@entity5337 is composed of domains A1-A2-B-A3-C1-C2 and is activated by thrombin through proteolytic cleavage at @entity534 709, @entity534 1018 and @entity534 1545. Upon thrombin activation, the B-domain is released and the active factor Va is formed by the heavy (A1-A2) and light chains (A3-C1-C2). Factor Va functions as an essential cofactor to @entity6236 in the conversion of prothrombin to thrombin during coagulation. Recently it was shown that @entity5337 , apart from being a precursor form to the procoagulant factor Va, also has anticoagulant properties, as it functions as a cofactor to @entity10855 ( @entity10855 ). @entity10855 is a member of the anticoagulant pathway and downregulates the coagulation process through proteolytic inactivation of factors @entity797 /VIIIa and factors V/Va. In a factor VIIIa degradation assay, the @entity10855 -mediated inactivation of factor VIIIa is potentiated by the synergistic cofactors protein S and factor V. Protein S alone has little cofactor activity, whereas in the presence of factor V it is dramatically enhanced. This study provides insights into the molecular mechanisms that regulate the anticoagulant activity of factor V. Thrombin cleavage of factor V occurs in a sequential order. The thrombin cleavage site @entity534 1545 is kinetically less favored than the other two sites, and cleavage at this site is the last to occur during thrombin activation of factor V As a consequence of this, different activation intermediates exist that express different levels of procoagulant activity. The anticoagulant activities of these intermediates have now been studied. It was found that factor V could be cleaved by thrombin at both @entity534 709 and @entity534 1018 and still work fully as a cofactor to @entity10855 , whereas cleavage at @entity534 1545 completely abolished the anticoagulant activity of factor V. This suggests that the @entity10855 cofactor function of factor V depends on the B-domain remaining attached to the A3 domain. This study further shows that @entity10855 converts @entity5337 into a member of the anticoagulant pathway by cleaving factor V in the A2 domain at @entity534 506. By cleavage of factor V, @entity10855 not only produces an anticoagulant cofactor, but at the same time eliminates the pool of procoagulant factor V, since @entity10855 cleaved factor V will have no future as a cofactor in the coagulation. The unique way by which @entity10855 and thrombin, through proteolytic cleavage, can convert factor V into either an anticoagulant or a procoagulant adds to the intriguing mechanisms that balance the procoagulant and anticoagulant forces.

Mechanisms that regulate the anticoagulant function of XXXX .

@entity5337 :: ('2153', 'Gene') :: ['Coagulation factor V', 'coagulation factor V'] @entity797 :: ('1351', 'Gene') :: ['VIII'] @entity10855 :: ('MESH:D020016', 'Disease') :: ['activated protein C', 'APC'] @entity534 :: ('CHEBI:16467', 'Chemical') :: ['Arg'] @entity6236 :: ('2159', 'Gene') :: ['factor Xa']
@entity5337 :: (2153,Gene) :: ['coagulation factor V']
