Factor VIIIa dissociates

Stable Identifier
Reaction [dissociation]
Homo sapiens
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Factor VIII (FVIII) circulates in plasma as a heterodimer (domain structure A1-A2-B:A3-C1-C2) that requires thrombin cleavage to elicit procoagulant activity (Kaufman RJ et al. 1997). Upon activation by thrombin FVIII is converted to the labile FVIIIa, a heterotrimer of A1, A2 and A3C1C2 subunits, which serves as a cofactor for FIXa (Fay PJ 2006). At physiological concentrations, FVIIIa decays as a result of A2 subunit dissociation, which is weakly associated with the A1:A3-C1-C2 dimer by primarily electrostatic interactions (Fay PJet al. 1991; Fay PJ & Smudzin TM 1992; Parker ET et al 2006). Site-directed mutagenesis, functional and structural studies suggest that multiple residues at the A1-A2 and A2-A3 domain interfaces contribute to non-covalent interactions in stabilizing the protein (Parker ET & Lollar P 2007; Wakabayashi H & Fay PJ 2008, 2013; Wakabayashi H et al. 2008; Monaghan M et al. 2016). Retention of A2 polypeptide is required for normal stability of FVIIIa and dissociation of A2 correlates with FVIIIa inactivation and consequent loss of FXase activity.

Literature References
Event Information
Orthologous Events
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