Factor V is a large, single chain, plasma glycoprotein which is an essential component in the blood coagulation cascade. During coagulation, the procofactor, factor V, is converted to the active cofactor , factor Va, via limited proteolysis by the serine protease α-thrombin, and less efficiently by factor Xa. The active cofactor is composed of an NH₂-terminal derived heavy chain (Mr = 94,000) and a COOH-terminal derived light chain (Mr = 74,000) which remain non-covalently associated in the presence of calcium ions. Factor Va serves as a cofactor for the serine protease factor Xa. Factor Va and Xa assemble on a phospholipid surface in a non-covalent and calcium ion-dependent manner, to form the prothrombinase complex.

Factor Va is a cofactor for the serine protease factor Xa, and in the presence of calcium ions they collectively assemble on a phospholipid surface to form the prothrombinase complex. The prothrombinase complex is responsible for the rapid conversion of prothrombin to thrombin. Factor Va is derived from the pro-cofactor, factor V, upon limited proteolysis by α-thrombin. The thrombin cleavage of factor V liberates two heavily glycosylated activation peptides from the central portion of the molecule which have no cofactor function.

Human factor VII is a single chain, vitamin K-dependent, plasma glycoprotein which is synthesized in the liver (1-3). Prior to secretion into the blood, post translational modification by a vitamin K-dependent carboxylase produces ten-carboxyglutamic acid (gla) residues located in the NH2-terminal portion of the molecule, which facilitate cell membrane binding. Factor VII is proteolytically activated to the serine protease, factor VIIa, during coagulation. Factor VII can be activated by thrombin, factor IXa, factor Xa or factor XIIa.

Human factor VII is a single chain plasma glycoprotein, and is zymogen in its native form (1-4). proteolytic activation of fator VII, yields the enzyme factor VIIa, which when bound to the integral membrane protein tissue factor, forms an enzyme complex that proteolytically converts factor X to factor Xa. This enzyme complex is best known as the extrinsic factor Xase (pronounced ten-ase) complek, since by virtue of its tissue factor component, it is composed of protein normally extrinsic to the plasma enviroment.

The zymogen factor lX is a single chain vitamin K-dependent glycoprotein which is synthesized in the liver. The domain structure of factor lX is similar to that of the other vitamin K dependent coagulation factors. The NH₂-terminal region contains 12 γ-carboxyglutamic acid (gla) residues which facilitate the calcium dependent binding of factor lX to negatively charged phospholipid surfaces. Two domains which are homologues to epidermal growth factor (EGF) span the region between the NH₂-terminal gla domain and the activation peptide (Ala-146 to Arg-180).

Factor IXa is produced from its inactive procursor, factor IX, via proteolytic cleavage by factor Xla or the tissue factor/factor Vlla/phospholipid complex. The activation results from the cleavage of two peptide bonds in the factor IX molecule, releasing an activation glycopeptide with an apparent molecular weight of 10,000. The havey chain of factor IXa (Mr = 28,000) containts the serine protease catalytic domain, while the light chain (Mr = 17,000) contains the membrane binding domain.

Factor X is a vitamin K-dependent protein zymogen which is synthesized in the liver and circulates in plasma as a two chain molecule linked by a disulfide bond. Prior to secretion into plasma, posttranslational modifications produce 11 gamma-carboxyglutamic acid (gla) residues and a single β-hydroxyaspartic acid residue, which are located within the NH₂-terminal light chain. The light chain also contains two epidermal growth factor (EGF) homology domains.

Activation of the zymogen, factor X, by either the intrinsic or extrinsic factor Xase complexes produces the active serine protease factor Xa (1,2). The activation of factor X requires proteolytic cleavage of the heavy chain, resulting in the release of an activation glycopeptide. The heavy chain region in factor Xa contains the serine protease catalytic domain, while the light chain, as in the zymogen, contains the membrane binding domain.

Factor XI is a plasma glycoprotein which circulates in a non-covalent complex with high molecular weight kininogen. The mature molecule is synthesized in the liver and is a two-chain homodimer with a molecular weight of approximately 160,000. It is estimated that 5% of the total mass is attributable to carbohydrate. The two identical monomers have molecular weights of 80,000, and are joined together by disulfide bonds. Thus by SDS-PAGE analysis, factor XI appears as a single band both nonreduced (Mr = 160,000), and reduced (Mr = 80,000).

Proteolysis of Xl by factor Xlla in the presence of high molecular weight kininogen (HMWK), yields the enzyme factor Xla (1-3). Factor Xla is a serine protease which participates in the intrinsic pathway of coagulation by catalyzing the conversion of factor lX to factor lXa. Because factor Xl is a Homodimer, the enzyme, Factor Xla, is compsed of the conversion of two identical heavy chains (Mr = 50,000), and two indentical light chains (Mr = 30,000), all of which are held together by disulfide bonds. This latter property makes factor Xla unique among the serine proteases, since it contains two active sites per molecule (1-3).

Factor Xll (Xll) (Hageman Factor) is a single chain (Mr = 78,000) glycoprotein zymogen that circulates in plasma at a concentration of 40 µg/ml (1-5). Reciprical activation of Xll to the active serine protease factor Xlla (Xlla) by kallikrein is central to initation of the intrinsic coagulation pathway. Surface bound α-Xlla in turn activates factor Xl to Xla. Secondary cleavage of α-Xlla by kallikrein yields β-Xlla, which catalyzes solution phase activation of kallikrein, factor Vll and the classical complement cascade. 

Factor Xlll is the zymogenic form of the glutaminyl-peptide γ-glutamyl transferase factor Xllla (fibrinoligase, plasma transglutaminase, fibrin stabalizing factor , E.C. 2.3.2.13) . Factor Xlll is unique among transamidases in that it is a zymogen in vivo. Factor Xlll is found both extracellularly in plasma and intracelulary in platelets, megakaryocytes, monocytes, placenta, uterus, liver and prostrate tissues. Plasma factor Xlll is syntesized in the liver circulates as a tetramer (Mr = 320,000), composed of 2 pairs of nonidentical subunits (A₂B₂).

Factor Xllla (FXllla) (fibrinoligase, plasma transglutaminase, fibrin stabilizing factor, E.C. 2.3.2.13) is a glutaminyl-peptide γ-glutamyl transferase functioning in the final stages of the coagulation cascade, stabilzing the fibrin clot by crosslinking the α and γ chains of fibrin to form homopolymers. Several unique features of FXllla set it apart form proteins with which it is generally associated, Factor Xllla is the only non-proteolytic enzyme of the coagulation cascade. Unlike other transamidases, it exists totally in zymogenic form and is the only sulfhydrylase  enzyme which functions extracellularly.