Amino acid homology and binding characteristics of human and murine ligands to EPCR. (A) The amino acid residues in human protein C (hPC) that are involved in binding to human EPCR and the corresponding residues in other proteins were highlighted (light green color). Ability of these proteins to bind either human or murine EPCR is shown relative to human protein C binding to human EPCR, which was assigned 4 checkmarks. The binding properties reported earlier,^{1,5-7,11,12,23-25,98}  including K_d values, relative amounts of the ligand bound to a constant amount of EPCR, and in vivo displacement of the bound ligand by exogenously administered competing ligand, were used cumulatively in assigning the relative binding. X, no detectable or significant binding; ND, not determined. Both the zymogen and the corresponding active protease ligand interact with EPCR with similar affinities. (B) Amino acid homology of the extracellular region of human and murine EPCR. The 10 residues highlighted with orange boxes are those that, when mutated to alanine, resulted in the loss of APC binding to hEPCR.⁹⁹  Residues highlighted in red were shown to be important for proper EPCR conformation. Therefore, when these residues are mutated to alanine, they result in the loss of APC binding and all mAb epitopes.⁹⁹