Protein : F3

Name F3
Description coagulation factor III (thromboplastin, tissue factor)
Owner Public
URN urn:agi-llid:2152
Connectivity 55
Notes 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. 15d-PGJ2 down-regulates LPS- and TNFalpha-induced TF activity through inhibition of TF gene transcription. Arg(74) mutant of TF was defective in enhancing both the amidolytic and proteolytic activity of fVIIa, suggesting that this residue may be required for the allosteric activation of the protease. CRP regulation of monocyte TF could contribute to the higher than expected atherosclerotic vascular disease seen in patients with inflammatory rheumatic disease. Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque. Data suggest that Rac-dependent activation of the NFkappaB pathway may be a critical element promoting thrombin-induced tissue factor expression and activity, and thus a prothrombotic state in pulmonary hypertension. Despite indistinguishable stability under physiological conditions of mutant tissue factor(R200W) and wild-type TF, important clues are revealed regarding misfolding and aggregation propensities of the mutant TF(R200W) to explain why it is lost in vivo. EGFR, PYK2, Yes, and SHP-2 are involved in transduction of the TF/FVIIa signal possibly via transactivation of the EGF receptor. Endothelin-1 enhances TF expression in monocytes from health individuals. No additional stimulation was seen in monocytes from heart failure subjects, who nonetheless have 2.5 times as much TF as controls. Enhanced monocyte tissue factor expression is implicated in the hemostatic diathesis characterizing hepatosplenic schistosomiasis. FVIIa induces PRIM1 and ensuing cellular proliferation via a TF- and of the PARs entirely PAR-2-dependent pathway, in distinction to that of thrombin which is PAR-1-dependent and TF-independent. FVIIa/TF-interaction produces STAT5 phosphorylation, STAT5 nuclear translocation and transactivation of a reporter gene. Fluvastatin upregulated IkappaB alpha in unstimulated as well as in TNFalpha-stimulated HUVEC cells and also impaired the TNFalpha-induced Cdc42 prenylation, indicating that fluvastatin interferes with transcriptional activation of tissue factor gene. In children with sepsis-induced multiple organ failure, a cytokine-associated increase in circulating TF and systemic activity was predicted. Increased TF was associated with the development of coagulopathy and tended to be associated with mortality. In response to endotoxin, there was an increase in IL-6, TF and CD11b expression and a procoagulant shift of clotting onset time, which was normalized by 4 mmol L-1 nicotinamide. M type 1 and 3 strains of group A streptococci are potent inducers of TF synthesis; findings suggest that a novel interaction between group A streptococci and host cells contributes to the observed coagulopathy in Strep toxic shock syndrome. Mice expressing low levels of human TF in an mTF(-/-) background had significantly shorter lifespans than wild-type mice, in part, because of spontaneous fatal hemorrhages. Low-TF mice had a selective heart defect with hemosiderin deposition & fibrosis. Pancreatic duct cells exert a potent factor VII-dependent procoagulant activity related to their expression of tissue factor. Progesterone-dependent up-regulation of tissue fasctor provides a survival advantage to burgeoning breast cancer cells. REVIEW: model of the intravascular TF pathway in which adhesive interactions of the TF bearing platelets and microvesicles to neutrophils and monocytes enable blood coagulation. REVIEW: role of tissue factor-FVIIa complex in pathophysiological processes and effect of the inhibitors of the tissue factor:factor VII pathway. REVIEW:clotting-dependent and -independent mechanisms of TF-induced angiogenesis in cancer. Resveratrol does not inhibit the activation or translocation of NF-kappaB/Rel proteins but inhibits NF-kappaB/Rel-dependent transcription of the gene for TF by impairing the transactivation potential of p65. Review. This review focuses on the roles of TF in hemostasis, thrombosis, and vascular development. Substitutions on the TF surface that contacts the protease domain of factor VIIa have nearly identical effects on the affinities for both factors VII and VIIa--hence zymogen VII can readily adopt a VIIa-like conformation required for binding to TF. TF and TFPI mRNA expression, protein levels and activity in trophoblast cells were determined and compared to human umbilical vein endothelial cells. TF cytoplasmic domain-independent stimulation of protein synthesis via activation of S6 kinase contributes to FVIIa effects in pathophysiology. TF expression in leukocytes plays an important role in various diseases but the expression level does not always correlate with plasma levels of TF antigen. TF is enhanced by Shiga toxin and has a role in the coagulopathy observed in hemolytic uremic syndrome. TF may influence tumor growth and metastasis by modulating VEGF expression and neoangiogenesis. TF promotes metastasis by a pathway that does not involve high expression of known PARs by tumor cells. PAR1 enhances the metastatic potential of cells with high TF expression. TF-FVIIa interaction elicits intracellular signalling events implicated in sepsis, inflammation, angiogenesis, metastasis and atherosclerosis. These include the sequential activation of Src-like kinases, MAP kinases, small GTPases and calcium signalling. TF-apoprotein selectively binds Hb, most probably via the carbohydrate moieties (alpha-d-glucosyl; alpha-d-mannosyl and N-acetyl-beta-d-glucosaminyl residues) of TF, and enhances its procoagulant activity. The TF and TFPI levels depend significantly on the renal function; elevated TF and TFPI levels may be related to thrombosis and atherosclerosis in chronic renal failure patients on peritoneal dialysis. The TF-603A/G gene promoter polymorphism significantly influences constitutive TF gene expression in human monocytes but has no major effect on TF gene expression or on whole blood coagulation time in LPS stimulated conditions. The