PRKN_HUMAN
ID PRKN_HUMAN Reviewed; 465 AA.
AC O60260; A3FG77; A8K975; D3JZW7; D3K2X0; Q5TFV8; Q5VVX4; Q6Q2I6; Q8NI41;
AC Q8NI43; Q8NI44; Q8WW07;
DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=E3 ubiquitin-protein ligase parkin {ECO:0000305};
DE Short=Parkin;
DE EC=2.3.2.31 {ECO:0000269|PubMed:23770887, ECO:0000269|PubMed:32047033};
DE AltName: Full=Parkin RBR E3 ubiquitin-protein ligase {ECO:0000312|HGNC:HGNC:8607};
DE AltName: Full=Parkinson juvenile disease protein 2;
DE Short=Parkinson disease protein 2;
GN Name=PRKN {ECO:0000312|HGNC:HGNC:8607}; Synonyms=PARK2;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INVOLVEMENT IN PARK2, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Fetal brain, and Skeletal muscle;
RX PubMed=9560156; DOI=10.1038/33416;
RA Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S.,
RA Yokochi M., Mizuno Y., Shimizu N.;
RT "Mutations in the parkin gene cause autosomal recessive juvenile
RT parkinsonism.";
RL Nature 392:605-608(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP VARIANTS ARG-311 AND THR-371, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19501131; DOI=10.1016/j.neulet.2009.05.079;
RA Kasap M., Akpinar G., Sazci A., Idrisoglu H.A., Vahaboglu H.;
RT "Evidence for the presence of full-length PARK2 mRNA and Parkin protein in
RT human blood.";
RL Neurosci. Lett. 460:196-200(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
RA D'Agata V., Scapagnini G., Cavallaro S.;
RT "Functional and molecular diversity of parkin.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 7 AND 8).
RC TISSUE=Retina;
RA Campello L., Esteve-Rudd J., Cuenca N., Martin-Nieto J.;
RT "Homo sapiens PARK2 transcript variants.";
RL Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Testis;
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 312-361.
RA Zou H.Q., Chan P.;
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=10319893;
RX DOI=10.1002/1531-8249(199905)45:5<668::aid-ana19>3.0.co;2-z;
RA Shimura H., Hattori N., Kubo S., Yoshikawa M., Kitada T., Matsumine H.,
RA Asakawa S., Minoshima S., Yamamura Y., Shimizu N., Mizuno Y.;
RT "Immunohistochemical and subcellular localization of Parkin protein:
RT absence of protein in autosomal recessive juvenile parkinsonism patients.";
RL Ann. Neurol. 45:668-672(1999).
RN [11]
RP FUNCTION IN UBIQUITINATION.
RX PubMed=10973942; DOI=10.1074/jbc.c000447200;
RA Imai Y., Soda M., Takahashi R.;
RT "Parkin suppresses unfolded protein stress-induced cell death through its
RT E3 ubiquitin-protein ligase activity.";
RL J. Biol. Chem. 275:35661-35664(2000).
RN [12]
RP FUNCTION, AND CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND ARG-240.
RX PubMed=10888878; DOI=10.1038/77060;
RA Shimura H., Hattori N., Kubo S., Mizuno Y., Asakawa S., Minoshima S.,
RA Shimizu N., Iwai K., Chiba T., Tanaka K., Suzuki T.;
RT "Familial Parkinson disease gene product, parkin, is a ubiquitin-protein
RT ligase.";
RL Nat. Genet. 25:302-305(2000).
RN [13]
RP INTERACTION WITH UBE2L6 AND SEPTIN5, AND UBIQUITINATION OF SEPTIN5.
RX PubMed=11078524; DOI=10.1073/pnas.240347797;
RA Zhang Y., Gao J., Chung K.K.K., Huang H., Dawson V.L., Dawson T.M.;
RT "Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes
RT the degradation of the synaptic vesicle-associated protein, CDCrel-1.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:13354-13359(2000).
RN [14]
RP UBIQUITINATION OF GPR37.
RX PubMed=11439185; DOI=10.1016/s0092-8674(01)00407-x;
RA Imai Y., Soda M., Inoue H., Hattori N., Mizuno Y., Takahashi R.;
RT "An unfolded putative transmembrane polypeptide, which can lead to
RT endoplasmic reticulum stress, is a substrate of Parkin.";
RL Cell 105:891-902(2001).
RN [15]
RP FUNCTION, INTERACTION WITH SNCAIP, CHARACTERIZATION OF VARIANTS PARK2
RP ARG-240; CYS-256; TRP-275 AND ASN-415, AND MUTAGENESIS OF CYS-337; CYS-421
RP AND CYS-431.
RX PubMed=11590439; DOI=10.1038/nm1001-1144;
RA Chung K.K.K., Zhang Y., Lim K.L., Tanaka Y., Huang H., Gao J., Ross C.A.,
RA Dawson V.L., Dawson T.M.;
RT "Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1:
RT implications for Lewy-body formation in Parkinson disease.";
RL Nat. Med. 7:1144-1150(2001).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS PARK2
RP PRO-42 AND ARG-240.
RX PubMed=11431533; DOI=10.1126/science.1060627;
RA Shimura H., Schlossmacher M.G., Hattori N., Frosch M.P., Trockenbacher A.,
RA Schneider R., Mizuno Y., Kosik K.S., Selkoe D.J.;
RT "Ubiquitination of a new form of alpha-synuclein by parkin from human
RT brain: implications for Parkinson's disease.";
RL Science 293:263-269(2001).
RN [17]
RP PRESENCE OF ATYPICAL RING FINGER DOMAINS.
RX PubMed=12446796; DOI=10.1093/oxfordjournals.molbev.a004029;
RA Marin I., Ferrus A.;
RT "Comparative genomics of the RBR family, including the Parkinson's disease-
RT related gene parkin and the genes of the ariadne subfamily.";
RL Mol. Biol. Evol. 19:2039-2050(2002).
RN [18]
RP FUNCTION, INTERACTION WITH STUB1; HSP70 AND GPR37, AND UBIQUITINATION OF
RP STUB1.
RX PubMed=12150907; DOI=10.1016/s1097-2765(02)00583-x;
RA Imai Y., Soda M., Hatakeyama S., Akagi T., Hashikawa T., Nakayama K.,
RA Takahashi R.;
RT "CHIP is associated with Parkin, a gene responsible for familial
RT Parkinson's disease, and enhances its ubiquitin ligase activity.";
RL Mol. Cell 10:55-67(2002).
RN [19]
RP INTERACTION WITH SYT11, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF
RP VARIANTS PARK2 GLY-289 AND ARG-418.
RX PubMed=12925569; DOI=10.1093/hmg/ddg269;
RA Huynh D.P., Scoles D.R., Nguyen D., Pulst S.M.;
RT "The autosomal recessive juvenile Parkinson disease gene product, parkin,
RT interacts with and ubiquitinates synaptotagmin XI.";
RL Hum. Mol. Genet. 12:2587-2597(2003).
RN [20]
RP INTERACTION WITH PACRG.
RX PubMed=14532270; DOI=10.1074/jbc.m309655200;
RA Imai Y., Soda M., Murakami T., Shoji M., Abe K., Takahashi R.;
RT "A product of the human gene adjacent to parkin is a component of Lewy
RT bodies and suppresses Pael receptor-induced cell death.";
RL J. Biol. Chem. 278:51901-51910(2003).
RN [21]
RP FUNCTION, INTERACTION WITH FBXW7 AND CUL1, TISSUE SPECIFICITY, AND
RP UBIQUITINATION OF CYCLIN E.
RX PubMed=12628165; DOI=10.1016/s0896-6273(03)00084-9;
RA Staropoli J.F., McDermott C., Martinat C., Schulman B., Demireva E.,
RA Abeliovich A.;
RT "Parkin is a component of an SCF-like ubiquitin ligase complex and protects
RT postmitotic neurons from kainate excitotoxicity.";
RL Neuron 37:735-749(2003).
RN [22]
RP INVOLVEMENT IN CANCER, AND TISSUE SPECIFICITY.
RX PubMed=14614460; DOI=10.1038/sj.onc.1207072;
RA Denison S.R., Wang F., Becker N.A., Schuele B., Kock N., Phillips L.A.,
RA Klein C., Smith D.I.;
RT "Alterations in the common fragile site gene Parkin in ovarian and other
RT cancers.";
RL Oncogene 22:8370-8378(2003).
RN [23]
RP FUNCTION, INVOLVEMENT IN CANCER, AND TISSUE SPECIFICITY.
RX PubMed=12719539; DOI=10.1073/pnas.0931262100;
RA Cesari R., Martin E.S., Calin G.A., Pentimalli F., Bichi R., McAdams H.,
RA Trapasso F., Drusco A., Shimizu M., Masciullo V., D'Andrilli G.,
RA Scambia G., Picchio M.C., Alder H., Godwin A.K., Croce C.M.;
RT "Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is
RT a candidate tumor suppressor gene on chromosome 6q25-q27.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:5956-5961(2003).
RN [24]
RP REVIEW.
RX PubMed=15229644; DOI=10.1038/sj.embor.7400188;
RA Kahle P.J., Haass C.;
RT "How does parkin ligate ubiquitin to Parkinson's disease?";
RL EMBO Rep. 5:681-685(2004).
RN [25]
RP FUNCTION, UBIQUITINATION, AND S-NITROSYLATION.
RX PubMed=15105460; DOI=10.1126/science.1093891;
RA Chung K.K.K., Thomas B., Li X., Pletnikova O., Troncoso J.C., Marsh L.,
RA Dawson V.L., Dawson T.M.;
RT "S-nitrosylation of parkin regulates ubiquitination and compromises
RT parkin's protective function.";
RL Science 304:1328-1331(2004).
RN [26]
RP INTERACTION WITH PSMA7.
RX PubMed=15987638; DOI=10.1016/j.febslet.2005.06.003;
RA Dachsel J.C., Lucking C.B., Deeg S., Schultz E., Lalowski M.,
RA Casademunt E., Corti O., Hampe C., Patenge N., Vaupel K., Yamamoto A.,
RA Dichgans M., Brice A., Wanker E.E., Kahle P.J., Gasser T.;
RT "Parkin interacts with the proteasome subunit alpha4.";
RL FEBS Lett. 579:3913-3919(2005).
RN [27]
RP FUNCTION, AND INTERACTION WITH SNCAIP.
RX PubMed=15728840; DOI=10.1523/jneurosci.4474-04.2005;
RA Lim K.L., Chew K.C., Tan J.M., Wang C., Chung K.K., Zhang Y., Tanaka Y.,
RA Smith W., Engelender S., Ross C.A., Dawson V.L., Dawson T.M.;
RT "Parkin mediates nonclassical, proteasomal-independent ubiquitination of
RT synphilin-1: implications for Lewy body formation.";
RL J. Neurosci. 25:2002-2009(2005).
RN [28]
RP FUNCTION, AND INTERACTION WITH AIMP2.
RX PubMed=16135753; DOI=10.1523/jneurosci.2172-05.2005;
RA Ko H.S., von Coelln R., Sriram S.R., Kim S.W., Chung K.K.K., Pletnikova O.,
RA Troncoso J., Johnson B., Saffary R., Goh E.L., Song H., Park B.-J.,
RA Kim M.J., Kim S., Dawson V.L., Dawson T.M.;
RT "Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase
RT cofactor, p38/JTV-1, leads to catecholaminergic cell death.";
RL J. Neurosci. 25:7968-7978(2005).
RN [29]
RP INTERACTION WITH LRRK2.
RX PubMed=16352719; DOI=10.1073/pnas.0508052102;
RA Smith W.W., Pei Z., Jiang H., Moore D.J., Liang Y., West A.B., Dawson V.L.,
RA Dawson T.M., Ross C.A.;
RT "Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant
RT LRRK2 induces neuronal degeneration.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:18676-18681(2005).
RN [30]
RP INTERACTION WITH RANBP2.
RX PubMed=16332688; DOI=10.1074/jbc.m504994200;
RA Um J.W., Min D.S., Rhim H., Kim J., Paik S.R., Chung K.C.;
RT "Parkin ubiquitinates and promotes the degradation of RanBP2.";
RL J. Biol. Chem. 281:3595-3603(2006).
RN [31]
RP INTERACTION WITH SUMO1, AND SUBCELLULAR LOCATION.
RX PubMed=16955485; DOI=10.1002/jnr.21041;
RA Um J.W., Chung K.C.;
RT "Functional modulation of parkin through physical interaction with SUMO-
RT 1.";
RL J. Neurosci. Res. 84:1543-1554(2006).
RN [32]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17846173; DOI=10.1083/jcb.200611128;
RA Olzmann J.A., Li L., Chudaev M.V., Chen J., Perez F.A., Palmiter R.D.,
RA Chin L.S.;
RT "Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to
RT aggresomes via binding to HDAC6.";
RL J. Cell Biol. 178:1025-1038(2007).
RN [33]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-175 AND THR-217, AND
RP MUTAGENESIS OF THR-175; THR-217 AND CYS-238.
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 [34]
RP FUNCTION IN MITOCHONDRIAL AUTOPHAGY, AND SUBCELLULAR LOCATION.
RX PubMed=19029340; DOI=10.1083/jcb.200809125;
RA Narendra D., Tanaka A., Suen D.F., Youle R.J.;
RT "Parkin is recruited selectively to impaired mitochondria and promotes
RT their autophagy.";
RL J. Cell Biol. 183:795-803(2008).
RN [35]
RP INTERACTION WITH RNF41, UBIQUITINATION, MUTAGENESIS OF CYS-421, AND
RP FUNCTION.
RX PubMed=18541373; DOI=10.1016/j.neulet.2008.05.052;
RA Yu F., Zhou J.;
RT "Parkin is ubiquitinated by Nrdp1 and abrogates Nrdp1-induced oxidative
RT stress.";
RL Neurosci. Lett. 440:4-8(2008).
RN [36]
RP FUNCTION, COMPONENT OF A COMPLEX COMPOSED OF PRKN; PARK7 AND PINK1,
RP SUBCELLULAR LOCATION, UBIQUITINATION, AND CHARACTERIZATION OF VARIANT PARK2
RP PRO-42.
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 [37]
RP FUNCTION IN PROTECTION OF APOPTOSIS, CHARACTERIZATION OF VARIANTS PARK2
RP ASN-161; CYS-256; TRP-275; ARG-418 AND ARG-441, AND DOMAIN.
