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F3
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 1AHW,1BOY,1DAN,1FAK,1J9C,1JPS,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,2HFT,2PUQ,2ZP0,2ZWL,2ZZU,3ELA,3TH2,3TH3,3TH4,4IBL,4M7L,4Z6A,4ZMA,4YLQ,2FLR
Identifiers
Aliases	F3, CD142, TF, TFA, coagulation factor III, tissue factor
External IDs	OMIM:134390;MGI:88381;HomoloGene:1511;GeneCards:F3;OMA:F3 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p21.3 Start 94,529,173bp[1] End 94,541,759bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3 G1|3 52.94 cM Start 121,517,186bp[2] End 121,528,697bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of paranasal sinus palpebral conjunctiva nasal epithelium olfactory zone of nasal mucosa amniotic fluid stromal cell of endometrium left uterine tube lower lobe of lung gallbladder left ovary Top expressed in Eustachian tube corneal stroma skin of external ear cervix tunica adventitia of aorta respiratory epithelium olfactory epithelium esophagus conjunctival fornix deep cerebellar nuclei More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding cytokine receptor activity phospholipid binding serine-type endopeptidase activity protease binding Cellular component membrane extracellular matrix intrinsic component of external side of plasma membrane plasma membrane extracellular region extracellular exosome cell surface extracellular space serine-type peptidase complex integral component of membrane collagen-containing extracellular matrix Biological process hemostasis positive regulation of protein kinase B signaling positive regulation of endothelial cell proliferation cytokine-mediated signaling pathway positive regulation of cell migration activation of blood coagulation via clotting cascade positive regulation of platelet-derived growth factor receptor signaling pathway positive regulation of angiogenesis blood coagulation, extrinsic pathway activation of plasma proteins involved in acute inflammatory response activation of cysteine-type endopeptidase activity involved in apoptotic process positive regulation of positive chemotaxis blood coagulation protein processing Sources:Amigo /QuickGO
Orthologs Species Human Mouse Entrez 2152 14066 Ensembl ENSG00000117525 ENSMUSG00000028128 UniProt P13726 P20352 RefSeq (mRNA) NM_001993 NM_001178096 NM_010171 RefSeq (protein) NP_001171567 NP_001984 NP_034301 Location (UCSC) Chr 1: 94.53 – 94.54 Mb Chr 3: 121.52 – 121.53 Mb PubMed search [3] [4]
Wikidata
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Tissue factor, also calledplatelet tissue factor or Coagulation factor III,^[5] is aprotein present insubendothelial tissue andleukocytes which plays a major role incoagulation and, in humans, is encoded byF3gene. Its role in the blood clotting is the initiation ofthrombin formation from thezymogenprothrombin.Thromboplastin defines the cascade that leads to the activation offactor X—the tissue factor pathway. In doing so, it has replaced the previously named extrinsic pathway in order to eliminate ambiguity.

TheF3 gene encodes tissue factor also known as coagulation factor III, which is a cell surfaceglycoprotein. This factor enables cells to initiate the blood coagulation cascades, and it functions as the high-affinity receptor for thecoagulation 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.^[6] In addition to the membrane-bound tissue factor, soluble form of tissue factor was also found which results fromalternatively spliced tissue factor mRNA transcripts, in whichexon 5 is absent and exon 4 is spliced directly to exon 6.^[7][8]

Tissue factor (TF) is the cell surface receptor for theserine protease factor VIIa.

The best known function of tissue factor is its role inblood coagulation. The complex of TF withfactor VIIa catalyzes the conversion of the inactive proteasefactor X into the active proteasefactor Xa.

Together with factor VIIa, tissue factor forms the extrinsic pathway of coagulation. This is opposed to the intrinsic (amplification) pathway, which involves both activatedfactor IX andfactor VIII. Both pathways lead to the activation offactor X (the common pathway), which combines with activatedfactor V in the presence of calcium andphospholipid to producethrombin (thromboplastin activity).

TF is related to a protein family known as thecytokine receptor class II family. The members of this receptor family are activated bycytokines. Cytokines are small proteins that can influence the behavior ofwhite 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 inangiogenesis andapoptosis. Pro-inflammatory and pro-angiogenic responses are activated by TF/VIIa-mediated cleavage by the protease-activated receptor 2 (PAR2).^[9] EphB2 and EphA2 of the Eph tyrosine kinase receptor (RTK) family can also be cleaved by TF/VIIa.^[10]

Tissue factor belongs to thecytokine receptorprotein superfamily and consists of threedomains:^[11]

1. an extracellular domain, which consists of twofibronectin type III modules whose hydrophobic cores merge in the domain-domain interface. This serves as a (probably rigid) template forfactor VIIa binding.
2. atransmembrane 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,GLA domain, binds in the presence of calcium to negatively chargedphospholipids, and this binding greatly enhances factor VIIa binding to tissue factor.

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 ofatherosclerotic 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 astumor necrosis factor-alpha (TNF-alpha). Another cell type that expresses TF on the cell surface in inflammatory conditions is themonocyte (a white blood cell).

Historically,thromboplastin was a lab reagent, usually derived from placental sources, used to assayprothrombin 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 theaPTT, 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.

Tissue factor has been shown tointeract withFactor VII.^[12][13]

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

• Hemostasis

• Online Mendelian Inheritance in Man (OMIM):134390
• PDB Molecule of the MonthTissue factor—March 2006
• PDBe-KB provides an overview of all the structure information available in the PDB for Human Tissue factor

• Genes on human chromosome 1
• Clusters of differentiation
• Coagulation system

• CS1 maint: DOI inactive as of October 2025
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