- Factor XII
Coagulation factor XII also known as Hageman factor is a plasma protein. It is the zymogen form of factor XIIa, an enzyme (EC 188.8.131.52) of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the F12 gene.
Factor XII is part of the coagulation cascade and activates factor XI and prekallikrein. Factor XII itself is activated to factor XIIa by negatively charged surfaces, such as glass.
In vivo, factor XII is activated by contact to polyanions. Activated platelets secrete inorganic polymers, polyphosphates. Contact to polyphosphates activates factor XII and initiates fibrin formation by the intrinsic pathway of coagulation with critical importance for thrombus formation.Targeting polyphosphates with phosphatases interfered with procoagulant activity of activated platelets and blocked platelet-induced thrombosis in mice. Addition of polyphosphates restored defective plasma clotting of Hermansky-Pudlak syndrome patients, indicating that the inorganic polymer is the endogenous factor XII activator in vivo. Platelet polyphosphate-driven factor XII activation provides the link from primary hemostasis (formation of a platelet plug) with secondary hemostasis (fibrin meshwork formation).
The gene for factor XII is located on the tip of the long arm of the fifth chromosome (5q33-qter).
Role in disease
Factor XII deficiency does not contribute to bleeding, as in vivo it plays little part in clot formation (the intrinsic pathway instead being activated mostly at factor XI by thrombin generated by the extrinsic pathway) but can predispose towards greater risk of venous thrombosis due to factor XII's role as one of the catalysts for conversion of plasminogen to its active fibrinolytic form of plasmin.
Hageman factor is also activated by Endotoxin, especially Lipid A.
Hageman factor was first discovered in 1955 when a routine preoperative blood sample of the 37-year-old railroad brakeman John Hageman (1918) was found to have prolonged clotting time in test tubes, even though he had no hemorrhagic symptoms. Hageman was then examined by Dr. Oscar Ratnoff who found that Mr. Hageman lacked a previously unidentified clotting factor. Dr. Ratnoff later found that the Hageman factor deficiency is an autosomal recessive disorder, when examining several related people who had the deficiency. Paradoxically, pulmonary embolism contributed to Hageman's death after an occupational accident. Since then, case series clinical studies identified an association between thrombosis and Factor XII deficiency. Hepatocytes express blood coagulation factor XII.
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- The MEROPS online database for peptidases and their inhibitors: S01.211
- MeSH Factor+XII
Proteins: coagulation Coagulation factorsHMWK/Bradykinin · Prekallikrein/Kallikrein · XII "Hageman"
XI · IX · VIIIX · V · II "(Pro)thrombin" · I "Fibrin" · Fibrinogen (FGA, FGG)
Coagulation inhibitors Thrombolysis/fibrinolysis Digestive enzymes Coagulationfactors: Thrombin · Factor VIIa · Factor IXa · Factor Xa · Factor XIa · Factor XIIa · Kallikrein (PSA, KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, KLK15)
fibrinolysis: Plasmin · Plasminogen activator (Tissue plasminogen activator · Urinary plasminogen activator)
Complement system Other immune system Venombin OtherAcrosin · Prolyl endopeptidase · Pronase · Proprotein convertases (1, 2) · Reelin · Subtilisin/Furin · Streptokinase · S1P · Cathepsin (A, G)Categories:
- Human proteins
- Coagulation system
- EC 3.4.21
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