstrom K.M., Treis A., Skujat D., Weber S.S., Fiesel F.C., RA Kahle P.J., Springer W.; RT "The PINK1/Parkin-mediated mitophagy is compromised by PD-associated RT mutations."; RL Autophagy 6:871-878(2010). RN [13] RP FUNCTION, AND CHARACTERIZATION OF VARIANT PARK6 492-ARG--LYS-581 DEL. RX PubMed=20547144; DOI=10.1016/j.brainres.2010.06.005; RA Yuan X.L., Guo J.F., Shi Z.H., Xiao Z.Q., Yan X.X., Zhao B.L., Tang B.S.; RT "R492X mutation in PTEN-induced putative kinase 1 induced cellular RT mitochondrial dysfunction and oxidative stress."; RL Brain Res. 1351:229-237(2010). RN [14] RP FUNCTION IN MITOCHONDRIAL AUTOPHAGY, AND PHOSPHORYLATION. RX PubMed=20404107; DOI=10.1083/jcb.200910140; RA Matsuda N., Sato S., Shiba K., Okatsu K., Saisho K., Gautier C.A., RA Sou Y.S., Saiki S., Kawajiri S., Sato F., Kimura M., Komatsu M., RA Hattori N., Tanaka K.; RT "PINK1 stabilized by mitochondrial depolarization recruits Parkin to RT damaged mitochondria and activates latent Parkin for mitophagy."; RL J. Cell Biol. 189:211-221(2010). RN [15] RP FUNCTION IN MITOCHONDRIAL AUTOPHAGY, AND INTERACTION WITH PRKN. RX PubMed=19966284; DOI=10.1073/pnas.0911187107; RA Vives-Bauza C., Zhou C., Huang Y., Cui M., de Vries R.L., Kim J., May J., RA Tocilescu M.A., Liu W., Ko H.S., Magrane J., Moore D.J., Dawson V.L., RA Grailhe R., Dawson T.M., Li C., Tieu K., Przedborski S.; RT "PINK1-dependent recruitment of Parkin to mitochondria in mitophagy."; RL Proc. Natl. Acad. Sci. U.S.A. 107:378-383(2010). RN [16] RP INVOLVEMENT IN PARK6. RX PubMed=22043288; DOI=10.1371/journal.pone.0025622; RA Abramov A.Y., Gegg M., Grunewald A., Wood N.W., Klein C., Schapira A.H.; RT "Bioenergetic consequences of PINK1 mutations in Parkinson disease."; RL PLoS ONE 6:E25622-E25622(2011). RN [17] RP PROTEOLYTIC CLEAVAGE, AND SUBCELLULAR LOCATION. RX PubMed=22354088; DOI=10.1038/embor.2012.14; RA Greene A.W., Grenier K., Aguileta M.A., Muise S., Farazifard R., RA Haque M.E., McBride H.M., Park D.S., Fon E.A.; RT "Mitochondrial processing peptidase regulates PINK1 processing, import and RT Parkin recruitment."; RL EMBO Rep. 13:378-385(2012). RN [18] RP PHOSPHORYLATION AT SER-228 AND SER-402. RX PubMed=22910362; DOI=10.1038/ncomms2016; RA Okatsu K., Oka T., Iguchi M., Imamura K., Kosako H., Tani N., Kimura M., RA Go E., Koyano F., Funayama M., Shiba-Fukushima K., Sato S., Shimizu H., RA Fukunaga Y., Taniguchi H., Komatsu M., Hattori N., Mihara K., Tanaka K., RA Matsuda N.; RT "PINK1 autophosphorylation upon membrane potential dissipation is essential RT for Parkin recruitment to damaged mitochondria."; RL Nat. Commun. 3:1016-1016(2012). RN [19] RP FUNCTION, AND CHARACTERIZATION OF VARIANT PARK6 PRO-347. RX PubMed=22396657; DOI=10.1371/journal.pgen.1002537; RA Liu S., Sawada T., Lee S., Yu W., Silverio G., Alapatt P., Millan I., RA Shen A., Saxton W., Kanao T., Takahashi R., Hattori N., Imai Y., Lu B.; RT "Parkinson's disease-associated kinase PINK1 regulates Miro protein level RT and axonal transport of mitochondria."; RL PLoS Genet. 8:E1002537-E1002537(2012). RN [20] RP FUNCTION. RX PubMed=23754282; DOI=10.1074/jbc.m113.467530; RA Iguchi M., Kujuro Y., Okatsu K., Koyano F., Kosako H., Kimura M., RA Suzuki N., Uchiyama S., Tanaka K., Matsuda N.; RT "Parkin-catalyzed ubiquitin-ester transfer is triggered by PINK1-dependent RT phosphorylation."; RL J. Biol. Chem. 288:22019-22032(2013). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH FBXO7. RX PubMed=23933751; DOI=10.1038/nn.3489; RA Burchell V.S., Nelson D.E., Sanchez-Martinez A., Delgado-Camprubi M., RA Ivatt R.M., Pogson J.H., Randle S.J., Wray S., Lewis P.A., Houlden H., RA Abramov A.Y., Hardy J., Wood N.W., Whitworth A.J., Laman H., RA Plun-Favreau H.; RT "The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to RT mediate mitophagy."; RL Nat. Neurosci. 16:1257-1265(2013). RN [22] RP FUNCTION IN MITOPHAGY, AND MUTAGENESIS OF LYS-219; ASP-362 AND ASP-384. RX PubMed=23620051; DOI=10.1126/science.1231031; RA Chen Y., Dorn G.W. II; RT "PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged RT mitochondria."; RL Science 340:471-475(2013). RN [23] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=24660806; DOI=10.1042/bj20140334; RA Kazlauskaite A., Kondapalli C., Gourlay R., Campbell D.G., Ritorto M.S., RA Hofmann K., Alessi D.R., Knebel A., Trost M., Muqit M.M.; RT "Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at RT Ser65."; RL Biochem. J. 460:127-139(2014). RN [24] RP FUNCTION. RX PubMed=24898855; DOI=10.7554/elife.01958; RA Yun J., Puri R., Yang H., Lizzio M.A., Wu C., Sheng Z.H., Guo M.; RT "MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin RT and compensates for loss of PINK1/parkin."; RL Elife 3:E01958-E01958(2014). RN [25] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=24751536; DOI=10.1083/jcb.201402104; RA Kane L.A., Lazarou M., Fogel A.I., Li Y., Yamano K., Sarraf S.A., RA Banerjee S., Youle R.J.; RT "PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase RT activity."; RL J. Cell Biol. 205:143-153(2014). RN [26] RP FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANTS PARK6 RP PRO-168 AND ALA-386. 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 [27] RP FUNCTION. RX PubMed=24896179; DOI=10.1038/nature13418; RA Bingol B., Tea J.S., Phu L., Reichelt M., Bakalarski C.E., Song Q., RA Foreman O., Kirkpatrick D.S., Sheng M.; RT "The mitochondrial deubiquitinase USP30 opposes parkin-mediated RT mitophagy."; RL Nature 510:370-375(2014). RN [28] RP FUNCTION. 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 [29] RP VARIANTS PARK6 GLY-170 AND 456-GLN--LEU-581 DEL. 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 [30] RP FUNCTION. RX PubMed=25527291; DOI=10.15252/embj.201489847; RA Wauer T., Swatek K.N., Wagstaff J.L., Gladkova C., Pruneda J.N., RA Michel M.A., Gersch M., Johnson C.M., Freund S.M., Komander D.; RT "Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain RT assembly and hydrolysis."; RL EMBO J. 34:307-325(2015). RN [31] RP PROTEOLYTIC CLEAVAGE, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP 112-GLU--GLU-117. RX PubMed=30733118; DOI=10.1016/j.molcel.2019.01.002; RA Sekine S., Wang C., Sideris D.P., Bunker E., Zhang Z., Youle R.J.; RT "Reciprocal roles of Tom7 and OMA1 during mitochondrial import and RT activation of PINK1."; RL Mol. Cell 73:1028-1043(2019). RN [32] RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH NENF, AND SUBCELLULAR RP 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 [33] RP FUNCTION, AND MUTAGENESIS OF LYS-219; ASP-362 AND ASP-384. RX PubMed=32047033; DOI=10.1073/pnas.1909814117; RA Ham S.J., Lee D., Yoo H., Jun K., Shin H., Chung J.; RT "Decision between mitophagy and apoptosis by Parkin via VDAC1 RT ubiquitination."; RL Proc. Natl. Acad. Sci. U.S.A. 117:4281-4291(2020). RN [34] RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLY-309 AND ASP-384, AND RP CHARACTERIZATION OF VARIANTS ASP-309; MET-313 AND 492-ARG--LYS-581 DEL. 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). RN [35] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=29123128; DOI=10.1038/s41467-017-01435-1; RA Huang E., Qu D., Huang T., Rizzi N., Boonying W., Krolak D., Ciana P., RA Woulfe J., Klein C., Slack R.S., Figeys D., Park D.S.; RT "PINK1-mediated phosphorylation of LETM1 regulates mitochondrial calcium RT transport and protects neurons against mitochondrial stress."; RL Nat. Commun. 