Activation of coagulation factor IX

The structure of factor IX includes an amino-terminal Gla domain (green dashed oval), two epidermal growth factor domains (solid red ovals, designated EGF1 and EGF2), an activation peptide (light gray bar, designated AP), and a catalytic domain (light gray circle, designated CAT). Cleavages take place at Arg145 and Arg180. The following series of activation steps occur:

• Factor VIIa and tissue factor initially cleave factor IX after Arg145 to form the intermediate factor IXα (upper solid arrow).
• Factor IXα is subsequently cleaved after Arg180 to form factor IXaβ (lower solid arrow).
• Simultaneously, factor IXa cleaves factor IX after Arg180 to generate factor IXaα (dashed arrow). This form contains the active catalytic domain (three-fourths light gray circle). This is converted to factor IXaβ (lower dashed arrow). The dashed arrows represent a minor contribution to generation of factor IXaβ.