Factor VII

Source: Wikipedia, the free encyclopedia.

F7
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000057593

ENSMUSG00000031443

UniProt

P08709

P70375

RefSeq (mRNA)

NM_000131
NM_001267554
NM_019616

NM_010172

RefSeq (protein)

NP_000122
NP_001254483
NP_062562

NP_034302

Location (UCSC)Chr 13: 113.11 – 113.12 MbChr 8: 13.08 – 13.09 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Coagulation factor VII (EC 3.4.21.21, formerly known as proconvertin) 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

hemophilia.[5] 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 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.

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.[6]

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 the liver. Use of warfarin or similar anticoagulants decreases hepatic synthesis of FVII.[citation needed]

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.[7]

Structure

See also: Factor_IX § Domain_architecture

Factor VII shares a common domain architecture with factors IX and X.

Genetics

The gene for factor VII is located on chromosome 13 (13q34).

Role in disease

Main article: Factor VII deficiency

AryoSeven). Gene therapy approaches for treating FVII deficiency are very promising ([8]
)

Medical uses

hemophilia (with Factor VIII or IX
deficiency) who have developed antibodies against replacement coagulation factor.

It has also been used in the setting of uncontrollable hemorrhage,[9][10] but its role in this setting is controversial with insufficient evidence to support its use outside of clinical trials.[11] The first report of its use in hemorrhage was in an Israeli soldier with uncontrollable bleeding in 1999.[12] Risks of its use include an increase in arterial thrombosis.[11] However, animal studies have not shown complications as seen in humans, in fact same of the studies show a better prognosis. In the military settings it is used as an off label intervention in complications related to disseminated intravascular coagulation related haemorrhage caused by penetrating trauma.[13]

Recombinant human factor VII while initially looking promising in intracerebral hemorrhage failed to show benefit following further study and this is no longer recommended.[14][15]

Interactions

Factor VII has been shown to

interact with tissue factor and endothelial protein C receptor.[16][17]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000057593 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031443 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. S2CID 58538425
    .
  6. S2CID 205121835
    .
  7. PMID 23615029
    .
  8. PMID 26702064
    .
  9. PMID 15328151
    .
  10. ^ "Uncontrolled Bleeding and Injury Lawsuit Claims". Archived from the original on 2016-06-16. Retrieved 2015-08-26.
  11. ^
    PMID 22419303
    .
  12. S2CID 23159895
    .
  13. S2CID 10776054
    .
  14. PMID 15728810
    .
  15. PMID 18480205
    .
  16. PMID 12787023
    .
  17. PMID 9925787
    .

Further reading
Retrieved from "https://en.wikipedia.org/w/index.php?title=Factor_VII&oldid=1223217890"