RX PubMed=19801972; DOI=10.1038/ncb1981;
RA da Costa C.A., Sunyach C., Giaime E., West A., Corti O., Brice A., Safe S.,
RA Abou-Sleiman P.M., Wood N.W., Takahashi H., Goldberg M.S., Shen J.,
RA Checler F.;
RT "Transcriptional repression of p53 by parkin and impairment by mutations
RT associated with autosomal recessive juvenile Parkinson's disease.";
RL Nat. Cell Biol. 11:1370-1375(2009).
RN [38]
RP INTERACTION WITH PINK1.
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 [39]
RP FUNCTION, INTERACTION WITH BCL2, SUBCELLULAR LOCATION, AND CHARACTERIZATION
RP OF VARIANTS PARK2 ASN-161; ARG-240; PHE-431 AND LEU-437.
RX PubMed=20889974; DOI=10.1074/jbc.m110.101469;
RA Chen D., Gao F., Li B., Wang H., Xu Y., Zhu C., Wang G.;
RT "Parkin mono-ubiquitinates Bcl-2 and regulates autophagy.";
RL J. Biol. Chem. 285:38214-38223(2010).
RN [40]
RP FUNCTION IN MITOCHONDRIAL AUTOPHAGY, SUBCELLULAR LOCATION, INTERACTION WITH
RP PINK1, AND CHARACTERIZATION OF VARIANTS PARK ASN-415 AND ASP-430.
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 [41]
RP FUNCTION, INTERACTION WITH ZNF746, AND CHARACTERIZATION OF VARIANTS PARK2
RP TRP-275; ASP-430 AND PHE-431.
RX PubMed=21376232; DOI=10.1016/j.cell.2011.02.010;
RA Shin J.H., Ko H.S., Kang H., Lee Y., Lee Y.I., Pletinkova O.,
RA Troconso J.C., Dawson V.L., Dawson T.M.;
RT "PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration
RT in Parkinson's disease.";
RL Cell 144:689-702(2011).
RN [42]
RP CHARACTERIZATION OF VARIANTS PARK2 PRO-42 AND GLY-289.
RX PubMed=20889486; DOI=10.1093/hmg/ddq428;
RA Rose J.M., Novoselov S.S., Robinson P.A., Cheetham M.E.;
RT "Molecular chaperone-mediated rescue of mitophagy by a Parkin RING1 domain
RT mutant.";
RL Hum. Mol. Genet. 20:16-27(2011).
RN [43]
RP FUNCTION.
RX PubMed=21753002; DOI=10.1523/jneurosci.1917-11.2011;
RA Van Humbeeck C., Cornelissen T., Hofkens H., Mandemakers W., Gevaert K.,
RA De Strooper B., Vandenberghe W.;
RT "Parkin interacts with Ambra1 to induce mitophagy.";
RL J. Neurosci. 31:10249-10261(2011).
RN [44]
RP FUNCTION, REACTION MECHANISM, AND INTERACTION WITH UBE2L3.
RX PubMed=21532592; DOI=10.1038/nature09966;
RA Wenzel D.M., Lissounov A., Brzovic P.S., Klevit R.E.;
RT "UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT
RT hybrids.";
RL Nature 474:105-108(2011).
RN [45]
RP FUNCTION, INTERACTION WITH CHPF, AND SUBCELLULAR LOCATION.
RX PubMed=22082830; DOI=10.1093/hmg/ddr530;
RA Kuroda Y., Sako W., Goto S., Sawada T., Uchida D., Izumi Y., Takahashi T.,
RA Kagawa N., Matsumoto M., Matsumoto M., Takahashi R., Kaji R., Mitsui T.;
RT "Parkin interacts with Klokin1 for mitochondrial import and maintenance of
RT membrane potential.";
RL Hum. Mol. Genet. 21:991-1003(2012).
RN [46]
RP FUNCTION, AND MUTAGENESIS OF LYS-211 AND THR-415.
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 [47]
RP PHOSPHORYLATION AT SER-65, FUNCTION, AND SUBCELLULAR LOCATION.
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 [48]
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 [49]
RP INTERACTION WITH BAG4; BAG5; HSPA1L; HSPA1A AND HSPA8.
RX PubMed=24270810; DOI=10.1038/nature12748;
RA Hasson S.A., Kane L.A., Yamano K., Huang C.H., Sliter D.A., Buehler E.,
RA Wang C., Heman-Ackah S.M., Hessa T., Guha R., Martin S.E., Youle R.J.;
RT "High-content genome-wide RNAi screens identify regulators of parkin
RT upstream of mitophagy.";
RL Nature 504:291-295(2013).
RN [50]
RP UBIQUITINATION, AND MUTAGENESIS OF GLY-429 AND GLY-430.
RX PubMed=23770917; DOI=10.1038/ncomms2983;
RA Spratt D.E., Martinez-Torres R.J., Noh Y.J., Mercier P., Manczyk N.,
RA Barber K.R., Aguirre J.D., Burchell L., Purkiss A., Walden H., Shaw G.S.;
RT "A molecular explanation for the recessive nature of parkin-linked
RT Parkinson's disease.";
RL Nat. Commun. 4:1983-1983(2013).
RN [51]
RP FUNCTION IN MITOPHAGY, INTERACTION WITH MFN2, AND SUBCELLULAR LOCATION.
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 [52]
RP FUNCTION, PHOSPHORYLATION AT SER-65, UBIQUITIN-BINDING, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF SER-65.
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 [53]
RP SUBCELLULAR LOCATION.
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 [54]
RP FUNCTION, PHOSPHORYLATION AT SER-65, UBIQUITIN-BINDING, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF SER-65 AND CYS-431.
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 [55]
RP FUNCTION, AND ACTIVITY REGULATION.
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 [56]
RP FUNCTION, PHOSPHORYLATION AT SER-65, UBIQUITIN-BINDING, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF SER-65 AND TRP-403.
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 [57]
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 [58]
RP FUNCTION, AND ACTIVITY REGULATION.
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 [59]
RP FUNCTION.
RX PubMed=25621951; DOI=10.1038/ncb3097;
RA Cunningham C.N., Baughman J.M., Phu L., Tea J.S., Yu C., Coons M.,
RA Kirkpatrick D.S., Bingol B., Corn J.E.;
RT "USP30 and parkin homeostatically regulate atypical ubiquitin chains on
RT mitochondria.";
RL Nat. Cell Biol. 17:160-169(2015).
RN [60]
RP FUNCTION, AND MUTAGENESIS OF THR-415 AND CYS-431.
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 [61]
RP FUNCTION.
RX PubMed=33499712; DOI=10.1080/15548627.2021.1874133;
RA Kojima W., Yamano K., Kosako H., Imai K., Kikuchi R., Tanaka K.,
RA Matsuda N.;
RT "Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site
RT in response to selective and non-selective autophagy.";
RL Autophagy 1:1-26(2021).
RN [62]
RP STRUCTURE BY NMR OF 1-76, AND INTERACTION WITH PSMD4.
RX PubMed=12634850; DOI=10.1038/sj.embor.embor764;
RA Sakata E., Yamaguchi Y., Kurimoto E., Kikuchi J., Yokoyama S., Yamada S.,
RA Kawahara H., Yokosawa H., Hattori N., Mizuno Y., Tanaka K., Kato K.;
RT "Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-
RT like domain.";
RL EMBO Rep. 4:301-306(2003).
RN [63]
RP STRUCTURE BY NMR OF 307-384 IN COMPLEX WITH ZINC IONS, CHARACTERIZATION OF
RP VARIANT PARK2 PRO-351, MUTAGENESIS OF CYS-332 AND CYS-365, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17360614; DOI=10.1073/pnas.0610548104;
RA Beasley S.A., Hristova V.A., Shaw G.S.;
RT "Structure of the Parkin in-between-ring domain provides insights for E3-
RT ligase dysfunction in autosomal recessive Parkinson's disease.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:3095-3100(2007).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 137-465, ACTIVITY REGULATION, AND
RP MUTAGENESIS OF CYS-431; HIS-433 AND GLU-444.
RX PubMed=23727886; DOI=10.1038/emboj.2013.125;
RA Wauer T., Komander D.;
RT "Structure of the human Parkin ligase domain in an autoinhibited state.";
RL EMBO J. 32:2099-2112(2013).
RN [65]
RP X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 137-465, ACTIVE SITE, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF CYS-431; HIS-433 AND
RP GLU-444.
RX PubMed=23770887; DOI=10.1038/ncomms2982;
RA Riley B.E., Lougheed J.C., Callaway K., Velasquez M., Brecht E., Nguyen L.,
RA Shaler T., Walker D., Yang Y., Regnstrom K., Diep L., Zhang Z., Chiou S.,
RA Bova M., Artis D.R., Yao N., Baker J., Yednock T., Johnston J.A.;
RT "Structure and function of Parkin E3 ubiquitin ligase reveals aspects of
RT RING and HECT ligases.";
RL Nat. Commun. 4:1982-1982(2013).
RN [66]
RP REVIEW ON VARIANTS.
RX PubMed=14976155; DOI=10.1093/hmg/ddh089;
RA Mata I.F., Lockhart P.J., Farrer M.J.;
RT "Parkin genetics: one model for Parkinson's disease.";
RL Hum. Mol. Genet. 13:R127-R133(2004).
RN [67]
RP VARIANT PARK2 ARG-240.
RX PubMed=9731209; DOI=10.1006/bbrc.1998.9134;
RA Hattori N., Matsumine H., Asakawa S., Kitada T., Yoshino H., Elibol B.,
RA Brookes A.J., Yamamura Y., Kobayashi T., Wang M., Yoritaka A.,
RA Minoshima S., Shimizu N., Mizuno Y.;
RT "Point mutations (Thr240Arg and Gln311Stop) in the Parkin gene.";
RL Biochem. Biophys. Res. Commun. 249:754-758(1998).
RN [68]
RP ERRATUM OF PUBMED:9731209.
RA Hattori N., Matsumine H., Asakawa S., Kitada T., Yoshino H., Elibol B.,
RA Brookes A.J., Yamamura Y., Kobayashi T., Wang M., Yoritaka A.,
RA Minoshima S., Shimizu N., Mizuno Y.;
RL Biochem. Biophys. Res. Commun. 251:666-666(1998).
RN [69]
RP VARIANTS PARK2 ASN-161; CYS-256; TRP-275 AND ASN-415, AND VARIANTS ASN-167;
RP LEU-380 AND ASN-394.
RX PubMed=10072423; DOI=10.1093/hmg/8.4.567;
RA Abbas N., Luecking C.B., Ricard S., Duerr A., Bonifati V., De Michele G.,
RA Bouley S., Vaughan J.R., Gasser T., Marconi R., Broussolle E.,
RA Brefel-Courbon C., Harhangi B.S., Oostra B.A., Fabrizio E., Bohme G.A.,
RA Pradier L., Wood N.W., Filla A., Meco G., Denefle P., Agid Y., Brice A.;
RT "A wide variety of mutations in the parkin gene are responsible for
RT autosomal recessive parkinsonism in Europe.";
RL Hum. Mol. Genet. 8:567-574(1999).
RN [70]
RP VARIANT ASN-167.
RX PubMed=10511432; DOI=10.1097/00001756-199909090-00008;
RA Satoh J., Kuroda Y.;
RT "Association of codon 167 Ser/Asn heterozygosity in the parkin gene with
RT sporadic Parkinson's disease.";
RL NeuroReport 10:2735-2739(1999).
RN [71]
RP VARIANT PARK2 PHE-431.
RX PubMed=10939576;
RX DOI=10.1002/1531-8249(200008)48:2<245::aid-ana15>3.0.co;2-2;
RA Maruyama M., Ikeuchi T., Saito M., Ishikawa A., Yuasa T., Tanaka H.,
RA Hayashi S., Wakabayashi K., Takahashi H., Tsuji S.;
RT "Novel mutations, pseudo-dominant inheritance, and possible familial
RT affects in patients with autosomal recessive juvenile parkinsonism.";
RL Ann. Neurol. 48:245-250(2000).
RN [72]
RP VARIANTS ASN-167; TRP-366 AND LEU-380.
RX PubMed=10965160; DOI=10.1159/000008203;
RA Hu C.-J., Sung S.-M., Liu H.-C., Lee C.-C., Tsai C.-H., Chang J.-G.;
RT "Polymorphisms of the parkin gene in sporadic Parkinson's disease among
RT Chinese in Taiwan.";
RL Eur. Neurol. 44:90-93(2000).
RN [73]
RP VARIANTS PARK2 ASN-161; ASN-211; CYS-256; TRP-275; ASN-280; GLY-289;
RP GLU-328; ASN-415 AND ASP-430, AND VARIANT CYS-334.
RX PubMed=10824074; DOI=10.1056/nejm200005253422103;
RA Luecking C.B., Duerr A., Bonifati V., Vaughan J.R., De Michele G.,
RA Gasser T., Harhangi B.S., Meco G., Denefle P., Wood N.W., Agid Y.,
RA Brice A.;
RT "Association between early-onset Parkinson's disease and mutations in the
RT parkin gene.";
RL N. Engl. J. Med. 342:1560-1567(2000).
RN [74]
RP VARIANTS PARK2 ASN-211; TRP-275 AND ASP-430.
RX PubMed=11179010; DOI=10.1086/318791;
RA Periquet M., Luecking C.B., Vaughan J.R., Bonifati V., Duerr A.,
RA De Michele G., Horstink M., Farrer M., Illarioshkin S.N., Pollak P.,
RA Borg M., Brefel-Courbon C., Denefle P., Meco G., Gasser T., Breteler M.M.,
RA Wood N.W., Agid Y., Brice A.;
RT "Origin of the mutations in the parkin gene in Europe: exon rearrangements
RT are independent recurrent events, whereas point mutations may result from
RT founder effects.";
RL Am. J. Hum. Genet. 68:617-626(2001).
RN [75]
RP VARIANT PARK2 GLU-82.
RX PubMed=11487568; DOI=10.1093/hmg/10.16.1649;
RA Hedrich K., Kann M., Lanthaler A.J., Dalski A., Eskelson C., Landt O.,
RA Schwinger E., Vieregge P., Lang A.E., Breakefield X.O., Ozelius L.J.,
RA Pramstaller P.P., Klein C.;
RT "The importance of gene dosage studies: mutational analysis of the parkin
RT gene in early-onset parkinsonism.";
RL Hum. Mol. Genet. 10:1649-1656(2001).
RN [76]
RP VARIANT PARK2 TYR-212.
RX PubMed=11163284; DOI=10.1016/s0304-3940(00)01733-x;
RA Pineda-Trujillo N., Carvajal-Carmona L.G., Buritica O., Moreno S.,
RA Uribe C., Pineda D., Toro M., Garcia F., Arias W., Bedoya G., Lopera F.,
RA Ruiz-Linares A.;
RT "A novel Cys212Tyr founder mutation in parkin and allelic heterogeneity of
RT juvenile parkinsonism in a population from North West Colombia.";
RL Neurosci. Lett. 298:87-90(2001).
