Figure 1.

Human and rat protein primary sequence comparisons for PD-linked genes. For each gene, the amino acid residues at the beginning and end of each domain are shown below the human sequence. PD-linked missense and nonsense mutations are shown on top of the human protein sequence. Functionally important amino acids are indicated at the bottom of the human protein sequence. The percent sequence identity between rat and human for each domain is indicated in the rat primary sequence. (A) α-Synuclein domains are annotated as follows: N-terminal domain (N-term); Non-Amyloid component domain (NAC); C-terminal domain (C-term). Phosphorylation of serine 129, shown below, is a marker of pathological forms of α-synuclein. (B) LRRK2 domains are as follows: Armadillo-like repeat (ARM); Ankyrin repeat (ANK); Leucine rich repeat (LRR); Roc (ras of complex) GTPase domain (GTPase); C-terminal of Roc (COR); Kinase domain (Kinase); WD40 domain (WD40). Known sites of LRRK2 phosphorylation are shown below. (C) PINK1 domains are annotated as follows: Mitochondrial Targeting Sequence (MTS); transmembrane domain (TMD); N-terminal regulatory region (NT); Kinase domain (Kinase); C-terminal regulatory sequence (C-term). Known sites of PINK1 phosphorylation are shown below. (D) Parkin domains are as follows: Ubiquitin Like domain (Ubl); really interesting new gene (RING0, RING1, RING2, respectively); In between RING domain (IBR); repressor domain (REP). Parkin is activated by PINK1 phosphorylation of serine 65, shown below the ubiquitin-like domain, and the identical serine 65 in ubiquitin. Cysteine 431 is required for Parkin mitochondrial translocation and Parkin E3 ligase activity. (E) DJ-1 domains are as follows: Core domains (Core); dimerization domain (Dimerization). Cysteine 106, shown below, is highly sensitive to oxidation and required for mitochondrial translocation.