Tissue factor

Transmembrane protein which acts as a receptor and cofactor for factor VII.

Tissue factor, also called factor III, or CD142.

Tissue factor is a protein encoded by the F3 gene, present in subendothelial tissue and leukocytes.

F3 gene encodes coagulation factor III, which is a cell surface glycoprotein, enabling  cells to initiate the blood coagulation cascade.

Coagulation factor III, functions as the high-affinity receptor for the coagulation factor VII. 

This protein is the only one in the coagulation pathway for which a congenital deficiency has not been described.

It is responsible for initiation of the coagulation protease cascades by specific limited proteolysis. 

This factor is fully functional when expressed on cell surfaces. 

Most important function is the initiation of clotting.

Factor VII bound to TF changes to zymogen factor VII which is rapidly converted to factor VIIa.

Tissue factor has three distinct domains of this factor: extracellular, transmembrane, and cytoplasmic. 

This protein is the only one in the coagulation pathway without a reported congenital deficiency.

TF is the cell surface receptor for the serine protease factor VIIa.

The complex of TF with factor VIIa catalyzes the conversion of the inactive protease factor X into the active protease factor Xa.

Together with factor VIIa, tissue factor forms the extrinsic pathway of coagulation. 

It initiates thrombin formation from the zymogen prothrombin. 

Tissue factor belongs to the cytokine receptor protein superfamily.

It has 3 domains: extracellular domain, a transmembrane domain and a GLA domain.

Some cells release TF in response to blood vessel damage and some do only in response to inflammatory mediators such as endothelial cells/macrophages.

TF is expressed by cells which are normally not exposed to flowing blood: sub-endothelial cells, such as, smooth muscle cells and fibroblasts cells surrounding blood vessels.

Factor VII and TF form an equimolar complex in the presence of calcium ions, leading to the activation of factor VII on a membrane surface.

Endothelial cells do not express TF except when they are exposed to inflammatory molecules such as tumor necrosis factor-alpha (TNF-alpha). 

Monocytes express TF on the cell surface in inflammatory conditions.

Thromboplastin could activate the extrinsic coagulation pathway. 

Exposure can change when blood vessels are damaged by, for example, physical injury or rupture of atherosclerotic plaques, allows the complex formation of TF with factor VII. 

Thromboplastin defines the cascade that leads to the activation of factor X—the tissue factor pathway. 

Partial thromboplastin is used to measure the intrinsic pathway: 

aPTT, or activated partial thromboplastin time. 

Thromboplastin contains phospholipids as well as tissue factor, both of which are needed in the activation of the extrinsic pathway, whereas partial thromboplastin does not contain tissue factor. 

Tissue factor is not needed to activate the intrinsic pathway.

Tissue factor has been shown to interact with Factor VII.

Factor VIIa/TF complex catalyzes activation of factor X and IX.

Expressed it maximum procoagulant activity when incorporated into phospholipid membranes.

Its excessive function triggers thrombosis.

Molecular weight approximately 47-kDa.

Expression around blood vessels initiates clotting after blood vessel injury.

It is present in blood and is referred to as blood-borne TF.

Found on microparticles the small membrane fragments derived from activated or apoptotic cells.

Staining for TF positive on surface of activated platelets.

Present in platelet alpha granules.

Key mediator in hypercoagulability in patients with cancer, inflammatory diseases and other chronic illnesses.

The molecule consists of a 219 amino-acid extracellular domain, a 21 amino-acid transmembrane domain, and a 23 amino-acid cytoplasmic domain.

The extracellular domain is required for pro coagulant function, and consists of 2 fibronectin type-III like domains that resemble several growth factors and cytokine receptors.

Its abnormal expression in tumors and related vascular endothelial cells may contribute to excessive clot formation in patients with cancer.

The cytoplasmic domain contains three serine residues that can be phosphorylated and have been implicated in cell signaling.

It is essential for normal hemostasis and embryonic development.

Expressed in a variety of tumor cell types and may play a role in the pathogenesis of cancer.

The  intrinsic pathway, which involves both activated factor IX and factor VIII. 

Both pathways lead to the activation of factor X, the common pathway, which combines with activated factor V in the presence of calcium and phospholipid to produce thrombin.

The signaling function of TF/VIIa plays a role in angiogenesis and apoptosis. 

Pro-inflammatory and pro-angiogenic responses are activated by TF/VIIa mediated-cleavage.



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