Schematic diagram for the proteolytic cleavages of human F.V and F.Va by HNE. The domain structure of human F.V is made up of the heavy chain (residues 1-709) comprising two A domains (A1-A2) and connecting regions.38 51 The B domain spans residues 710 to 1545 and connects the heavy and light chains. The light chain (residues 1546-2196) is composed of one A and two C domains (A3-C1-C2). The results of the NH₂ -terminal sequencing indicated HNE activates human F.V cofactor activity after cleavage at Ile⁸¹⁹ and Ile¹⁴⁸⁴ (HNE-labeled light arrows) and inactivates human F.Va cofactor activity after cleaving at Ala³⁴¹, Ile⁵⁰⁸, and Thr¹⁷⁶⁷ (HNE-labeled dark arrows). The positions of the HNE cleavage sites within the F.V/F.Va molecule are shown below the cartoon representation of intact F.V, while the thrombin (IIa-labeled light arrows) activation and the Activated Protein C (APC-labeled dark arrows) inactivation cleavage sites are shown above for comparison.