Coagulation Factor VIII (Fused Form) (F8) Antibody – Rabbit

This gene encodes coagulation factor VIII, which participates in the intrinsic pathway of blood coagulation; factor VIII is a cofactor for factor IXa which, in the presence of Ca+2 and phospholipids, converts factor X to the activated form Xa. This gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity. Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder. [provided by RefSeq]

Function: Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts factor X to the activated form, factor Xa.

Subunit structure: Interacts with vWF. vWF binding is essential for the stabilization of F8 in circulation. Ref.10 Ref.11

Subcellular location: Secreted › extracellular space.

Domain: Domain F5/8 type C 2 is responsible for phospholipid-binding and essential for factor VIII activity.

Post-translational modification: Sulfation on Tyr-1699 is essential for binding vWF.

Involvement in disease: Defects in F8 are the cause of hemophilia A (HEMA) [

MIM:306700]. 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. Note=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. Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41 Ref.42 Ref.43 Ref.44 Ref.45 Ref.46 Ref.47 Ref.48 Ref.49 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.55 Ref.56 Ref.57 Ref.58 Ref.59 Ref.60 Ref.61 Ref.62 Ref.63 Ref.64 Ref.65 Ref.66 Ref.67 Ref.68 Ref.69 Ref.70 Ref.71 Ref.72 Ref.73 Ref.74 Ref.75 Ref.76 Ref.77 Ref.78 Ref.79 Ref.80 Ref.82 Ref.83 Ref.84 Ref.85 Ref.86 Ref.87 Ref.88 Ref.89 Ref.90 Ref.91 Ref.92 Ref.93 Ref.94 Ref.95 Ref.96 Ref.97

Pharmaceutical use: Available under the names Kogenate (Bayer) and Recombinate (Baxter and American Home Products). Used to treat hemophilia A.

Sequence similarities: Belongs to the multicopper oxidase family.Contains 3 F5/8 type A domains.Contains 2 F5/8 type C domains.Contains 6 plastocyanin-like domains.

Mass spectrometry: Molecular mass is 1367.6 Da from positions 356 - 378. Determined by ESI. Nonsulfated. Ref.8Molecular mass is 1407.4 Da from positions 356 - 378. Determined by ESI. Sulfated. Ref.8Molecular mass is 2975.4 Da from positions 400 - 424. Determined by ESI. Nonsulfated. Ref.8Molecular mass is 3024 Da from positions 727 - 752. Determined by ESI. Nonsulfated. Ref.8Molecular mass is 3104 Da from positions 727 - 752. Determined by ESI. Monosulfated. Ref.8Molecular mass is 3183.5 Da from positions 727 - 752. Determined by ESI. Disulfated. Ref.8Molecular mass is 3262.5 Da from positions 727 - 752. Determined by ESI. Trisulfated. Ref.8Molecular mass is 2460.9 Da from positions 1672 - 1692. Determined by ESI. Nonsulfated. Ref.8Molecular mass is 2540.7 Da from positions 1672 - 1692. Determined by ESI. Sulfated. Ref.8Molecular mass is 2000.7 Da from positions 1691 - 1708. Determined by ESI. Nonsulfated. Ref.8Molecular mass is 2080.7 Da from positions 1691 - 1708. Determined by ESI. Sulfated. Ref.8