BACKGROUND Parkin is a protein that in humans is encoded by the PARK2 gene.1 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.2 Mutations in this gene are known to cause a familial form of Parkinson's disease called autosomal recessive juvenile Parkinson disease. Such patients develop a syndrome that closely resembles the sporadic form of PD; however, they tend to develop symptoms at a much younger age.
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. 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 protein CASK/Lin2 to exert functions in synaptic transmission as well as neurodegeneration.3
1. Kitada, T. et al: Nature. 392(6676): 605-608, 1998.
2. Chin, L. S. et al: Biochem. Soc. Trans. 38(Pt1): 144-9, 2010.
3. Fallon, L. et al: J. Biol. Chem. 277:486-491, 2002.
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