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Description

Parkin is an E3-ubiquitin ligase belonging to the RBR (RING - In Between RING - RING) family. Mutations in Parkin that result in a loss-of-function are the most frequent cause of familial Parkinson's disease and are responsible for a large percentage of autosomal recessive juvenile parkinsonism (AR-JP). In addition to its auto-ubiquitination, Parkin can also ubiquitinate various substrates, including the CDK2-interacting protein cyclin E1, the a-synuclein-interacting protein synphilin-1, the synaptic vesicle-associated CDC-rel1 and the p38 subunit of aminoacyl-tRNA synthetase/JTV-1. Ubiquitination of substrates occurs in conjunction with the E2 enzymes UbcH7, UbcH8 or UbcH13/Uev1.