8:1399-1399(2017). RN [36] RP INTERACTION WITH TOMM70. RX PubMed=35391620; DOI=10.1007/s00109-022-02191-6; RA Maruszczak K.K., Jung M., Rasool S., Trempe J.F., Rapaport D.; RT "The role of the individual TOM subunits in the association of PINK1 with RT depolarized mitochondria."; RL J. Mol. Med. 100:747-762(2022). RN [37] RP INTERACTION WITH TIMM23, AND CHARACTERIZATION OF VARIANTS LEU-52; PHE-67; RP PRO-68; VAL-78; PHE-92; TRP-98; SER-111; LEU-115; VAL-124; GLY-125; RP PRO-126; MET-145; HIS-147; TRP-148; PRO-168; LYS-240; GLN-271; ASP-309; RP PRO-347; ALA-386; VAL-409; GLY-417 AND GLN-534 INS. RX PubMed=37160114; DOI=10.1016/j.celrep.2023.112454; RA Akabane S., Watanabe K., Kosako H., Yamashita S.I., Nishino K., Kato M., RA Sekine S., Kanki T., Matsuda N., Endo T., Oka T.; RT "TIM23 facilitates PINK1 activation by safeguarding against OMA1-mediated RT degradation in damaged mitochondria."; RL Cell Rep. 42:112454-112454(2023). RN [38] RP INTERACTION WITH TOM AND TIM23 COMPLEXES, INTERACTION WITH TOMM20, RP MUTAGENESIS OF ILE-131; ALA-536; LEU-540 AND ARG-543, AND CHARACTERIZATION RP OF VARIANTS SER-111; LEU-115; GLY-125 AND PRO-126. RX PubMed=38416681; DOI=10.1073/pnas.2313540121; RA Eldeeb M.A., Bayne A.N., Fallahi A., Goiran T., MacDougall E.J., RA Soumbasis A., Zorca C.E., Tabah J.J., Thomas R.A., Karpilovsky N., RA Mathur M., Durcan T.M., Trempe J.F., Fon E.A.; RT "Tom20 gates PINK1 activity and mediates its tethering of the TOM and TIM23 RT translocases upon mitochondrial stress."; RL Proc. Natl. Acad. Sci. U.S.A. 121:e2313540121-e2313540121(2024). RN [39] RP INTERACTION WITH TOMM20, MUTAGENESIS OF LEU-532; LEU-539 AND LEU-540, AND RP CHARACTERIZATION OF VARIANTS PRO-126; LYS-240; ASP-309 AND GLN-534 INS. RX PubMed=38848361; DOI=10.1126/sciadv.adn7191; RA Raimi O.G., Ojha H., Ehses K., Dederer V., Lange S.M., Rivera C.P., RA Deegan T.D., Chen Y., Wightman M., Toth R., Labib K.P.M., Mathea S., RA Ranson N., Fernandez-Busnadiego R., Muqit M.M.K.; RT "Mechanism of human PINK1 activation at the TOM complex in a reconstituted RT system."; RL Sci. Adv. 10:Eadn7191-Eadn7191(2024). RN [40] {ECO:0007744|PDB:9EIH, ECO:0007744|PDB:9EII, ECO:0007744|PDB:9EIJ} RP STRUCTURE BY ELECTRON MICROSCOPY (2.75 ANGSTROMS) IN COMPLEX WITH VDAC2 AND RP THE TOM COMPLEX, FUNCTION, INTERACTION WITH VDAC2 AND THE TOM COMPLEX, AND RP SUBCELLULAR LOCATION. RX PubMed=40080546; DOI=10.1126/science.adu6445; RA Callegari S., Kirk N.S., Gan Z.Y., Dite T., Cobbold S.A., Leis A., RA Dagley L.F., Glukhova A., Komander D.; RT "Structure of human PINK1 at a mitochondrial TOM-VDAC array."; RL Science 0:0-0(2025). RN [41] RP VARIANTS PARK6 PHE-92; PRO-168 AND HIS-464, AND VARIANTS LEU-296; THR-340; RP THR-442; LYS-476; THR-521 AND ASN-525. RX PubMed=15349860; DOI=10.1002/ana.20256; RA Valente E.M., Salvi S., Ialongo T., Marongiu R., Elia A.E., Caputo V., RA Romito L., Albanese A., Dallapiccola B., Bentivoglio A.R.; RT "PINK1 mutations are associated with sporadic early-onset parkinsonism."; RL Ann. Neurol. 56:336-341(2004). RN [42] RP VARIANTS PARK6 GLN-271; PRO-347 AND GLY-417. RX PubMed=15349870; DOI=10.1002/ana.20251; RA Hatano Y., Li Y., Sato K., Asakawa S., Yamamura Y., Tomiyama H., RA Yoshino H., Asahina M., Kobayashi S., Hassin-Baer S., Lu C.-S., Ng A.R., RA Rosales R.L., Shimizu N., Toda T., Mizuno Y., Hattori N.; RT "Novel PINK1 mutations in early-onset parkinsonism."; RL Ann. Neurol. 56:424-427(2004). RN [43] RP ERRATUM OF PUBMED:15349870. RA Hatano Y., Li Y., Sato K., Asakawa S., Yamamura Y., Tomiyama H., RA Yoshino H., Asahina M., Kobayashi S., Hassin-Baer S., Lu C.-S., Ng A.R., RA Rosales R.L., Shimizu N., Toda T., Mizuno Y., Hattori N.; RL Ann. Neurol. 56:603-603(2004). RN [44] RP VARIANTS PARK6 LYS-240; PRO-347 AND PRO-489, AND VARIANTS GLY-231; ILE-235; RP GLY-263; LEU-318; THR-339; THR-340; HIS-362; SER-425; LYS-476 AND THR-521. RX PubMed=15596610; DOI=10.1001/archneur.61.12.1898; RA Rogaeva E., Johnson J., Lang A.E., Gulick C., Gwinn-Hardy K., Kawarai T., RA Sato C., Morgan A., Werner J., Nussbaum R., Petit A., Okun M.S., RA McInerney A., Mandel R., Groen J.L., Fernandez H.H., Postuma R., RA Foote K.D., Salehi-Rad S., Liang Y., Reimsnider S., Tandon A., Hardy J., RA St George-Hyslop P., Singleton A.B.; RT "Analysis of the PINK1 gene in a large cohort of cases with Parkinson RT disease."; RL Arch. Neurol. 61:1898-1904(2004). RN [45] RP VARIANT PARK6 HIS-147. RX PubMed=15505171; DOI=10.1212/01.wnl.0000142089.38301.8e; RA Healy D.G., Abou-Sleiman P.M., Gibson J.M., Ross O.A., Jain S., Gandhi S., RA Gosal D., Muqit M.M.K., Wood N.W., Lynch T.; RT "PINK1 (PARK6) associated Parkinson disease in Ireland."; RL Neurology 63:1486-1488(2004). RN [46] RP VARIANT PARK6 ASP-309, CHARACTERIZATION OF VARIANT PARK6 ASP-309, FUNCTION, RP AND SUBCELLULAR LOCATION. RX PubMed=15087508; DOI=10.1126/science.1096284; RA Valente E.M., Abou-Sleiman P.M., Caputo V., Muqit M.M.K., Harvey K., RA Gispert S., Ali Z., Del Turco D., Bentivoglio A.R., Healy D.G., RA Albanese A., Nussbaum R., Gonzalez-Maldonado R., Deller T., Salvi S., RA Cortelli P., Gilks W.P., Latchman D.S., Harvey R.J., Dallapiccola B., RA Auburger G., Wood N.W.; RT "Hereditary early-onset Parkinson's disease caused by mutations in PINK1."; RL Science 304:1158-1160(2004). RN [47] RP VARIANT PARK6 VAL-268. RX PubMed=16207217; DOI=10.1111/j.1399-0004.2005.00500.x; RA Tan E.K., Yew K., Chua E., Shen H., Jamora R.D., Lee E., Puong K.Y., RA Zhao Y., Pavanni R., Wong M.C., Puvan K., Yih Y., Tan L.C.S.; RT "Analysis of PINK1 in Asian patients with familial parkinsonism."; RL Clin. Genet. 68:468-470(2005). RN [48] RP VARIANTS PARK6 HIS-279 AND GLN-534 INS, AND VARIANT LEU-115. RX PubMed=15970950; DOI=10.1038/sj.ejhg.5201455; RA Klein C., Djarmati A., Hedrich K., Schaefer N., Scaglione C., Marchese R., RA Kock N., Schuele B., Hiller A., Lohnau T., Winkler S., Wiegers K., RA Hering R., Bauer P., Riess O., Abbruzzese G., Martinelli P., RA Pramstaller P.P.; RT "PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset RT parkinsonism."; RL Eur. J. Hum. Genet. 13:1086-1093(2005). RN [49] RP CHARACTERIZATION OF VARIANTS PARK6 PRO-168 AND ASP-309. RX PubMed=16207731; DOI=10.1093/hmg/ddi377; RA Silvestri L., Caputo V., Bellacchio E., Atorino L., Dallapiccola B., RA Valente E.M., Casari G.; RT "Mitochondrial import and enzymatic activity of PINK1 mutants associated to RT recessive parkinsonism."; RL Hum. Mol. Genet. 14:3477-3492(2005). RN [50] RP VARIANT PARK6 ARG-388. RX PubMed=15955953; DOI=10.1212/01.wnl.0000164009.36740.4e; RA Li Y., Tomiyama H., Sato K., Hatano Y., Yoshino H., Atsumi M., RA Kitaguchi M., Sasaki S., Kawaguchi S., Miyajima H., Toda T., Mizuno Y., RA Hattori N.; RT "Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset RT parkinsonism."; RL Neurology 64:1955-1957(2005). RN [51] RP VARIANTS PARK6 PRO-168 AND LEU-196, AND VARIANTS LEU-115; THR-340; LYS-476 RP AND THR-521. RX PubMed=16009891; DOI=10.1212/01.wnl.0000167546.39375.82; RG The Italian Parkinson genetics network; RA Bonifati V., Rohe C.F., Breedveld G.J., Fabrizio E., De Mari M., RA Tassorelli C., Tavella A., Marconi R., Nicholl D.J., Chien H.F., RA Fincati E., Abbruzzese G., Marini P., De Gaetano A., Horstink M.W., RA Maat-Kievit J.A., Sampaio C., Antonini A., Stocchi F., Montagna P., RA Toni V., Guidi M., Dalla Libera A., Tinazzi M., De Pandis F., Fabbrini G., RA Goldwurm S., de Klein A., Barbosa E., Lopiano L., Martignoni E., RA Lamberti P., Vanacore N., Meco G., Oostra B.A.; RT "Early-onset parkinsonism associated with PINK1 mutations: frequency, RT genotypes, and phenotypes."; RL Neurology 65:87-95(2005). RN [52] RP VARIANTS ILE-317; THR-339; THR-383; SER-411; HIS-431; SER-451; SER-461; RP LYS-476; PRO-501 AND ARG-575, AND CHARACTERIZATION OF VARIANTS HIS-431; RP SER-451; LYS-476; PRO-501 AND ARG-575. RX PubMed=16969854; DOI=10.1002/ana.20960; RA Abou-Sleiman P.M., Muqit M.M.K., McDonald N.Q., Yang Y.X., Gandhi S., RA Healy D.G., Harvey K., Harvey R.J., Deas E., Bhatia K., Quinn N., Lees A., RA Latchman D.S., Wood N.W.; RT "A heterozygous effect for PINK1 mutations in Parkinson's disease?"; RL Ann. Neurol. 60:414-419(2006). RN [53] RP VARIANT PARK6 ASP-217. RX PubMed=16966503; DOI=10.1001/archneur.63.9.1257; RA Leutenegger A.-L., Salih M.A.M., Ibanez P., Mukhtar M.M., Lesage S., RA Arabi A., Lohmann E., Duerr A., Ahmed A.E.M., Brice A.; RT "Juvenile-onset Parkinsonism as a result of the first mutation in the RT adenosine triphosphate orientation domain of PINK1."; RL Arch. Neurol. 