WordNet

be a contributing factor; "make things factor into a companys profitability"
any of the numbers (or symbols) that form a product when multiplied together
an independent variable in statistics
anything that contributes causally to a result; "a number of factors determined the outcome"
consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
a concept whose truth can be proved; "scientific hypotheses are not facts"
a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
the 24th letter of the Roman alphabet (同)x, ex

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(…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
Christ / Christian

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/03/20 21:14:37」(JST)

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Factor X, also known by the eponym Stuart–Prower factor, is an enzyme (EC 3.4.21.6) of the coagulation cascade. It is a serine endopeptidase (protease group S1, PA clan).

Physiology

Factor X is synthesized in the liver and requires vitamin K for its synthesis.

Factor X is activated, by hydrolysis, into factor Xa by both factor IX (with its cofactor, factor VIII in a complex known as intrinsic Xase) and factor VII with its cofactor, tissue factor (a complex known as extrinsic Xase). It is therefore the first member of the final common pathway or thrombin pathway.

It acts by cleaving prothrombin in two places (an arg-thr and then an arg-ile bond), which yields the active thrombin. This process is optimized when factor Xa is complexed with activated co-factor V in the prothrombinase complex.

Factor Xa is inactivated by protein Z-dependent protease inhibitor (ZPI), a serine protease inhibitor (serpin). The affinity of this protein for factor Xa is increased 1000-fold by the presence of protein Z, while it does not require protein Z for inactivation of factor XI. Defects in protein Z lead to increased factor Xa activity and a propensity for thrombosis.

The half life of factor X is 40–45 hours.

Structure of factor Xa

The first crystal structure of human factor Xa was deposited in May 1993. To date, 191 crystal structures of factor Xa with various inhibitors have been deposited in the protein data bank. The active site of factor Xa is divided into four sub pockets as S1, S2, S3 and S4. The S1 subpocket determines the major component of selectivity and binding. The S2 sub-pocket is small, shallow and not well defined. It merges with the S4 subpocket. The S3 sub-pocket is located on the rim of the S1 pocket and is quite exposed to solvent. The S4 sub-pocket has three ligand binding domains: the "hydrophobic box", the "cationic hole" and the water site. Factor Xa inhibitors generally bind in an L-shaped conformation, where one group of the ligand occupies the anionic S1 pocket lined by residues Asp189, Ser195, and Tyr228, and another group of the ligand occupies the aromatic S4 pocket lined by residues Tyr99, Phe174, and Trp215. Typically, a fairly rigid linker group bridges these two interaction sites.^[1]

Genetics

The human factor X gene is located on the thirteenth chromosome (13q34).

Role in disease

Inborn deficiency of factor X is very rare (1:500,000), and may present with epistaxis (nosebleeds), hemarthrosis (bleeding into joints) and gastrointestinal blood loss. Apart from congenital deficiency, low factor X levels may occur occasionally in a number of disease states. For example, factor X deficiency may be seen in amyloidosis, where factor X is adsorbed to the amyloid fibrils in the vasculature.

Deficiency of vitamin K or antagonism by warfarin (or similar medication) leads to the production of an inactive factor X. In warfarin therapy, this is desirable to prevent thrombosis. As of late 2007, four out of five emerging anti-coagulation therapeutics targeted this enzyme.^[2]

Inhibiting Factor Xa would offer an alternate method for anticoagulation. Direct Xa inhibitors are popular anticoagulants.

Laboratory findings in various platelet and coagulation disorders (V - T)
Condition	Prothrombin time	Partial thromboplastin time	Bleeding time	Platelet count
Vitamin K deficiency or warfarin	Prolonged	Normal or mildly prolonged	Unaffected	Unaffected
Disseminated intravascular coagulation	Prolonged	Prolonged	Prolonged	Decreased
Von Willebrand disease	Unaffected	Prolonged or unaffected	Prolonged	Unaffected
Haemophilia	Unaffected	Prolonged	Unaffected	Unaffected
Aspirin	Unaffected	Unaffected	Prolonged	Unaffected
Thrombocytopenia	Unaffected	Unaffected	Prolonged	Decreased
Liver failure, early	Prolonged	Unaffected	Unaffected	Unaffected
Liver failure, end-stage	Prolonged	Prolonged	Prolonged	Decreased
Uremia	Unaffected	Unaffected	Prolonged	Unaffected
Congenital afibrinogenemia	Prolonged	Prolonged	Prolonged	Unaffected
Factor V deficiency	Prolonged	Prolonged	Unaffected	Unaffected
Factor X deficiency as seen in amyloid purpura	Prolonged	Prolonged	Unaffected	Unaffected
Glanzmann's thrombasthenia	Unaffected	Unaffected	Prolonged	Unaffected
Bernard-Soulier syndrome	Unaffected	Unaffected	Prolonged	Decreased or unaffected
Factor XII deficiency	Unaffected	Prolonged	Unaffected	Unaffected
C1INH deficiency	Unaffected	Shortened	Unaffected	Unaffected

