Mutations in the Parkin (PRKN2) gene is considered to be a major cause of autosomal recessive juvenile parkinsonism (AR-PJ). Parkin functions as an E3 ligase having an N-terminal ubiquitin-like motif and a C-terminal RING domain composed of two RING-finger motifs separated by two IBR domains. Parkin can auto-ubiquitinate itself and ubiquitinate various substrates (eg. CDCrel- 1 and rel-2a, cyclin E, synphilin-1, the O-glycosylated form of α-synuclein (αSp22), PAel-R, FBP1, α/β tubulin, RanBP2, Hsp70, synaptotagmin XI) in an E2-dependent manner, targeting them for degradation. Parkin functions in conjunction with E2 enzymes UbcH7 (E2-640), UbcH8 (E2-644) and UbcH13/Uev1 (E2-664). Parkin disease-associated mutations often affect E3 ligase activity through decreased E2 and/or substrate interactions which may thus result in the dysfunction of proteasomal degradation pathways and the neurotoxic accumulation of misfolded proteins. It has been suggested that Parkin is a neuroprotectant via regulation in the unfolded protein stress response and targeting of various substrates in proteasomal degradation pathways.This protein contains a N-terminal His₆-tag.