63:1257-1261(2006). RN [54] RP VARIANT PARK6 MET-313. RX PubMed=17030667; DOI=10.1001/archneur.63.10.1483; RA Chishti M.A., Bohlega S., Ahmed M., Loualich A., Carroll P., Sato C., RA St George-Hyslop P., Westaway D., Rogaeva E.; RT "T313M PINK1 mutation in an extended highly consanguineous Saudi family RT with early-onset Parkinson disease."; RL Arch. Neurol. 63:1483-1485(2006). RN [55] RP VARIANTS PARK6 GLY-125; LYS-240; PRO-369; ALA-386 AND VAL-409. RX PubMed=16401616; DOI=10.1093/brain/awl005; RG The French Parkinson's disease genetics study group; RA Ibanez P., Lesage S., Lohmann E., Thobois S., De Michele G., Borg M., RA Agid Y., Durr A., Brice A.; RT "Mutational analysis of the PINK1 gene in early-onset parkinsonism in RT Europe and North Africa."; RL Brain 129:686-694(2006). RN [56] RP VARIANT LEU-399. RX PubMed=16632486; DOI=10.1093/hmg/ddl104; RA Tang B., Xiong H., Sun P., Zhang Y., Wang D., Hu Z., Zhu Z., Ma H., Pan Q., RA Xia J.-H., Xia K., Zhang Z.; RT "Association of PINK1 and DJ-1 confers digenic inheritance of early-onset RT Parkinson's disease."; RL Hum. Mol. Genet. 15:1816-1825(2006). RN [57] RP VARIANT PARK6 THR-280, AND VARIANTS THR-340 AND THR-521. RX PubMed=16482571; DOI=10.1002/mds.20810; RA Tan E.-K., Yew K., Chua E., Puvan K., Shen H., Lee E., Puong K.-Y., RA Zhao Y., Pavanni R., Wong M.-C., Jamora D., de Silva D., Moe K.-T., RA Woon F.-P., Yuen Y., Tan L.; RT "PINK1 mutations in sporadic early-onset Parkinson's disease."; RL Mov. Disord. 21:789-793(2006). RN [58] RP VARIANT PARK6 GLN-407, AND VARIANTS THR-340 AND THR-521. RX PubMed=16257123; DOI=10.1016/j.neulet.2005.10.005; RA Fung H.-C., Chen C.-M., Hardy J., Singleton A.B., Lee-Chen G.-J., Wu Y.-R.; RT "Analysis of the PINK1 gene in a cohort of patients with sporadic early- RT onset parkinsonism in Taiwan."; RL Neurosci. Lett. 394:33-36(2006). RN [59] RP VARIANTS [LARGE SCALE ANALYSIS] TRP-148; SER-196; LEU-209; LEU-215; RP THR-339; THR-340; ILE-341; PHE-377; THR-477 AND THR-521. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [60] RP VARIANTS PHE-67; PRO-68; TRP-98; SER-111; VAL-124; MET-145; ASN-186; RP ILE-257; VAL-268; GLN-276; LEU-296; ILE-317; LEU-322; THR-339; THR-383; RP VAL-395; THR-442; LYS-476; ASN-525 AND THR-537. RX PubMed=18330912; DOI=10.1002/humu.20719; RG The Italian PD study group; RA Marongiu R., Ferraris A., Ialongo T., Michiorri S., Soleti F., Ferrari F., RA Elia A.E., Ghezzi D., Albanese A., Altavista M.C., Antonini A., Barone P., RA Brusa L., Cortelli P., Martinelli P., Pellecchia M.T., Pezzoli G., RA Scaglione C., Stanzione P., Tinazzi M., Zecchinelli A., Zeviani M., RA Cassetta E., Garavaglia B., Dallapiccola B., Bentivoglio A.R., RA Valente E.M.; RT "PINK1 heterozygous rare variants: prevalence, significance and phenotypic RT spectrum."; RL Hum. Mutat. 29:565-565(2008). RN [61] RP VARIANT PARK6 PRO-126. RX PubMed=18286320; DOI=10.1007/s00415-008-0763-4; RA Prestel J., Gempel K., Hauser T.K., Schweitzer K., Prokisch H., Ahting U., RA Freudenstein D., Bueltmann E., Naegele T., Berg D., Klopstock T., RA Gasser T.; RT "Clinical and molecular characterisation of a Parkinson family with a novel RT PINK1 mutation."; RL J. Neurol. 255:643-648(2008). RN [62] RP VARIANTS PARK6 MET-313 AND 492-ARG--LYS-581 DEL. RX PubMed=18785233; DOI=10.1002/mds.22156; RA Guo J.F., Xiao B., Liao B., Zhang X.W., Nie L.L., Zhang Y.H., Shen L., RA Jiang H., Xia K., Pan Q., Yan X.X., Tang B.S.; RT "Mutation analysis of Parkin, PINK1, DJ-1 and ATP13A2 genes in Chinese RT patients with autosomal recessive early-onset Parkinsonism."; RL Mov. Disord. 23:2074-2079(2008). RN [63] RP VARIANT PARK6 LEU-52. RX PubMed=19351622; DOI=10.1136/jmg.2008.063917; RA Brooks J., Ding J., Simon-Sanchez J., Paisan-Ruiz C., Singleton A.B., RA Scholz S.W.; RT "Parkin and PINK1 mutations in early-onset Parkinson's disease: RT comprehensive screening in publicly available cases and control."; RL J. Med. Genet. 46:375-381(2009). RN [64] RP VARIANT PARK6 PRO-347. RX PubMed=22956510; DOI=10.1002/mds.25132; RA Kilarski L.L., Pearson J.P., Newsway V., Majounie E., Knipe M.D., RA Misbahuddin A., Chinnery P.F., Burn D.J., Clarke C.E., Marion M.H., RA Lewthwaite A.J., Nicholl D.J., Wood N.W., Morrison K.E., RA Williams-Gray C.H., Evans J.R., Sawcer S.J., Barker R.A., RA Wickremaratchi M.M., Ben-Shlomo Y., Williams N.M., Morris H.R.; RT "Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ- RT 1) and LRRK2 in early-onset Parkinson's disease."; RL Mov. Disord. 27:1522-1529(2012). CC -!- FUNCTION: Serine/threonine-protein kinase which acts as a sensor of CC mitochondrial damage and protects against mitochondrial dysfunction CC during cellular stress (PubMed:40080546). It phosphorylates CC mitochondrial proteins to coordinate mitochondrial quality control CC mechanisms that remove and replace dysfunctional mitochondrial CC components (PubMed:14607334, PubMed:15087508, PubMed:18443288, CC PubMed:18957282, PubMed:19229105, PubMed:19966284, PubMed:20404107, CC PubMed:20547144, PubMed:20798600, PubMed:22396657, PubMed:23620051, CC PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24751536, CC PubMed:24784582, PubMed:24896179, PubMed:24898855, PubMed:25527291, CC PubMed:32484300). In healthy mitochondria, PINK1 is translocated across CC the mitochondrial outer membrane (MOM) via the translocase of the outer CC membrane (TOM) complex, and inserted into the mitochondrial inner CC membrane (MIM) via the translocase of the inner membrane (TIM23) CC complex where it is cleaved and released into the cytosol CC (PubMed:40080546). Depending on the severity of mitochondrial damage, CC activity ranges from preventing apoptosis and stimulating mitochondrial CC biogenesis to eliminating severely damaged mitochondria via PINK1-PRKN- CC dependent mitophagy (PubMed:14607334, PubMed:15087508, PubMed:18443288, CC PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:22396657, CC PubMed:23620051, PubMed:23933751, PubMed:24898855, PubMed:32047033, CC PubMed:32484300). When cellular stress results in irreversible CC mitochondrial damage, PINK1 accumulates at the outer mitochondrial CC membrane (OMM) where it phosphorylates pre-existing polyubiquitin CC chains at 'Ser-65', recruits PRKN from the cytosol to the OMM and CC activates PRKN by phosphorylation at 'Ser-65'; activated PRKN then CC ubiquitinates VDAC1 and other OMM proteins to initiate mitophagy CC (PubMed:14607334, PubMed:15087508, PubMed:19966284, PubMed:20404107, CC PubMed:20798600, PubMed:23754282, PubMed:23933751, PubMed:24660806, CC PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291, CC PubMed:32047033, PubMed:40080546). The PINK1-PRKN pathway also promotes CC fission of damaged mitochondria through phosphorylation and PRKN- CC dependent degradation of mitochondrial proteins involved in fission CC such as MFN2 (PubMed:18443288, PubMed:23620051, PubMed:24898855). This CC prevents the refusion of unhealthy mitochondria with the mitochondrial CC network or initiates mitochondrial fragmentation facilitating their CC later engulfment by autophagosomes (PubMed:18443288, PubMed:23620051). CC Also promotes mitochondrial fission independently of PRKN and ATG7- CC mediated mitophagy, via the phosphorylation and activation of DNM1L CC (PubMed:18443288, PubMed:32484300). Regulates motility of damaged CC mitochondria by promoting the ubiquitination and subsequent degradation CC of MIRO1 and MIRO2; in motor neurons, this likely inhibits CC mitochondrial intracellular anterograde transport along the axons which CC probably increases the chance of the mitochondria undergoing mitophagy CC in the soma (PubMed:22396657). Required for ubiquinone reduction by CC mitochondrial complex I by mediating phosphorylation of complex I CC subunit NDUFA10 (By similarity). Phosphorylates LETM1, positively CC regulating its mitochondrial calcium transport activity CC (PubMed:29123128). {ECO:0000250|UniProtKB:Q99MQ3, CC ECO:0000269|PubMed:14607334, ECO:0000269|PubMed:15087508, CC ECO:0000269|PubMed:18443288, ECO:0000269|PubMed:18957282, CC ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19966284, CC ECO:0000269|PubMed:20404107, ECO:0000269|PubMed:20547144, CC ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:22396657, CC ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:23754282, CC ECO:0000269|PubMed:23933751, ECO:0000269|PubMed:24660806, CC ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582, CC ECO:0000269|PubMed:24896179, ECO:0000269|PubMed:24898855, CC ECO:0000269|PubMed:25474007, ECO:0000269|PubMed:25527291, CC ECO:0000269|PubMed:29123128, ECO:0000269|PubMed:32047033, CC ECO:0000269|PubMed:32484300, ECO:0000269|PubMed:40080546}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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:18957282, ECO:0000269|PubMed:24660806, CC ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582, CC ECO:0000269|PubMed:32484300}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; CC Evidence={ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:24660806, CC ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582, CC ECO:0000269|PubMed:29123128, ECO:0000269|PubMed:32484300}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- SUBUNIT: Upon mitochondrial depolarization, associates with the TOM CC complex and the VDAC2 homodimer; its import into the mitochondria is CC stalled at the TOM complex (PubMed:40080546). Upon mitochondrial CC depolarization, interacts with TIMM23 (PubMed:38416681). Forms a CC supercomplex with TOM and TIM23 complexes; PINK1-TOM-TIM23 supercomplex CC formation requires PINK1 interaction with TOMM20 and TOMM70 CC (PubMed:38416681). The interaction with TOM and TIM23 complexes is CC critical for PINK1 stabilization at the outer mitochondrial membrane, CC kinase activation and downstream mitophagy (PubMed:35391620, CC PubMed:38416681, PubMed:38848361, PubMed:40080546). Interacts with PRKN CC (PubMed:19966284, PubMed:20798600). Interacts with FBXO7 CC (PubMed:23933751). Forms a complex with PRKN and PARK7 CC (PubMed:19229105). Interacts with NENF (PubMed:31536960). CC {ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19966284, CC ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:23933751, CC ECO:0000269|PubMed:31536960, ECO:0000269|PubMed:35391620, CC ECO:0000269|PubMed:37160114, ECO:0000269|PubMed:38416681, CC ECO:0000269|PubMed:38848361, ECO:0000269|PubMed:40080546}. CC -!- INTERACTION: CC Q9BXM7; P63010-2: AP2B1; NbExp=3; IntAct=EBI-2846068, EBI-11529439; CC Q9BXM7; P05067: APP; NbExp=3; IntAct=EBI-2846068, EBI-77613; CC Q9BXM7; O15392: BIRC5; NbExp=3; IntAct=EBI-2846068, EBI-518823; CC Q9BXM7; Q9Y3I1: FBXO7; NbExp=8; IntAct=EBI-2846068, EBI-1161222; CC Q9BXM7; Q9Y3I1-1: FBXO7; NbExp=2; IntAct=EBI-2846068, EBI-9102965; CC Q9BXM7; Q9UHY8: FEZ2; NbExp=3; IntAct=EBI-2846068, EBI-396453; CC Q9BXM7; P08238: HSP90AB1; NbExp=3; IntAct=EBI-2846068, EBI-352572; CC Q9BXM7; P42858: HTT; NbExp=9; IntAct=EBI-2846068, EBI-466029; CC Q9BXM7; Q6DN90-2: IQSEC1; NbExp=3; IntAct=EBI-2846068, EBI-21911304; CC Q9BXM7; Q9BYZ2: LDHAL6B; NbExp=3; IntAct=EBI-2846068, EBI-1108377; CC Q9BXM7; Q9GZQ8: MAP1LC3B; NbExp=3; IntAct=EBI-2846068, EBI-373144; CC Q9BXM7; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-2846068, EBI-716063; CC Q9BXM7; P00491: PNP; NbExp=3; IntAct=EBI-2846068, EBI-712238; CC Q9BXM7; O60260: PRKN; NbExp=7; IntAct=EBI-2846068, EBI-716346; CC Q9BXM7; Q8IXI2: RHOT1; NbExp=3; IntAct=EBI-2846068, EBI-1396430; CC Q9BXM7; Q8WXH5: SOCS4; NbExp=3; IntAct=EBI-2846068, EBI-3942425; CC Q9BXM7; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-2846068, EBI-11959123; CC Q9BXM7; P28347-2: TEAD1; NbExp=3; IntAct=EBI-2846068, EBI-12151837; CC Q9BXM7; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-2846068, EBI-11141397; CC Q9BXM7; Q8N895: ZNF366; NbExp=3; IntAct=EBI-2846068, EBI-2813661; CC Q9BXM7-1; O60260: PRKN; NbExp=2; IntAct=EBI-15643376, EBI-716346; CC Q9BXM7-1; Q12931: TRAP1; NbExp=4; IntAct=EBI-15643376, EBI-1055869; CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane CC {ECO:0000269|PubMed:15087508, ECO:0000269|PubMed:16672980, CC ECO:0000269|PubMed:18687899, ECO:0000269|PubMed:18957282, CC ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20798600, CC ECO:0000269|PubMed:23933751, ECO:0000269|PubMed:31536960}. CC Mitochondrion inner membrane {ECO:0000250|UniProtKB:Q99MQ3}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:19229105, CC ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:22354088}. CC Note=Localizes mostly in mitochondrion and the two smaller proteolytic CC processed fragments localize mainly in cytosol (PubMed:19229105). In CC healthy mitochondria, PINK1 is translocated across the mitochondrial CC membranes (PubMed:40080546). Upon mitochondrial membrane depolarization CC following damage, PINK1 import is stalled, which induces its CC accumulation in the outer mitochondrial membrane and the activation of CC its kinase activity (PubMed:18957282, PubMed:40080546). CC {ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:19229105, CC ECO:0000269|PubMed:40080546}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1 {ECO:0000269|PubMed:14607334}; CC IsoId=Q9BXM7-1; Sequence=Displayed; CC Name=2 {ECO:0000305}; CC IsoId=Q9BXM7-2; Sequence=VSP_050754, VSP_050755; CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle and CC testis, and at lower levels in brain, placenta, liver, kidney, CC pancreas, prostate, ovary and small intestine. Present in the embryonic CC testis from an early stage of development. CC {ECO:0000269|PubMed:11494141}. CC -!- PTM: Proteolytically cleaved (PubMed:19229105, PubMed:22354088, CC PubMed:30733118). In healthy cells, the precursor is continuously CC imported into the inner mitochondrial membrane (IMM), where it is CC proteolytically cleaved by mitochondrial-processing peptidase (MPP) and CC then undergoes further proteolytic cleavage by PARL or AFG3L2 to give CC rise to the 52 kDa short form (PubMed:19229105, PubMed:22354088). The CC 52 kDa short form is then released into the cytosol where it rapidly CC undergoes proteasome-dependent degradation (PubMed:20404107). In CC unhealthy cells, when cellular stress conditions lead to the loss of CC mitochondrial membrane potential, mitochondrial import is impaired CC leading to the precursor accumulating on the outer mitochondrial CC membrane (OMM) (PubMed:20404107, PubMed:30733118). If accumulation at CC the OMM 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 (PubMed:30733118). CC {ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20404107, CC ECO:0000269|PubMed:22354088, ECO:0000269|PubMed:30733118}. CC -!- PTM: Autophosphorylated (PubMed:18957282, PubMed:20404107, CC PubMed:22910362). Loss of mitochondrial membrane potential results in CC the precursor accumulating on the outer mitochondrial membrane (OMM) CC where it is activated by autophosphorylation (PubMed:18957282, CC PubMed:20404107, PubMed:22910362). Autophosphorylation at Ser-228 and CC Ser-402 is sufficient and essential for selective recruitment of PRKN CC to depolarized mitochondria, via PINK1-dependent phosphorylation of CC ubiquitin and maybe PRKN (PubMed:18957282, PubMed:22910362). CC {ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:20404107, CC ECO:0000269|PubMed:22910362}. CC -!