Therapeutic use

Factor X is part of fresh frozen plasma and the prothrombinase complex. There are two commercially available Factor X concentrates: "Factor X P Behring" manufactured by CSL Behring,^[3] and high purity Factor X "Coagadex" produced by Bio Products Laboratory and approved for use in the United States by the FDA in October 2015 and in the EU on 16th March 2016 after earlier acceptance by CHMP and COMP.^[4]^{[self-published source]}^[5]

Use in biochemistry

The factor Xa protease can be used in biochemistry to cleave off protein tags that improve expression or purification of a protein of interest. Its preferred cleavage site (after the arginine in the sequence Ile-Glu/Asp-Gly-Arg, IEGR or IDGR) can easily be engineered between a tag sequence and the protein of interest. After expression and purification, the tag is then proteolytically removed by factor Xa.

Factor Xa

Blood coagulation pathways in vivo showing the central role played by thrombin

Factor Xa is the activated form of the coagulation factor thrombokinase, known eponymously as Stuart-Prower factor. Factor X is an enzyme, a serine endopeptidase, which plays a key role at several stages of the coagulation system. Factor X is synthesized in the liver. The most commonly used anticoagulants in clinical practice, warfarin and the heparin series of anticoagulants and fondaparinux, act to inhibit the action of Factor Xa in various degrees.

Traditional models of coagulation developed in the 1960s envisaged two separate cascades, the extrinsic (tissue factor (TF)) pathway and the intrinsic pathway. These pathways converge to a common point, the formation of the Factor Xa/Va complex which together with calcium and bound on a phospholipids surface generate thrombin (Factor IIa) from prothrombin (Factor II).

A new model, the cell-based model of anticoagulation appears to explain more fully the steps in coagulation. This model has three stages: 1) initiation of coagulation on TF-bearing cells, 2) amplification of the procoagulant signal by thrombin generated on the TF-bearing cell and 3) propagation of thrombin generation on the platelet surface. Factor Xa plays a key role in all three of these stages.^[6]

In stage 1, Factor VII binds to the transmembrane protein TF on the surface of cells and is converted to Factor VIIa. The result is a Factor VIIa/TF complex which catalyzes the activation of Factor X and Factor IX. Factor Xa formed on the surface of the TF-bearing cell interacts with Factor Va to form the prothrombinase complex which generates small amounts of thrombin on the surface of TF-bearing cells.

In stage 2, the amplification stage, if enough thrombin has been generated, then activation of platelets and platelet associated cofactors occurs.

In stage 3, thrombin generation, Factor XIa activates free Factor IX on the surface of activated platelets. The activated Factor IXa with Factor VIIIa forms the "tenase" complex. This "tenase" complex activates more Factor X, which in turn forms new prothrombinase complexes with Factor Va. Factor Xa is the prime component of the prothrombinase complex which converts large amounts of prothrombin—the "thrombin burst". Each molecule of Factor Xa can generate 1000 molecules of thrombin. This large burst of thrombin is responsible for fibrin polymerization to form a thrombus.

Inhibition of the synthesis or activity of Factor X is the mechanism of action for many anticoagulants in use today. Warfarin, a synthetic derivative of coumarin, is the most widely used oral anticoagulant in the US. In some European countries, other coumarin derivatives (phenprocoumon and acenocoumarol) are used. These agents, so-called vitamin K antagonists (VKA), inhibit the vitamin K-dependent carboxylation of Factors II (prothrombin), VII, IX, X in the hepatocyte. This carboxylation after the translation is essential for the physiological activity.^[7]

Heparin (unfractionated heparin) and its derivatives low molecular weight heparin (LMWH) bind to a plasma cofactor, antithrombin (AT) to inactivate several coagulation factors IIa, Xa, XIa and XIIa. The affinity of unfractionated heparin and the various LMWHs for Factor Xa varies considerably. The efficacy of heparin-based anticoagulants increases as selectivity for Factor Xa increases. LMWH shows increased inactivation of Factor Xa compared to unfractionated heparin, and fondaparinux, an agent based on the critical pentasacharide sequence of heparin, shows more selectivity than LMWH. This inactivation of Factor Xa by heparins is termed "indirect" since it relies on the presence of AT and not a direct interaction with Factor Xa.

