Misplaced Pages

#614385

24-531: 1CFH , 1CFI , 1EDM , 1IXA , 1MGX , 1NL0 , 1RFN , 2WPH , 2WPI , 2WPJ , 2WPK , 2WPL , 2WPM , 3KCG , 3LC3 , 3LC5 , 4YZU , 4Z0K , 4ZAE , 4WM0 , 4WMA , 4WMI , 4WMK , 4WN2 , 4WNH , 5EGM , 5JBC , 5JB9 , 5JBB , 5JB8 , 5JBA 2158 14071 ENSG00000101981 ENSMUSG00000031138 P00740 P16294 NM_000133 NM_001313913 NM_007979 NM_001305797 NP_000124 NP_001300842 NP_001292726 NP_032005 Factor IX ( EC 3.4.21.22 ), also known as Christmas factor ,

48-489: A zymogen , an inactive precursor. It is processed to remove the signal peptide , glycosylated and then cleaved by factor XIa (of the contact pathway) or factor VIIa (of the tissue factor pathway) to produce a two-chain form, where the chains are linked by a disulfide bridge . When activated into factor IXa , in the presence of Ca, membrane phospholipids, and a Factor VIII cofactor, it hydrolyses one arginine - isoleucine bond in factor X to form factor Xa. Factor IX

72-589: A complex with tissue factor to activate factor X to Xa, thereby bypassing FVIII and FIX. The activation of Factor X to Xa initiates the coagulation cascade’s common pathway, leading to clot formation at the site of hemorrhage. Activated FVII binds to endothelial protein C receptor (EPCR), which enhances hemostasis.14 One study showed that eptacog beta binds to EPCR with 25% to 30% more affinity than eptacog alfa, displacing protein C from EPCR binding sites and downregulating activated protein C generation, contributing to its hemostatic effect. The main role of factor VII (FVII)

96-635: A cysteine to a serine. Recombinant factor IX is used to treat Christmas disease. Formulations include: Some rare mutations of factor IX result in elevated clotting activity, and can result in clotting diseases, such as deep vein thrombosis . This gain of function mutation renders the protein hyperfunctional and is associated with familial early-onset thrombophilia. Factor IX deficiency is treated by injection of purified factor IX produced through cloning in various animal or animal cell vectors. Tranexamic acid may be of value in patients undergoing surgery who have inherited factor IX deficiency in order to reduce

120-623: A progressively finer classification of the enzyme. Preliminary EC numbers exist and have an 'n' as part of the fourth (serial) digit (e.g. EC 3.5.1.n3). For example, the tripeptide aminopeptidases have the code "EC 3.4.11.4", whose components indicate the following groups of enzymes: NB:The enzyme classification number is different from the 'FORMAT NUMBER' Oxidation /reduction reactions; transfer of H and O atoms or electrons from one substance to another Similarity between enzymatic reactions can be calculated by using bond changes, reaction centres or substructure metrics (formerly EC-BLAST], now

144-488: Is a protein involved in coagulation and, in humans, is encoded by gene F7 . It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa (or blood-coagulation factor VIIa , activated blood coagulation factor VII ), which in turn activates factor IX and factor X . Using genetic recombination a recombinant factor VIIa (eptacog alfa) (trade names include NovoSeven) has been approved by

168-454: Is inhibited by antithrombin . Factor IX expression increases with age in humans and mice. In mouse models, mutations within the promoter region of factor IX have an age-dependent phenotype. Factors VII , IX, and X all play key roles in blood coagulation and also share a common domain architecture. The factor IX protein is composed of four protein domains : the Gla domain , two tandem copies of

192-414: Is located on the X chromosome (Xq27.1-q27.2), loss-of-function mutations thereof are X-linked recessive : males experience the disease phenotype much more frequently than females. At least 534 disease-causing mutations in this gene have been discovered. The F9 gene was first cloned in 1982 by Kotoku Kurachi and Earl Davie . Polly , a transgenic cloned Poll Dorset sheep carrying the gene for factor IX,

216-471: Is one of the serine proteases involved in coagulation ; it belongs to peptidase family S1. Deficiency of this protein causes haemophilia B . It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to haemophilia . Coagulation factor IX is on the World Health Organization's List of Essential Medicines . Factor IX is produced as

240-498: Is rare and inherited recessively. It presents as a hemophilia-like bleeding disorder. It is treated with recombinant factor VIIa (NovoSeven or AryoSeven ). Gene therapy approaches for treating FVII deficiency are very promising ( ) Recombinant factor VIIa , marketed under the trade names AryoSeven and NovoSeven , is used for people with hemophilia (with Factor VIII or IX deficiency) who have developed antibodies against replacement coagulation factor. It has also been used in

264-414: Is to initiate the process of coagulation in conjunction with tissue factor (TF/factor III). Tissue factor is found on the outside of blood vessels - normally not exposed to the bloodstream. Upon vessel injury, tissue factor is exposed to the blood and circulating factor VII. Once bound to TF, FVII is activated to FVIIa by different proteases, among which are thrombin (factor IIa), factor Xa, IXa, XIIa, and

SECTION 10

#1732899149615

288-484: The EGF domain and a C-terminal trypsin -like peptidase domain which carries out the catalytic cleavage. The N-terminal EGF domain has been shown to at least in part be responsible for binding tissue factor . Wilkinson et al . conclude that residues 88 to 109 of the second EGF domain mediate binding to platelets and assembly of the factor X activating complex. The structures of all four domains have been solved. A structure of

