Gamma-Thrombin (F2) Human Protein

Coagulation factor II is proteolytically cleaved to form thrombin in the first step of the coagulation cascade which ultimately results in the stemming of blood loss. F2 also plays a role in maintaining vascular integrity during development and postnatal life. Mutations in F2 leads to various forms of thrombosis and dysprothrombinemia. [provided by RefSeq, Jul 2008]

prothrombin: Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing. Defects in F2 are the cause of factor II deficiency (FA2D). It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels. Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR); also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1). It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2). A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. Belongs to the peptidase S1 family.

Protein type: EC 3.4.21.5; Apoptosis; Secreted; Secreted, signal peptide; Protease

Chromosomal Location of Human Ortholog: 11p11

Cellular Component: extracellular space; Golgi lumen; endoplasmic reticulum lumen; plasma membrane; extracellular region

Molecular Function: protein binding; growth factor activity; serine-type endopeptidase activity; calcium ion binding; receptor binding

Biological Process: positive regulation of blood coagulation; multicellular organismal development; positive regulation of collagen biosynthetic process; proteolysis; regulation of cell shape; cell surface receptor linked signal transduction; negative regulation of fibrinolysis; positive regulation of cell proliferation; response to wounding; acute-phase response; negative regulation of proteolysis; platelet activation; cytosolic calcium ion homeostasis; post-translational protein modification; peptidyl-glutamic acid carboxylation; positive regulation of cell growth; positive regulation of phosphoinositide 3-kinase cascade; fibrinolysis; cellular protein metabolic process; regulation of gene expression; regulation of blood coagulation; negative regulation of astrocyte differentiation; positive regulation of protein amino acid phosphorylation; positive regulation of release of sequestered calcium ion into cytosol; blood coagulation; blood coagulation, intrinsic pathway; leukocyte migration

Disease: Thrombophilia Due To Thrombin Defect; Stroke, Ischemic; Prothrombin Deficiency, Congenital; Pregnancy Loss, Recurrent, Susceptibility To, 2