Recently a new series of specific, direct acting inhibitors of Factor Xa has been developed. These include the drugs rivaroxaban, apixaban, betrixaban, LY517717, darexaban (YM150), edoxaban and 813893. These agents have several theoretical advantages over current therapy. They may be given orally. They have rapid onset of action. And they may be more effective against Factor Xa in that they inhibit both free Factor Xa and Factor Xa in the prothrombinase complex.^[8]

History

American and British scientists described deficiency of factor X independently in 1953 and 1956, respectively. As with some other coagulation factors, the factor was initially named after these patients, a Mr Rufus Stuart (1921) and a Miss Audrey Prower (1934).

Interactions

Factor X has been shown to interact with Tissue factor pathway inhibitor.^[9]

References

^ Presentation on Direct Factor Xa Inhibitors
^ Ron Winslow; Avery Johnson (2007-12-10). "Race Is on for the Next Blood Thinner". Wall Street Journal. p. A12. Retrieved 2008-01-06. The flurry of interest reflects increasing understanding of what doctors call the coagulation cascade... Four new blood thinners target an enzyme called factor Xa, one of several enzymes that play an important role in the cascade.
^ Mark Brooker (2008): "Registry of Clotting Factor Concentrates". Eighth Edition, 2008, World Federation of Hemophilia
^ "BPL Announces: Strong progress on the world's first licensed Factor X product" (Press release). Bio Products Laboratory. August 10, 2015. Retrieved October 21, 2015.
^ "FDA approves first Factor X concentrate to treat patients with rare hereditary bleeding disorder" (Press release). US FDA. October 20, 2015. Retrieved October 21, 2015. Until today’s orphan drug approval, no specific coagulation factor replacement therapy was available for patients with hereditary Factor X deficiency.
^ Hoffman M; Monroe MM (2007). "Coagulation 2006: A Modern View of Hemostasis". Hematology and Oncology Clinics of North America 21 (1): 1–11. doi:10.1016/j.hoc.2006.11.004. PMID 17258114.
^ Golan, D. E. (2012). Principles of Pharmacology The Pathophysiologic Basis of Drug Therapy. Philadelphia: Lippincott Williams & Wilkins. p. 387. ISBN 978-1-4511-1805-6.
^ Turpie AG (2007). "Oral, Direct Factor Xa Inhibitors in Development for the Prevention and Treatment of Thromboembolic Diseases". Arterioscler Thromb Vasc Biol 27 (6): 1238–47. doi:10.1161/ATVBAHA.107.139402. PMID 17379841.
^ Broze, G J; Warren L A; Novotny W F; Higuchi D A; Girard J J; Miletich J P (Feb 1988). "The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action". Blood (UNITED STATES) 71 (2): 335–43. ISSN 0006-4971. PMID 3422166.

External links

The MEROPS online database for peptidases and their inhibitors: S01.216
med/3495 at eMedicine
Factor X deficiency

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. Anticoagulation with direct thrombin inhibitors and direct factor Xa inhibitors
2. 凝固検査の臨床使用 clinical use of coagulation tests
3. Management of bleeding in patients receiving target-specific oral anticoagulants
4. ヘパリンおよび低分子ヘパリンの治療使用 therapeutic use of heparin and low molecular weight heparin
5. 稀な（劣性遺伝性）凝固異常 rare recessively inherited coagulation disorders

English Journal

Rivaroxaban in the Treatment of Heparin-Induced Thrombocytopenia.

Sartori M1, Favaretto E, Cini M, Legnani C, Cosmi B.
Journal of thrombosis and thrombolysis.J Thromb Thrombolysis.2015 Oct;40(3):392-4. doi: 10.1007/s11239-015-1208-4.
Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition and it is associated with increased in vivo thrombin generation that needs to be treated with non-heparin anticoagulants such as direct thrombin inhibitors (DTIs). DTIs require parenteral administration and are associated with a non
PMID 25804370

Increased Plasma Levels of Xanthurenic and Kynurenic Acids in Type 2 Diabetes.