RN [77]
RP VARIANTS PARK2 GLU-82; CYS-256; TRP-275; GLU-328 AND ARG-441.
RX PubMed=12116199; DOI=10.1002/ajmg.10525;
RG French Parkinson's disease genetics study group;
RG European consortium on genetic susceptibility on Parkinson's disease;
RA West A., Periquet M., Lincoln S., Luecking C.B., Nicholl D., Bonifati V.,
RA Rawal N., Gasser T., Lohmann E., Deleuze J.-F., Maraganore D., Levey A.,
RA Wood N.W., Duerr A., Hardy J., Brice A., Farrer M.;
RT "Complex relationship between parkin mutations and Parkinson disease.";
RL Am. J. Med. Genet. 114:584-591(2002).
RN [78]
RP ERRATUM OF PUBMED:12116199.
RG French Parkinson's disease genetics study group;
RG European consortium on genetic susceptibility on Parkinson's disease;
RA West A., Periquet M., Lincoln S., Luecking C.B., Nicholl D., Bonifati V.,
RA Rawal N., Gasser T., Lohmann E., Deleuze J.-F., Maraganore D., Levey A.,
RA Wood N.W., Duerr A., Hardy J., Brice A., Farrer M.J.;
RL Am. J. Med. Genet. 114:992-992(2002).
RN [79]
RP VARIANTS PARK2 LEU-37 AND PRO-351.
RX PubMed=12112109; DOI=10.1002/ana.10179;
RA Kann M., Jacobs H., Mohrmann K., Schumacher K., Hedrich K., Garrels J.,
RA Wiegers K., Schwinger E., Pramstaller P.P., Breakefield X.O., Ozelius L.J.,
RA Vieregge P., Klein C.;
RT "Role of parkin mutations in 111 community-based patients with early-onset
RT parkinsonism.";
RL Ann. Neurol. 51:621-625(2002).
RN [80]
RP VARIANTS PARK2 GLU-56 AND TYR-212.
RX PubMed=12056932; DOI=10.1001/archneur.59.6.966;
RA Hoenicka J., Vidal L., Morales B., Ampuero I., Jimenez-Jimenez F.J.,
RA Berciano J., del Ser T., Jimenez A., Ruiz P.G., de Yebenes J.G.;
RT "Molecular findings in familial Parkinson disease in Spain.";
RL Arch. Neurol. 59:966-970(2002).
RN [81]
RP VARIANTS PARK2 ASN-211; TRP-275; ASP-430 AND LEU-437.
RX PubMed=12114481; DOI=10.1136/jmg.39.7.489;
RA Nichols W.C., Pankratz N., Uniacke S.K., Pauciulo M.W., Halter C.,
RA Rudolph A., Conneally P.M., Foroud T.;
RT "Linkage stratification and mutation analysis at the parkin locus
RT identifies mutation positive Parkinson's disease families.";
RL J. Med. Genet. 39:489-492(2002).
RN [82]
RP VARIANT PARK2 MET-15, AND VARIANTS LEU-380 AND ASN-394.
RX PubMed=12397156; DOI=10.1136/jnnp.73.5.582;
RA Munoz E., Tolosa E., Pastor P., Marti M.J., Valldeoriola F.,
RA Campdelacreu J., Oliva R.;
RT "Relative high frequency of the c.255delA parkin gene mutation in Spanish
RT patients with autosomal recessive parkinsonism.";
RL J. Neurol. Neurosurg. Psych. 73:582-584(2002).
RN [83]
RP VARIANTS PARK2 PRO-42; LEU-192; CYS-256; TRP-275; ASP-430 AND LEU-437.
RX PubMed=11971093; DOI=10.1212/wnl.58.8.1239;
RA Hedrich K., Marder K., Harris J., Kann M., Lynch T., Meija-Santana H.,
RA Pramstaller P.P., Schwinger E., Bressman S.B., Fahn S., Klein C.;
RT "Evaluation of 50 probands with early-onset Parkinson's disease for parkin
RT mutations.";
RL Neurology 58:1239-1246(2002).
RN [84]
RP VARIANT PARK2 PRO-46.
RX PubMed=12362318;
RA Xu Y., Liu Z., Wang Y., Tao E., Chen G., Chen B.;
RT "A new point mutation on exon 2 of parkin gene in Parkinson's disease.";
RL Zhonghua Yi Xue Yi Chuan Xue Za Zhi 19:409-411(2002).
RN [85]
RP VARIANTS PARK2 GLN-33; GLU-82; ASP-430 AND LEU-437, VARIANTS PARK TYR-253;
RP CYS-256; TRP-275 AND ASN-280, AND VARIANTS LEU-380 AND ASN-394.
RX PubMed=12730996; DOI=10.1002/ana.10524;
RA Oliveira S.A., Scott W.K., Martin E.R., Nance M.A., Watts R.L.,
RA Hubble J.P., Koller W.C., Pahwa R., Stern M.B., Hiner B.C., Ondo W.G.,
RA Allen F.H. Jr., Scott B.L., Goetz C.G., Small G.W., Mastaglia F.,
RA Stajich J.M., Zhang F., Booze M.W., Winn M.P., Middleton L.T., Haines J.L.,
RA Pericak-Vance M.A., Vance J.M.;
RT "Parkin mutations and susceptibility alleles in late-onset Parkinson's
RT disease.";
RL Ann. Neurol. 53:624-629(2003).
RN [86]
RP VARIANTS PARK2 VAL-192; ASN-211; MET-240 AND LEU-437, VARIANT ASN-167, AND
RP INVOLVEMENT IN LATE-ONSET PARK.
RX PubMed=12629236; DOI=10.1212/01.wnl.0000049470.00180.07;
RA Foroud T., Uniacke S.K., Liu L., Pankratz N., Rudolph A., Halter C.,
RA Shults C., Marder K., Conneally P.M., Nichols W.C.;
RT "Heterozygosity for a mutation in the parkin gene leads to later onset
RT Parkinson disease.";
RL Neurology 60:796-801(2003).
RN [87]
RP VARIANTS HIS-100; SER-271 AND SER-339.
RX PubMed=12781599; DOI=10.1016/s1353-8020(03)00018-x;
RA Chen R., Gosavi N.S., Langston J.W., Chan P.;
RT "Parkin mutations are rare in patients with young-onset parkinsonism in a
RT US population.";
RL Parkinsonism Relat. Disord. 9:309-312(2003).
RN [88]
RP VARIANTS PARK2 PRO-42; CYS-402; ASN-415 AND ARG-418.
RX PubMed=15584030; DOI=10.1002/mds.20343;
RG Italian Parkinson Genetics Network;
RA Bertoli-Avella A.M., Giroud-Benitez J.L., Akyol A., Barbosa E., Schaap O.,
RA van der Linde H.C., Martignoni E., Lopiano L., Lamberti P., Fincati E.,
RA Antonini A., Stocchi F., Montagna P., Squitieri F., Marini P.,
RA Abbruzzese G., Fabbrini G., Marconi R., Dalla Libera A., Trianni G.,
RA Guidi M., De Gaetano A., Boff Maegawa G., De Leo A., Gallai V., de Rosa G.,
RA Vanacore N., Meco G., van Duijn C.M., Oostra B.A., Heutink P., Bonifati V.;
RT "Novel parkin mutations detected in patients with early-onset Parkinson's
RT disease.";
RL Mov. Disord. 20:424-431(2005).
RN [89]
RP CHARACTERIZATION OF VARIANTS PARK2 ASN-161; ASN-211; ARG-240; ASN-280 AND
RP GLU-328.
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 [90]
RP VARIANT PARK2 TRP-275.
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).
RN [91]
RP VARIANT CYS-334.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
RN [92]
RP CHARACTERIZATION OF VARIANTS PARK PRO-42 AND TRP-275, AND FUNCTION.
RX PubMed=29311685; DOI=10.1038/s41467-017-02593-y;
RA Wang C., Kang X., Zhou L., Chai Z., Wu Q., Huang R., Xu H., Hu M., Sun X.,
RA Sun S., Li J., Jiao R., Zuo P., Zheng L., Yue Z., Zhou Z.;
RT "Synaptotagmin-11 is a critical mediator of parkin-linked neurotoxicity and
RT Parkinson's disease-like pathology.";
RL Nat. Commun. 9:81-81(2018).
CC -!- FUNCTION: Functions within a multiprotein E3 ubiquitin ligase complex,
CC catalyzing the covalent attachment of ubiquitin moieties onto substrate
CC proteins (PubMed:10888878, PubMed:10973942, PubMed:11431533,
CC PubMed:12150907, PubMed:12628165, PubMed:15105460, PubMed:16135753,
CC PubMed:21376232, PubMed:21532592, PubMed:23754282, PubMed:23620051,
CC PubMed:24660806, PubMed:24751536, PubMed:32047033, PubMed:29311685,
CC PubMed:22396657). Substrates include SYT11 and VDAC1 (PubMed:32047033,
CC PubMed:29311685). Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1,
CC MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and
CC AIMP2 (PubMed:10888878, PubMed:10973942, PubMed:11431533,
CC PubMed:12150907, PubMed:12628165, PubMed:15105460, PubMed:16135753,
CC PubMed:21376232, PubMed:21532592, PubMed:23754282, PubMed:23620051,
CC PubMed:24660806, PubMed:24751536, PubMed:22396657). Mediates
CC monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and
CC 'Lys-63'-linked polyubiquitination of substrates depending on the
CC context (PubMed:19229105, PubMed:20889974, PubMed:25621951,
CC PubMed:32047033, PubMed:25474007). Participates in the removal and/or
CC detoxification of abnormally folded or damaged protein by mediating
CC 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7:
CC 'Lys-63'-linked polyubiquitinated misfolded proteins are then
CC recognized by HDAC6, leading to their recruitment to aggresomes,
CC followed by degradation (PubMed:17846173, PubMed:19229105). Mediates
CC 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated
CC isoform of SNCAIP, possibly playing a role in Lewy-body formation
CC (PubMed:11431533, PubMed:11590439, PubMed:15105460, PubMed:19229105,
CC PubMed:15728840). Mediates monoubiquitination of BCL2, thereby acting
CC as a positive regulator of autophagy (PubMed:20889974). Protects
CC against mitochondrial dysfunction during cellular stress, by acting
CC downstream of PINK1 to coordinate mitochondrial quality control
CC mechanisms that remove and replace dysfunctional mitochondrial
CC components (PubMed:32047033, PubMed:19029340, PubMed:19966284,
CC PubMed:23620051, PubMed:24896179, PubMed:25527291, PubMed:18957282,
CC PubMed:21376232, PubMed:22396657, PubMed:24660806, PubMed:25474007,
CC PubMed:24784582, PubMed:11439185, PubMed:22082830, PubMed:23933751).
CC Depending on the severity of mitochondrial damage and/or dysfunction,
CC activity ranges from preventing apoptosis and stimulating mitochondrial
CC biogenesis to regulating mitochondrial dynamics and eliminating
CC severely damaged mitochondria via mitophagy (PubMed:32047033,
CC PubMed:19029340, PubMed:19801972, PubMed:19966284, PubMed:23620051,
CC PubMed:24896179, PubMed:25527291, PubMed:21376232, PubMed:22396657,
CC PubMed:11439185, PubMed:22082830, PubMed:23933751, PubMed:33499712).
CC Activation and recruitment onto the outer membrane of
CC damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated
CC phosphorylation of both PRKN and ubiquitin (PubMed:24660806,
CC PubMed:25474007, PubMed:24784582, PubMed:25527291). After mitochondrial
CC damage, functions with PINK1 to mediate the decision between mitophagy
CC or preventing apoptosis by inducing either the poly- or
CC monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1
CC promotes mitophagy, while monoubiquitination of VDAC1 decreases
CC mitochondrial calcium influx which ultimately inhibits apoptosis
CC (PubMed:32047033). When cellular stress results in irreversible
CC mitochondrial damage, promotes the autophagic degradation of
CC dysfunctional depolarized mitochondria (mitophagy) by promoting the
CC ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1,
CC MFN1 and USP30 (PubMed:19029340, PubMed:19966284, PubMed:21753002,
CC PubMed:23620051, PubMed:24896179, PubMed:25527291, PubMed:22396657,
CC PubMed:23933751). Preferentially assembles 'Lys-6'-, 'Lys-11'- and
CC 'Lys-63'-linked polyubiquitin chains, leading to mitophagy
CC (PubMed:25621951, PubMed:32047033). The PINK1-PRKN pathway also
CC promotes fission of damaged mitochondria by PINK1-mediated
CC phosphorylation which promotes the PRKN-dependent degradation of
CC mitochondrial proteins involved in fission such as MFN2
CC (PubMed:23620051). This prevents the refusion of unhealthy mitochondria
CC with the mitochondrial network or initiates mitochondrial fragmentation
CC facilitating their later engulfment by autophagosomes
CC (PubMed:23620051). Regulates motility of damaged mitochondria via the
CC ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor
CC neurons, this likely inhibits mitochondrial intracellular anterograde
CC transport along the axons which probably increases the chance of the
CC mitochondria undergoing mitophagy in the soma (PubMed:22396657).
CC Involved in mitochondrial biogenesis via the 'Lys-48'-linked
CC polyubiquitination of transcriptional repressor ZNF746/PARIS which
CC leads to its subsequent proteasomal degradation and allows activation
CC of the transcription factor PPARGC1A (PubMed:21376232). Limits the
CC production of reactive oxygen species (ROS) (PubMed:18541373).
CC Regulates cyclin-E during neuronal apoptosis (PubMed:12628165). In
CC collaboration with CHPF isoform 2, may enhance cell viability and
CC protect cells from oxidative stress (PubMed:22082830). Independently of
CC its ubiquitin ligase activity, protects from apoptosis by the
CC transcriptional repression of p53/TP53 (PubMed:19801972). May protect
CC neurons against alpha synuclein toxicity, proteasomal dysfunction,
CC GPR37 accumulation, and kainate-induced excitotoxicity
CC (PubMed:11439185). May play a role in controlling neurotransmitter
CC trafficking at the presynaptic terminal and in calcium-dependent
CC exocytosis. May represent a tumor suppressor gene (PubMed:12719539).
