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Thrombomodulin (TM), CD141 or BDCA-3 is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. It reduces blood coagulation by converting thrombin to an anticoagulant enzyme from a procoagulant enzyme. [ 5 ]
Thrombin bound to thrombomodulin activates protein C, an inhibitor of the coagulation cascade. The activation of protein C is greatly enhanced following the binding of thrombin to thrombomodulin, an integral membrane protein expressed by endothelial cells. Activated protein C inactivates factors Va and VIIIa.
Protein C Anticoagulant Pathway: Thrombin escaping from a site of vascular injury binds to its receptor thrombomodulin (TM) on the intact cell surface. As a result, thrombin loses its procoagulant properties and instead becomes a potent activator of protein C. Activated protein C (APC) functions as a circulating anticoagulant, which ...
When this occurs, endothelial cells downregulate substances such as thrombomodulin, which is a key modulator of thrombin activity. [35] The result is a sustained activation of thrombin and reduced production of protein C and tissue factor inhibitor, which furthers the pro-thrombotic state. [34]
Calcium is also required at other points in the coagulation cascade. Calcium ions play a major role in the regulation of coagulation cascade that is paramount in the maintenance of hemostasis. Other than platelet activation, calcium ions are responsible for complete activation of several coagulation factors, including coagulation Factor XIII. [42]
When it is activated by proteolysis at residue Arg92 by the thrombin/thrombomodulin complex, CPB2 exhibits carboxypeptidase activity. Activated CPB2 reduces fibrinolysis by removing the fibrin C-terminal residues that are important for the binding and activation of plasminogen. [8] [9] Carboxypeptidases are enzymes that hydrolyze C-terminal ...
The presence of thrombomodulin accelerates activation by several orders of magnitude, [7]: 34 and EPCR speeds up activation by a factor of 20. If either of these two proteins is absent in murine specimens, the mouse dies from excessive blood-clotting while still in an embryonic state.
10544 19124 Ensembl ENSG00000101000 ENSMUSG00000027611 UniProt Q9UNN8 Q64695 RefSeq (mRNA) NM_006404 NM_011171 RefSeq (protein) NP_006395 NP_035301 Location (UCSC) Chr 20: 35.17 – 35.22 Mb Chr 2: 155.59 – 155.6 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse Endothelial protein C receptor (EPCR) also known as activated protein C receptor (APC receptor) is a protein that in humans ...