Figure 1.

Genes associated with autosomal recessive early onset parkinsonism. The DJ-1, PINK1 and parkin proteins are drawn approximately to scale, with pathogenic mutations listed above each diagram. DJ-1 is a single domain protein with a critical Cysteine residue (C106) that can be modified in the presence of reactive oxygen species (ROS) to form a sulfinic acid, as indicated. PINK1 contains a mitochondrial targeting sequence (MTS) and a putative transmembrane (TM) region that directs the kinase domain to the outer face of the mitochondria, as well as a C-terminal tail of uncertain function. Parkin is structured with a ubiquitin-like (Ubl) domain at the N-terminus followed by three RING finger domains (R0–R2 for historical regions) separated by an in between RING (IBR) domain, each of which bind two Zn²⁺ atoms. For all three genes, there whole exon deletions and duplications that result in loss of protein as well as point mutations that either destabilize or otherwise functionally inactivate the proteins.