Multiple partial alignments of factor V, factor VIII, and ceruloplasmin from different species around FVIII positions where novel mutations were found in the current work. For simplicity, only mutations within domain A1 and the A1-A2 linker (part A) and domains C1/C2 (part B) are represented; a complete alignment is available from the authors upon request. Strictly conserved residues are white with black shading, and conservative changes are shaded gray. Numberings refer to the mature human proteins. The activation cleavage site is indicated with an arrow in panel A, and loops important for membrane association are boxed in panel B. The secondary structure elements given below FV and ceruloplasmin sequences correspond to the crystal structures of bovine inactivated FVa (PDB 1SDD, Adams et al² ), FVIII C2 domain (1D7P, Pratt et al⁸ ), and human ceruloplasmin (1KCW, Zaitseva et al⁹ ), as deposited in the corresponding PDB entries. Residues that are disordered in the crystal structure of ceruloplasmin are underlined.