|Coagulation factor VII (serum prothrombin conversion accelerator)|
Anchoring of coagulation factor VIIa (PDB 1dan) to the membrane through its Gla domain
|PDB||Ortholog search: PDBe, RCSB|
|List of PDB id codes|
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, 4ISI
|External IDs||OMIM: 613878 MGI: 109325 HomoloGene: 7710 ChEMBL: 3991 GeneCards: F7 Gene|
|RNA expression pattern|
|More reference expression data|
|Location (UCSC)||Chr 13:|
113.76 – 113.77 Mb
13.03 – 13.04 Mb
Factor VII (formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade. It is an enzyme (EC 18.104.22.168) of the serine protease class. A recombinant form of human factor VIIa (NovoSeven, eptacog alfa [activated]) has U.S. Food and Drug Administration approval for uncontrolled bleeding in hemophilia patients. 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 manufacturing by AryoGen Biopharma and since 2012 is available in the market.
The main role of factor VII (FVII) 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 the FVIIa-TF complex itself. The most important substrates for FVIIa-TF are Factor X and Factor IX.
The action of the factor is impeded by tissue factor pathway inhibitor (TFPI), which is released almost immediately after initiation of coagulation. Factor VII is vitamin K dependent; it is produced in the liver. Use of warfarin or similar anticoagulants decreases hepatic synthesis of FVII.
The gene for factor VII is located on chromosome 13 (13q34).
Role in disease
Deficiency is rare (congenital proconvertin deficiency) and inherits recessively. Factor VII deficiency presents as a hemophilia-like bleeding disorder. It is treated with recombinant factor VIIa (NovoSeven or AryoSeven).
Recombinant factor VIIa is used for people with hemophilia (with Factor VIII or IX deficiency) who have developed inhibitors against replacement coagulation factor.
It has also been used in 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.
Recombinant human factor VII while initially looking promising in intracerebral hemorrhage failed to show benefit following further study and this is no longer recommended.
Factor VII has been shown to interact with Tissue factor.
- ^ Banner, D. W.; d'Arcy, A.; Chène, C.; Winkler, F. K.; Guha, A.; Konigsberg, W. H.; Nemerson, Y.; Kirchhofer, D. (1996). "The crystal structure of the complex of blood coagulation factor VIIa with soluble tissue factor". Nature 380 (6569): 41–46. doi:10.1038/380041a0. PMID 8598903.
- ^ Roberts H, Monroe D, White G (2004). "The use of recombinant factor VIIa in the treatment of bleeding disorders". Blood 104 (13): 3858–64. doi:10.1182/blood-2004-06-2223. PMID 15328151.
- ^ a b Simpson, E; Lin, Y; Stanworth, S; Birchall, J; Doree, C; Hyde, C (2012 Mar 14). "Recombinant factor VIIa for the prevention and treatment of bleeding in patients without haemophilia.". Cochrane database of systematic reviews (Online) 3: CD005011. PMID 22419303.
- ^ Kenet G, Walden R, Eldad A, Martinowitz U (1999). "Treatment of traumatic bleeding with recombinant factor VIIa". Lancet 354 (9193): 1879. doi:10.1016/S0140-6736(99)05155-7. PMID 10584732.
- ^ Mayer S, Brun N, Begtrup K, Broderick J, Davis S, Diringer M, Skolnick B, Steiner T (2005). "Recombinant activated factor VII for acute intracerebral hemorrhage". N. Engl. J. Med. 352 (8): 777–85. doi:10.1056/NEJMoa042991. PMID 15728810.
- ^ Mayer SA, Brun NC, Begtrup K, et al. (May 2008). "Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage". N. Engl. J. Med. 358 (20): 2127–37. doi:10.1056/NEJMoa0707534. PMID 18480205. http://www.nejm.org/doi/full/10.1056/NEJMoa0707534.
- ^ Carlsson, Karin; Freskgård Per-Ola, Persson Egon, Carlsson Uno, Svensson Magdalena (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. (Germany) 270 (12): 2576–82. doi:10.1046/j.1432-1033.2003.03625.x. ISSN 0014-2956. 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. (ENGLAND) 285 (5): 2089–104. doi:10.1006/jmbi.1998.2452. ISSN 0022-2836. PMID 9925787.
- Broze GJ Jr, Majerus PW (1980). "Purification and properties of human coagulation factor VII". J. Biol. Chem. 255 (4): 1242–7. PMID 7354023.
- Versteeg HH, Peppelenbosch MP, Spek CA (2002). "The pleiotropic effects of tissue factor: a possible role for factor VIIa-induced intracellular signalling?". Thromb. Haemost. 86 (6): 1353–9. PMID 11776298.
