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, Jul 2008].
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: Interacts with vWF. vWF binding is essential for the stabilization of F8 in circulation.
Post-translational modifications: Sulfation on Tyr-1699 is essential for binding vWF.
DISEASE: 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=The disease is caused by mutations 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.
Similarity: 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.
SWISS: P00451
Gene ID: 2157
Database links:
Entrez Gene: 403875 Dog
Entrez Gene: 2157 Human
Entrez Gene: 14069 Mouse
Entrez Gene: 397339 Pig
Omim: 300841 Human
SwissProt: O3766 Dog
SwissProt: P00451 Human
SwissProt: Q06194 Mouse
SwissProt: P12263 Pig
Unigene: 654450 Human
Unigene: 365 Mouse
Picture
Sample:
Raji (human)cell Lysate at 30 ug
Primary: Anti- Factor VIIIa light chain (SL10417R)at 1/300 dilution
Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution
Predicted band size: 75kD
Observed band size: 85kD
Sample:
Lymph node (Mouse) Lysate at 40 ug
Testis (Mouse) Lysate at 40 ug
Primary: Anti-Factor VIIIa light chain (SL10417R) at 1/300 dilution
Secondary: IRDye800CW Goat Anti-Rabbit IgG at 1/20000 dilution
Predicted band size: 75 kD
Observed band size: 75 kD
