Coagulation factor XIII

Factor XIII or fibrin stabilizing factor is an enzyme (EC 2.3.2.13) of the blood coagulation system that crosslinks fibrin. Deficiency of this factor (FXIIID) affects clot stability. Factor XIII or fibrin stabilizing factor is an enzyme (EC 2.3.2.13) of the blood coagulation system that crosslinks fibrin. Deficiency of this factor (FXIIID) affects clot stability. Factor XIII is a transglutaminase that circulates in the plasma as a heterotetramer of two catalytic A subunits and two carrier B subunits. When thrombin has converted fibrinogen to fibrin, the latter forms a proteinaceous network in which every E-unit is crosslinked to only one D-unit. Factor XIII is activated by thrombin into factor XIIIa; its activation into Factor XIIIa requires calcium as a cofactor. A cleavage by thrombin between residue Arg37 and Gly38 on the N-terminus of the A subunit, leads to the release of the activation peptide (MW 4000 da). In the presence of calcium the carrier subunits dissociate from the catalytic subunits, leading to a 3D change in conformation of factor XIII and hence the exposure of catalytic cysteine residue. Upon activation by thrombin, factor XIIIa acts on fibrin to form γ-glutamyl-Є-lysyl amide cross links between fibrin molecules to form an insoluble clot. FXIII is also known as Laki–Lorand factor, after Kalman Laki and Laszlo Lorand, the scientists who first proposed its existence in 1948. A 2005 conference recommended standardization of nomenclature. Zymogen factor XIII is a 320kDa glycoprotein tetramer consisting of two twin subunits (2 A and 2 B), the genes for which are on different chromosomes: Factor XIII has two forms: a plasmatic form that flows freely in the blood plasma, and a cellular form carried inside platelet alpha-granules. The cellular form is a dimer of two identical subunits, FXIII-A, each consisting of an activation peptide that is cleaved upon activation, a β-sandwich domain, a catalytic transglutaminase domain and two β-barrel domains. The plasmatic form includes two additional identical subunits, FXIII-B, that is released in a calcium-dependent manner upon activation peptide cleavage. Each FXIII-B is both inhibitory and serves as a plasma carrier, and consists of ten repetitive sushi domains held together by two internal disulfide bond each. During circulation, this subunit binds fibrinogen.