Factor VII

Coagulation factor VII (serum prothrombin conversion accelerator)
250px Anchoring of coagulation factor VIIa (PDB 1dan) to the membrane through its Gla domain
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BF9, 1CVW, 1DAN, 1DVA, 1F7E, 1F7M, 1FAK, 1FF7, 1FFM, 1J9C, 1JBU, 1KLI, 1KLJ, 1NL8, 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, 4YT7
Identifiers
Symbols	F7 ; SPCA
External IDs	OMIM: 613878 MGI: 109325 HomoloGene: 7710 ChEMBL: 3991 GeneCards: F7 Gene
EC number	3.4.21.21
Gene ontology Molecular function • glycoprotein binding • serine-type endopeptidase activity • receptor binding • calcium ion binding • protein binding • serine-type peptidase activity Cellular component • extracellular region • extracellular space • endoplasmic reticulum lumen • Golgi lumen • plasma membrane • vesicle Biological process • positive regulation of leukocyte chemotaxis • proteolysis • blood coagulation • blood coagulation, extrinsic pathway • circadian rhythm • positive regulation of platelet-derived growth factor receptor signaling pathway • peptidyl-glutamic acid carboxylation • positive regulation of blood coagulation • positive regulation of cell migration • organ regeneration • response to vitamin K • response to estrogen • post-translational protein modification • cellular protein metabolic process • positive regulation of positive chemotaxis • positive regulation of protein kinase B signaling • response to growth hormone Sources: Amigo / QuickGO
RNA expression pattern
File:PBB GE F7 207300 s at tn.png
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2155	14068
Ensembl	ENSG00000057593	ENSMUSG00000031443
UniProt	P08709	P70375
RefSeq (mRNA)	NM_000131	NM_010172
RefSeq (protein)	NP_000122	NP_034302
Location (UCSC)	Chr 13: 113.11 – 113.12 Mb	Chr 8: 13.03 – 13.04 Mb
PubMed search	[1]	[2]

Factor VII (EC 3.4.21.21, blood-coagulation factor VIIa, activated blood coagulation factor VII, formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade. It is an enzyme of the serine protease class. A recombinant form of human factor VIIa (eptacog alfa [activated], NovoSeven) 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 also available, but does not play any considerable role in the market.

Physiology

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 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 is vitamin K dependent; it is produced in the liver. Use of warfarin or similar anticoagulants decreases hepatic synthesis of FVII.

Genetics

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).

Medical uses

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 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.

Interactions

Factor VII has been shown to interact with tissue factor.

External links

• Official website
• The MEROPS online database for peptidases and their inhibitors: S01.215