| Tbio | 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, SEPT5, 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). Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context (PubMed:19229105, PubMed:20889974, PubMed:25621951). 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 (PubMed:20889974). 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 (PubMed:25621951). 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 (PubMed:21376232). 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 (PubMed:22082830). Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53 (PubMed:19801972). May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity (PubMed:11439185). May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.
The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]
The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]
Comments
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Leprosy | 73 | 3.642 | 1.8 |
| Autistic Disorder | 364 | 0.0 | 0.0 |
| Colonic Neoplasms | 142 | 0.0 | 0.0 |
| Lung Neoplasms | 232 | 0.0 | 0.0 |
| Manganese Poisoning | 11 | 0.0 | 0.0 |
| Nerve Degeneration | 121 | 0.0 | 0.0 |
| Ovarian Cysts | 41 | 0.0 | 0.0 |
| Ovarian Neoplasms | 102 | 0.0 | 0.0 |
| Parkinson Disease | 64 | 0.0 | 0.0 |
| Parkinsonian Disorders | 56 | 0.0 | 0.0 |
| glioblastoma | 5792 | 0.0 | 0.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Rheumatoid arthritis | 1191 | 0.0 | 1.3 |
| pancreatic cancer | 2398 | 0.0 | 0.9 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Neurodegenerative disease | 414 | 0.0 | 4.0 |
| Disease | Target Count | Z-score | Confidence |
|---|---|---|---|
| Dementia | 175 | 4.04 | 2.0 |
| Toxic encephalopathy | 141 | 3.679 | 1.8 |
| progressive supranuclear palsy | 676 | 3.345 | 1.7 |
| Alzheimer's disease | 658 | 3.337 | 1.7 |
| Multiple system atrophy | 29 | 3.144 | 1.6 |
MIVFVRFNSSHGFPVEVDSDTSIFQLKEVVAKRQGVPADQLRVIFAGKELRNDWTVQNCDLDQQSIVHIV 1 - 70 QRPWRKGQEMNATGGDDPRNAAGGCEREPQSLTRVDLSSSVLPGDSVGLAVILHTDSRKDSPPAGSPAGR 71 - 140 SIYNSFYVYCKGPCQRVQPGKLRVQCSTCRQATLTLTQGPSCWDDVLIPNRMSGECQSPHCPGTSAEFFF 141 - 210 KCGAHPTSDKETSVALHLIATNSRNITCITCTDVRSPVLVFQCNSRHVICLDCFHLYCVTRLNDRQFVHD 211 - 280 PQLGYSLPCVAGCPNSLIKELHHFRILGEEQYNRYQQYGAEECVLQMGGVLCPRPGCGAGLLPEPDQRKV 281 - 350 TCEGGNGLGCGFAFCRECKEAYHEGECSAVFEASGTTTQAYRVDERAAEQARWEAASKETIKKTTKPCPR 351 - 420 CHVPVEKNGGCMHMKCPQPQCRLEWCWNCGCEWNRVCMGDHWFDV 421 - 465 //