complex between tissue factor and factor VIIa initiates coagulation and intracellular signaling, alters gene expression, and promotes metastasis. The ectopic expression of the acute promyelocytic leukemia-specific PML/RARalpha oncoprotein in U-937 cells results in induction of TF mRNA and promoter activity. The influence of several eicosanoids of the lipoxygenase pathway on regulation of LPS-induced tissue factor was examined in whole blood. These data support a transcriptional role for both nuclear factor-kappaB and p38 mitogen-activated protein kinase, but not MEK1, in tissue factor gene expression in human dermal microvascular endothelial cells. Thrombin functions studied during tissue factor-induced blood coagulation. Tissue factor activity is upregulated in human endothelial cells exposed to oscillatory shear stress. Tissue factor expression by colorectal cancer cells appears to act as both a regulatory target and an important mediator of oncogene-driven tumor growth and neovascularization. Tissue factor expression induced by local inflammation is involved in the pathogenesis of thrombosis in patients with nonvalvular atrial fibrillation. Tissue factor initiates blood coagulation via circulating microvesicles and platelets. Tissue factor is the receptor for plasminogen type 1 on 1-LN human prostate cancer cells; Plasminogen type 2, containing only one O-linked oligosaccharide chain, did not bind to tissue factor on 1-LN human prostate cancer cells. Tissue factor(TF) expression may contribute to the aggressiveness of pancreatic ductal adenocarcinoma by stimulating tumor invasiveness, and that evaluation of the primary tumor for TF expression may identify patients with a poor prognosis. A three-dimensional model of the ternary complex between FVIIa:TF:FIX was built using a full-space search algorithm in combination with computational graphics. Cell surface location-dependent phosphorylation of the TF cytoplasmic domain is regulated at multiple levels. Circulating microparticles from platelets, erythrocytes, and granulocytes exposed TF; microparticle-exposed TF antigen levels were higher in cardiac patients compared with healthy individuals. Correlation between tissue factor (TF) expression and hepatic metastasis and prognosis in rectal cancer. Data indicate that endothelial cell surface expression of TF and extrinsic clotting factors are critical in augmenting capillary leak following intravascular tumor necrosis factor administration. Demonstrate the occurrence of two forms of non-cell-bound TF. One form, which is microparticle-associated, supports thrombin generation via FVII. The other form, which is fluid-phase, does not stimulate thrombin formation. Differentiation of human monocytes into macrophages in culture enhances their tissue factor expression. Dissociation of fVIIai from TF occurred by a two-step mechanism. Effect of platelet-derived CD40L on the tissue factor activity of human CD40-positive melanoma cells and monocytes. Expression of TF and TFPI in human melanoma. Expression on monocyte subpopulations during normal pregnancy. Human B lymphocytes can express a functional Tissue Factor in response to phorbol myristate acetate. Hyperchemotaxis towards PDGFRB is likely to depend in part on phosphorylation of the cytoplasmic domain of TF. Levels of tissue factor in placenta and myometrium, over tissue factor in blood plasma may be clinically significant in obstetrics, for instance, in the etiology of DIC in placental abruption. Membrane cholesterol functions as a positive regulator of TF function by maintaining TF receptors, probably in noncaveolar lipid rafts, in a high-affinity state for VIIa binding. Model characterizes likely enzyme-binding exosites on FVIIa and Xa that may be involved in the ternary complex (sTF-VIIa-Xa) formation and the membrane binding region of the ternary complex. Monocyte adhesion and transmigration induce tissue factor expression. Non-activated and activated platelets contain an inactive form of TF that may develop functional activity following its release. PH dependence of fVIIa amidolytic activity in complex with soluble tissue factor. Polymorphisms in the 5'-UTR of the tissue factor gene are associated with altered expression in human endothelial cells. Results suggest involvement of tissue factor in the process of metastasis and progression of colorectal cancer may depend on increased angiogenesis. Review of role of tissue factor in thrombosis. Review: role of TF in hypercoagulability and clotting-dependent induction of tumor angiogenesis. Review: role of TF up-regulation in cancer pathogenesis and tumor angiogenesis. Selective activation of NF-kappaB (p50/p65) during intensive physical exercise does not result in the expression. Signaling increased transcription as well as mRNA stabilization leading to up-regulation of interleukin-8 synthesis. Some protease inhibitors might act as stress and induced TF expression with direct phosphorylation of JNK and p38, followed by phosphorylation and activation of AP-1 in monocytic cells. Superantigens from S. aureus activate the extrinsic coagulation pathway by inducing expression of TF in monocytes, and that the expression is mainly triggered by superantigen-induced IL-1 beta release. The Gla and first epidermal growth factor-like domains of factor X play a role in the prothrombinase and tissue factor-factor VIIa complexes. The concentration of physiologically active TF in non-cytokine-stimulated blood from healthy individuals cannot exceed and is probably lower than 20 fM. The transfer of TF to monocytes is not simply an CD62P-mediated adhesion of platelets or platelet-derived microvesicles to monocytes, but may involve other not yet identified mechanisms. Tissue factor expression by LPS-stimulated human monocytes is inhibited by adenosine and involves the adenosine A3 receptor, specifically. Tissue factor has a role in affecting proliferative ability in meningioma. Tissue factor/tissue factor pathway inhibitor imbalance is associated with myocardial infarction at young age in Japanese men.

