A schematic comparison of F.XIa and HNE cleavage of human F.IX. Human F.IX is composed of a light chain (residues 1-145), an activation peptide (residues 146-180), and a heavy chain (residues 181-415). The light chain is composed of a γ-carboxylglutamyl-(GLA) containing domain, two domains with homology to human epidermal growth factor (EGF), and a linker (L) domain.10 The activation peptide (AP) is cleaved upon F.IX activation by F.XIa. The catalytic domain (CD) contains the active site formed by the triad of Asp²⁶⁹, His²²¹, and Ser³⁶⁵residues. The results of the NH₂-terminal sequencing indicate that HNE inactivates human F.IX coagulant activity after cleaving at Thr¹⁴⁰, Thr¹⁴⁴, Ile¹⁶⁴, Thr¹⁷², and Val¹⁸¹. Human F.IX is shown with the position of the cleavage sites for either F.XIa (top) or HNE (bottom).