- DISEASE: Parkinson disease 6 (PARK6) [MIM:605909]: An early-onset form CC of Parkinson disease, a neurodegenerative disorder characterized by CC parkinsonian signs such as rigidity, resting tremor and bradykinesia. A CC subset of patients manifest additional symptoms including CC hyperreflexia, autonomic instability, dementia and psychiatric CC disturbances. Symptoms show diurnal fluctuation and can improve after CC sleep. PARK6 pathogenesis involves respiratory complex I deficiency CC causing mitochondrial depolarization and dysfunction. Inheritance is CC autosomal recessive. {ECO:0000269|PubMed:15087508, CC ECO:0000269|PubMed:15349860, ECO:0000269|PubMed:15349870, CC ECO:0000269|PubMed:15505171, ECO:0000269|PubMed:15596610, CC ECO:0000269|PubMed:15955953, ECO:0000269|PubMed:15970950, CC ECO:0000269|PubMed:16009891, ECO:0000269|PubMed:16207217, CC ECO:0000269|PubMed:16207731, ECO:0000269|PubMed:16257123, CC ECO:0000269|PubMed:16401616, ECO:0000269|PubMed:16482571, CC ECO:0000269|PubMed:16632486, ECO:0000269|PubMed:16966503, CC ECO:0000269|PubMed:17030667, ECO:0000269|PubMed:18286320, CC ECO:0000269|PubMed:18785233, ECO:0000269|PubMed:19229105, CC ECO:0000269|PubMed:19351622, ECO:0000269|PubMed:20547144, CC ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:22043288, CC ECO:0000269|PubMed:22396657, ECO:0000269|PubMed:22956510, CC ECO:0000269|PubMed:24652937, ECO:0000269|PubMed:24784582}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB053323; BAB55647.1; -; mRNA. DR EMBL; AF316873; AAK28062.1; -; mRNA. DR EMBL; AK075225; BAC11484.1; -; mRNA. DR EMBL; AL391357; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009534; AAH09534.1; -; mRNA. DR EMBL; BC028215; AAH28215.1; -; mRNA. DR CCDS; CCDS211.1; -. [Q9BXM7-1] DR RefSeq; NP_115785.1; NM_032409.3. [Q9BXM7-1] DR PDB; 9EIH; EM; 3.10 A; A/B=1-581. DR PDB; 9EII; EM; 2.75 A; B=1-581. DR PDB; 9EIJ; EM; 3.30 A; B=1-581. DR PDBsum; 9EIH; -. DR PDBsum; 9EII; -. DR PDBsum; 9EIJ; -. DR AlphaFoldDB; Q9BXM7; -. DR EMDB; EMD-48083; -. DR EMDB; EMD-48084; -. DR EMDB; EMD-48085; -. DR SMR; Q9BXM7; -. DR BioGRID; 122376; 696. DR CORUM; Q9BXM7; -. DR DIP; DIP-29427N; -. DR FunCoup; Q9BXM7; 1190. DR IntAct; Q9BXM7; 177. DR MINT; Q9BXM7; -. DR STRING; 9606.ENSP00000364204; -. DR ChEMBL; CHEMBL3337330; -. DR TCDB; 8.A.104.1.16; the 5'-amp-activated protein kinase (ampk) family. DR CarbonylDB; Q9BXM7; -. DR GlyGen; Q9BXM7; 3 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q9BXM7; -. DR PhosphoSitePlus; Q9BXM7; -. DR BioMuta; PINK1; -. DR DMDM; 48428484; -. DR MassIVE; Q9BXM7; -. DR PaxDb; 9606-ENSP00000364204; -. DR PeptideAtlas; Q9BXM7; -. DR ProteomicsDB; 79455; -. [Q9BXM7-1] DR ProteomicsDB; 79456; -. [Q9BXM7-2] DR ABCD; Q9BXM7; 4 sequenced antibodies. DR Antibodypedia; 1105; 806 antibodies from 48 providers. DR DNASU; 65018; -. DR Ensembl; ENST00000321556.5; ENSP00000364204.3; ENSG00000158828.9. [Q9BXM7-1] DR GeneID; 65018; -. DR KEGG; hsa:65018; -. DR MANE-Select; ENST00000321556.5; ENSP00000364204.3; NM_032409.3; NP_115785.1. DR UCSC; uc001bdm.3; human. [Q9BXM7-1] DR AGR; HGNC:14581; -. DR ClinPGx; PA33325; -. DR CTD; 65018; -. DR DisGeNET; 65018; -. DR GeneCards; PINK1; -. DR GeneReviews; PINK1; -. DR HGNC; HGNC:14581; PINK1. DR HPA; ENSG00000158828; Tissue enhanced (skeletal muscle, tongue). DR MalaCards; PINK1; -. DR MIM; 168600; phenotype. DR MIM; 605909; phenotype. DR MIM; 608309; gene. DR OpenTargets; ENSG00000158828; -. DR Orphanet; 2828; Young-onset Parkinson disease. DR VEuPathDB; HostDB:ENSG00000158828; -. DR eggNOG; KOG4158; Eukaryota. DR GeneTree; ENSGT00390000001206; -. DR HOGENOM; CLU_022208_1_0_1; -. DR InParanoid; Q9BXM7; -. DR OMA; TCCSLRN; -. DR OrthoDB; 1405469at2759; -. DR PAN-GO; Q9BXM7; 6 GO annotations based on evolutionary models. DR PhylomeDB; Q9BXM7; -. DR PathwayCommons; Q9BXM7; -. DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy. DR Reactome; R-HSA-9614657; FOXO-mediated transcription of cell death genes. DR SignaLink; Q9BXM7; -. DR SIGNOR; Q9BXM7; -. DR Agora; ENSG00000158828; -. DR BioGRID-ORCS; 65018; 17 hits in 1195 CRISPR screens. DR ChiTaRS; PINK1; human. DR GeneWiki; PINK1; -. DR GenomeRNAi; 65018; -. DR Pharos; Q9BXM7; Tbio. DR PRO; PR:Q9BXM7; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9BXM7; protein. DR Bgee; ENSG00000158828; Expressed in tendon of biceps brachii and 210 other cell types or tissues. DR GO; GO:0097449; C:astrocyte projection; IDA:ParkinsonsUK-UCL. DR GO; GO:0030424; C:axon; IDA:ParkinsonsUK-UCL. DR GO; GO:0044297; C:cell body; IDA:ParkinsonsUK-UCL. DR GO; GO:0000785; C:chromatin; IDA:ParkinsonsUK-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:ParkinsonsUK-UCL. DR GO; GO:0005856; C:cytoskeleton; IDA:ParkinsonsUK-UCL. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0030426; C:growth cone; IEA:Ensembl. DR GO; GO:0097413; C:Lewy body; TAS:ParkinsonsUK-UCL. DR GO; GO:0016020; C:membrane; IDA:ParkinsonsUK-UCL. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ParkinsonsUK-UCL. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:ParkinsonsUK-UCL. DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:ParkinsonsUK-UCL. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ParkinsonsUK-UCL. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0055131; F:C3HC4-type RING finger domain binding; IPI:BHF-UCL. DR GO; GO:0016301; F:kinase activity; IDA:MGI. DR GO; GO:0019900; F:kinase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0016504; F:peptidase activator activity; TAS:ParkinsonsUK-UCL. DR GO; GO:0002020; F:protease binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0004672; F:protein kinase activity; IMP:UniProtKB. DR GO; GO:0043422; F:protein kinase B binding; IDA:ParkinsonsUK-UCL. 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; IMP:ParkinsonsUK-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0000422; P:autophagy of mitochondrion; IMP:UniProtKB. 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; TAS:ParkinsonsUK-UCL. DR GO; GO:0014046; P:dopamine secretion; IEA:Ensembl. DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; IMP:UniProtKB. DR GO; GO:0030097; P:hemopoiesis; IGI:ARUK-UCL. DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB. DR GO; GO:0016236; P:macroautophagy; TAS:Reactome. DR GO; GO:0072656; P:maintenance of protein location in mitochondrion; IMP:ParkinsonsUK-UCL. DR GO; GO:0007005; P:mitochondrion organization; IMP:ParkinsonsUK-UCL. DR GO; GO:0099074; P:mitochondrion to lysosome vesicle-mediated transport; IMP:ParkinsonsUK-UCL. DR GO; GO:0000423; P:mitophagy; IDA:UniProt. DR GO; GO:1902902; P:negative regulation of autophagosome assembly; IMP:ParkinsonsUK-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; ISS:ParkinsonsUK-UCL. DR GO; GO:1903384; P:negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL. DR GO; GO:1903298; P:negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:1903751; P:negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide; IDA:ParkinsonsUK-UCL. DR GO; GO:0046329; P:negative regulation of JNK cascade; TAS:ParkinsonsUK-UCL. DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0090258; P:negative regulation of mitochondrial fission; IMP:ParkinsonsUK-UCL. DR GO; GO:1901525; P:negative regulation of mitophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:ParkinsonsUK-UCL. DR GO; GO:1903377; P:negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:ParkinsonsUK-UCL. DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; TAS:ParkinsonsUK-UCL. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:ParkinsonsUK-UCL. DR GO; GO:1903852; P:positive regulation of cristae formation; IMP:ParkinsonsUK-UCL. DR GO; GO:0033603; P:positive regulation of dopamine secretion; IEA:Ensembl. DR GO; GO:1904544; P:positive regulation of free ubiquitin chain polymerization; ISS:ParkinsonsUK-UCL. DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:ParkinsonsUK-UCL. DR GO; GO:1902958; P:positive regulation of mitochondrial electron transport, NADH to ubiquinone; TAS:ParkinsonsUK-UCL. DR GO; GO:0090141; P:positive regulation of mitochondrial fission; IBA:GO_Central. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:ParkinsonsUK-UCL. DR GO; GO:1903955; P:positive regulation of protein targeting to mitochondrion; HMP:ParkinsonsUK-UCL. