F8
Domain
Domain F5/8 type C 2 is responsible for phospholipid-binding and essential for factor VIII activity.
Function
Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa.
Involvement in disease
Hemophilia A
HEMA
A disorder of blood coagulation characterized by a permanent tendency to hemorrhage. About 50% of patients have severe hemophilia resulting in frequent spontaneous bleeding into joints, muscles and internal organs. Less severe forms are characterized by bleeding after trauma or surgery.
None
The disease is caused by variants affecting the gene represented in this entry. Of particular interest for the understanding of the function of F8 is the category of CRM (cross-reacting material) positive patients (approximately 5%) that have considerable amount of F8 in their plasma (at least 30% of normal), but the protein is non-functional; i.e. the F8 activity is much less than the plasma protein level. CRM-reduced is another category of patients in which the F8C antigen and activity are reduced to approximately the same level. Most mutations are CRM negative, and probably affect the folding and stability of the protein.
Thrombophilia 13, X-linked, due to factor VIII defect
THPH13
An X-linked dominant, hemostatic disorder associated with markedly elevated F8 levels, and characterized by severe thrombophilia.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Sulfation on Tyr-1699 is essential for binding vWF.
Proteolytically cleaved by cathepsin CTSG to produce a partially activated form.
Sequence Similarities
Belongs to the multicopper oxidase family.
Cellular localization
- Secreted
- Extracellular space
Alternative names
F8C, F8, Coagulation factor VIII, Antihemophilic factor, Procoagulant component, AHF