Alignment of C domain sequences.

Amino acids are aligned by CLUSTAL W 1.7, GenomeNet. Factor VIII (VIII) sequences are as indicated for different species: human (h),1 porcine (p),19 murine (m),18canine (c)20; factor V(V) sequences are: human (h),17,34 murine (m),35 bovine (b).36 Bold residues indicate differences from human factor VIII, underlined are C2 residues that may bind to phospholipids, and boxes indicate a potential Asn-linked carbohydrate. HphA (above each human factor VIII sequence row) indicates hemophilic mutations; an asterisk is for those associated with an inhibitor (see Table 3). Shading is for β-strands in the human C2 crystal structure.22 In panel A, C1 homologous sequences are shown and β-strands are distinguished from those in C2 with a prime, with no β3′ nor β4′ (see Figure 2). In panel B, C2 homologous sequences are shown including a C2 inhibitor epitope as defined by Healey et al.13 Note that exact residues at the ends of β-strands are subject to interpretation as they often end within a residue (coordinates are available; see Acknowledgments).