同: Thromboplastin, Tissue factor
関: also Tissue factor

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/19 01:36:46」(JST)

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Tissue factor, also called platelet tissue factor, factor III, thromboplastin, or CD142 is a protein present in subendothelial tissue and leukocytes necessary for the initiation of thrombin formation from the zymogen 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

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.^[2]^[3]

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 blood coagulation. The complex of TF with factor VIIa activates factor IX and catalyzes the conversion of the inactive protease factor X into the active protease factor Xa.

Together with factor VIIa, 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).

Cytokine signaling

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.

Structure

The protein structure of TF consists of three domains:

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.
1. 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.
a domain which crosses the hydrophobic membrane.
a domain of 21 amino acids length inside the cell which is involved in the signaling function of TF.

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. 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).

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. Partial thromboplastin 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 is the combination of both phospholipids and tissue factor, both needed in the activation of the extrinsic pathway, and partial thromboplastin is just phospholipids without tissue factor. Tissue factor is not needed to activate the intrinsic pathway.

Interactions

Tissue factor has been shown to interact with Factor VII.^[4]^[5]

Additional images

Tissue factor
Blood plasma after the addition of tissue factor

References

^ "Entrez Gene: F3 coagulation factor III (thromboplastin, tissue factor)".
^ Guo W, Wang H, Zhao W, Zhu J, Ju B, Wang X (2001). "Effect of all-trans retinoic acid and arsenic trioxide on tissue factor expression in acute promyelocytic leukemia cells". Chin. Med. J. 114 (1): 30–4. PMID 11779431.
^ Bogdanov VY, Balasubramanian V, Hathcock J, Vele O, Lieb M, Nemerson Y (April 2003). "Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein". Nat. Med. 9 (4): 458–62. doi:10.1038/nm841. PMID 12652293.
^ Carlsson K, Freskgård PO, Persson E, Carlsson U, Svensson M (Jun 2003). "Probing the interface between factor Xa and tissue factor in the quaternary complex tissue factor-factor VIIa-factor Xa-tissue factor pathway inhibitor". Eur. J. Biochem. 270 (12): 2576–82. doi:10.1046/j.1432-1033.2003.03625.x. PMID 12787023.
^ Zhang E, St Charles R, Tulinsky A (Feb 1999). "Structure of extracellular tissue factor complexed with factor VIIa inhibited with a BPTI mutant". J. Mol. Biol. 285 (5): 2089–104. doi:10.1006/jmbi.1998.2452. PMID 9925787.

External links

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

English Journal

Circulating microparticle signature in coronary and peripheral blood of ST elevation myocardial infarction patients in relation to pain-to-PCI elapsed time.

Suades R1, Padró T1, Crespo J1, Ramaiola I1, Martin-Yuste V2, Sabaté M2, Sans-Roselló J3, Sionis A3, Badimon L4.
International journal of cardiology.Int J Cardiol.2016 Jan 1;202:378-87. doi: 10.1016/j.ijcard.2015.09.011. Epub 2015 Sep 12.
BACKGROUND: Circulating microparticle (cMP) levels are increased in the acute phase of ST-elevation myocardial infarction (STEMI) and associate with microvascular obstruction; however, the precise cMP-parental cell signature and activation level are not elucidated. Here, we aimed to study the cMP si
PMID 26432487

High levels of TSP1+/CD142+ platelet-derived microparticles characterise young patients with high cardiovascular risk and subclinical atherosclerosis.

Suades R, Padró T, Alonso R, Mata P, Badimon L1.
Thrombosis and haemostasis.Thromb Haemost.2015 Nov 25;114(6):1310-21. doi: 10.1160/TH15-04-0325. Epub 2015 Jul 16.
Circulating microparticles (cMPs) play important roles in cellular crosstalk and are messengers of cell activation. We have previously reported that platelet-released microparticles (pMPs) stimulate thrombosis and that lipid-lowering treatment as per guidelines in patients with familial hypercholest
PMID 26178021

Atraumatic Pulsatile Leukocyte Circulation for Long-Term In Vitro Dynamic Culture and Adhesion Assays.

Mazza G1,2, Stoiber M3, Pfeiffer D1,4, Schima H2.
Artificial organs.Artif Organs.2015 Nov;39(11):973-8. doi: 10.1111/aor.12474. Epub 2015 Apr 20.
Low flow rate pumping of cell suspensions finds current applications in bioreactors for short-term dynamic cell culture and adhesion assays. The aim of this study was to develop an atraumatic pump and hemodynamically adapted test circuit to allow operating periods of at least several hours. A comput
PMID 25894522

Japanese Journal

サルのアレルギーモデルの特徴〔含臨床の立場から〕 (特集アレルギーの動物モデル)

中村伸,後藤穣,大久保公裕
アレルギ-・免疫 13(10), 1430-1439, 2006-10
NAID 40007471339

癌と Tissue Factor (CD142)

中村伸
日本血栓止血学会誌 = The Journal of Japanese Society on Thrombosis and Hemostasis 16(5), 481, 2005-10-01
NAID 10024481746

Related Pictures

Thuis Turku Doopjurk cd142 -ACCIAIO-uomo-donna-STAINLESS-STEEL-CD142 cd142-www.oliprik.dk-Oli-Prik-Turku-cd142 Turku Doopjurk cd142 van Oli Prik voor €

★リンクテーブル★

リンク元	「トロンボプラスチン」「tissue factor」
関連記事	「CD14」「CD1」

「トロンボプラスチン」

Coagulation factor III (thromboplastin, tissue factor)
	PDB rendering based on 1ahw.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1AHW, 1BOY, 1DAN, 1FAK, 1J9C, 1JPS, 1NL8, 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, 2FLR, 2HFT, 2PUQ, 2ZP0, 2ZWL, 2ZZU, 3ELA, 3TH2, 3TH3, 3TH4, 4IBL, 4M7L
Identifiers
Symbols	F3 ; CD142; TF; TFA
External IDs	OMIM: 134390 MGI: 88381 HomoloGene: 1511 ChEMBL: 4081 GeneCards: F3 Gene
Gene ontology
Molecular function	• protease binding; • cytokine receptor activity; • protein binding; • phospholipid binding;
Cellular component	• extracellular space; • cytoplasm; • plasma membrane; • cell surface; • integral component of membrane; • extracellular matrix; • intrinsic component of external side of plasma membrane; • extracellular exosome;
Biological process	• positive regulation of endothelial cell proliferation; • activation of plasma proteins involved in acute inflammatory response; • activation of blood coagulation via clotting cascade; • activation of cysteine-type endopeptidase activity involved in apoptotic process; • aging; • blood coagulation; • blood coagulation, extrinsic pathway; • response to temperature stimulus; • response to mechanical stimulus; • positive regulation of platelet-derived growth factor receptor signaling pathway; • positive regulation of smooth muscle cell migration; • cytokine-mediated signaling pathway; • positive regulation of cell migration; • response to estradiol; • response to lipopolysaccharide; • response to fluid shear stress; • positive regulation of angiogenesis; • positive regulation of positive chemotaxis; • positive regulation of protein kinase B signaling; • response to low-density lipoprotein particle; • cellular response to hydrogen peroxide;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: thromboplastin
同: 第III因子 factor III。CD142？
関: 血液凝固因子

単にトロンボプラスチンという場合は完全トロンボプラスチン(組織トロンボプラスチン)を指す。