This F3 gene encodes coagulation factor III which is a cell surface glycoprotein. Tissue factor enables cells to initiate the blood coagulation cascades, and it functions as the high-affinity receptor for the coagulation factor VII. The resulting complex provides a catalytic event that is responsible for initiation of the coagulation protease cascades by specific limited proteolysis. Unlike the other cofactors of these protease cascades, which circulate as nonfunctional precursors, tissue factor is a potent initiator that is fully functional when expressed on cell surfaces. There are 3 distinct domains of this factor: extracellular, transmembrane, and cytoplasmic. Tissue factor is the only one in the coagulation pathway for which a congenital deficiency has not been described. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
OMIM-Description for Coagulation Factor III / Tissue Factor / CD142N
The extrinsic pathway of blood coagulation is initiated by contact of plasma factor VII (F7; 613878) with tissue factor (F3), a cellular membrane glycoprotein that normally is segregated from the bloodstream but can be exposed after tissue injury or newly synthesized in endothelial cells or leukocytes after stimulation by endotoxin and cytokines. Once formed, the tissue factor/factor VII complex converts to a complex of tissue factor and enzymatically active factor VII (F7a); this conversion leads to activation of factors X (F10; 613872) and IX (300746) and prothrombin (176930), and ultimately to formation of fibrin (134570/134580). These processes are regulated by plasma protease inhibitors and by the thrombomodulin (188040)-protein C (612283) pathway. A further regulatory mechanism in the extrinsic pathway is called tissue factor pathway inhibitor (TFPI; 152310). For a review, see Davie et al. (1991).
Coagulation Factor III / Tissue Factor / CD142
Tissue factor, also called platelet tissue factor, factor III, thrombokinase, or CD142 is a protein present in subendothelial tissue, platelets, and leukocytes necessary for the initiation of thrombin formation from the zymogen prothrombin. An incorrect synonym is thromboplastin. In addition to the membrane-bound tissue factor, soluble form of tissue factor was also found which results from alternatively spliced tissue factor mRNA transcripts, in which exon 5 is absent and exon 4 is spliced directly to exon 6.
Interacts with HSPE; the interaction, inhibited by heparin, promotes the generation of activated factor X and activates coagulation in the presence of activated factor VII.
Isoform 1: Membrane; Single-pass type I membrane protein. Isoform 2: Secreted.
Lung, placenta and pancreas.
TF expression is highly dependent upon cell type. TF can also be induced by the inflammatory mediators interleukin 1 and TNF-alpha, as well as by endotoxin, to appear on monocytes and vascular endothelial cells as a component of cellular immune response.
Tissue factor initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. Tissue factor plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade.
Tissue factor initiates blood coagulation by complexing with FVII or FVIIa
Tissue factor participates in hemostatic and inflammatory processes
Tissue factor plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade
Tissue factor is prime initiator of blood coagulation playing a critical role in thrombosis and hemostasis
Tissue factor has an important role in the initiation of coagulation and in the increase in thrombin activity at the site of inflammation (Isada 2010)