1. Factor V: a combination of Dr Jekyll and Mr Hyde
by Kenneth G. Mann, and Michael Kalafatis
Blood
Volume 101(1):20-30
January 1, 2003
©2003 by American Society of Hematology

2. Human factor V molecule
Human factor V molecule.(A) Diagram of the organization of the human factor V molecule.
Human factor V molecule.(A) Diagram of the organization of the human factor V molecule. The arrows on the top represent activation cleavages by α-thrombin, factor Xa, and RVV-V activator. The arrows at the bottom indicate inactivation cleavages by APC and plasmin. The positions of posttranslational modifications are also shown. (B) Active factor V (factor Va). Following activation by α-thrombin, the active cofactor is a heterodimer composed of a heavy chain divalent cation associated with light chain. The B region of the cofactor is released as 2 fragments. (C) Inactive factor Va (factor Vai). The upper part shows inactivation of factor Va by APC, resulting in the dissociation of the A2 domain as 2 fragments, A2N and A2C. The lower part shows inactivation of factor Va by α-thrombin following cleavage of the heavy chain at Arg643.
Kenneth G. Mann, and Michael Kalafatis Blood 2003;101:20-30
©2003 by American Society of Hematology

3. Participation of the factor V molecule in the hemostatic process
Participation of the factor V molecule in the hemostatic process.Four stages of the participation of the factor V molecule in the hemostatic process are illustrated in in cartoon form.
Participation of the factor V molecule in the hemostatic process.Four stages of the participation of the factor V molecule in the hemostatic process are illustrated in in cartoon form. (A) The factor V molecule is presented with the activation peptide “B domain” illustrated as a loop structure which connects the heavy (A1A2) and light chain (A3C1C2) domains of the factor Va molecule. The single chain factor V interacts with membranes through its carboxyl terminal region. (B) Factor V is activated to Factor Va by thrombin (IIa), which excises the B domain, leaving the noncovalently associated light and heavy chains of the factor Va molecule. (C) The membrane-bound factor Va molecule binds factor Xa through regions of both the light and heavy chains. These interactions together with factor Xa membrane binding provide the tightly associated enzymatic complex (prothrombinase) which converts prothrombin (II) to thrombin (IIa). (D) Activated protein C (APC) cleaves at 3 sites of the heavy chain of the factor Va molecule, resulting in the dissociation of the A2 domain as 2 fragments, A2N and A2C. The resulting product (factor Vai), composed of the A1 domain noncovalently associated with the membrane-bound light chain, binds APC but will no longer function efficiently in generating thrombin.
Kenneth G. Mann, and Michael Kalafatis Blood 2003;101:20-30
©2003 by American Society of Hematology