Welcome to the MedLibrary.org Wikipedia Supplement on Tissue factor -- Please Click to Return to Front Page

Coagulation factor III (thromboplastin, tissue factor)
PDB rendering based on 1ahw.
Available structures: 1ahw, 1boy, 1dan, 1fak, 1j9c, 1jps, 1o5d, 1tfh, 1uj3, 1w0y, 1w2k, 1wqv, 1wss, 1wtg, 1wun, 1wv7, 1z6j, 2a2q, 2aei, 2aer, 2b7d, 2b8o, 2c4f, 2f9b, 2fir, 2flb, 2flr, 2hft, 2puq
Identifiers
Symbols	F3; CD142; TF; TFA
External IDs	OMIM: 134390 MGI: 88381 HomoloGene: 1511
Gene ontology Molecular function: • transmembrane receptor activity Cellular component: • plasma membrane • integral to membrane Biological process: • immune response • blood coagulation
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	2152	14066
Ensembl	ENSG00000117525	ENSMUSG00000028128
Uniprot	P13726	Q8R3Q1
Refseq	NM_001993 (mRNA) NP_001984 (protein)	NM_010171 (mRNA) NP_034301 (protein)
Location	Chr 1: 94.77 - 94.78 Mb	Chr 3: 121.72 - 121.73 Mb
Pubmed search	[1]	[2]

Tissue factor, also called thromboplastin, factor III or CD142 is a protein present in subendothelial tissue, platelets, and leukocytes necessary for the initiation of thrombin formation from the zymogen prothrombin. Thrombin formation ultimately leads to the coagulation of blood. 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.¹ 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 6.²³

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.
  • 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.

Functions

Coagulation

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 catalyzes the conversion of the inactive protease factor X into the active protease factor Xa.

Together with factor VII, 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).

The coagulation cascade.

Cytokine

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.

Location

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).

Additional images

Tissue factor

Tissue factor activation

References

Further reading

• Online 'Mendelian Inheritance in Man' (OMIM) 134390
• PDB Molecule of the Month pdb75_1 - March 2006

See also

• hemostasis

Wikipedia content modification information:

• This page was last modified on 23 October 2008, at 22:30.

Wikipedia Authorship and Review

Wikipedia content provided here is not reviewed directly by MedLibrary.org. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with MedLibrary.org.

Wikipedia Usage Guidelines

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "Tissue factor".

The URL for this specific entry is:

• http://medlibrary.org/medwiki/Tissue_factor

All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.