Tissue factor

Source: Wikipedia, the free encyclopedia.
F3
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_001993
NM_001178096

NM_010171

RefSeq (protein)

NP_001171567
NP_001984

NP_034301

Location (UCSC)Chr 1: 94.53 – 94.54 MbChr 3: 121.52 – 121.53 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Tissue factor, also called platelet tissue factor, factor III, or

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

The F3 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 three 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.[5] 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.[6][7]

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

factor Xa
.

Together with factor VIIa, tissue factor forms the 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

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. Pro-inflammatory and pro-angiogenic responses are activated by TF/VIIa-mediated cleavage by the protease-activated receptor 2 (PAR2).[8] EphB2 and EphA2 of the Eph tyrosine kinase receptor (RTK) family can also be cleaved by TF/VIIa.[9]

Structure

Tissue factor belongs to the cytokine receptor protein superfamily and consists of three domains:[10]

  1. an extracellular domain, which consists of two
    factor VIIa
    binding.
  2. a
    transmembrane
    domain.
  3. a cytosolic domain of 21 amino acids length inside the cell which is involved in the signaling function of TF.

Note that one of factor VIIa's domains,

phospholipids
, and this binding greatly enhances factor VIIa binding to tissue factor.

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.

atherosclerotic plaques
. Exposure of TF-expressing cells during injury allows the complex formation of TF with factor VII. 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.

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, which 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 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.

Interactions

Tissue factor has been shown to

Factor VII.[11][12]

Additional images

  • Tissue factor
    Tissue factor
  • Blood plasma after the addition of tissue factor
    Blood plasma after the addition of tissue factor

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000117525 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028128 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: F3 coagulation factor III (thromboplastin, tissue factor)".
  6. PMID 11779431
    .
  7. .
  8. .
  9. .
  10. .
  11. .
  12. .

Further reading

External links