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:ParkinsonsUK-UCL. DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IMP:BHF-UCL. DR GO; GO:0032226; P:positive regulation of synaptic transmission, dopaminergic; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0045727; P:positive regulation of translation; IEA:Ensembl. DR GO; GO:1905091; P:positive regulation of type 2 mitophagy; 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; IMP:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central. DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; TAS:ParkinsonsUK-UCL. DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; IMP:ParkinsonsUK-UCL. DR GO; GO:0010310; P:regulation of hydrogen peroxide metabolic process; IEA:Ensembl. DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IMP:ParkinsonsUK-UCL. DR GO; GO:0010821; P:regulation of mitochondrion organization; IMP:ParkinsonsUK-UCL. DR GO; GO:0002082; P:regulation of oxidative phosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; NAS:ParkinsonsUK-UCL. DR GO; GO:1903214; P:regulation of protein targeting to mitochondrion; IMP:ParkinsonsUK-UCL. DR GO; GO:0031396; P:regulation of protein ubiquitination; IDA:BHF-UCL. DR GO; GO:0043254; P:regulation of protein-containing complex assembly; IDA:BHF-UCL. DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:ParkinsonsUK-UCL. DR GO; GO:1902803; P:regulation of synaptic vesicle transport; TAS:ParkinsonsUK-UCL. DR GO; GO:0022904; P:respiratory electron transport chain; IEA:Ensembl. DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IGI:ParkinsonsUK-UCL. DR GO; GO:0038203; P:TORC2 signaling; IDA:ParkinsonsUK-UCL. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ParkinsonsUK-UCL. DR CDD; cd14018; STKc_PINK1; 1. DR FunFam; 1.10.510.10:FF:000418; PTEN induced kinase 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR051511; MitoQC_Scaffold_Kinases. DR InterPro; IPR040110; PINK1_STKc. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR22972; SERINE/THREONINE PROTEIN KINASE; 1. DR PANTHER; PTHR22972:SF7; SERINE_THREONINE-PROTEIN KINASE PINK1, MITOCHONDRIAL; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Autophagy; Cytoplasm; KW Disease variant; Kinase; Magnesium; Membrane; Metal-binding; Mitochondrion; KW Mitochondrion inner membrane; Mitochondrion outer membrane; KW Neurodegeneration; Nucleotide-binding; Parkinson disease; Parkinsonism; KW Phosphoprotein; Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Serine/threonine-protein kinase; Transferase; KW Transit peptide. FT TRANSIT 1..77 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 78..581 FT /note="Serine/threonine-protein kinase PINK1, FT mitochondrial" FT /id="PRO_0000024369" FT DOMAIN 156..511 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; this FT region is trapped in the TOM complex upon mitochondrial FT depolarization" FT /evidence="ECO:0000269|PubMed:30733118, FT ECO:0000269|PubMed:40080546" FT REGION 189..208 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 362 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 228 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:22910362" FT MOD_RES 402 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:22910362" FT VAR_SEQ 1..307 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_050754" FT VAR_SEQ 308..320 FT /note="LGHGRTLFLVMKN -> MCGSQRPSPLSTS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_050755" FT VARIANT 52 FT /note="P -> L (in PARK6; uncertain significance; no effect FT on interaction with TIMM23; dbSNP:rs776293086)" FT /evidence="ECO:0000269|PubMed:19351622, FT ECO:0000269|PubMed:37160114" FT /id="VAR_089730" FT VARIANT 67 FT /note="L -> F (no effect on interaction with TIMM23; FT dbSNP:rs763142730)" FT /evidence="ECO:0000269|PubMed:18330912, FT ECO:0000269|PubMed:37160114" FT /id="VAR_046566" FT VARIANT 68 FT /note="R -> P (no effect on interaction with TIMM23; FT dbSNP:rs1385309950)" FT /evidence="ECO:0000269|PubMed:18330912, FT ECO:0000269|PubMed:37160114" FT /id="VAR_046567" FT VARIANT 78 FT /note="A -> V (severely decreased interaction with TIMM23; FT dbSNP:rs1409111496)" FT /evidence="ECO:0000269|PubMed:37160114" FT /id="VAR_089731" FT VARIANT 92 FT /note="C -> F (in PARK6; uncertain significance; no effect FT on interaction with TIMM23; dbSNP:rs1553145550)" FT /evidence="ECO:0000269|PubMed:15349860, FT ECO:0000269|PubMed:37160114" FT /id="VAR_046568" FT VARIANT 98 FT /note="R -> W (severely decreased interaction with TIMM23; FT dbSNP:rs575668171)" FT /evidence="ECO:0000269|PubMed:18330912, FT ECO:0000269|PubMed:37160114" FT /id="VAR_046569" FT VARIANT 111 FT /note="I -> S (found in a patient with Parkinson disease; FT uncertain significance; under depolarizing conditions, it FT fails to support PINK1-TOM-TIM23 complex assembly and FT mitophagy activation; no effect on interaction with TIMM23; FT dbSNP:rs1553145560)" FT /evidence="ECO:0000269|PubMed:18330912, FT ECO:0000269|PubMed:37160114, ECO:0000269|PubMed:38416681" FT /id="VAR_046570" FT VARIANT 115 FT /note="Q -> L (under depolarizing conditions, does not FT affect PINK1-TOM-TIM23 complex assembly and mitophagy FT activation; no effect on interaction with TIMM23; FT dbSNP:rs148871409)" FT /evidence="ECO:0000269|PubMed:15970950, FT ECO:0000269|PubMed:16009891, ECO:0000269|PubMed:37160114, FT ECO:0000269|PubMed:38416681" FT /id="VAR_046571" FT VARIANT 124 FT /note="A -> V (no effect on interaction with TIMM23; FT dbSNP:rs1274588239)" FT /evidence="ECO:0000269|PubMed:18330912, FT ECO:0000269|PubMed:37160114" FT /id="VAR_046572" FT VARIANT 125 FT /note="C -> G (in PARK6; under depolarizing conditions, it FT fails to support PINK1-TOM-TIM23 complex assembly and FT mitophagy activation; no effect on interaction with FT TIMM23)" FT /evidence="ECO:0000269|PubMed:16401616, FT ECO:0000269|PubMed:37160114, ECO:0000269|PubMed:38416681" FT /id="VAR_062773" FT VARIANT 126 FT /note="Q -> P (in PARK6; strongly reduces interaction with FT PRKN; under depolarizing conditions, it fails to support FT PINK1-TOM-TIM23 complex assembly and mitophagy activation; FT loss of autophosphorylation on S-228 and kinase activation; FT no effect on interaction with TIMM23; dbSNP:rs775809722)" FT /evidence="ECO:0000269|PubMed:18286320, FT ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:37160114, FT ECO:0000269|PubMed:38416681, ECO:0000269|PubMed:38848361" FT /id="VAR_064344" FT VARIANT 145 FT /note="T -> M (no effect on interaction with TIMM23; FT dbSNP:rs45604240)" FT /evidence="ECO:0000269|PubMed:18330912, FT ECO:0000269|PubMed:37160114" FT /id="VAR_046573" FT VARIANT 147 FT /note="R -> H (in PARK6; uncertain significance; no effect FT on interaction with TIMM23; dbSNP:rs138050841)" FT /evidence="ECO:0000269|PubMed:15505171, FT ECO:0000269|PubMed:37160114" FT /id="VAR_046574" FT VARIANT 148 FT /note="L -> W (no effect on interaction with TIMM23; FT dbSNP:rs56297806)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:37160114" FT /id="VAR_041010" FT VARIANT 168 FT /note="A -> P (in PARK6; no effect on autophosphorylation; FT localizes to the mitochondria and immunogold experiments FT reveal that both wild-type and mutant proteins face the FT mitochondrial intermembrane space; no effect on interaction FT with TIMM23; dbSNP:rs768091663)" FT /evidence="ECO:0000269|PubMed:15349860, FT ECO:0000269|PubMed:16009891, ECO:0000269|PubMed:16207731, FT ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:37160114" FT /id="VAR_046575" FT VARIANT 170 FT /note="V -> G (in PARK6; dbSNP:rs1553145929)" FT /evidence="ECO:0000269|PubMed:24652937" FT /id="VAR_078934" FT VARIANT 186 FT /note="K -> N (in dbSNP:rs143204084)" FT /evidence="ECO:0000269|PubMed:18330912" FT /id="VAR_046576" FT VARIANT 196 FT /note="P -> L (in PARK6; dbSNP:rs138302371)" FT /evidence="ECO:0000269|PubMed:16009891" FT /id="VAR_046577" FT VARIANT 196 FT /note="P -> S (in dbSNP:rs35802484)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041011" FT VARIANT 209 FT /note="P -> L (in dbSNP:rs34677717)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041012" FT VARIANT 215 FT /note="P -> L (in a glioblastoma multiforme sample; somatic FT mutation; dbSNP:rs371854396)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041013" FT VARIANT 217 FT /note="A -> D (in PARK6; dbSNP:rs74315360)" FT /evidence="ECO:0000269|PubMed:16966503" FT /id="VAR_046578" FT VARIANT 231 FT /note="E -> G (in dbSNP:rs1303935100)" FT /evidence="ECO:0000269|PubMed:15596610" FT /id="VAR_046579" FT VARIANT 235 FT /note="N -> I (in dbSNP:rs1557562082)" FT /evidence="ECO:0000269|PubMed:15596610" FT /id="VAR_046580" FT VARIANT 240 FT /note="E -> K (in PARK6; loss of autophosphorylation on S- FT 228 and kinase activation; no effect on interaction with FT TIMM23; dbSNP:rs573931674)" FT /evidence="ECO:0000269|PubMed:15596610, FT ECO:0000269|PubMed:16401616, ECO:0000269|PubMed:37160114, FT ECO:0000269|PubMed:38848361" FT /id="VAR_046581" FT VARIANT 257 FT /note="T -> I (in dbSNP:rs370906995)" FT /evidence="ECO:0000269|PubMed:18330912" FT /id="VAR_046582" FT VARIANT 263 FT /note="R -> G (in dbSNP:rs1553146419)" FT /evidence="ECO:0000269|PubMed:15596610" FT /id="VAR_046583" FT VARIANT 268 FT /note="L -> V (in PARK6; dbSNP:rs372280083)" FT /evidence="ECO:0000269|PubMed:16207217, FT ECO:0000269|PubMed:18330912" FT /id="VAR_046584" FT VARIANT 271 FT /note="H -> Q (in PARK6; no effect on interaction with FT TIMM23; dbSNP:rs28940284)" FT /evidence="ECO:0000269|PubMed:15349870, FT ECO:0000269|PubMed:37160114" FT /id="VAR_046585" FT VARIANT 276 FT /note="R -> Q (in dbSNP:rs548506734)" FT /evidence="ECO:0000269|PubMed:18330912" FT /id="VAR_046586" FT VARIANT 279 FT /note="R -> H (in PARK6; dbSNP:rs74315358)" FT /evidence="ECO:0000269|PubMed:15970950" FT /id="VAR_046587" FT VARIANT 280 FT /note="A -> T (in PARK6; dbSNP:rs772510148)" FT /evidence="ECO:0000269|PubMed:16482571" FT /id="VAR_062774" FT VARIANT 296 FT /note="P -> L (in dbSNP:rs779060308)" FT /evidence="ECO:0000269|PubMed:15349860, FT ECO:0000269|PubMed:18330912" FT /id="VAR_046588" FT VARIANT 305 FT /note="P -> L (in dbSNP:rs7349186)" FT /id="VAR_018993" FT VARIANT 309 FT /note="G -> D (in PARK6; affects cellular response to FT stress resulting in increased mitochondrial depolarization FT under stress conditions compared to wild type; has no FT effect on autophosphorylation; strongly reduces interaction FT with PRKN; decreases PRKN and SNCAIP ubiquitination and FT degradation; decreases Drp1 phosphorylation; loss of FT ubiquitin phosphorylation; no effect on interaction with FT TIMM23; dbSNP:rs74315355)" FT /evidence="ECO:0000269|PubMed:15087508, FT ECO:0000269|PubMed:16207731, ECO:0000269|PubMed:19229105, FT ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:32484300, FT ECO:0000269|PubMed:37160114, ECO:0000269|PubMed:38848361" FT /id="VAR_018994" FT VARIANT 313 FT /note="T -> M (in PARK6; decreases PRKN and SNCAIP FT ubiquitination and degradation; slightly decreases Drp1 FT phosphorylation; dbSNP:rs74315359)" FT /evidence="ECO:0000269|PubMed:17030667, FT ECO:0000269|PubMed:18785233, ECO:0000269|PubMed:19229105, FT ECO:0000269|PubMed:32484300" FT /id="VAR_046589" FT VARIANT 317 FT /note="V -> I (in dbSNP:rs200949139)" FT /evidence="ECO:0000269|PubMed:16969854, FT ECO:0000269|PubMed:18330912" FT /id="VAR_046590" FT VARIANT 318 FT /note="M -> L (in dbSNP:rs139226733)" FT /evidence="ECO:0000269|PubMed:15596610" FT /id="VAR_046591" FT VARIANT 322 FT /note="P -> L (in dbSNP:rs768019187)" FT /evidence="ECO:0000269|PubMed:18330912" FT /id="VAR_046592" FT VARIANT 339 FT /note="A -> T (in dbSNP:rs55831733)" FT /evidence="ECO:0000269|PubMed:15596610, FT ECO:0000269|PubMed:16969854, ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:18330912" FT /id="VAR_041014" FT VARIANT 340 FT /note="A -> T (in dbSNP:rs3738136)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15349860, ECO:0000269|PubMed:15596610, FT ECO:0000269|PubMed:16009891, ECO:0000269|PubMed:16257123, FT ECO:0000269|PubMed:16482571, ECO:0000269|PubMed:17344846" FT /id="VAR_018995" FT VARIANT 341 FT /note="M -> I (in dbSNP:rs35813094)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041015" FT VARIANT 347 FT /note="L -> P (in PARK6; strongly reduces interaction with FT PRKN; reduced ubiquitination of MIRO1; severely decreased FT interaction with TIMM23; dbSNP:rs28940285)" FT /evidence="ECO:0000269|PubMed:15349870, FT ECO:0000269|PubMed:15596610, ECO:0000269|PubMed:20798600, FT ECO:0000269|PubMed:22396657, ECO:0000269|PubMed:22956510, FT ECO:0000269|PubMed:37160114" FT /id="VAR_046593" FT VARIANT 362 FT /note="D -> H" FT /evidence="ECO:0000269|PubMed:15596610" FT /id="VAR_046594" FT VARIANT 369 FT /note="L -> P (in PARK6; dbSNP:rs1195888869)" FT /evidence="ECO:0000269|PubMed:16401616" FT /id="VAR_062775" FT VARIANT 377 FT /note="C -> F (in dbSNP:rs34203620)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041016" FT VARIANT 383 FT /note="A -> T (in dbSNP:rs45515602)" FT /evidence="ECO:0000269|PubMed:16969854, FT ECO:0000269|PubMed:18330912" FT /id="VAR_046595" FT VARIANT 386 FT /note="G -> A (in PARK6; abolishes kinase activity; no FT effect on interaction with TIMM23)" FT /evidence="ECO:0000269|PubMed:16401616, FT ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:37160114" FT /id="VAR_062776" FT VARIANT 388 FT /note="C -> R (in PARK6; dbSNP:rs1553146806)" FT /evidence="ECO:0000269|PubMed:15955953" FT /id="VAR_046596" FT VARIANT 395 FT /note="G -> V (in dbSNP:rs1035071310)" FT /evidence="ECO:0000269|PubMed:18330912" FT /id="VAR_046597" FT VARIANT 399 FT /note="P -> L (found in early-onset Parkinson disease with FT digenic inheritance; likely pathogenic; the patient also FT has mutation S-39 in PARK7; decreases PRKN and SNCAIP FT ubiquitination and degradation; dbSNP:rs119451946)" FT /evidence="ECO:0000269|PubMed:16632486, FT ECO:0000269|PubMed:19229105" FT /id="VAR_062777" FT VARIANT 407 FT /note="R -> Q (in PARK6; early-onset; dbSNP:rs556540177)" FT /evidence="ECO:0000269|PubMed:16257123" FT /id="VAR_062778" FT VARIANT 409 FT /note="G -> V (in PARK6; no effect on interaction with FT TIMM23; dbSNP:rs1553146818)" FT /evidence="ECO:0000269|PubMed:16401616, FT ECO:0000269|PubMed:37160114" FT /id="VAR_062779" FT VARIANT 411 FT /note="G -> S (in dbSNP:rs45478900)" FT /evidence="ECO:0000269|PubMed:16969854" FT /id="VAR_046598" FT VARIANT 417 FT /note="E -> G (in PARK6; no effect on interaction with FT TIMM23; dbSNP:rs1553146822)" FT /evidence="ECO:0000269|PubMed:15349870, FT ECO:0000269|PubMed:37160114" FT /id="VAR_046599" FT VARIANT 425 FT /note="P -> S (in dbSNP:rs554114655)" FT /evidence="ECO:0000269|PubMed:15596610" FT /id="VAR_046600" FT VARIANT 431 FT /note="Y -> H (may predispose to Parkinson disease FT development; affects cellular response to stress resulting FT in increased mitochondrial depolarization under stress FT conditions compared to wild type; dbSNP:rs74315361)" FT /evidence="ECO:0000269|PubMed:16969854" FT /id="VAR_046601" FT VARIANT 442 FT /note="I -> T (in dbSNP:rs1553146877)" FT /evidence="ECO:0000269|PubMed:15349860, FT ECO:0000269|PubMed:18330912" FT /id="VAR_046602" FT VARIANT 451 FT /note="N -> S (may predispose to Parkinson disease FT development; affects cellular response to stress resulting FT in increased mitochondrial depolarization under stress FT conditions compared to wild type; dbSNP:rs747400197)" FT /evidence="ECO:0000269|PubMed:16969854" FT /id="VAR_046603" FT VARIANT 456..581 FT /note="Missing (in PARK6)" FT /evidence="ECO:0000269|PubMed:24652937" FT /id="VAR_078935" FT VARIANT 461 FT /note="L -> S" FT /evidence="ECO:0000269|PubMed:16969854" FT /id="VAR_046604" FT VARIANT 464 FT /note="R -> H (in PARK6; dbSNP:rs764328076)" FT /evidence="ECO:0000269|PubMed:15349860" FT /id="VAR_046605" FT VARIANT 476 FT /note="E -> K (may predispose to Parkinson disease FT development; affects cellular response to stress resulting FT in increased mitochondrial depolarization under stress FT conditions compared to wild type; dbSNP:rs115477764)" FT /evidence="ECO:0000269|PubMed:15349860, FT ECO:0000269|PubMed:15596610, ECO:0000269|PubMed:16009891, FT ECO:0000269|PubMed:16969854, ECO:0000269|PubMed:18330912" FT /id="VAR_046606" FT VARIANT 477 FT /note="S -> T (in dbSNP:rs34416410)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041017" FT VARIANT 489 FT /note="L -> P (in PARK6; dbSNP:rs1553146903)" FT /evidence="ECO:0000269|PubMed:15596610" FT /id="VAR_046607" FT VARIANT 492..581 FT /note="Missing (in PARK6; mitochondria are deformed and FT dysfunctional with decreased mitochondrial membrane FT potential; shows increased apoptosis; increased oxidative FT stress; decreased phosphorylation of DNM1L and Drp1; FT dbSNP:rs34208370)" FT /evidence="ECO:0000269|PubMed:18785233, FT ECO:0000269|PubMed:20547144, ECO:0000269|PubMed:32484300" FT /id="VAR_084338" FT VARIANT 