- Golino P (2003). "The inhibitors of the tissue factor:factor VII pathway". Thromb. Res. 106 (3): V257–65. doi:10.1016/S0049-3848(02)00079-8. PMID 12356487.
1bf9: N-TERMINAL EGF-LIKE DOMAIN FROM HUMAN FACTOR VII, NMR, 23 STRUCTURES
1cvw: CRYSTAL STRUCTURE OF ACTIVE SITE-INHIBITED HUMAN COAGULATION FACTOR VIIA (DES-GLA)
1dan: COMPLEX OF ACTIVE SITE INHIBITED HUMAN BLOOD COAGULATION FACTOR VIIA WITH HUMAN RECOMBINANT SOLUBLE TISSUE FACTOR
1dva: Crystal Structure of the Complex Between the Peptide Exosite Inhibitor E-76 and Coagulation Factor VIIA
1f7e: THE FIRST EGF-LIKE DOMAIN FROM HUMAN BLOOD COAGULATION FVII, NMR, 20 STRUCTURES
1f7m: THE FIRST EGF-LIKE DOMAIN FROM HUMAN BLOOD COAGULATION FVII, NMR, MINIMIZED AVERAGE STRUCTURE
1fak: HUMAN TISSUE FACTOR COMPLEXED WITH COAGULATION FACTOR VIIA INHIBITED WITH A BPTI-MUTANT
1ff7: THE FIRST EGF-LIKE DOMAIN FROM HUMAN BLOOD COAGULATION FVII (FUCOSYLATED AT SER-60), NMR, 20 STRUCTURES
1ffm: THE FIRST EGF-LIKE DOMAIN FROM HUMAN BLOOD COAGULATION FVII (FUCOSYLATED AT SER-60), NMR, MINIMIZED AVERAGE STRUCTURE
1j9c: Crystal Structure of tissue factor-factor VIIa complex
1jbu: Coagulation Factor VII Zymogen (EGF2/Protease) in Complex with Inhibitory Exosite Peptide A-183
1kli: Cofactor-and substrate-assisted activation of factor VIIa
1klj: Crystal structure of uninhibited factor VIIa
1o5d: Dissecting and Designing Inhibitor Selectivity Determinants at the S1 site Using an Artificial Ala190 Protease (Ala190 uPA)
1qfk: STRUCTURE OF HUMAN FACTOR VIIA AND ITS IMPLICATIONS FOR THE TRIGGERING OF BLOOD COAGULATION
1w0y: TF7A_3771 COMPLEX
1w2k: TF7A_4380 COMPLEX
1w7x: FACTOR7- 413 COMPLEX
1w8b: FACTOR7 - 413 COMPLEX
1wqv: Human Factor Viia-Tissue Factor Complexed with propylsulfonamide-D-Thr-Met-p-aminobenzamidine
1wss: Human Factor Viia-Tissue Factor in Complex with peprid mimetic inhibitor that has two charge groups in P2 and P4
1wtg: Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-biphenylalanine-Gln-p-aminobenzamidine
1wun: Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-Trp-Gln-p-aminobenzamidine
1wv7: Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-5-propoxy-Trp-Gln-p-aminobenzamidine
1ygc: Short Factor VIIa with a small molecule inhibitor
1z6j: Crystal Structure of a ternary complex of Factor VIIa/Tissue Factor/Pyrazinone Inhibitor
2a2q: Complex of Active-site Inhibited Human Coagulation Factor VIIa with Human Soluble Tissue Factor in the Presence of Ca2+, Mg2+, Na+, and Zn2+
2aei: Crystal structure of a ternary complex of factor VIIa/tissue factor and 2-[[6-[3-(aminoiminomethyl)phenoxy]-3,5-difluro-4-[(1-methyl-3-phenylpropyl)amino]-2-pyridinyl]oxy]-benzoic acid
2aer: Crystal Structure of Benzamidine-Factor VIIa/Soluble Tissue Factor complex.
2b7d: Factor VIIa Inhibitors: Chemical Optimization, Preclinical Pharmacokinetics, Pharmacodynamics, and Efficacy in a Baboon Thrombosis Model
2b8o: Crystal Structure of Glu-Gly-Arg-Chloromethyl Ketone-Factor VIIa/Soluble Tissue Factor Complex
2bz6: ORALLY AVAILABLE FACTOR7A INHIBITOR
2c4f: CRYSTAL STRUCTURE OF FACTOR VII.STF COMPLEXED WITH PD0297121
2f9b: Discovery of Novel Heterocyclic Factor VIIa Inhibitors
2fir: Crystal structure of DFPR-VIIa/sTF
2flb: Discovery of a Novel Hydroxy Pyrazole Based Factor IXa Inhibitor
2flr: Novel 5-Azaindole Factor VIIa Inhibitors
2puq: Crystal structure of active site inhibited coagulation factor VIIA in complex with soluble tissue factor