Schematic representation of F9, FIX, and FIXa. Eight exons (E1-8) in the F9 gene (32.7 kb)¹³³ encode (parts of) specific FIX (UniProt, P00740) protein regions, which are indicated by corresponding colors. FIX protein maturation and activation are schematically depicted and proceed via a precursor and immature protein state to posttranslationally modified mature FIX and FIXa. The signal peptide (SP), propeptide (Pro), Gla, EGF1, EGF2, linker region, activation peptide, and (serine) protease domain regions are defined by legacy numbering, in which residue 1 corresponds to the first amino acid of the Gla domain. Proteolytic activation represents limited proteolysis by extrinsic tissue factor-FVIIa and intrinsic FXIa at the cleavage sites Arg145 and Arg180 generating FIXa. Professional illustration by Somersault18:24.