Microarray ID 1369182_at
u07619_at
A_43_P11683
1417408_at
97689_at
m26071-2_s_at
A_51_P236846
A_52_P683413
A_65_P08971
A_65_P16447
J02931
36543_at
204363_at
M27436_s_at
209057_x_at
69036_f_at
73626_f_at
A_23_P126782
A_14_P107208
OH0965A
OR1535
MB188
RA0704

GenBank ID P42533
U07619
AAA16966
AAH81846
BC081846
NC_005101
NM_013057
J02931
M16553
M27436
NC_000001
NM_001993
NP_001984
NT_032977
NT_086583
P13726
X07680
A19048
AAA36734
AAA61150
AAA61151
AAA61152
AAH11029
AAN01236
AAO61150
AAO61151
AAO61152
AAO61153
AAV38611
AF487337
AF497569
AF497570
AF497571
AF540377
BC011029
BT019808
CAA01438
CAA30527
CAG46591
CR541792
J02846
AAA40414
AAA63400
AAH16397
AAH24886
AAS15646
AI642673
AK137642
AK144872
AY500273
BC016397
BC024886
CAJ18574
CT010367
M26071
M57896
M80785
NC_000069
NM_010171
NP_034301
NT_039240
P20352
NP_037189
NW_047627

Chromosome position 2q41
3 50.0 cM
1p22-p21

GO ID 0004896
0005886
0006955
0007596
0016021
0005615
0016020

Alias CD142
CD142 antigen
Coagulation factor F3
Coagulation factor III
coagulation factor III (thromboplastin, tissue factor)
TF_HUMAN
tissue factor precursor
coagulation factor 3
Thromboplastin
Cf III
coagulating factor III (thromboplastin, tissue factor)
mgc93621
cf3
Cf-3
CF 3
CF(3)

Organism Mus musculus
Rattus norvegicus
Homo sapiens

MedLine Reference 10896200
3037536
11511099
12466851

LocusLink ID 99486
2152
14066
25584

FunctionalClass hematopoietin/interferon-class (D200-domain) cytokine receptor

KEGG pathway Complement and coagulation cascades

GO Cellular Component extracellular space
membrane
integral to membrane
plasma membrane

Cell Localization Extracellular

Pathway LXR

GO Biological Process blood coagulation
immune response

Group Ligands

Source Curated