Schematic representation of thrombomodulin domain structure. The amino terminal portion of TM, which projects into the vascular lumen, contains a lectin-like domain and 6 EGF-like domains. EGF-like domains 5 and 6 are required for thrombin binding, and EGF-like domains 4 to 6 (yellow) are necessary for efficient activation of protein C. The location of the oxidation-sensitive regulatory methionine (M388) is in the short linker region between EGF-like domains 4 and 5 (arrow). TM also contains a transmembrane domain and a cytoplasmic tail (CYTO).