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- Table of Contents
Facts about 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 and'Lys-6','Lys-11','Lys-48'-connected and'Lys-63'-linked polyubiquitination of substrates depending on the circumstance (PubMed:19229105, PubMed:20889974, PubMed:25621951).Participates in the elimination and/or detox of abnormally folded or damaged protein by mediating'Lys-63'-linked polyubiquitination of misfolded proteins like PARK7:'Lys-63'- linked polyubiquitinated misfolded proteins are then recognized by HDAC6, resulting in 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).
Human | |
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Gene Name: | PRKN |
Uniprot: | O60260 |
Entrez: | 5071 |
Belongs to: |
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RBR family |
AR-JP; E3 ubiquitin ligase; E3 ubiquitin-protein ligase parkin; EC 6.3.2.-; LPRS2; PARK2; parkin 2; Parkin; Parkinson disease protein 2; Parkinson juvenile disease protein 2; parkinson protein 2, E3 ubiquitin protein ligase (parkin); PDJ; PDJjuvenile) 2, parkin; PRKN
Mass (kDA):
51.641 kDA
Human | |
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Location: | 6q26 |
Sequence: | 6; NC_000006.12 (161347417..162727802, complement) |
Highly expressed in the brain including the substantia nigra. Expressed in heart, testis and skeletal muscle. Expression is down-regulated or absent in tumor biopsies, and absent in the brain of PARK2 patients. Overexpression protects dopamine neurons from kainate-mediated apoptosis. Found in serum (at protein level).
Cytoplasm, cytosol. Nucleus. Endoplasmic reticulum. Mitochondrion. Mainly localizes in the cytosol. Co-localizes with SYT11 in neutrites. Co-localizes with SNCAIP in brainstem Lewy bodies. Mitochondrial localization gradually increases with cellular growth. Also relocates to dysfunctional mitochondria that have lost the mitochondrial membrane potential; recruitment to mitochondria is PINK1-dependent.
PMID: 9560156 by Kitada T., et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism.
PMID: 19501131 by Kasap M., et al. Evidence for the presence of full-length PARK2 mRNA and Parkin protein in human blood.