Reconstructing the Evolution of Vertebrate Blood Coagulation from a Consideration of the Amino Acid Sequences of Clotting Proteins

Vertebrate blood coagulation is a delicately balanced phenomenon whose central feature is the thrombin-catalyzed conversion of fibrinogen to fibrin. A large number of accessory proteins are involved, both in the generation of thrombin and in the mobilization, degra-dation, or neutralization of other components. The general theme of events embodies restrained and highly selective proteolysis. To this end, there are two main routes for the production of thrombin, denoted the extrinsic and intrinsic systems, respectively. The extrinsic system begins with the release or expo-sure of the membrane-associated tissue factor (TF) that activates the protease precursor denoted factor VII. Activated factor VII, in turn, attacks factor X, which, in league with the accessory protein factor V and cal-