Under normal physiological conditions, activated protein C (...
| created | [InstanceEdit:9930429] Shamovsky, Veronica, 2024-12-03 |
| dbId | 9930424 |
| displayName | Under normal physiological conditions, activated protein C (... |
| literatureReference |
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| schemaClass | Summation |
| text | Under normal physiological conditions, activated protein C (APC) regulates clotting by cleaving factor Va (FVa) at residues R534 and R334, thereby preventing excessive clot formation. This Reactome event describes two APC-resistant FV variants, FV R334T (FV Cambridge) and FV I387T (FV Liverpool), that impair APC ability to inactivate FVa by cleaving it at R334. The defective cleavage of these FV variants at R344 may also interfere with APC-mediated inactivation of factor VIIIa (FVIIIa), where non-activated but APC-cleaved FV functions as an APC cofactor. The FV R334T (FV Cambridge) mutation leads to incomplete inactivation of FVa by APC, an effect that is partially mitigated by the presence of protein S (Norström E et al., 2002; reviewed by Moore GW et al., 2023). In contrast, FV I387T (FV Liverpool) exerts more pronounced effects due to the the gain of a glycosylation site near residue R334, which impairs APC-mediated cleavage of FVa (Steen M et al., 2004). These conditions results in prolonged clotting activity of FVa, potentially increasing the risk of venous thromboembolism (VTE) in individuals carrying either of these mutations (Williamson D et al., 1998; Franco RF et al., 1998; Norström E et al., 2002; Mumford AD et al., 2003; Steen M et al., 2004; reviewed by Moore GW et al., 2023). |
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