Oxenkrug GF1.
Molecular neurobiology.Mol Neurobiol.2015 Oct;52(2):805-10. doi: 10.1007/s12035-015-9232-0. Epub 2015 Jun 9.
About 350 million people worldwide have type 2 diabetes (T2D). The major risk factor of T2D is impaired glucose tolerance (pre-diabetes) with 10 % of pre-diabetes subjects develop T2D every year. Understanding of mechanisms of development of T2D from pre-diabetes is important for prevention and tre
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Japanese Journal

Effects of the Factor Ⅹa Inhibitor, Fondaparinux, on the Stability of Atherosclerotic Lesions in Apolipoprotein E-Deficient Mice

Circulation journal : official journal of the Japanese Circulation Society 79(11), 2499-2508, 2015-11
NAID 40020625315

For Vol.69, No.4, pp205-212 Venous Thromboembolism after Total Hip Arthroplasty Diagnosed by Enhanced Computed Tomography : Comparison of Selective Thromboprophylaxis and No Thromboprophylaxis

Acta Medica Okayama 69(5), 325-325, 2015-10
NAID 120005666072

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★リンクテーブル★

リンク元	「活性化第X因子」「activated factor X」
拡張検索	「coagulation factor Xa」
関連記事	「fact」「factor」「X」

「活性化第X因子」

Coagulation factor X
	PDB rendering based on 1c5m.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1C5M, 1EZQ, 1F0R, 1F0S, 1FAX, 1FJS, 1FXY, 1G2L, 1G2M, 1HCG, 1IOE, 1IQE, 1IQF, 1IQG, 1IQH, 1IQI, 1IQJ, 1IQK, 1IQL, 1IQM, 1IQN, 1KSN, 1LPG, 1LPK, 1LPZ, 1LQD, 1MQ5, 1MQ6, 1MSX, 1NFU, 1NFW, 1NFX, 1NFY, 1NL8, 1P0S, 1V3X, 1WU1, 1XKA, 1XKB, 1Z6E, 2BMG, 2BOH, 2BOK, 2BQ6, 2BQ7, 2BQW, 2CJI, 2D1J, 2EI6, 2EI7, 2EI8, 2FZZ, 2G00, 2GD4, 2H9E, 2J2U, 2J34, 2J38, 2J4I, 2J94, 2J95, 2JKH, 2P16, 2P3F, 2P3T, 2P3U, 2P93, 2P94, 2P95, 2PHB, 2PR3, 2Q1J, 2RA0, 2UWL, 2UWO, 2UWP, 2VH0, 2VH6, 2VVC, 2VVU, 2VVV, 2VWL, 2VWM, 2VWN, 2VWO, 2W26, 2W3I, 2W3K, 2WYG, 2WYJ, 2XBV, 2XBW, 2XBX, 2XBY, 2XC0, 2XC4, 2XC5, 2Y5F, 2Y5G, 2Y5H, 2Y7X, 2Y7Z, 2Y80, 2Y81, 2Y82, 3CEN, 3CS7, 3ENS, 3FFG, 3HPT, 3IIT, 3K9X, 3KL6, 3KQB, 3KQC, 3KQD, 3KQE, 3LIW, 3M36, 3M37, 3Q3K, 3SW2, 3TK5, 3TK6, 4A7I, 4BTI, 4BTT, 4BTU
Identifiers
Symbols	F10 ; FX; FXA
External IDs	OMIM: 613872 MGI: 103107 HomoloGene: 30976 ChEMBL: 244 GeneCards: F10 Gene
EC number	3.4.21.6
Gene ontology
Molecular function	• serine-type endopeptidase activity; • calcium ion binding; • protein binding; • phospholipid binding;
Cellular component	• extracellular region; • endoplasmic reticulum lumen; • Golgi lumen; • plasma membrane; • intrinsic component of external side of plasma membrane;
Biological process	• proteolysis; • blood coagulation; • blood coagulation, intrinsic pathway; • blood coagulation, extrinsic pathway; • peptidyl-glutamic acid carboxylation; • positive regulation of cell migration; • post-translational protein modification; • cellular protein metabolic process; • positive regulation of protein kinase B signaling;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;