| Primary Identifier | IPR015669 | Type | Family |
| Short Name | Endothetial_C_recpt |
| description | Upon vascular injury, flowing blood is exposed to cells expressing tissue factor (TF) on their surfaces and FVII/FVIIa binds to its receptor/cofactor TF and is rapidly activated to FVIIa and the activity of bound FVIIa is dramatically enhanced. The TF/FVIIa complex activates zymogens factor X (FX) and factor IX (FIX). The FXa, in the absence of activated cofactor factor Va (FVa) generates only trace amounts of thrombin. Although insufficient to initiate fibrin polymerisation alone, these small amounts of thrombin, however, back activate factors V (FV), VIII (FVIII), and XI(FXI). FVIII and FV function as membrane-bound cofactors for proteinases FIXa and FXa, respectively increasing the Vmax of the reaction complexes dramatically. Amplification of the pro-coagulant response consequently occurs through formation of the tenase complex FIXa/FVIIIa and the thrombinase complex FXa/FVa that generate sufficient amounts of thrombin to mediate sustained haemostasis.In addition to its function in cleaving soluble fibrinogen to form insoluble fibrin monomers, thrombin can also activate an anticoagulant pathway. Thrombomodulin (TM), a receptor present on the endothelial cell surface, binds thrombin and alters thrombin's substrate specificity through an allosteric mechanism. Bound to TM, thrombin can no longer efficiently proteolyse its pro-coagulant substrates FV, FVIII and fibrinogen. The thrombin-TM complex proteolytically activates its substrate protein C (PC) to activated protein C (APC). In complex with its cofactor protein S (PS), APC rapidly inactivates pro-coagulant factors FVa and FVIIIa by further proteolysis in a negative feedback loop. Activation of protein C by thrombin bound to thrombomodulin is enhanced by endothelial protein C receptor (EPCR). The EPCR is an N-glycosylated type I membrane protein and mutations in this EPCR gene have been associated with venous thromboembolism and myocardial infarction, as well as with late foetal loss during pregnancy. |