312-562: The EMBL-EBI Enzyme Portal). Before the development of the EC number system, enzymes were named in an arbitrary fashion, and names like old yellow enzyme and malic enzyme that give little or no clue as to what reaction was catalyzed were in common use. Most of these names have fallen into disuse, though a few, especially proteolyic enzymes with very low specificity, such as pepsin and papain , are still used, as rational classification on

336-596: The FDA for the control of bleeding in hemophilia . It is sometimes used unlicensed in severe uncontrollable bleeding, although there have been safety concerns. A biosimilar form of recombinant activated factor VII (AryoSeven) is also available, but does not play any considerable role in the market. In April 2020, the US FDA approved a new rFVIIa product, eptacog beta (SEVENFACT), the first bypassing agent (BPA) approved in more than 2 decades. As an rFVIIa product, eptacog beta works in

360-459: The liver . Use of warfarin or similar anticoagulants decreases hepatic synthesis of FVII. A coagulation enzyme cascade may begin with a few molecules of factor XII and culminate in the activation of millions of times more fibrin molecules. Factor VII shares a common domain architecture with factors IX and X . The gene for factor VII is located on chromosome 13 (13q34). Factor VII deficiency (congenital proconvertin deficiency)

384-533: The Enzyme Commission was dissolved at that time, though its name lives on in the term EC Number . The current sixth edition, published by the International Union of Biochemistry and Molecular Biology in 1992 as the last version published as a printed book, contains 3196 different enzymes. Supplements 1-4 were published 1993–1999. Subsequent supplements have been published electronically, at the website of

408-473: The FVIIa-TF complex itself. The complex of factor VIIa with TF catalyzes the conversion of factor IX and factor X into the active proteases, factor IXa and factor Xa, respectively. The action of the factor is impeded by tissue factor pathway inhibitor (TFPI), which is released almost immediately after initiation of coagulation. Factor VII, which was discovered around 1950, is vitamin K -dependent and produced in

432-1249: The Nomenclature Committee of the International Union of Biochemistry and Molecular Biology. In August 2018, the IUBMB modified the system by adding the top-level EC 7 category containing translocases. Factor VII 4YT7 , 1BF9 , 1CVW , 1DAN , 1DVA , 1F7E , 1F7M , 1FAK , 1FF7 , 1FFM , 1J9C , 1JBU , 1KLI , 1KLJ , 1O5D , 1QFK , 1W0Y , 1W2K , 1W7X , 1W8B , 1WQV , 1WSS , 1WTG , 1WUN , 1WV7 , 1YGC , 1Z6J , 2A2Q , 2AEI , 2AER , 2B7D , 2B8O , 2BZ6 , 2C4F , 2EC9 , 2F9B , 2FIR , 2FLB , 2FLR , 2PUQ , 2ZP0 , 2ZWL , 2ZZU , 3ELA , 3TH2 , 3TH3 , 3TH4 , 4IBL , 4ISH , 4ISI , 4JYU , 4JYV , 4JZD , 4JZE , 4JZF , 4NA9 , 4NG9 , 4NGA , 4X8S , 4X8T , 4X8U , 4X8V , 4YT6 , 4ZXX , 4ZXY , 4Z6A , 4ZMA , 4YLQ , 5I46 2155 14068 ENSG00000057593 ENSMUSG00000031443 P08709 P70375 NM_000131 NM_001267554 NM_019616 NM_010172 NP_000122 NP_001254483 NP_062562 NP_034302 Coagulation factor VII ( EC 3.4.21.21 , formerly known as proconvertin )

456-584: The basis of specificity has been very difficult. By the 1950s the chaos was becoming intolerable, and after Hoffman-Ostenhof and Dixon and Webb had proposed somewhat similar schemes for classifying enzyme-catalyzed reactions, the International Congress of Biochemistry in Brussels set up the Commission on Enzymes under the chairmanship of Malcolm Dixon in 1955. The first version was published in 1961, and

480-470: The perioperative risk of bleeding. A list of all the mutations in Factor IX is compiled and maintained by EAHAD. Coagulation factor IX is on the World Health Organization's List of Essential Medicines . Enzyme Commission number EC numbers do not specify enzymes but enzyme-catalyzed reactions. If different enzymes (for instance from different organisms) catalyze the same reaction, then they receive

504-470: The same EC number. Furthermore, through convergent evolution , completely different protein folds can catalyze an identical reaction (these are sometimes called non-homologous isofunctional enzymes ) and therefore would be assigned the same EC number. By contrast, UniProt identifiers uniquely specify a protein by its amino acid sequence. Every enzyme code consists of the letters "EC" followed by four numbers separated by periods. Those numbers represent

SECTION 20

#1732899149615

528-423: The setting of uncontrollable hemorrhage, but its role in this setting is controversial with insufficient evidence to support its use outside of clinical trials. The first report of its use in hemorrhage was in an Israeli soldier with uncontrollable bleeding in 1999. Risks of its use include an increase in arterial thrombosis. However, animal studies have not shown complications as seen in humans, in fact same of

552-447: The two EGF domains and the trypsin-like domain was determined for the pig protein. The structure of the Gla domain, which is responsible for Ca(II)-dependent phospholipid binding, was also determined by NMR . Several structures of 'super active' mutants have been solved, which reveal the nature of factor IX activation by other proteins in the clotting cascade. Because the gene for factor IX

576-481: Was produced by Dr Ian Wilmut at the Roslin Institute in 1997. Deficiency of factor IX causes Christmas disease ( hemophilia B ). Over 3000 variants of factor IX have been described, affecting 73% of the 461 residues; some cause no symptoms, but many lead to a significant bleeding disorder. The original Christmas disease mutation was identified by sequencing of Christmas' DNA, revealing a mutation which changed

#614385