Blood coagulation factor XIII: A multifunctional transglutaminase

Abstract

Factor XIII is a pro-enzyme of plasma transglutaminase consisting of two enzymatic A subunits and two non-catalytic B subunits, and platelet transglutaminase consisting of two enzymatic A subunits. FXIII plays a critical role in the generation of a stable hemostatic plug, wound healing, maintaining pregnancy, angiogenesis, apoptosis and bacterial immobilization. FXIII catalyzes intermolecular cross-linking reactions between fibrin monomers and α2- antiplasmin. These reactions increase the mechanical strength of the fibrin clot and its resistance to proteolytic degradation. Congenital FXIII deficiency is a rare autosomal recessive disorder, most cases of which are caused by defects in the FXIII-A gene, leading to a bleeding tendency. An autoimmune hemophilia-like disease is caused by anti-FXIII antibodies. Platelet surface FXIII-A2 is involved in fibrin translocation to lipid rafts and outside-in signaling, leading to clot retraction. FXIII-A2-mediated protein cross-linking is associated with assembly of the extracellular matrix on a variety of cell surfaces in physiological events such as differentiation.