Schematic illustration for the protein structure; typical and atypical cleavage activies of human PCSK1, PCSK3, PCSK5, PCSK6, and PCSK9. The figure illustrates the peptide domains and cleavage site of human PCSK1, PCSK3, PCSK5, PCSK6, and PCSK9. The five PCSK members consist of several peptide domains: a signal peptide/transmembrane domain (S/T) at the amino-terminus, a pro-segment domain (Pro), a catalytic domain (Cat), a P domain (P), a Cys-rich domain (Cys), a cytoplasmic tail (Cyt), and a Cys-His-rich domain (CHRD) at the carboxyl-terminus. Three protein domains are common between five PCSK members: S/T, Pro, and Cat domains. Typical members (PCSK1, PCSK3, PCSK5, and PCSK6) cleaves single or paired basic amino acids with the motif (R/K)X
(R/K)↓, where the arrow indicates the cleavage site and X
corresponds to a 0-, 2-, 4-, or 6-amino-acid spacer at (R/K)X
(R/K)↓, meanwhile atypical member (PCSK9) cleaves non-basic residues at the C-terminal end of the motif (V/I/L)FAQ↓.