CC {ECO:0000269|PubMed:10888878, ECO:0000269|PubMed:10973942,
CC ECO:0000269|PubMed:11431533, ECO:0000269|PubMed:11439185,
CC ECO:0000269|PubMed:11590439, ECO:0000269|PubMed:12150907,
CC ECO:0000269|PubMed:12628165, ECO:0000269|PubMed:12719539,
CC ECO:0000269|PubMed:15105460, ECO:0000269|PubMed:15728840,
CC ECO:0000269|PubMed:16135753, ECO:0000269|PubMed:17846173,
CC ECO:0000269|PubMed:18541373, ECO:0000269|PubMed:18957282,
CC ECO:0000269|PubMed:19029340, ECO:0000269|PubMed:19229105,
CC ECO:0000269|PubMed:19801972, ECO:0000269|PubMed:19966284,
CC ECO:0000269|PubMed:20889974, ECO:0000269|PubMed:21376232,
CC ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:21753002,
CC ECO:0000269|PubMed:22082830, 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:25474007,
CC ECO:0000269|PubMed:25527291, ECO:0000269|PubMed:25621951,
CC ECO:0000269|PubMed:29311685, ECO:0000269|PubMed:32047033,
CC ECO:0000269|PubMed:33499712}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine.;
CC EC=2.3.2.31; Evidence={ECO:0000269|PubMed:23770887};
CC -!- ACTIVITY REGULATION: In the autoinhibited state the side chain of Phe-
CC 463 inserts into a hydrophobic groove in RING-0, occluding the
CC ubiquitin acceptor site Cys-431, whereas the REP repressor element
CC binds RING-1 and blocks its E2-binding site (PubMed:23727886,
CC PubMed:23770887). Activation of PRKN requires 2 steps: (1)
CC phosphorylation at Ser-65 by PINK1 and (2) binding to phosphorylated
CC ubiquitin, leading to unlock repression of the catalytic Cys-431 by the
CC RING-0 region via an allosteric mechanism and converting PRKN to its
CC fully-active form (PubMed:24660806, PubMed:25474007, PubMed:24784582,
CC PubMed:25527291). According to another report, phosphorylation at Ser-
CC 65 by PINK1 is not essential for activation and only binding to
CC phosphorylated ubiquitin is essential to unlock repression
CC (PubMed:24751536). {ECO:0000269|PubMed:23727886,
CC ECO:0000269|PubMed:23770887, ECO:0000269|PubMed:24660806,
CC ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582,
CC ECO:0000269|PubMed:25474007, ECO:0000269|PubMed:25527291}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Forms an E3 ubiquitin ligase complex with UBE2L3 or UBE2L6
CC (PubMed:21532592, PubMed:11078524). Mediates 'Lys-63'-linked
CC polyubiquitination by associating with UBE2V1. Part of a SCF-like
CC complex, consisting of PRKN, CUL1 and FBXW7 (PubMed:12628165).
CC Interacts with SNCAIP (PubMed:11590439, PubMed:15728840). Binds to the
CC C2A and C2B domains of SYT11 (PubMed:12925569). Interacts and regulates
CC the turnover of SEPTIN5 (PubMed:11078524). Part of a complex, including
CC STUB1, HSP70 and GPR37 (PubMed:12150907). The amount of STUB1 in the
CC complex increases during ER stress (PubMed:12150907). STUB1 promotes
CC the dissociation of HSP70 from PRKN and GPR37, thus facilitating PRKN-
CC mediated GPR37 ubiquitination (PubMed:12150907). HSP70 transiently
CC associates with unfolded GPR37 and inhibits the E3 activity of PRKN,
CC whereas, STUB1 enhances the E3 activity of PRKN through promotion of
CC dissociation of HSP70 from PRKN-GPR37 complexes (PubMed:12150907).
CC Interacts with PSMD4 and PACRG (PubMed:12634850, PubMed:14532270).
CC Interacts with LRRK2 (PubMed:16352719). Interacts with RANBP2
CC (PubMed:16332688). Interacts with SUMO1 but not SUMO2, which promotes
CC nuclear localization and autoubiquitination (PubMed:16955485).
CC Interacts (via first RING-type domain) with AIMP2 (via N-terminus)
CC (PubMed:16135753). Interacts with PSMA7 and RNF41 (PubMed:15987638,
CC PubMed:18541373). Interacts with PINK1 (PubMed:19966284,
CC PubMed:20798600). Forms a complex with PINK1 and PARK7
CC (PubMed:19229105). Interacts with CHPF, the interaction with isoform 2
CC may facilitate PRKN transport into the mitochondria (PubMed:22082830).
CC Interacts with MFN2 (phosphorylated), promotes PRKN localization in
CC dysfunctional depolarized mitochondria (PubMed:23620051). Interacts
CC with FBXO7; this promotes translocation to dysfunctional depolarized
CC mitochondria (PubMed:23933751). Interacts with ZNF746
CC (PubMed:21376232). Interacts with heat shock protein 70 family members,
CC including HSPA1L, HSPA1A and HSPA8; interaction HSPA1L promotes
CC translocation to damaged mitochondria (PubMed:24270810). Interacts with
CC BAG4 and, to a lesser extent, BAG5; interaction with BAG4 inhibits
CC translocation to damaged mitochondria (PubMed:24270810). Forms a
CC complex with PRKN and PARK7 (PubMed:19229105). Interacts with AMBRA1
CC (By similarity). {ECO:0000250|UniProtKB:Q9WVS6,
CC ECO:0000269|PubMed:11078524, ECO:0000269|PubMed:11590439,
CC ECO:0000269|PubMed:12150907, ECO:0000269|PubMed:12628165,
CC ECO:0000269|PubMed:12634850, ECO:0000269|PubMed:12925569,
CC ECO:0000269|PubMed:14532270, ECO:0000269|PubMed:15728840,
CC ECO:0000269|PubMed:15987638, ECO:0000269|PubMed:16135753,
CC ECO:0000269|PubMed:16332688, ECO:0000269|PubMed:16352719,
CC ECO:0000269|PubMed:16955485, ECO:0000269|PubMed:18541373,
CC ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19966284,
CC ECO:0000269|PubMed:20798600, ECO:0000269|PubMed:21376232,
CC ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:22082830,
CC ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:23933751,
CC ECO:0000269|PubMed:24270810}.
CC -!- INTERACTION:
CC O60260; P54252-2: ATXN3; NbExp=5; IntAct=EBI-716346, EBI-9684323;
CC O60260; Q8IZ52-2: CHPF; NbExp=5; IntAct=EBI-716346, EBI-9029620;
CC O60260; Q9Y3I1: FBXO7; NbExp=10; IntAct=EBI-716346, EBI-1161222;
CC O60260; Q9Y3I1-1: FBXO7; NbExp=2; IntAct=EBI-716346, EBI-9102965;
CC O60260; Q9UBN7: HDAC6; NbExp=6; IntAct=EBI-716346, EBI-301697;
CC O60260; P08238: HSP90AB1; NbExp=2; IntAct=EBI-716346, EBI-352572;
CC O60260; Q5S007: LRRK2; NbExp=3; IntAct=EBI-716346, EBI-5323863;
CC O60260; O95140: MFN2; NbExp=4; IntAct=EBI-716346, EBI-3324756;
CC O60260; Q16342: PDCD2; NbExp=5; IntAct=EBI-716346, EBI-359462;
CC O60260; Q9BXM7: PINK1; NbExp=7; IntAct=EBI-716346, EBI-2846068;
CC O60260; Q9BXM7-1: PINK1; NbExp=2; IntAct=EBI-716346, EBI-15643376;
CC O60260; O60260: PRKN; NbExp=5; IntAct=EBI-716346, EBI-716346;
CC O60260; P49792: RANBP2; NbExp=11; IntAct=EBI-716346, EBI-973138;
CC O60260; Q8IXI2: RHOT1; NbExp=3; IntAct=EBI-716346, EBI-1396430;
CC O60260; Q15645: TRIP13; NbExp=4; IntAct=EBI-716346, EBI-358993;
CC O60260; Q6NUN9: ZNF746; NbExp=6; IntAct=EBI-716346, EBI-3862525;
CC O60260; Q9Z2Q6: Septin5; Xeno; NbExp=2; IntAct=EBI-716346, EBI-772125;
CC O60260; P68510: Ywhah; Xeno; NbExp=6; IntAct=EBI-716346, EBI-444641;
CC O60260; PRO_0000045592 [Q99IB8]; Xeno; NbExp=3; IntAct=EBI-716346, EBI-6858513;
CC O60260-5; Q6ZTN6-2: ANKRD13D; NbExp=3; IntAct=EBI-21251460, EBI-25840993;
CC O60260-5; Q86WR3: ANUBL1; NbExp=3; IntAct=EBI-21251460, EBI-25880850;
CC O60260-5; P63010-2: AP2B1; NbExp=6; IntAct=EBI-21251460, EBI-11529439;
CC O60260-5; P05067: APP; NbExp=5; IntAct=EBI-21251460, EBI-77613;
CC O60260-5; Q0P5N6: ARL16; NbExp=6; IntAct=EBI-21251460, EBI-10186132;
CC O60260-5; Q86TN1: ARNT2; NbExp=3; IntAct=EBI-21251460, EBI-25844820;
CC O60260-5; Q8WXK3: ASB13; NbExp=3; IntAct=EBI-21251460, EBI-707573;
CC O60260-5; Q8WXK3-2: ASB13; NbExp=3; IntAct=EBI-21251460, EBI-12015080;
CC O60260-5; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-21251460, EBI-14199987;
CC O60260-5; Q9H672-2: ASB7; NbExp=3; IntAct=EBI-21251460, EBI-12104328;
CC O60260-5; Q96DX5: ASB9; NbExp=3; IntAct=EBI-21251460, EBI-745641;
CC O60260-5; Q96DX5-3: ASB9; NbExp=3; IntAct=EBI-21251460, EBI-25843552;
CC O60260-5; Q9H0Y0: ATG10; NbExp=3; IntAct=EBI-21251460, EBI-1048913;
CC O60260-5; P54253: ATXN1; NbExp=6; IntAct=EBI-21251460, EBI-930964;
CC O60260-5; O14867: BACH1; NbExp=3; IntAct=EBI-21251460, EBI-1263541;
CC O60260-5; P46379-2: BAG6; NbExp=3; IntAct=EBI-21251460, EBI-10988864;
CC O60260-5; A8KA13: BCL6B; NbExp=3; IntAct=EBI-21251460, EBI-10174813;
CC O60260-5; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-21251460, EBI-2837444;
CC O60260-5; P29466-3: CASP1; NbExp=6; IntAct=EBI-21251460, EBI-12248206;
CC O60260-5; Q13939: CCIN; NbExp=3; IntAct=EBI-21251460, EBI-25879469;
CC O60260-5; P78396-2: CCNA1; NbExp=3; IntAct=EBI-21251460, EBI-21770675;
CC O60260-5; Q00535: CDK5; NbExp=3; IntAct=EBI-21251460, EBI-1041567;
CC O60260-5; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-21251460, EBI-350590;
CC O60260-5; Q9UBU7: DBF4; NbExp=3; IntAct=EBI-21251460, EBI-372690;
CC O60260-5; Q5QP82-2: DCAF10; NbExp=3; IntAct=EBI-21251460, EBI-10983996;
CC O60260-5; P61962: DCAF7; NbExp=3; IntAct=EBI-21251460, EBI-359808;
CC O60260-5; Q5TAQ9-2: DCAF8; NbExp=3; IntAct=EBI-21251460, EBI-25842815;
CC O60260-5; Q9BW61: DDA1; NbExp=3; IntAct=EBI-21251460, EBI-2510241;
CC O60260-5; Q8NDP9: DKFZp547K2416; NbExp=3; IntAct=EBI-21251460, EBI-25842538;
CC O60260-5; P78352-2: DLG4; NbExp=6; IntAct=EBI-21251460, EBI-631152;
CC O60260-5; P31689: DNAJA1; NbExp=6; IntAct=EBI-21251460, EBI-347834;
CC O60260-5; A0A024RCP2: DOM3Z; NbExp=3; IntAct=EBI-21251460, EBI-25847826;
CC O60260-5; O75530-2: EED; NbExp=3; IntAct=EBI-21251460, EBI-11132357;
CC O60260-5; Q8TC29: ENKUR; NbExp=6; IntAct=EBI-21251460, EBI-9246952;
CC O60260-5; Q6P1L5: FAM117B; NbExp=3; IntAct=EBI-21251460, EBI-3893327;
CC O60260-5; O00757: FBP2; NbExp=3; IntAct=EBI-21251460, EBI-719781;
CC O60260-5; P57775: FBXW4; NbExp=3; IntAct=EBI-21251460, EBI-2372268;
CC O60260-5; Q9UHY8: FEZ2; NbExp=3; IntAct=EBI-21251460, EBI-396453;
CC O60260-5; P22607: FGFR3; NbExp=3; IntAct=EBI-21251460, EBI-348399;
CC O60260-5; Q9H2C0: GAN; NbExp=3; IntAct=EBI-21251460, EBI-764342;
CC O60260-5; Q9NXC2: GFOD1; NbExp=3; IntAct=EBI-21251460, EBI-8799578;
CC O60260-5; Q96IK5: GMCL1; NbExp=3; IntAct=EBI-21251460, EBI-2548508;
CC O60260-5; P62879: GNB2; NbExp=3; IntAct=EBI-21251460, EBI-356942;
CC O60260-5; Q7Z602: GPR141; NbExp=3; IntAct=EBI-21251460, EBI-21649723;
CC O60260-5; P06396: GSN; NbExp=3; IntAct=EBI-21251460, EBI-351506;
CC O60260-5; P68431: H3C12; NbExp=3; IntAct=EBI-21251460, EBI-79722;
CC O60260-5; Q86YM7: HOMER1; NbExp=6; IntAct=EBI-21251460, EBI-746815;
CC O60260-5; P0DMV8: HSPA1A; NbExp=6; IntAct=EBI-21251460, EBI-11052499;
CC O60260-5; P11142: HSPA8; NbExp=9; IntAct=EBI-21251460, EBI-351896;
CC O60260-5; Q6DN90-2: IQSEC1; NbExp=6; IntAct=EBI-21251460, EBI-21911304;
CC O60260-5; Q8NA54: IQUB; NbExp=3; IntAct=EBI-21251460, EBI-10220600;
CC O60260-5; P05161: ISG15; NbExp=3; IntAct=EBI-21251460, EBI-746466;
