Recombinant Human Parkin Protein, CF

The Parkin protein (encoded by the PARK2 gene) is an E3 ubiquitin ligase that plays an essential role in the removal of damaged mitochondria. Mutations in PARK2 are known to cause a form of Parkinson's disease known as autosomal recessive juvenile Parkinson's disease (AR-JP), and the mechanisms by which the defective Parkin protein contributes to dopaminergic cell death in this disease is an area of intense investigation. Reported substrates of the Parkin protein include BCL2, GPR37, MIRO1, MFN1, MFN2, TOMM20, USP30, and many others. The structure of the Parkin protein (an RBR-class Ubiquitin ligase) has been reported by multiple groups. These reports showed that the ligase is folded upon itself to produce an auto-inhibited state. This auto-inhibition is relieved by interactions with PINK1 kinase, which can phosphorylate both the Parkin protein and Ubiquitin at serine residue number 65, and pS65 phospho-Ubiquitin by mechanisms that are under investigation. In vitro, the Parkin protein may be activated by treatment with recombinant PINK1, or addition of low concentrations of pS65-phospho-Ubiquitin. Parkin has been reported to generate poly-Ubiquitin chains in K6, K11, K48, and K63 linkages both in vitro and in vivo.