InterPro domain: IPR003977

Parkinson's disease (PD) is a common neurodegenerative disorder with complex clinical features and a poorly understood aetiology. PD is accompanied by a progressive loss of dopamine-containing neurons in the substantia nigra, with patients suffering from rigidity, slowness of movement, tremour and disturbances of balance. Autosomal recessive juvenile parkinsonism (AR-JP) is a rare form of familial PD mapped to chromosome 6 and linked strongly to a pair of markers. One of these markers has been cloned, yielding a sequence that encodes a protein, 465 amino acids long [ 1 ]. The protein sequence, named parkin, shows moderate similarity with ubiquitin at the N terminus and a ring-finger domain at the C terminus.

In normal individuals, parkin binds to the E2 ubiquitin-conjugating human enzyme 8 (UbcH8) through the C-terminal ring-finger domain. In the presence of UbcH8, parkin has ubiquitin-protein ligase activity and even catalyses its own ubiquitination. Furthermore, parkin appears to target the synaptic vesicle-associated protein CDCrel-1 for ubiquitination and thus promotes its degradation. The mutated forms of parkin implicated in AR-JP appear to be defective in terms of UbcH8 binding, E3 ubiquitin protein-ligase activity, self-ubiquitination, and CDCrel-1 binding and ubiquitination [ 2 ].

1. TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family. J. Biol. Chem. 275, 17412-9
2. Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc. Natl. Acad. Sci. U.S.A. 97, 13354-9