CC O60260-5; Q9UKP3-2: ITGB1BP2; NbExp=3; IntAct=EBI-21251460, EBI-25856470;
CC O60260-5; Q9NVX7-2: KBTBD4; NbExp=3; IntAct=EBI-21251460, EBI-25871195;
CC O60260-5; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-21251460, EBI-2796400;
CC O60260-5; Q6TDP4: KLHL17; NbExp=3; IntAct=EBI-21251460, EBI-21328926;
CC O60260-5; O94889: KLHL18; NbExp=3; IntAct=EBI-21251460, EBI-2510096;
CC O60260-5; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-21251460, EBI-714379;
CC O60260-5; Q8WZ60: KLHL6; NbExp=3; IntAct=EBI-21251460, EBI-6426464;
CC O60260-5; Q3SY46: KRTAP13-3; NbExp=3; IntAct=EBI-21251460, EBI-10241252;
CC O60260-5; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-21251460, EBI-1044640;
CC O60260-5; Q9BYZ2: LDHAL6B; NbExp=6; IntAct=EBI-21251460, EBI-1108377;
CC O60260-5; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-21251460, EBI-739832;
CC O60260-5; O95777: LSM8; NbExp=6; IntAct=EBI-21251460, EBI-347779;
CC O60260-5; Q9GZQ8: MAP1LC3B; NbExp=3; IntAct=EBI-21251460, EBI-373144;
CC O60260-5; P10636-6: MAPT; NbExp=3; IntAct=EBI-21251460, EBI-7796455;
CC O60260-5; P61244-4: MAX; NbExp=3; IntAct=EBI-21251460, EBI-25848049;
CC O60260-5; Q8TDB4: MGARP; NbExp=6; IntAct=EBI-21251460, EBI-4397720;
CC O60260-5; A4FUJ8: MKL1; NbExp=6; IntAct=EBI-21251460, EBI-21250407;
CC O60260-5; P51948: MNAT1; NbExp=3; IntAct=EBI-21251460, EBI-716139;
CC O60260-5; Q8N594: MPND; NbExp=3; IntAct=EBI-21251460, EBI-2512452;
CC O60260-5; Q9Y483-4: MTF2; NbExp=3; IntAct=EBI-21251460, EBI-10698053;
CC O60260-5; Q9NPC7: MYNN; NbExp=3; IntAct=EBI-21251460, EBI-3446748;
CC O60260-5; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-21251460, EBI-1058491;
CC O60260-5; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-21251460, EBI-25830200;
CC O60260-5; P68402: PAFAH1B2; NbExp=3; IntAct=EBI-21251460, EBI-713724;
CC O60260-5; Q9NR21-5: PARP11; NbExp=3; IntAct=EBI-21251460, EBI-17159452;
CC O60260-5; Q9HBE1-4: PATZ1; NbExp=3; IntAct=EBI-21251460, EBI-11022007;
CC O60260-5; Q96MG8: PCMTD1; NbExp=3; IntAct=EBI-21251460, EBI-2561395;
CC O60260-5; Q9NV79: PCMTD2; NbExp=3; IntAct=EBI-21251460, EBI-6309018;
CC O60260-5; Q13113: PDZK1IP1; NbExp=6; IntAct=EBI-21251460, EBI-716063;
CC O60260-5; Q96LB9: PGLYRP3; NbExp=3; IntAct=EBI-21251460, EBI-12339509;
CC O60260-5; Q6ZR37: PLEKHG7; NbExp=6; IntAct=EBI-21251460, EBI-12891828;
CC O60260-5; P25786: PSMA1; NbExp=6; IntAct=EBI-21251460, EBI-359352;
CC O60260-5; P40306: PSMB10; NbExp=3; IntAct=EBI-21251460, EBI-603329;
CC O60260-5; P28070: PSMB4; NbExp=3; IntAct=EBI-21251460, EBI-603350;
CC O60260-5; O60671: RAD1; NbExp=6; IntAct=EBI-21251460, EBI-721835;
CC O60260-5; Q8NDN9-2: RCBTB1; NbExp=3; IntAct=EBI-21251460, EBI-25880533;
CC O60260-5; P41220: RGS2; NbExp=6; IntAct=EBI-21251460, EBI-712388;
CC O60260-5; A0A087WUY2: RGS3; NbExp=6; IntAct=EBI-21251460, EBI-25879714;
CC O60260-5; O94844: RHOBTB1; NbExp=3; IntAct=EBI-21251460, EBI-6426999;
CC O60260-5; Q8N5U6: RNF10; NbExp=3; IntAct=EBI-21251460, EBI-714023;
CC O60260-5; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-21251460, EBI-396669;
CC O60260-5; Q6ZNA4-2: RNF111; NbExp=6; IntAct=EBI-21251460, EBI-21535400;
CC O60260-5; Q9ULX5: RNF112; NbExp=6; IntAct=EBI-21251460, EBI-25829984;
CC O60260-5; Q8WVD3: RNF138; NbExp=3; IntAct=EBI-21251460, EBI-749039;
CC O60260-5; Q9UBS8: RNF14; NbExp=3; IntAct=EBI-21251460, EBI-2130308;
CC O60260-5; Q96A37: RNF166; NbExp=3; IntAct=EBI-21251460, EBI-2130320;
CC O60260-5; Q96D59: RNF183; NbExp=3; IntAct=EBI-21251460, EBI-743938;
CC O60260-5; Q96BH1: RNF25; NbExp=3; IntAct=EBI-21251460, EBI-2129220;
CC O60260-5; P08865: RPSA; NbExp=3; IntAct=EBI-21251460, EBI-354112;
CC O60260-5; Q8N488: RYBP; NbExp=6; IntAct=EBI-21251460, EBI-752324;
CC O60260-5; Q15393: SF3B3; NbExp=3; IntAct=EBI-21251460, EBI-346977;
CC O60260-5; Q2NKQ1-4: SGSM1; NbExp=6; IntAct=EBI-21251460, EBI-10182463;
CC O60260-5; Q14190-2: SIM2; NbExp=3; IntAct=EBI-21251460, EBI-21623725;
CC O60260-5; Q9HCE7-2: SMURF1; NbExp=3; IntAct=EBI-21251460, EBI-9845742;
CC O60260-5; P37840: SNCA; NbExp=8; IntAct=EBI-21251460, EBI-985879;
CC O60260-5; Q9Y6H5-5: SNCAIP; NbExp=6; IntAct=EBI-21251460, EBI-25880040;
CC O60260-5; Q96DI7: SNRNP40; NbExp=3; IntAct=EBI-21251460, EBI-538492;
CC O60260-5; O14544: SOCS6; NbExp=3; IntAct=EBI-21251460, EBI-3929549;
CC O60260-5; Q99932-2: SPAG8; NbExp=6; IntAct=EBI-21251460, EBI-11959123;
CC O60260-5; Q8IUW3: SPATA2L; NbExp=3; IntAct=EBI-21251460, EBI-2510414;
CC O60260-5; Q8TCT7-2: SPPL2B; NbExp=3; IntAct=EBI-21251460, EBI-8345366;
CC O60260-5; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-21251460, EBI-5235340;
CC O60260-5; Q9C004: SPRY4; NbExp=3; IntAct=EBI-21251460, EBI-354861;
CC O60260-5; Q96BD6: SPSB1; NbExp=3; IntAct=EBI-21251460, EBI-2659201;
CC O60260-5; Q99619: SPSB2; NbExp=3; IntAct=EBI-21251460, EBI-2323209;
CC O60260-5; O75886: STAM2; NbExp=3; IntAct=EBI-21251460, EBI-373258;
CC O60260-5; O95630: STAMBP; NbExp=3; IntAct=EBI-21251460, EBI-396676;
CC O60260-5; Q9UNE7: STUB1; NbExp=6; IntAct=EBI-21251460, EBI-357085;
CC O60260-5; Q9BT88: SYT11; NbExp=6; IntAct=EBI-21251460, EBI-751770;
CC O60260-5; Q13148: TARDBP; NbExp=3; IntAct=EBI-21251460, EBI-372899;
CC O60260-5; Q16650: TBR1; NbExp=6; IntAct=EBI-21251460, EBI-1047158;
CC O60260-5; Q15554-4: TERF2; NbExp=6; IntAct=EBI-21251460, EBI-25840535;
CC O60260-5; Q04724: TLE1; NbExp=3; IntAct=EBI-21251460, EBI-711424;
CC O60260-5; Q71RG4-4: TMUB2; NbExp=3; IntAct=EBI-21251460, EBI-25831574;
CC O60260-5; Q9H0E2: TOLLIP; NbExp=3; IntAct=EBI-21251460, EBI-74615;
CC O60260-5; P19474: TRIM21; NbExp=3; IntAct=EBI-21251460, EBI-81290;
CC O60260-5; Q9UPQ4-2: TRIM35; NbExp=3; IntAct=EBI-21251460, EBI-17716262;
CC O60260-5; Q8NBM4-4: UBAC2; NbExp=3; IntAct=EBI-21251460, EBI-25840976;
CC O60260-5; P57075-2: UBASH3A; NbExp=6; IntAct=EBI-21251460, EBI-7353612;
CC O60260-5; P0CG47: UBB; NbExp=6; IntAct=EBI-21251460, EBI-413034;
CC O60260-5; O15205: UBD; NbExp=3; IntAct=EBI-21251460, EBI-6657186;
CC O60260-5; Q9Y385: UBE2J1; NbExp=3; IntAct=EBI-21251460, EBI-988826;
CC O60260-5; P68036: UBE2L3; NbExp=3; IntAct=EBI-21251460, EBI-711173;
CC O60260-5; P61081: UBE2M; NbExp=3; IntAct=EBI-21251460, EBI-1041660;
CC O60260-5; Q9C0C9: UBE2O; NbExp=3; IntAct=EBI-21251460, EBI-2339946;
CC O60260-5; Q13404: UBE2V1; NbExp=3; IntAct=EBI-21251460, EBI-1050671;
CC O60260-5; Q04323-2: UBXN1; NbExp=3; IntAct=EBI-21251460, EBI-11530712;
CC O60260-5; Q9Y3C8: UFC1; NbExp=3; IntAct=EBI-21251460, EBI-1045733;
CC O60260-5; Q96RL1-2: UIMC1; NbExp=3; IntAct=EBI-21251460, EBI-17761788;
CC O60260-5; O75604-3: USP2; NbExp=3; IntAct=EBI-21251460, EBI-10696113;
CC O60260-5; P18206-2: VCL; NbExp=6; IntAct=EBI-21251460, EBI-11027067;
CC O60260-5; P45880: VDAC2; NbExp=6; IntAct=EBI-21251460, EBI-354022;
CC O60260-5; P40337-2: VHL; NbExp=3; IntAct=EBI-21251460, EBI-12157263;
CC O60260-5; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-21251460, EBI-11141397;
CC O60260-5; Q9GZS3: WDR61; NbExp=6; IntAct=EBI-21251460, EBI-358545;
CC O60260-5; O00308: WWP2; NbExp=3; IntAct=EBI-21251460, EBI-743923;
CC O60260-5; Q04917: YWHAH; NbExp=6; IntAct=EBI-21251460, EBI-306940;
CC O60260-5; O43167-2: ZBTB24; NbExp=3; IntAct=EBI-21251460, EBI-25842419;
CC O60260-5; Q15916: ZBTB6; NbExp=3; IntAct=EBI-21251460, EBI-7227791;
CC O60260-5; Q9Y649; NbExp=3; IntAct=EBI-21251460, EBI-25900580;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:10319893,
CC ECO:0000269|PubMed:16955485, ECO:0000269|PubMed:17846173,
CC ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:19029340,
CC ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19501131,
CC ECO:0000269|PubMed:22082830, ECO:0000269|PubMed:23620051,
CC ECO:0000269|PubMed:23933751, ECO:0000269|PubMed:24898855}. Nucleus
CC {ECO:0000269|PubMed:16955485}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:19501131}. Mitochondrion
CC {ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:19029340,
CC ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:20889974,
CC ECO:0000269|PubMed:22082830, ECO:0000269|PubMed:23620051,
CC ECO:0000269|PubMed:23754282, ECO:0000269|PubMed:23933751,
CC ECO:0000269|PubMed:24898855}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q9WVS6}. Cell projection, neuron projection
CC {ECO:0000269|PubMed:12925569}. Postsynaptic density
CC {ECO:0000250|UniProtKB:Q9WVS6}. Presynapse
CC {ECO:0000250|UniProtKB:Q9WVS6}. Note=Mainly localizes in the cytosol
CC (PubMed:19029340, PubMed:19229105). Co-localizes with SYT11 in
CC neutrites (PubMed:12925569). Co-localizes with SNCAIP in brainstem Lewy
CC bodies (PubMed:10319893, PubMed:11431533). Translocates to
CC dysfunctional mitochondria that have lost the mitochondrial membrane
CC potential; recruitment to mitochondria is PINK1-dependent
CC (PubMed:24898855, PubMed:18957282, PubMed:19966284, PubMed:23620051).
CC Mitochondrial localization also gradually increases with cellular
CC growth (PubMed:22082830). {ECO:0000269|PubMed:10319893,
CC ECO:0000269|PubMed:11431533, ECO:0000269|PubMed:12925569,
CC ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:19029340,
CC ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19966284,
CC ECO:0000269|PubMed:22082830, ECO:0000269|PubMed:23620051,
CC ECO:0000269|PubMed:24898855}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1;
CC IsoId=O60260-1; Sequence=Displayed;
CC Name=2; Synonyms=SV5DEL;
CC IsoId=O60260-2; Sequence=VSP_011707;
CC Name=3;
CC IsoId=O60260-3; Sequence=VSP_011706, VSP_011709, VSP_011710;
CC Name=4;
CC IsoId=O60260-4; Sequence=VSP_011705;
CC Name=5;
CC IsoId=O60260-5; Sequence=VSP_011708, VSP_011711, VSP_011712;
CC Name=6;
CC IsoId=O60260-6; Sequence=VSP_041563;
CC Name=7; Synonyms=SV5,9DEL;
CC IsoId=O60260-7; Sequence=VSP_011707, VSP_053651;
CC Name=8; Synonyms=SV9DEL;
CC IsoId=O60260-8; Sequence=VSP_053651;
CC -!- TISSUE SPECIFICITY: Highly expressed in the brain including the
CC substantia nigra (PubMed:9560156, PubMed:19501131). Expressed in heart,
CC testis and skeletal muscle (PubMed:9560156). Expression is down-
CC regulated or absent in tumor biopsies, and absent in the brain of PARK2
CC patients (PubMed:14614460, PubMed:12719539). Overexpression protects
CC dopamine neurons from kainate-mediated apoptosis (PubMed:12628165).
CC Found in serum (at protein level) (PubMed:19501131).
CC {ECO:0000269|PubMed:12628165, ECO:0000269|PubMed:12719539,
CC ECO:0000269|PubMed:14614460, ECO:0000269|PubMed:19501131,
CC ECO:0000269|PubMed:9560156}.
