Species Human Entrez 5071 | Human Mouse Ensembl ENSG00000185345 | |
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Aliases PARK2, parkin RBR E3 ubiquitin protein ligase, AR-JP, LPRS2, PDJ, PRKN External IDs OMIM: 602544 MGI: 1355296 HomoloGene: 3355 GeneCards: PARK2 | ||
Parkin is a protein which in humans is encoded by the PARK2 gene. The precise function of this protein is unknown; however, the protein is a component of a multiprotein E3 ubiquitin ligase complex which in turn is part of the ubiquitin-proteasome system that mediates the targeting of proteins for degradation. Mutations in this gene are known to cause a familial form of Parkinson's disease known as autosomal recessive juvenile Parkinson's disease (AR-JP). Moreover, Parkin is described to be necessary for mitophagy (autophagy of mitochondria).
Contents
However, how loss of function of the parkin protein leads to dopaminergic cell death in this disease is unclear. The prevailing hypothesis is that parkin helps degrade one or more proteins toxic to dopaminergic neurons. Putative substrates of parkin include synphilin-1, CDC-rel1, cyclin E, p38 tRNA synthase, Pael-R, synaptotagmin XI, sp22 and parkin itself (see also ubiquitin ligase). Additionally, Parkin contains a C-terminal motif that binds PDZ domains. Parkin has been shown to associate in a PDZ dependent manner with the PDZ domain containing proteins CASK and PICK1.
Parkinson's disease
PARK2 (OMIM *602544) is the parkin gene that may cause a form of autosomal recessive juvenile Parkinson disease (OMIM 600116) due to a mutation in the parkin protein. This form of genetic mutation may be one of the most common known genetic causes of early-onset Parkinson disease. In one study of patients with onset of Parkinson disease prior to age 40 (10% of all PD patients), 18% had parkin mutations, with 5% homozygous mutations. Patients with an autosomal recessive family history of parkinsonism are much more likely to carry parkin mutations if age at onset is less than 20 (80% vs. 28% with onset over age 40).
Patients with parkin mutations (PARK2) do not have Lewy bodies. Such patients develop a syndrome that closely resembles the sporadic form of PD; however, they tend to develop symptoms at a much younger age.
Interactions
Parkin (ligase) has been shown to interact with: