{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:45:12Z","timestamp":1781109912809,"version":"3.54.1"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,11,21]]},"abstract":"<jats:p>Parkinson's disease is a common neurodegenerative disorder in\n which familial-linked genes have provided novel insights into the\n pathogenesis of this disorder. Mutations in Parkin, a\n ring-finger-containing protein of unknown function, are implicated in\n the pathogenesis of autosomal recessive familial Parkinson's disease.\n Here, we show that Parkin binds to the E2 ubiquitin-conjugating human\n enzyme 8 (UbcH8) through its C-terminal ring-finger. Parkin has\n ubiquitin\u2013protein ligase activity in the presence of UbcH8. Parkin\n also ubiquitinates itself and promotes its own degradation. We also\n identify and show that the synaptic vesicle-associated protein,\n CDCrel-1, interacts with Parkin through its ring-finger domains.\n Furthermore, Parkin ubiquitinates and promotes the degradation of\n CDCrel-1. Familial-linked mutations disrupt the ubiquitin\u2013protein\n ligase function of Parkin and impair Parkin and CDCrel-1 degradation.\n These results suggest that Parkin functions as an E3 ubiquitin\u2013protein\n ligase through its ring domains and that it may control protein levels\n via ubiquitination. The loss of Parkin's ubiquitin\u2013protein ligase\n function in familial-linked mutations suggests that this may be the\n cause of familial autosomal recessive Parkinson's disease.<\/jats:p>","DOI":"10.1073\/pnas.240347797","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"13354-13359","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":790,"title":["Parkin functions as an E2-dependent ubiquitin\u2013 protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1"],"prefix":"10.1073","volume":"97","author":[{"given":"Yi","family":"Zhang","sequence":"first","affiliation":[{"name":"Departments of Neurology, Neuroscience, and\r Physiology, Johns Hopkins University School of Medicine,\r Baltimore, MD 21287-0005"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Gao","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Neuroscience, and\r Physiology, Johns Hopkins University School of Medicine,\r Baltimore, MD 21287-0005"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenny K. K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Neuroscience, and\r Physiology, Johns Hopkins University School of Medicine,\r Baltimore, MD 21287-0005"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Huang","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Neuroscience, and\r Physiology, Johns Hopkins University School of Medicine,\r Baltimore, MD 21287-0005"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valina L.","family":"Dawson","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Neuroscience, and\r Physiology, Johns Hopkins University School of Medicine,\r Baltimore, MD 21287-0005"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ted M.","family":"Dawson","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Neuroscience, and\r Physiology, Johns Hopkins University School of Medicine,\r Baltimore, MD 21287-0005"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,11,14]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810083391506"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810153391607"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440712"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/399a032"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199305000-00001"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2000.0319"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2045"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-106"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/42166"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400432"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5456.1265"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/35006074"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80629-7"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/26652"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.1.81"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0398-262"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.2.504"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/33416"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005253422103"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)60746-5"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.4.567"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(99)01381-X"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(200001)182:1<1::AID-JCP1>3.0.CO;2-V"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(200005)22:5<442::AID-BIES6>3.0.CO;2-Q"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5438.309"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.20.11364"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_3_3_28_2","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J","year":"1989","unstructured":"J Sambrook, E F Fritsch, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Press, 2nd Ed., Plainview, NY, 1989).","edition":"2"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.43.30963"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00823-6"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1159\/000134639"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.12.8945"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/8100"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/77060"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5263"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002329900519"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(99)01632-3"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0230059"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90459-6"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst020155s"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65743-4"},{"key":"e_1_3_3_42_2","first-page":"809","volume":"140","author":"Galloway P G","year":"1992","unstructured":"P G Galloway, P Mulvihill, G Perry Am J Pathol 140, 809\u2013822 (1992).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.3_Part_1.437"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.3.890"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/PL00007745"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.240347797","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T09:18:06Z","timestamp":1649841486000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.240347797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,11,14]]},"references-count":45,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2000,11,21]]}},"alternative-id":["10.1073\/pnas.240347797"],"URL":"https:\/\/doi.org\/10.1073\/pnas.240347797","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,11,14]]},"assertion":[{"value":"2000-07-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-11-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}