CC -!- DOMAIN: The ubiquitin-like domain binds the PSMD4 subunit of 26S
CC proteasomes. {ECO:0000269|PubMed:19801972}.
CC -!- DOMAIN: The RING-type 1 zinc finger domain is required to repress
CC p53/TP53 transcription. {ECO:0000269|PubMed:19801972}.
CC -!- DOMAIN: Members of the RBR family are atypical E3 ligases. They
CC interact with the E2 conjugating enzyme UBE2L3 and function like HECT-
CC type E3 enzymes: they bind E2s via the first RING domain, but require
CC an obligate trans-thiolation step during the ubiquitin transfer,
CC requiring a conserved cysteine residue in the second RING domain.
CC {ECO:0000269|PubMed:23770917, ECO:0000305|PubMed:21532592}.
CC -!- PTM: Auto-ubiquitinates in an E2-dependent manner leading to its own
CC degradation (PubMed:19229105, PubMed:25474007, PubMed:23770917). Also
CC polyubiquitinated by RNF41 for proteasomal degradation
CC (PubMed:19229105). {ECO:0000269|PubMed:19229105,
CC ECO:0000269|PubMed:23770917, ECO:0000269|PubMed:25474007}.
CC -!- PTM: S-nitrosylated. The inhibition of PRKN ubiquitin E3 ligase
CC activity by S-nitrosylation could contribute to the degenerative
CC process in PD by impairing the ubiquitination of PRKN substrates.
CC {ECO:0000269|PubMed:15105460}.
CC -!- PTM: Phosphorylated (PubMed:23754282, PubMed:24660806, PubMed:24784582,
CC PubMed:18957282, PubMed:25474007). Activation requires phosphorylation
CC at Ser-65 by PINK1 and binding to PINK1 phosphorylated ubiquitin
CC (PubMed:23754282, PubMed:24660806, PubMed:24784582, PubMed:18957282,
CC PubMed:25474007). Phosphorylation at Thr-175 by PINK1 and at Thr-217 is
CC important for mitochondrial localization (PubMed:18957282).
CC {ECO:0000269|PubMed:18957282, ECO:0000269|PubMed:23754282,
CC ECO:0000269|PubMed:24660806, ECO:0000269|PubMed:24784582,
CC ECO:0000269|PubMed:25474007}.
CC -!- DISEASE: Parkinson disease (PARK) [MIM:168600]: A complex
CC neurodegenerative disorder characterized by bradykinesia, resting
CC tremor, muscular rigidity and postural instability. Additional features
CC are characteristic postural abnormalities, dysautonomia, dystonic
CC cramps, and dementia. The pathology of Parkinson disease involves the
CC loss of dopaminergic neurons in the substantia nigra and the presence
CC of Lewy bodies (intraneuronal accumulations of aggregated proteins), in
CC surviving neurons in various areas of the brain. The disease is
CC progressive and usually manifests after the age of 50 years, although
CC early-onset cases (before 50 years) are known. The majority of the
CC cases are sporadic suggesting a multifactorial etiology based on
CC environmental and genetic factors. However, some patients present with
CC a positive family history for the disease. Familial forms of the
CC disease usually begin at earlier ages and are associated with atypical
CC clinical features. {ECO:0000269|PubMed:12629236,
CC ECO:0000269|PubMed:12730996, ECO:0000269|PubMed:19966284,
CC ECO:0000269|PubMed:29311685}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC Heterozygous mutations act as susceptibility alleles for late-onset
CC Parkinson disease (PubMed:12730996 and PubMed:12629236).
CC -!- DISEASE: Parkinson disease 2 (PARK2) [MIM:600116]: A neurodegenerative
CC disorder characterized by bradykinesia, rigidity, postural instability,
CC tremor, and onset usually before 40. It differs from classic Parkinson
CC disease by early DOPA-induced dyskinesia, diurnal fluctuation of the
CC symptoms, sleep benefit, dystonia and hyper-reflexia. Dementia is
CC absent. Pathologically, patients show loss of dopaminergic neurons in
CC the substantia nigra, similar to that seen in Parkinson disease;
CC however, Lewy bodies (intraneuronal accumulations of aggregated
CC proteins) are absent. {ECO:0000269|PubMed:10072423,
CC ECO:0000269|PubMed:10824074, ECO:0000269|PubMed:10888878,
CC ECO:0000269|PubMed:10939576, ECO:0000269|PubMed:11163284,
CC ECO:0000269|PubMed:11179010, ECO:0000269|PubMed:11431533,
CC ECO:0000269|PubMed:11487568, ECO:0000269|PubMed:11590439,
CC ECO:0000269|PubMed:11971093, ECO:0000269|PubMed:12056932,
CC ECO:0000269|PubMed:12112109, ECO:0000269|PubMed:12114481,
CC ECO:0000269|PubMed:12116199, ECO:0000269|PubMed:12362318,
CC ECO:0000269|PubMed:12397156, ECO:0000269|PubMed:12629236,
CC ECO:0000269|PubMed:12730996, ECO:0000269|PubMed:12925569,
CC ECO:0000269|PubMed:15584030, ECO:0000269|PubMed:17360614,
CC ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19801972,
CC ECO:0000269|PubMed:20404107, ECO:0000269|PubMed:20889486,
CC ECO:0000269|PubMed:20889974, ECO:0000269|PubMed:21376232,
CC ECO:0000269|PubMed:22956510, ECO:0000269|PubMed:9560156,
CC ECO:0000269|PubMed:9731209}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Note=Defects in PRKN may be involved in the development and/or
CC progression of ovarian cancer.
CC -!- MISCELLANEOUS: The parkin locus (PRKN), adjacent to the 6q telomere is
CC hyper-recombinable and lies within FRA6E, the third most common fragile
CC site in tumor tissue.
CC -!- SIMILARITY: Belongs to the RBR family. Parkin subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Life's tremors - Issue 131
CC of September 2011;
CC URL="https://web.expasy.org/spotlight/back_issues/131";
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DR EMBL; AB009973; BAA25751.1; -; mRNA.
DR EMBL; EF375726; ABN46990.1; -; mRNA.
DR EMBL; AF381282; AAM21457.1; -; mRNA.
DR EMBL; AF381283; AAM21458.1; -; mRNA.
DR EMBL; AF381286; AAM21461.1; -; mRNA.
DR EMBL; GU345839; ADB90270.1; -; mRNA.
DR EMBL; GU345840; ADB90271.1; -; mRNA.
DR EMBL; GU361467; ADB91979.1; -; mRNA.
DR EMBL; AK292590; BAF85279.1; -; mRNA.
DR EMBL; AL035697; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL132982; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445215; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000886; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000887; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001576; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001577; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001578; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003699; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW47573.1; -; Genomic_DNA.
DR EMBL; CH471051; EAW47574.1; -; Genomic_DNA.
DR EMBL; BC022014; AAH22014.1; -; mRNA.
DR EMBL; AY564225; AAS88422.1; -; Genomic_DNA.
DR CCDS; CCDS5281.1; -. [O60260-1]
DR CCDS; CCDS5282.1; -. [O60260-2]
DR CCDS; CCDS5283.1; -. [O60260-6]
DR RefSeq; NP_004553.2; NM_004562.2. [O60260-1]
DR RefSeq; NP_054642.2; NM_013987.2. [O60260-2]
DR RefSeq; NP_054643.2; NM_013988.2. [O60260-6]
DR PDB; 1IYF; NMR; -; A=1-76.
DR PDB; 2JMO; NMR; -; A=308-384.
DR PDB; 4BM9; X-ray; 2.25 A; A=137-465.
DR PDB; 4I1F; X-ray; 1.58 A; A=141-465.
DR PDB; 4I1H; X-ray; 2.00 A; A=141-465.
DR PDB; 5C1Z; X-ray; 1.79 A; A/B=1-465.
DR PDB; 5C23; X-ray; 2.37 A; A/B=1-465.
DR PDB; 5C9V; X-ray; 2.35 A; A=137-465.
DR PDB; 5N2W; X-ray; 2.68 A; A=1-465.
DR PDB; 5N38; X-ray; 2.60 A; A=1-465.
DR PDB; 5TR5; NMR; -; A=1-76.
DR PDB; 6GLC; X-ray; 1.80 A; A=1-382.
DR PDB; 6HUE; X-ray; 2.85 A; A/B=1-465.
DR PDB; 6N13; NMR; -; B=144-465.
DR PDBsum; 1IYF; -.
DR PDBsum; 2JMO; -.
DR PDBsum; 4BM9; -.
DR PDBsum; 4I1F; -.
DR PDBsum; 4I1H; -.
DR PDBsum; 5C1Z; -.
DR PDBsum; 5C23; -.
DR PDBsum; 5C9V; -.
DR PDBsum; 5N2W; -.
DR PDBsum; 5N38; -.
DR PDBsum; 5TR5; -.
DR PDBsum; 6GLC; -.
DR PDBsum; 6HUE; -.
DR PDBsum; 6N13; -.
DR AlphaFoldDB; O60260; -.
DR BMRB; O60260; -.
DR SMR; O60260; -.
DR BioGRID; 111105; 731.
DR CORUM; O60260; -.
DR DIP; DIP-37655N; -.
DR IntAct; O60260; 276.
DR MINT; O60260; -.
DR STRING; 9606.ENSP00000355865; -.
DR iPTMnet; O60260; -.
DR PhosphoSitePlus; O60260; -.
DR BioMuta; PRKN; -.
DR MassIVE; O60260; -.
DR PaxDb; O60260; -.
DR PeptideAtlas; O60260; -.
DR PRIDE; O60260; -.
DR ProteomicsDB; 49290; -. [O60260-1]
DR ProteomicsDB; 49291; -. [O60260-2]
DR ProteomicsDB; 49292; -. [O60260-3]
DR ProteomicsDB; 49293; -. [O60260-4]
DR ProteomicsDB; 49294; -. [O60260-5]
DR ProteomicsDB; 49295; -. [O60260-6]
DR Antibodypedia; 4264; 811 antibodies from 51 providers.
DR DNASU; 5071; -.
DR Ensembl; ENST00000366896.5; ENSP00000355862.1; ENSG00000185345.24. [O60260-6]
DR Ensembl; ENST00000366897.5; ENSP00000355863.1; ENSG00000185345.24. [O60260-2]
DR Ensembl; ENST00000366898.6; ENSP00000355865.1; ENSG00000185345.24. [O60260-1]
DR Ensembl; ENST00000479615.5; ENSP00000434414.1; ENSG00000185345.24. [O60260-3]
DR GeneID; 5071; -.
DR KEGG; hsa:5071; -.
DR MANE-Select; ENST00000366898.6; ENSP00000355865.1; NM_004562.3; NP_004553.2.
DR UCSC; uc003qty.5; human. [O60260-1]
DR CTD; 5071; -.
DR DisGeNET; 5071; -.
DR GeneCards; PRKN; -.
DR GeneReviews; PRKN; -.
DR HGNC; HGNC:8607; PRKN.
DR HPA; ENSG00000185345; Tissue enhanced (skeletal muscle, tongue).
DR MalaCards; PRKN; -.
DR MIM; 168600; phenotype.
DR MIM; 600116; phenotype.
DR MIM; 602544; gene.
DR neXtProt; NX_O60260; -.
DR OpenTargets; ENSG00000185345; -.
DR Orphanet; 2828; Young-onset Parkinson disease.
DR PharmGKB; PA32942; -.
DR VEuPathDB; HostDB:ENSG00000185345; -.
DR eggNOG; KOG0006; Eukaryota.
DR GeneTree; ENSGT00390000011034; -.
DR HOGENOM; CLU_050804_0_0_1; -.
DR InParanoid; O60260; -.
DR OMA; FAEFFFK; -.
DR OrthoDB; 1140368at2759; -.
DR PhylomeDB; O60260; -.
DR TreeFam; TF314529; -.
DR BRENDA; 2.3.2.27; 2681.
DR BRENDA; 2.3.2.31; 2681.
DR PathwayCommons; O60260; -.
DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-HSA-5689877; Josephin domain DUBs.
DR Reactome; R-HSA-9646399; Aggrephagy.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; O60260; -.
DR SIGNOR; O60260; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 5071; 13 hits in 1103 CRISPR screens.
DR ChiTaRS; PARK2; human.
DR EvolutionaryTrace; O60260; -.
DR GeneWiki; Parkin_(ligase); -.
DR GenomeRNAi; 5071; -.
DR Pharos; O60260; Tbio.
DR PRO; PR:O60260; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O60260; protein.
DR Bgee; ENSG00000185345; Expressed in sural nerve and 105 other tissues.
DR ExpressionAtlas; O60260; baseline and differential.
DR Genevisible; O60260; HS.
DR GO; GO:0016235; C:aggresome; IDA:BHF-UCL.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0097413; C:Lewy body; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:1990452; C:Parkin-FBXW7-Cul1 ubiquitin ligase complex; IPI:ParkinsonsUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0098793; C:presynapse; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0008013; F:beta-catenin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051087; F:chaperone binding; IPI:BHF-UCL.
DR GO; GO:0097602; F:cullin family protein binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0019899; F:enzyme binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:1990444; F:F-box domain binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0031072; F:heat shock protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0030544; F:Hsp70 protein binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; IPI:BHF-UCL.
DR GO; GO:0043274; F:phospholipase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0017124; F:SH3 domain binding; TAS:ParkinsonsUK-UCL.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0015631; F:tubulin binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IMP:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; TAS:ParkinsonsUK-UCL.
DR GO; GO:0008344; P:adult locomotory behavior; ISS:ParkinsonsUK-UCL.
DR GO; GO:0070842; P:aggresome assembly; IMP:BHF-UCL.
DR GO; GO:1990000; P:amyloid fibril formation; TAS:Reactome.
DR GO; GO:0000422; P:autophagy of mitochondrion; IDA:UniProtKB.
DR GO; GO:1903351; P:cellular response to dopamine; TAS:ParkinsonsUK-UCL.
DR GO; GO:0071287; P:cellular response to manganese ion; TAS:ParkinsonsUK-UCL.
DR GO; GO:0097237; P:cellular response to toxic substance; IMP:ParkinsonsUK-UCL.
DR GO; GO:0034620; P:cellular response to unfolded protein; TAS:ParkinsonsUK-UCL.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0042417; P:dopamine metabolic process; TAS:ParkinsonsUK-UCL.
DR GO; GO:0051583; P:dopamine uptake involved in synaptic transmission; IEA:Ensembl.
DR GO; GO:0036503; P:ERAD pathway; NAS:ParkinsonsUK-UCL.
DR GO; GO:0010994; P:free ubiquitin chain polymerization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0016236; P:macroautophagy; TAS:Reactome.
