Coagulation factor XII, also known as Hageman factor, is a plasma protein involved in coagulation. It is the zymogen form of factor XIIa (EC 3.4.21.38), an enzyme of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by F12 gene. Factor XII (FXII, Hageman factor) is a plasma glycoprotein of approximately 90 kDa and is part of the coagulation cascade. It activates factor XI and prekallikrein in vitro. FXII is activated to FXIIa by negatively charged surfaces such as glass, initiating the intrinsic pathway. FXII also plays a role in diagnostic coagulation assays called activated partial thromboplastin times (aPTT). In vivo, FXII is activated by binding to polyanions in a process termed contact activation. Various polymers, such as kaolin and glass, act as non-physiological activators of FXII. Activated platelets release inorganic polyphosphates, which activate FXII, initiating the intrinsic pathway and contributing to fibrin formation and thrombus development. Polyphosphates also accelerate thrombin-induced activation of factor XI. Polyphosphate forms calcium-rich nanoparticles in vivo, which accumulate on platelets and activate FXII. The regulation of platelet polyphosphates is still not fully understood, but the phosphate-exporter XPR1 has been identified as a key regulator. Targeting XPR1 increases polyphosphate levels, accelerating thrombosis in mouse models. Given FXII’s role in thrombosis while sparing hemostasis, it has become a target for anticoagulant drug development. Inhibitors targeting FXII are in clinical trials.
Background References
1. Shamanaev A et al. Factor XII Structure-Function Relationships. Semin Thromb Hemost. 2024 Oct
2. Sparkenbaugh EM et al. Factor XII contributes to thrombotic complications and vaso-occlusion in sickle cell disease. Blood. 2023 Apr
Western blot analysis of Factor XII on different lysates with Rabbit anti-Factor XII antibody (HA500586) at 1/5,000 dilution.
Lane 1: Mouse plasma lysate Lane 2: Mouse serum lysate
Lysates/proteins at 15 µg/Lane.
Predicted band size: 66 kDa Observed band size: 80 kDa
Exposure time: 10 seconds; ECL: K1801;
4-20% SDS-PAGE gel.
Proteins were transferred to a PVDF membrane and blocked with 5% NFDM/TBST for 1 hour at room temperature. The primary antibody (HA500586) at 1/5,000 dilution was used in primary antibody dilution (K1803) at 4℃ overnight. Goat Anti-Rabbit IgG - HRP Secondary Antibody (HA1001) at 1/50,000 dilution was used for 1 hour at room temperature.
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