Fig. 4.

Factor IX Activation. Factor (F) IX is converted to FIXaβ by cleavage after Arg¹⁴⁵ and Arg¹⁸⁰, releasing the activation peptide (white oval) that connects the catalytic domain (CD) to the non-catalytic light chain (Gla and EGF domains). FVIIa/TF initially cleaves FIX after Arg¹⁴⁵ to form the intermediate FIXα, with subsequent cleavage after Arg¹⁸⁰ forming FIXaβ (bold arrows). The active catalytic domain of FIXaβ is indicated by the three-quarter circle. During this reaction, FIXα accumulates prior to formation of FIXaβ. FXIa also cleaves FIX initially after Arg¹⁴⁵, however, no FIXα accumulates, suggesting that subsequent cleavage after Arg¹⁸⁰ is relatively rapid. Activation of FIX by initial cleavage after Arg¹⁸⁰ (through FIXaα) is a minor reaction (thin arrows).