DR GO; GO:0000266; P:mitochondrial fission; ISS:ParkinsonsUK-UCL.
DR GO; GO:0007005; P:mitochondrion organization; ISS:ParkinsonsUK-UCL.
DR GO; GO:0099074; P:mitochondrion to lysosome transport; IDA:ParkinsonsUK-UCL.
DR GO; GO:0000423; P:mitophagy; IDA:UniProtKB.
DR GO; GO:0044828; P:negative regulation by host of viral genome replication; IDA:AgBase.
DR GO; GO:0032232; P:negative regulation of actin filament bundle assembly; IDA:BHF-UCL.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; IDA:BHF-UCL.
DR GO; GO:1902236; P:negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903382; P:negative regulation of endoplasmic reticulum stress-induced neuron intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:1903542; P:negative regulation of exosomal secretion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0033132; P:negative regulation of glucokinase activity; IDA:MGI.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IDA:MGI.
DR GO; GO:1905366; P:negative regulation of intralumenal vesicle formation; IMP:ParkinsonsUK-UCL.
DR GO; GO:1902254; P:negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator; IMP:ParkinsonsUK-UCL.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISS:ParkinsonsUK-UCL.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; ISS:ParkinsonsUK-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:ParkinsonsUK-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; IGI:ParkinsonsUK-UCL.
DR GO; GO:1903202; P:negative regulation of oxidative stress-induced cell death; TAS:ParkinsonsUK-UCL.
DR GO; GO:1903377; P:negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:1902283; P:negative regulation of primary amine oxidase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IGI:ParkinsonsUK-UCL.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; IDA:BHF-UCL.
DR GO; GO:1904049; P:negative regulation of spontaneous neurotransmitter secretion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:ParkinsonsUK-UCL.
DR GO; GO:0070050; P:neuron cellular homeostasis; ISS:ParkinsonsUK-UCL.
DR GO; GO:0042415; P:norepinephrine metabolic process; IEA:Ensembl.
DR GO; GO:0061734; P:parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903599; P:positive regulation of autophagy of mitochondrion; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903861; P:positive regulation of dendrite extension; IEA:Ensembl.
DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ParkinsonsUK-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:ParkinsonsUK-UCL.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; ISS:ParkinsonsUK-UCL.
DR GO; GO:0010636; P:positive regulation of mitochondrial fusion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0098779; P:positive regulation of mitophagy in response to mitochondrial depolarization; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051582; P:positive regulation of neurotransmitter uptake; IMP:ParkinsonsUK-UCL.
DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; IGI:ParkinsonsUK-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:ParkinsonsUK-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; TAS:ParkinsonsUK-UCL.
DR GO; GO:1902530; P:positive regulation of protein linear polyubiquitination; IGI:ParkinsonsUK-UCL.
DR GO; GO:1905477; P:positive regulation of protein localization to membrane; IMP:ParkinsonsUK-UCL.
DR GO; GO:1905281; P:positive regulation of retrograde transport, endosome to Golgi; NAS:ParkinsonsUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010498; P:proteasomal protein catabolic process; IMP:BHF-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0031648; P:protein destabilization; IDA:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; TAS:Reactome.
DR GO; GO:0070979; P:protein K11-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0044314; P:protein K27-linked ubiquitination; TAS:ParkinsonsUK-UCL.
DR GO; GO:0035519; P:protein K29-linked ubiquitination; TAS:ParkinsonsUK-UCL.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0070585; P:protein localization to mitochondrion; IEA:Ensembl.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:0010506; P:regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; TAS:ParkinsonsUK-UCL.
DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; IDA:ParkinsonsUK-UCL.
DR GO; GO:0042053; P:regulation of dopamine metabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0014059; P:regulation of dopamine secretion; TAS:ParkinsonsUK-UCL.
DR GO; GO:0010906; P:regulation of glucose metabolic process; TAS:ParkinsonsUK-UCL.
DR GO; GO:0032368; P:regulation of lipid transport; TAS:ParkinsonsUK-UCL.
DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IEA:Ensembl.
DR GO; GO:0010821; P:regulation of mitochondrion organization; IDA:ParkinsonsUK-UCL.
DR GO; GO:0031647; P:regulation of protein stability; IMP:ParkinsonsUK-UCL.
DR GO; GO:1903214; P:regulation of protein targeting to mitochondrion; NAS:ParkinsonsUK-UCL.
DR GO; GO:0031396; P:regulation of protein ubiquitination; IMP:ParkinsonsUK-UCL.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:UniProtKB.
DR GO; GO:1902803; P:regulation of synaptic vesicle transport; NAS:ParkinsonsUK-UCL.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006979; P:response to oxidative stress; ISS:ParkinsonsUK-UCL.
DR GO; GO:0001964; P:startle response; IEA:Ensembl.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0055069; P:zinc ion homeostasis; ISS:ParkinsonsUK-UCL.
DR DisProt; DP01849; -.
DR IDEAL; IID00008; -.
DR InterPro; IPR002867; IBR_dom.
DR InterPro; IPR003977; Parkin.
DR InterPro; IPR041565; Parkin_Znf-RING.
DR InterPro; IPR044066; TRIAD_supradom.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR041170; Znf-RING_14.
DR Pfam; PF00240; ubiquitin; 1.
DR Pfam; PF17976; zf-RING_12; 1.
DR Pfam; PF17978; zf-RING_14; 1.
DR PIRSF; PIRSF037880; Parkin; 1.
DR PRINTS; PR01475; PARKIN.
DR SMART; SM00647; IBR; 2.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS51873; TRIAD; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autophagy; Cell projection; Cytoplasm;
KW Disease variant; Endoplasmic reticulum; Membrane; Metal-binding;
KW Mitochondrion; Mitochondrion outer membrane; Neurodegeneration; Nucleus;
KW Parkinson disease; Parkinsonism; Phosphoprotein; Reference proteome;
KW Repeat; S-nitrosylation; Synapse; Transcription; Transcription regulation;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..465
FT /note="E3 ubiquitin-protein ligase parkin"
FT /id="PRO_0000058576"
FT DOMAIN 1..76
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT ZN_FING 141..225
FT /note="RING-type 0; atypical"
FT ZN_FING 238..293
FT /note="RING-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 313..377
FT /note="IBR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT ZN_FING 418..449
FT /note="RING-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 77..237
FT /note="Necessary for PINK1-dependent localization to
FT mitochondria"
FT /evidence="ECO:0000269|PubMed:18957282"
FT REGION 77..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..238
FT /note="SYT11 binding 1"
FT /evidence="ECO:0000269|PubMed:12925569"
FT REGION 234..465
FT /note="TRIAD supradomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT REGION 257..293
FT /note="SYT11 binding 2"
FT /evidence="ECO:0000269|PubMed:12925569"
FT REGION 378..410
FT /note="REP"
FT /evidence="ECO:0000250|UniProtKB:Q9JK66"
FT ACT_SITE 431
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 238
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 241
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 253
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 257
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 260
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 263
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 289
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 293
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 332
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 337
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 352
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 360
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 365
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 368
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 373
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 377
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 418
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 421
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 436
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 441
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 446
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221,
FT ECO:0000269|PubMed:23770917"
FT BINDING 449
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 457
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT BINDING 461
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01221"
FT MOD_RES 65
FT /note="Phosphoserine; by PINK1"
FT /evidence="ECO:0000269|PubMed:18957282,
FT ECO:0000269|PubMed:23754282, ECO:0000269|PubMed:24660806,
FT ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:25474007"
FT MOD_RES 175
FT /note="Phosphothreonine; by PINK1"
FT /evidence="ECO:0000269|PubMed:18957282"
FT MOD_RES 217
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18957282"
FT VAR_SEQ 1..191
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_011705"
FT VAR_SEQ 1..79
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_011706"
FT VAR_SEQ 58..206
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_041563"
FT VAR_SEQ 179..206
FT /note="Missing (in isoform 2 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:9560156, ECO:0000303|Ref.4"
FT /id="VSP_011707"
FT VAR_SEQ 290
FT /note="V -> VGTGDTVVLRGALGGFRRGV (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011708"
FT VAR_SEQ 291..297
FT /note="AGCPNSL -> VCLLPGM (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_011709"
FT VAR_SEQ 298..465
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_011710"
FT VAR_SEQ 312..361
FT /note="Missing (in isoform 7 and isoform 8)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_053651"
FT VAR_SEQ 362..368
FT /note="FAFCREC -> YGQRRTK (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011711"
FT VAR_SEQ 369..465
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011712"
FT VARIANT 15
FT /note="V -> M (in PARK2; dbSNP:rs532703934)"
FT /evidence="ECO:0000269|PubMed:12397156"
FT /id="VAR_019733"
FT VARIANT 33
FT /note="R -> Q (in PARK2; dbSNP:rs147757966)"
FT /evidence="ECO:0000269|PubMed:12730996"
FT /id="VAR_019734"
FT VARIANT 37
FT /note="P -> L (in PARK2; dbSNP:rs148990138)"
FT /evidence="ECO:0000269|PubMed:12112109"
FT /id="VAR_019735"
FT VARIANT 42
FT /note="R -> P (in PARK2 and PARK; induces a conformational
FT change in the PSMD4-binding site of Ubl resulting in
FT impaired proteasomal binding; decreases ubiquitination and
FT degradation; increased aggregation; impairs the ability to
FT ubiquitinate and degrade SYT11; dbSNP:rs368134308)"
FT /evidence="ECO:0000269|PubMed:10888878,
FT ECO:0000269|PubMed:11431533, ECO:0000269|PubMed:11971093,
FT ECO:0000269|PubMed:15584030, ECO:0000269|PubMed:19229105,
FT ECO:0000269|PubMed:20889486, ECO:0000269|PubMed:29311685"
FT /id="VAR_019736"
FT VARIANT 46
FT /note="A -> P (in PARK2)"
FT /evidence="ECO:0000269|PubMed:12362318"
FT /id="VAR_019737"
FT VARIANT 56
FT /note="V -> E (in PARK2; dbSNP:rs137853059)"
FT /evidence="ECO:0000269|PubMed:12056932"
FT /id="VAR_070078"
FT VARIANT 82
FT /note="A -> E (in PARK2; dbSNP:rs55774500)"
FT /evidence="ECO:0000269|PubMed:11487568,
FT ECO:0000269|PubMed:12116199, ECO:0000269|PubMed:12730996"
FT /id="VAR_019738"
FT VARIANT 92
FT /note="A -> V (in PARK2; dbSNP:rs566229879)"
FT /id="VAR_019739"
FT VARIANT 100
FT /note="Q -> H (in dbSNP:rs1256316516)"
FT /evidence="ECO:0000269|PubMed:12781599"
FT /id="VAR_019740"
FT VARIANT 161
FT /note="K -> N (in PARK2; severely compromises the
FT mitochondrial localization; fails to stabilize BCL2;
FT decreased binding to the TP53 promoter; abolishes TP53
FT transcriptional repression; dbSNP:rs137853057)"
FT /evidence="ECO:0000269|PubMed:10072423,
FT ECO:0000269|PubMed:10824074, ECO:0000269|PubMed:19801972,
FT ECO:0000269|PubMed:20404107, ECO:0000269|PubMed:20889974"
FT /id="VAR_019741"
FT VARIANT 167
FT /note="S -> N (in dbSNP:rs1801474)"
FT /evidence="ECO:0000269|PubMed:10072423,
FT ECO:0000269|PubMed:10511432, ECO:0000269|PubMed:10965160,
FT ECO:0000269|PubMed:12629236"
FT /id="VAR_019742"
FT VARIANT 192
FT /note="M -> L (in PARK2; unknown pathological significance;
FT dbSNP:rs9456735)"
FT /evidence="ECO:0000269|PubMed:11971093"
FT /id="VAR_054107"
FT VARIANT 192
FT /note="M -> V (in PARK2; unknown pathological significance;
FT dbSNP:rs9456735)"
FT /evidence="ECO:0000269|PubMed:12629236"
FT /id="VAR_019743"
FT VARIANT 211
FT /note="K -> N (in PARK2; severely compromises the
FT mitochondrial localization; fails to stabilize BCL2;
FT dbSNP:rs137853060)"
FT /evidence="ECO:0000269|PubMed:10824074,
FT ECO:0000269|PubMed:11179010, ECO:0000269|PubMed:12114481,
