Schematic of TM structure with putative functional correlates. TM is represented by its 5 structural regions, with its traditional and nontraditional roles. Interactions of TM with thrombin that generate APC and CPB2 that dampen coagulation, inflammation, fibrinolysis, and complement are highlighted in the box on the left. The lectin-like domain of TM interferes with complement activation and inflammation. The lectin-like domain of TM also has several putative ligands, including fibronectin, HMGB1, and Le^y, which are reported to impact migration, inflammation, and angiogenesis. The EGF-like region and serine-threonine–rich (S-T) region, via the chondroitin sulfate (shown as black lines from S-T regions), bind to CD14 and adhesion molecules LFA-1 and MAC-1, modulating responses to endotoxin and regulating leukocyte trafficking. Connected to the ectodomain via the transmembrane region (Trans), the cytoplasmic region (Cyto) binds, in some cells, to the adaptor protein ezrin, which alters the actin cytoskeleton and modulates cell migration. EPCR and PF4 are not shown. IIa, thrombin.