Human prothrombin is a 72 kDa (579 amino acid) single-chain zymogen composed of four domains: a GLA, two kringles and a serine protease. Synthesised in the liver, prothrombin is post-translationally modified by a vitamin-K-dependent carboxylase to...

The serine protease α-thrombin is produced by proteolytic cleavage of the zymogen prothrombin by either factor Xa or the prothrombinase complex (factors Va–Xa). Full activation requires two cleavages between Arg273–Thr274 and Arg323–Ser324 ...

Factor IX is a 45 kDa (415 amino acid) vitamin-K-dependent coagulation factor composed of four domains (a GLA with 12 Gla residues, two EGFs and a serine protease domain) and an activation peptide. Factor IXa circulates in the plasma at 90 μM (5 ...

The physiological role of factor IXa is to activate the zymogen factor X to the enzyme factor Xa. The enzymatic activity of factor IXa is greatly enhanced by addition of its cofactor (factor VIIIa) with calcium ions on a phospholipid surface. The ...

When required the pro-cofactor is converted to the active cofactor (factor Va) via limited proteolysis by α-thrombin and less efficiently by factor Xa. The active cofactor is generated from the NH2-terminal-derived heavy chain (94 kDa) and a COOH...

Factor V is a large (330 kDa), single-chain, plasma glycoprotein which is an essential pro-cofactor for the coagulation cascade. Factor V shares approximately 40% identity with the corresponding domains in factor VIII. The C domains of the two fac...

Human factor VII is a 50 kDa (406 amino acid) single-chain zymogen composed of four domains: a GLA, two EGFs and a serine protease. As a single chain, factor VII is synthesised in the liver where 10 Gla residues are generated in the GLA domain pri...

In human plasma, approximately 99% of factor VII circulates as the zymogen, while the rest circulates as the active enzyme factor VIIa. Factor VII is proteolytically activated by cleavage of Arg152–Ile153 by thrombin...

is an essential blood clotting; a deficiency leads to haemophilia A . In humans, Factor VIII is encoded by the F8 gene.

Factor VIII is a 280 kDa (2351 amino acid) glycoprotein pro-cofactor synthesised by the endothelium and released into the plasma where it is bound to 50–100 von Willebrand factor (vWF) monomers at a concentration of 0.7 nM (0.2 μg/mL). The best...

Human factor X is a 59 kDa (407 amino acid) zymogen composed of four domains (a GLA with 11 Gla residues, two EGFs and a serine protease domain) with an activation peptide. It is yet another vitamin-K-dependent glycoprotein which is synthesised in...

Factor XI is a 160 kDa (617 amino acid) plasma glycoprotein which circulates (30 nM, 5 μg/mL) in a non-covalent complex with high molecular weight kininogen. The mature molecule is a two-chain homodimer connected by disulfide bonds where each mon...

Factor XIII is found both extracellularly in the plasma and intracellularly in platelets, megakaryocytes, monocytes, placenta, uterus, liver and prostrate tissues. Plasma factor XIII is a tetramer composed of two identical A subunits (657 amino ac...

A polymorphism of the A subunit of coagulation factor XIII (FXIII-A), leading to an amino-acid substitute (valine>leucine) located close to the thrombin cleavage site.

Plasma factor XIII is activated when thrombin cleaves between Arg36–Gly37 releasing an approximately 4 kDa activation peptide from the N-termini of each A subunit, exposing the active site. Full activity of factor XIIIa is achieved once Ca2+ and...