FT ECO:0000269|PubMed:12629236, ECO:0000269|PubMed:20404107"
FT /id="VAR_019744"
FT VARIANT 212
FT /note="C -> Y (in PARK2; dbSNP:rs137853058)"
FT /evidence="ECO:0000269|PubMed:11163284,
FT ECO:0000269|PubMed:12056932"
FT /id="VAR_019746"
FT VARIANT 240
FT /note="T -> M (in PARK2; dbSNP:rs137853054)"
FT /evidence="ECO:0000269|PubMed:12629236"
FT /id="VAR_019747"
FT VARIANT 240
FT /note="T -> R (in PARK2; impairs the ability to
FT ubiquitinate SNCAIP and BCL2; loss of UBE2L3 binding;
FT severely compromises the mitochondrial localization;
FT dbSNP:rs137853054)"
FT /evidence="ECO:0000269|PubMed:10888878,
FT ECO:0000269|PubMed:11431533, ECO:0000269|PubMed:11590439,
FT ECO:0000269|PubMed:20404107, ECO:0000269|PubMed:20889974,
FT ECO:0000269|PubMed:9731209"
FT /id="VAR_019748"
FT VARIANT 253
FT /note="C -> Y (in PARK; late onset; dbSNP:rs747427602)"
FT /evidence="ECO:0000269|PubMed:12730996"
FT /id="VAR_019749"
FT VARIANT 256
FT /note="R -> C (in PARK2 and PARK; at heterozygosity it is
FT associated with late onset Parkinson disease; impairs the
FT ability to ubiquitinate SNCAIP and ZNF746; decreased
FT binding to the TP53 promoter; abolishes TP53
FT transcriptional repression; dbSNP:rs150562946)"
FT /evidence="ECO:0000269|PubMed:10072423,
FT ECO:0000269|PubMed:10824074, ECO:0000269|PubMed:11590439,
FT ECO:0000269|PubMed:11971093, ECO:0000269|PubMed:12116199,
FT ECO:0000269|PubMed:12730996, ECO:0000269|PubMed:19801972"
FT /id="VAR_019750"
FT VARIANT 271
FT /note="R -> S (in dbSNP:rs772622421)"
FT /evidence="ECO:0000269|PubMed:12781599"
FT /id="VAR_019751"
FT VARIANT 275
FT /note="R -> W (in PARK2 and PARK; at heterozygosity it is
FT associated with late onset Parkinson disease; impairs the
FT ability to ubiquitinate SNCAIP; abolishes p53/TP53
FT transcriptional repression; impairs the ability to
FT ubiquitinate and degrade SYT11; dbSNP:rs34424986)"
FT /evidence="ECO:0000269|PubMed:10072423,
FT ECO:0000269|PubMed:10824074, ECO:0000269|PubMed:11179010,
FT ECO:0000269|PubMed:11590439, ECO:0000269|PubMed:11971093,
FT ECO:0000269|PubMed:12114481, ECO:0000269|PubMed:12116199,
FT ECO:0000269|PubMed:12730996, ECO:0000269|PubMed:19801972,
FT ECO:0000269|PubMed:21376232, ECO:0000269|PubMed:22956510,
FT ECO:0000269|PubMed:29311685"
FT /id="VAR_019752"
FT VARIANT 280
FT /note="D -> N (in PARK; does not affect PINK-1 dependent
FT localization to depolarized mitochondria;
FT dbSNP:rs72480422)"
FT /evidence="ECO:0000269|PubMed:10824074,
FT ECO:0000269|PubMed:12730996, ECO:0000269|PubMed:20404107"
FT /id="VAR_019753"
FT VARIANT 284
FT /note="G -> R (in PARK2; dbSNP:rs751037529)"
FT /id="VAR_019754"
FT VARIANT 289
FT /note="C -> G (in PARK2; increased aggregation; fails to
FT ubiquitinate SYT11; loses ability to bind SYT11; impaired
FT relocalization to damaged mitochondria; loss of function in
FT mitophagy; dbSNP:rs55961220)"
FT /evidence="ECO:0000269|PubMed:10824074,
FT ECO:0000269|PubMed:12925569, ECO:0000269|PubMed:20889486"
FT /id="VAR_019755"
FT VARIANT 311
FT /note="Q -> R (in a patient with Parkinson disease; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:19501131"
FT /id="VAR_062672"
FT VARIANT 328
FT /note="G -> E (in PARK2; does not affect PINK-1 dependent
FT localization to depolarized mitochondria)"
FT /evidence="ECO:0000269|PubMed:10824074,
FT ECO:0000269|PubMed:12116199, ECO:0000269|PubMed:20404107"
FT /id="VAR_019756"
FT VARIANT 334
FT /note="R -> C (in dbSNP:rs199657839)"
FT /evidence="ECO:0000269|PubMed:10824074,
FT ECO:0000269|PubMed:27535533"
FT /id="VAR_019757"
FT VARIANT 339
FT /note="A -> S (in dbSNP:rs1554274880)"
FT /evidence="ECO:0000269|PubMed:12781599"
FT /id="VAR_019758"
FT VARIANT 351
FT /note="T -> P (in PARK2; impairs folding of IBR domain;
FT dbSNP:rs1554274861)"
FT /evidence="ECO:0000269|PubMed:12112109,
FT ECO:0000269|PubMed:17360614"
FT /id="VAR_019759"
FT VARIANT 366
FT /note="R -> W (in dbSNP:rs56092260)"
FT /evidence="ECO:0000269|PubMed:10965160"
FT /id="VAR_019760"
FT VARIANT 371
FT /note="A -> T (in a patient with Parkinson disease; unknown
FT pathological significance)"
FT /evidence="ECO:0000269|PubMed:19501131"
FT /id="VAR_062673"
FT VARIANT 380
FT /note="V -> L (in dbSNP:rs1801582)"
FT /evidence="ECO:0000269|PubMed:10072423,
FT ECO:0000269|PubMed:10965160, ECO:0000269|PubMed:12397156,
FT ECO:0000269|PubMed:12730996"
FT /id="VAR_019761"
FT VARIANT 394
FT /note="D -> N (in dbSNP:rs1801334)"
FT /evidence="ECO:0000269|PubMed:10072423,
FT ECO:0000269|PubMed:12397156, ECO:0000269|PubMed:12730996"
FT /id="VAR_019762"
FT VARIANT 402
FT /note="R -> C (in PARK2; dbSNP:rs55830907)"
FT /evidence="ECO:0000269|PubMed:15584030"
FT /id="VAR_070079"
FT VARIANT 415
FT /note="T -> N (in PARK2; impairs the ability to
FT ubiquitinate SNCAIP; does not affect turnover of CDCRE1;
FT impairs PINK1-dependent localization to dysfunctional
FT depolarized mitochondria; dbSNP:rs778125254)"
FT /evidence="ECO:0000269|PubMed:10072423,
FT ECO:0000269|PubMed:10824074, ECO:0000269|PubMed:11590439,
FT ECO:0000269|PubMed:15584030, ECO:0000269|PubMed:19966284"
FT /id="VAR_019763"
FT VARIANT 418
FT /note="C -> R (in PARK2; decreased binding to the TP53
FT promoter; abolishes TP53 transcriptional repression; fails
FT to ubiquitinate SYT11 but does not loose ability to bind
FT SYT11; dbSNP:rs1554252200)"
FT /evidence="ECO:0000269|PubMed:12925569,
FT ECO:0000269|PubMed:15584030, ECO:0000269|PubMed:19801972"
FT /id="VAR_070080"
FT VARIANT 430
FT /note="G -> D (in PARK2; impairs PINK1-dependent
FT localization to dysfunctional depolarized mitochondria;
FT impaired E3 ubiquitin-protein ligase toward ZNF746;
FT dbSNP:rs191486604)"
FT /evidence="ECO:0000269|PubMed:10824074,
FT ECO:0000269|PubMed:11179010, ECO:0000269|PubMed:11971093,
FT ECO:0000269|PubMed:12114481, ECO:0000269|PubMed:12730996,
FT ECO:0000269|PubMed:19966284, ECO:0000269|PubMed:21376232"
FT /id="VAR_019764"
FT VARIANT 431
FT /note="C -> F (in PARK2; impaired E3 ubiquitin-protein
FT ligase toward ZNF746 and BCL2; dbSNP:rs397514694)"
FT /evidence="ECO:0000269|PubMed:10939576,
FT ECO:0000269|PubMed:20889974, ECO:0000269|PubMed:21376232"
FT /id="VAR_019765"
FT VARIANT 437
FT /note="P -> L (in PARK2; impaired E3 ubiquitin-protein
FT ligase toward BCL2; dbSNP:rs149953814)"
FT /evidence="ECO:0000269|PubMed:11971093,
FT ECO:0000269|PubMed:12114481, ECO:0000269|PubMed:12629236,
FT ECO:0000269|PubMed:12730996, ECO:0000269|PubMed:20889974"
FT /id="VAR_019766"
FT VARIANT 441
FT /note="C -> R (in PARK2; decreased binding to the TP53
FT promoter; abolishes TP53 transcriptional repression;
FT dbSNP:rs778305273)"
FT /evidence="ECO:0000269|PubMed:12116199,
FT ECO:0000269|PubMed:19801972"
FT /id="VAR_019767"
FT MUTAGEN 65
FT /note="S->A: Loss of phosphorylation. Undergoes
FT autoubiquitination in the presence of phosphorylated
FT ubiquitin."
FT /evidence="ECO:0000269|PubMed:25474007"
FT MUTAGEN 65
FT /note="S->E: Phosphomimetic mutant; still requires PINK1
FT for activation. PRKN is activated in presence of
FT phosphorylated ubiquitin."
FT /evidence="ECO:0000269|PubMed:24660806,
FT ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:25474007"
FT MUTAGEN 175
FT /note="T->A: Loss of phosphorylation. Reduced mitochondrial
FT localization; when associated with A-217."
FT /evidence="ECO:0000269|PubMed:18957282"
FT MUTAGEN 175
FT /note="T->E: Phosphomimetic mutant. Mostly localizes to the
FT mitochondria; when associated with E-217."
FT /evidence="ECO:0000269|PubMed:18957282"
FT MUTAGEN 211
FT /note="K->N: Loss of activity towards MIRO1."
FT /evidence="ECO:0000269|PubMed:22396657"
FT MUTAGEN 217
FT /note="T->A: Loss of phosphorylation. Reduced mitochondrial
FT localization; when associated with A-175."
FT /evidence="ECO:0000269|PubMed:18957282"
FT MUTAGEN 217
FT /note="T->E: Phosphomimetic mutant. Mostly localizes to the
FT mitochondria; when associated with E-175."
FT /evidence="ECO:0000269|PubMed:18957282"
FT MUTAGEN 238
FT /note="C->S: Loss of mitochondrial localization."
FT /evidence="ECO:0000269|PubMed:18957282"
FT MUTAGEN 332
FT /note="C->S: Impairs folding of IBR domain."
FT /evidence="ECO:0000269|PubMed:17360614"
FT MUTAGEN 337
FT /note="C->A: Impairs the ability to ubiquitinate SNCAIP."
FT /evidence="ECO:0000269|PubMed:11590439"
FT MUTAGEN 365
FT /note="C->S: Impairs protein folding."
FT /evidence="ECO:0000269|PubMed:17360614"
FT MUTAGEN 403
FT /note="W->A: Decreased autoinhibition and increased E3
FT activity."
FT /evidence="ECO:0000269|PubMed:24784582"
FT MUTAGEN 415
FT /note="T->N: Loss of activity and self-ubiquitination. Loss
FT of monoubiquitination resulting in an increase in
FT apoptosis. No effect on polyubiquitination or mitophagy."
FT /evidence="ECO:0000269|PubMed:22396657,
FT ECO:0000269|PubMed:23770917, ECO:0000269|PubMed:32047033"
FT MUTAGEN 421
FT /note="C->A: Impairs the ability of self-ubiquitination and
FT to ubiquitinate SNCAIP."
FT /evidence="ECO:0000269|PubMed:11590439,
FT ECO:0000269|PubMed:18541373"
FT MUTAGEN 429
FT /note="G->E: Reduced self-ubiquitination."
FT /evidence="ECO:0000269|PubMed:23770917"
FT MUTAGEN 430
FT /note="G->D: Loss of self-ubiquitination."
FT /evidence="ECO:0000269|PubMed:23770917"
FT MUTAGEN 431
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:23770917"
FT MUTAGEN 431
FT /note="C->S: Impairs the ability to ubiquitinate target
FT proteins. No effect on translocation to mitochondria."
FT /evidence="ECO:0000269|PubMed:11590439,
FT ECO:0000269|PubMed:23727886, ECO:0000269|PubMed:23770887,
FT ECO:0000269|PubMed:25474007, ECO:0000269|PubMed:32047033"
FT MUTAGEN 433
FT /note="H->N,A: Impaired activity."
FT /evidence="ECO:0000269|PubMed:23727886,
FT ECO:0000269|PubMed:23770887"
FT MUTAGEN 444
FT /note="E->Q,A: Impaired activity."
FT /evidence="ECO:0000269|PubMed:23727886,
FT ECO:0000269|PubMed:23770887"
FT CONFLICT 223
FT /note="S -> P (in Ref. 1; BAA25751 and 3; AAM21458/
FT AAM21457)"
FT /evidence="ECO:0000305"
FT CONFLICT 289..290
FT /note="CV -> MI (in Ref. 2; AAM21461)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="A -> V (in Ref. 9; AAS88422)"
FT /evidence="ECO:0000305"
FT STRAND 2..11
FT /evidence="ECO:0007829|PDB:5C1Z"
FT STRAND 13..16
FT /evidence="ECO:0007829|PDB:5C1Z"
FT STRAND 19..21
FT /evidence="ECO:0007829|PDB:1IYF"
FT HELIX 23..34
FT /evidence="ECO:0007829|PDB:5C1Z"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:5C1Z"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:5C1Z"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:5C1Z"
FT TURN 52..55
FT /evidence="ECO:0007829|PDB:1IYF"
FT HELIX 56..59
FT /evidence="ECO:0007829|PDB:5C1Z"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:5N2W"
FT STRAND 66..71
FT /evidence="ECO:0007829|PDB:5C1Z"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:6GLC"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:4I1F"
FT TURN 152..154
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 156..166
FT /evidence="ECO:0007829|PDB:4I1F"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 174..178
FT /evidence="ECO:0007829|PDB:4I1F"
FT HELIX 183..187
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:6N13"
FT STRAND 192..196
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:5N38"
FT STRAND 205..212
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:4I1H"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 257..260
FT /evidence="ECO:0007829|PDB:4I1F"
FT HELIX 261..273
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:4I1F"
FT TURN 281..283
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:6N13"
FT HELIX 301..307
FT /evidence="ECO:0007829|PDB:4I1F"
FT HELIX 309..326
FT /evidence="ECO:0007829|PDB:4I1F"
FT TURN 335..337
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:6GLC"
FT STRAND 348..351
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 355..358
FT /evidence="ECO:0007829|PDB:5N38"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:4I1F"
FT TURN 366..368
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 374..376
FT /evidence="ECO:0007829|PDB:6GLC"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:4BM9"
FT HELIX 395..400
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:5N38"
FT STRAND 414..417
FT /evidence="ECO:0007829|PDB:4I1F"
FT TURN 419..421
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 429..431
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 433..435
FT /evidence="ECO:0007829|PDB:4I1F"
FT TURN 439..441
FT /evidence="ECO:0007829|PDB:4I1F"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:4I1F"
FT TURN 447..449
FT /evidence="ECO:0007829|PDB:4I1F"
FT HELIX 455..461
FT /evidence="ECO:0007829|PDB:4I1F"
SQ SEQUENCE 465 AA; 51641 MW; 9A8BB802A3FC84C3 CRC64;
MIVFVRFNSS HGFPVEVDSD TSIFQLKEVV AKRQGVPADQ LRVIFAGKEL RNDWTVQNCD
LDQQSIVHIV QRPWRKGQEM NATGGDDPRN AAGGCEREPQ SLTRVDLSSS VLPGDSVGLA
VILHTDSRKD SPPAGSPAGR SIYNSFYVYC KGPCQRVQPG KLRVQCSTCR QATLTLTQGP
SCWDDVLIPN RMSGECQSPH CPGTSAEFFF KCGAHPTSDK ETSVALHLIA TNSRNITCIT
CTDVRSPVLV FQCNSRHVIC LDCFHLYCVT RLNDRQFVHD PQLGYSLPCV AGCPNSLIKE
LHHFRILGEE QYNRYQQYGA EECVLQMGGV LCPRPGCGAG LLPEPDQRKV TCEGGNGLGC
GFAFCRECKE AYHEGECSAV FEASGTTTQA YRVDERAAEQ ARWEAASKET IKKTTKPCPR
CHVPVEKNGG CMHMKCPQPQ CRLEWCWNCG CEWNRVCMGD HWFDV
