Tissue factor

Coagulation factor III (thromboplastin, tissue factor)
PDB rendering based on 1ahw.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1AHW, 1BOY, 1DAN, 1FAK, 1J9C, 1JPS, 1NL8, 1O5D, 1TFH, 1UJ3, 1W0Y, 1W2K, 1WQV, 1WSS, 1WTG, 1WUN, 1WV7, 1Z6J, 2A2Q, 2AEI, 2AER, 2B7D, 2B8O, 2C4F, 2CEF, 2CEH, 2CEZ, 2CFJ, 2EC9, 2F9B, 2FIR, 2FLB, 2FLR, 2HFT, 2PUQ, 2ZP0, 2ZWL, 2ZZU, 3ELA, 3TH2, 3TH3, 3TH4, 4IBL, 4M7L
Identifiers
Symbols	F3 ; CD142; TF; TFA
External IDs	OMIM: 134390 MGI: 88381 HomoloGene: 1511 ChEMBL: 4081 GeneCards: F3 Gene
Gene ontology Molecular function • protease binding • cytokine receptor activity • protein binding • phospholipid binding Cellular component • extracellular space • cytoplasm • plasma membrane • cell surface • integral component of membrane • extracellular matrix • intrinsic component of external side of plasma membrane • extracellular exosome Biological process • positive regulation of endothelial cell proliferation • activation of plasma proteins involved in acute inflammatory response • activation of blood coagulation via clotting cascade • activation of cysteine-type endopeptidase activity involved in apoptotic process • aging • blood coagulation • blood coagulation, extrinsic pathway • response to temperature stimulus • response to mechanical stimulus • positive regulation of platelet-derived growth factor receptor signaling pathway • positive regulation of smooth muscle cell migration • cytokine-mediated signaling pathway • positive regulation of cell migration • response to estradiol • response to lipopolysaccharide • response to fluid shear stress • positive regulation of angiogenesis • positive regulation of positive chemotaxis • positive regulation of protein kinase B signaling • response to low-density lipoprotein particle • cellular response to hydrogen peroxide Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2152	14066
Ensembl	ENSG00000117525	ENSMUSG00000028128
UniProt	P13726	P20352
RefSeq (mRNA)	NM_001178096	NM_010171
RefSeq (protein)	NP_001171567	NP_034301
Location (UCSC)	Chr 1: 94.53 – 94.54 Mb	Chr 3: 121.72 – 121.74 Mb
PubMed search	[1]	[2]

Tissue factor, also called platelet tissue factor, factor III, thromboplastin, or CD142 is a protein present in subendothelial tissue and leukocytes necessary for the initiation of thrombin formation from the zymogen prothrombin. Thromboplastin defines the cascade that leads to the activation of factor X - the tissue factor pathway. In doing so it has replaced the previously named extrinsic pathway in order to eliminate ambiguity.

Function

This gene encodes coagulation factor III which is a cell surface glycoprotein. This 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, this 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. This protein is the only one in the coagulation pathway for which a congenital deficiency has not been described. 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.

Coagulation

The coagulation cascade.

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

The best known function of tissue factor is its role in blood coagulation. The complex of TF with factor VIIa activates factor IX and catalyzes the conversion of the inactive protease factor X into the active protease factor Xa.

Together with factor VIIa, tissue factor forms the tissue factor or extrinsic pathway of coagulation. This is opposed to the intrinsic (amplification) 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 (thromboplastin activity).

Cytokine signaling

TF is related to a protein family known as the cytokine receptor class II family. The members of this receptor family are activated by cytokines. Cytokines are small proteins that can influence the behavior of white blood cells. Binding of VIIa to TF has also been found to start signaling processes inside the cell. The signaling function of TF/VIIa plays a role in angiogenesis and apoptosis.

Structure

The protein structure of TF consists of three domains:

1. a domain which is located outside the cell, this domain binds factor VIIa. The binding of VIIa to TF occurs via protein-protein interactions by both molecules.
   1. Factor VIIa is a protein which consists of several domains. One of these domains, the carboxylated GLA domain, binds in the presence of calcium to negatively charged phospholipids. Binding of VIIa to negatively charged phospholipids greatly enhances the protein-protein binding of VIIa to TF.
2. a domain which crosses the hydrophobic membrane.
3. a domain of 21 amino acids length inside the cell which is involved in the signaling function of TF.

Tissue distribution

Some cells release TF in response to blood vessel damage (see next paragraph) and some do only in response to inflammatory mediators (endothelial cells/macrophages).

TF is expressed by cells which are normally not exposed to flowing blood such as sub-endothelial cells (e.g. smooth muscle cells) and cells surrounding blood vessels (e.g. fibroblasts). This can change when the blood vessel is damaged by for example physical injury or rupture of atherosclerotic plaques. Exposure of TF expressing cells during injury allows the complex formation of TF with factor VII. Factor VII and TF form an equal molar complex in the presence of calcium ions and this leads to the activation of factor VII on a membrane surface.

The inner surface of the blood vessel consists of endothelial cells. Endothelial cells do not express TF except when they are exposed to inflammatory molecules such as tumor necrosis factor-alpha (TNF-alpha). Another cell type that expresses TF on the cell surface in inflammatory conditions is the monocyte (a white blood cell).

Thromboplastin

Historically, thromboplastin was a lab reagent, usually derived from placental sources, used to assay prothrombin times (PT time). Thromboplastin, by itself, could activate the extrinsic coagulation pathway. When manipulated in the laboratory, a derivative could be created called partial thromboplastin. Partial thromboplastin was used to measure the intrinsic pathway. This test is called the aPTT, or activated partial thromboplastin time. It was not until much later that the subcomponents of thromboplastin and partial thromboplastin were identified. Thromboplastin is the combination of both phospholipids and tissue factor, both needed in the activation of the extrinsic pathway, and partial thromboplastin is just phospholipids without tissue factor. Tissue factor is not needed to activate the intrinsic pathway.

Interactions

Tissue factor has been shown to interact with Factor VII.

Additional images

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  Tissue factor

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  Blood plasma after the addition of tissue factor

See also

• hemostasis

External links

• Online 'Mendelian Inheritance in Man' (OMIM) 134390
• PDB Molecule of the Month Tissue factor - March 2006