Tissue factor

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Tissue factor

Existing structural data: see UniProt entry

Properties of human protein
Mass / length primary structure 263 aa; 29.6 kDa
Secondary to quaternary structure extracell. + cytoplasm. (219 + 44 aa)
Identifier
Gene names F3  ; CD142; TF; TFA
External IDs
Occurrence
Homology family F3
Parent taxon Euteleostomi
Orthologue
human mouse
Entrez 2152 14066
Ensemble ENSG00000117525 ENSMUSG00000028128
UniProt P13726 Q8R3Q1
Refseq (mRNA) NM_001993 NM_010171
Refseq (protein) NP_001984 NP_034301
Gene locus Chr 1: 94.77 - 94.78 Mb Chr 3: 121.72 - 121.73 Mb
PubMed search 2152 14066

Tissue factor (also factor III or tissue thromboplastin , English also tissue factor ) is a protein involved in blood clotting . It is therefore included in the group of coagulation factors . It is found in tissue ( subendothelium ), in blood platelets and in leukocytes (white blood cells).

genetics

The gene for the tissue factor is located on chromosome 1 gene locus p22-p21.

construction

Tissue factor is a protein that consists of three domains :

1. A domain that is outside the cell . This binds to the activated proconvertin (factor VIIa) through protein-protein interactions . Proconvertin also consists of different domains. One of these domains, the carboxylated γ-carboxyglutamate domain, binds to negatively charged phospholipids in the presence of calcium . This binding increases the protein-protein bond between proconvertin and thrombokinase (factor X).

2. A domain that penetrates the hydrophobic cell membrane .

3. A domain of 21 amino acids in length within the cell that takes on the signaling functions of the thromboplastin.

function

Ribbon / surface model of factor Xa (blue / red) with factor VIIa (dark green / gray) and tissue factor (light green) according to PDB 1NL8 .

The tissue factor is the receptor on the cell membrane for activated proconvertin (factor VIIa).

The most well-studied function of tissue factor is its role in blood clotting. The complex of tissue factor with proconvertin catalyzes the conversion of the inactive Stuart-Prower factor (factor X) into activated factor Xa. Together with proconvertin, the tissue factor forms the extrinsic pathway of blood clotting , in which blood vessel damage is to be prevented by blood clotting as quickly as possible (see also hemostasis ). This contrasts with the intrinsic pathway, in which the Stuart-Prower factor is activated by a cascade of factors already in the blood.

In addition, the tissue factor belongs to a group of proteins that are summarized under the generic term "cytokine receptor class II". The members of this group are activated by cytokines , small proteins that affect the behavior of white blood cells. Furthermore, it was found that the binding of activated proconvertin to the tissue factor triggers signaling processes within the cell. These signal processes play a role in the formation of new blood vessels ( angiogenesis ) and in the inhibition of programmed cell death ( apoptosis ).

Occurrence

Tissue factor is expressed by cells that are not normally associated with flowing blood, such as cells in the subendothelium ( layer of connective tissue ) and cells that surround blood vessels (e.g. fibroblasts ). This changes when the blood vessels are damaged (e.g. through injury). The cells with thrombokinase come into contact with proconvertin , which circulates in the blood. This a thousandfold the activity of the proconvertin.

The inner wall of blood vessels consists of endothelial cells , which only develop tissue factor when they are exposed to inflammatory molecules such as tumor necrosis factor alpha (TNF-alpha). Monocytes also develop the tissue factor after contact with inflammatory molecules.

The tissue factor is also found on circulating microparticles . These are membrane vesicles , which consist of membrane fragments that are released by various blood cells such as platelets or monocytes . They are loaded with tissue factor and other proteins such as adhesion receptors ( e.g. P-selectin ) and play an important role in blood clotting .

Individual evidence

  1. ^ Robert F. Schmidt, Florian Lang, Gerhard Thews (ed.): Physiology of humans with pathophysiology. 29th edition. Springer Medizin Verlag, Heidelberg 2005, ISBN 3-540-21882-3 , p. 528.
  2. ↑ Tissue factor as an evolutionary conserved cytokine receptor: Implications for inflammation and signal transduction. PMID 14872439 .
  3. ↑ M. Belting, MI Dorrell, S. Sandgren, E. Aguilar, J. Ahamed, A. Dorfleutner, P. Carmeliet, BM Mueller, M. Friedlander, W. Ruf: Regulation of angiogenesis by tissue factor cytoplasmic domain signaling. PMID 15098027
  4. ↑ BB Sorensen, LV Rao, D. Tornehave, S. Gammeltoft, LC Petersen: Antiapoptotic effect of coagulation factor VIIa . PMID 12738672
  5. ↑ N. Mackman: Role of tissue factor in hemostasis and thrombosis. In: Blood Cells Mol Dis. 36 (2), 2006 Mar-Apr, pp. 104-107. Review.
  6. ^ KE Eilertsen, B. Østerud: The role of blood cells and their microparticles in blood coagulation. In: Biochem Soc Trans . 33 (Pt 2), 2005 Apr, pp. 418-422. Review.

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