DISEASES

Disease-gene associations mined from literature

Literature on PRKN

PRKN [ENSP00000355865]

E3 ubiquitin-protein ligase parkin; Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins, such as BCL2, SYT11, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746 and AIMP2 (PubMed:10973942, PubMed:10888878, PubMed:11431533, PubMed:12150907, PubMed:12628165, PubMed:16135753, PubMed:21376232, PubMed:23754282, PubMed:23620051, PubMed:24660806, PubMed:24751536, PubMed:29311685). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'- linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context . Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation (PubMed:17846173, PubMed:19229105). Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation (PubMed:11590439, PubMed:11431533, PubMed:19229105, PubMed:11590439, PubMed:15728840). Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy . Promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1 and USP30 (PubMed:19029340, PubMed:19966284, PubMed:23620051, PubMed:24896179, PubMed:25527291). Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains following mitochondrial damage, leading to mitophagy . Mediates 'Lys-48'-linked polyubiquitination of ZNF746, followed by degradation of ZNF746 by the proteasome; possibly playing a role in the regulation of neuron death . Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress . Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 . May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity . May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene. ECO:0000269|PubMed:11431533, ECO:0000269|PubMed:11590439, ECO:0000269|PubMed:12628165, ECO:0000269|PubMed:12719539, ECO:0000269|PubMed:15105460, ECO:0000269|PubMed:15728840, ECO:0000269|PubMed:16135753, ECO:0000269|PubMed:17846173, ECO:0000269|PubMed:18541373, ECO:0000269|PubMed:19029340, ECO:0000269|PubMed:19229105, ECO:0000269|PubMed:19801972, ECO:0000269|PubMed:19966284, ECO:0000269|PubMed:20889974, ECO:0000269|PubMed:21376232, ECO:0000269|PubMed:21532592, ECO:0000269|PubMed:22082830, ECO:0000269|PubMed:23620051, ECO:0000269|PubMed:23754282, ECO:0000269|PubMed:23933751, ECO:0000269|PubMed:24660806, ECO:0000269|PubMed:24751536, ECO:0000269|PubMed:24784582, ECO:0000269|PubMed:24896179, ECO:0000269|PubMed:25527291, ECO:0000269|PubMed:25621951,

Synonyms:  PRKN,  A0A087WU39,  A0A087WX46,  A0A087X0Z9,  A0A087X1E2 ...

Linkouts:  STRING  Pharos  UniProt  OMIM