501 FT /note="R -> P (may predispose to Parkinson disease FT development; affects cellular response to stress resulting FT in increased mitochondrial depolarization under stress FT conditions compared to wild type; dbSNP:rs61744200)" FT /evidence="ECO:0000269|PubMed:16969854" FT /id="VAR_046608" FT VARIANT 521 FT /note="N -> T (in dbSNP:rs1043424)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15349860, ECO:0000269|PubMed:15596610, FT ECO:0000269|PubMed:16009891, ECO:0000269|PubMed:16257123, FT ECO:0000269|PubMed:16482571, ECO:0000269|PubMed:17344846" FT /id="VAR_018996" FT VARIANT 525 FT /note="D -> N (in dbSNP:rs531477772)" FT /evidence="ECO:0000269|PubMed:15349860, FT ECO:0000269|PubMed:18330912" FT /id="VAR_046609" FT VARIANT 534 FT /note="Q -> QQ (in PARK6; loss of autophosphorylation on S- FT 228 and kinase activation; no effect on interaction with FT TIMM23)" FT /evidence="ECO:0000269|PubMed:15970950, FT ECO:0000269|PubMed:37160114, ECO:0000269|PubMed:38848361" FT /id="VAR_046610" FT VARIANT 537 FT /note="A -> T (in dbSNP:rs771032673)" FT /evidence="ECO:0000269|PubMed:18330912" FT /id="VAR_046611" FT VARIANT 575 FT /note="C -> R (may predispose to Parkinson disease FT development; affects cellular response to stress resulting FT in increased mitochondrial depolarization under stress FT conditions compared to wild type; dbSNP:rs1553147052)" FT /evidence="ECO:0000269|PubMed:16969854" FT /id="VAR_046612" FT MUTAGEN 112..117 FT /note="EEKQAE->AAKQAA: In 3EA; impaired ability to localize FT to the outer mitochondrial membrane." FT /evidence="ECO:0000269|PubMed:30733118" FT MUTAGEN 131 FT /note="I->E: Under depolarizing conditions, it results in FT loss of interaction with TOMM20 and fails to support PINK1- FT TOM-TIM23 complex assembly and mitophagy activation." FT /evidence="ECO:0000269|PubMed:38416681" FT MUTAGEN 219 FT /note="K->A: Abolishes MFN2 phosphorylation and interaction FT with PRKN; when associated with Ala-362 and Ala-384." FT /evidence="ECO:0000269|PubMed:23620051" FT MUTAGEN 219 FT /note="K->M: Loss of enzyme activity and impaired FT localization of PRKN to mitochondria; when associated with FT A-362 and A-384." FT /evidence="ECO:0000269|PubMed:18957282, FT ECO:0000269|PubMed:32047033" FT MUTAGEN 362 FT /note="D->A: Abolishes MFN2 phosphorylation and interaction FT with PRKN; when associated with A-219 and A-384. Loss of FT enzyme activity and impaired localization of PRKN to FT mitochondria; when associated with M-219 and A-384." FT /evidence="ECO:0000269|PubMed:18957282, FT ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:32047033" FT MUTAGEN 384 FT /note="D->A: Abolishes MFN2 phosphorylation and interaction FT with PRKN; when associated with A-219 and A-362. Loss of FT enzyme activity and impaired localization of PRKN to FT mitochondria; when associated with M-219 and A-362." FT /evidence="ECO:0000269|PubMed:18957282, FT ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:32047033" FT MUTAGEN 384 FT /note="D->N: Loss of activity. Abolishes Drp1 FT phosphorylation. No effect on localization to FT mitochondria." FT /evidence="ECO:0000269|PubMed:32484300" FT MUTAGEN 532 FT /note="L->A: Under depolarizing conditions, it results in FT severely reduced autophosphorylation on S-228 and loss of FT kinase activation." FT /evidence="ECO:0000269|PubMed:38848361" FT MUTAGEN 536 FT /note="A->E: Under depolarizing conditions, it results in FT loss of interaction with TOMM20 and fails to support PINK1- FT TOM-TIM23 complex assembly and mitophagy activation." FT /evidence="ECO:0000269|PubMed:38416681" FT MUTAGEN 536 FT /note="A->S: Under depolarizing conditions, it fails to FT support PINK1-TOM-TIM23 complex assembly and mitophagy FT activation." FT /evidence="ECO:0000269|PubMed:38416681" FT MUTAGEN 539 FT /note="L->A: Under depolarizing conditions, it results in FT severely reduced autophosphorylation on S-228 and loss of FT kinase activation." FT /evidence="ECO:0000269|PubMed:38848361" FT MUTAGEN 540 FT /note="L->A: Under depolarizing conditions, does not affect FT autophosphorylation on S-228 and kinase activation." FT /evidence="ECO:0000269|PubMed:38848361" FT MUTAGEN 540 FT /note="L->K: Under depolarizing conditions, it results in FT loss of interaction with TOMM20 and fails to support PINK1- FT TOM-TIM23 complex assembly and mitophagy activation." FT /evidence="ECO:0000269|PubMed:38416681" FT MUTAGEN 543 FT /note="R->D: No effect on interaction with TOMM20 and FT mitophagy activation under depolarizing conditions." FT /evidence="ECO:0000269|PubMed:38416681" FT MUTAGEN 543 FT /note="R->G: Under depolarizing conditions, it fails to FT support PINK1-TOM-TIM23 complex assembly and mitophagy FT activation." FT /evidence="ECO:0000269|PubMed:38416681" FT CONFLICT 209 FT /note="P -> A (in Ref. 5; AAH28215)" FT /evidence="ECO:0000305" FT CONFLICT 419 FT /note="S -> P (in Ref. 3; BAC11484)" FT /evidence="ECO:0000305" FT HELIX 64..66 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 67..69 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 71..73 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 77..90 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 108..135 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 142..144 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 153..155 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 157..164 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 166..174 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 216..222 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 230..236 FT /evidence="ECO:0007829|PDB:9EII" FT TURN 237..243 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 248..250 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 277..283 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 313..319 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 322..324 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 325..331 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 336..356 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 367..372 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 378..382 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 385..387 FT /evidence="ECO:0007829|PDB:9EII" FT TURN 392..396 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 397..399 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 408..412 FT /evidence="ECO:0007829|PDB:9EIJ" FT HELIX 416..419 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 428..430 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 434..446 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 454..456 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 457..459 FT /evidence="ECO:0007829|PDB:9EII" FT TURN 463..465 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 468..470 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 480..489 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 494..496 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 500..512 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 514..517 FT /evidence="ECO:0007829|PDB:9EII" FT STRAND 519..521 FT /evidence="ECO:0007829|PDB:9EIH" FT HELIX 524..544 FT /evidence="ECO:0007829|PDB:9EII" FT TURN 545..547 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 550..560 FT /evidence="ECO:0007829|PDB:9EII" FT HELIX 564..578 FT /evidence="ECO:0007829|PDB:9EII" SQ SEQUENCE 581 AA; 62769 MW; 721FE01F63263A64 CRC64; MAVRQALGRG LQLGRALLLR FTGKPGRAYG LGRPGPAAGC VRGERPGWAA GPGAEPRRVG LGLPNRLRFF RQSVAGLAAR LQRQFVVRAW GCAGPCGRAV FLAFGLGLGL IEEKQAESRR AVSACQEIQA IFTQKSKPGP DPLDTRRLQG FRLEEYLIGQ SIGKGCSAAV YEATMPTLPQ NLEVTKSTGL LPGRGPGTSA PGEGQERAPG APAFPLAIKM MWNISAGSSS EAILNTMSQE LVPASRVALA GEYGAVTYRK SKRGPKQLAP HPNIIRVLRA FTSSVPLLPG ALVDYPDVLP SRLHPEGLGH GRTLFLVMKN YPCTLRQYLC VNTPSPRLAA MMLLQLLEGV DHLVQQGIAH RDLKSDNILV ELDPDGCPWL VIADFGCCLA DESIGLQLPF SSWYVDRGGN GCLMAPEVST ARPGPRAVID YSKADAWAVG AIAYEIFGLV NPFYGQGKAH LESRSYQEAQ LPALPESVPP DVRQLVRALL QREASKRPSA RVAANVLHLS LWGEHILALK NLKLDKMVGW LLQQSAATLL ANRLTEKCCV ETKMKMLFLA NLECETLCQA ALLLCSWRAA L //