| Type: | Family | Name: | Coagulation factor 8 |
| Description: | This subfamily of contains coagulation factor VIII, the cofactor of activated factor IX in the factor X-activating complex of the intrinsic coagulation pathway. The structure and function of factor VIII have been reviewed []. The domain architecture of the precursor molecules can be represented as A1-A2-B-A3-C1-C2. The A domains are diverged versions of the multicopper oxidase domain (). The B domain is highly variable and is removed during activation to yield noncovalently associated heavy and light chains. The C domains () promote membrane binding.Defects of the human gene, located on the X chromosome, give rise to hemophilia A. Although factor VIII can be expressed in a variety of tissues, most probably hepatocytes are the major source. These large molecules undergo extensive post-translational modification, including both N- and O-linked glycosylation, disulphide bond formation, and sulphation of a particular tyrosine residue. They are cleaved to form a heavy and a light chain that associate in the presence of divalent metal ions. Although one copper ion is bound per molecule, calcium or manganese ions are more efficient in promoting reassociation.As soon as it reaches the blood stream, factor VIII becomes tightly bound to von Willebrand factor, which may prevent premature binding of factor VIII to the factor X-activating complex. Further proteolytic cleavages of factor VIII are required for it to serve as a cofactor that enhances the activity of factor IXa. After initiation of the coagulation cascade, factors IXa and VIIIa form the membrane-bound complex that activates factor X. Factor VIIIa is rapidly inactivated both by dissociation from the complex and by further proteolytic degradation. | Short Name: | Factor_8 |
