F8

What is F8 protein?

F8 (coagulation factor VIII) is a protein coding gene which situated on the long arm of chromosome X at locus Xq28. 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. F8 protein also known as factor VIII, contains the signal peptide at the N-terminal and the enzyme activity center at the C-terminal. The F8 protein is a giant protein found in the human body, consisted of 2351 amino acids and its molecular mass is approximately 267 kDa.

What is the function of F8 protein?

The function of the F8 protein, also known as coagulation factor VIII, is to play a critical role in the blood clotting process. It is a crucial factor in the intrinsic pathway of the clotting cascade. Specifically, F8 protein acts as a cofactor for the enzyme activated factor IX (FIXa) in the conversion of factor X (FX) to activated factor X (FXa). This conversion is essential for the subsequent formation of thrombin, which ultimately leads to the formation of a stable blood clot.

F8 related Signaling pathways

The main signaling pathway involving F8 is the intrinsic pathway of the coagulation cascade. This pathway is initiated when blood vessels are damaged, and it involves a series of enzymatic reactions that ultimately lead to the activation of factor X and the conversion of prothrombin to thrombin.

F8 Related Diseases

Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder. According to the report, a large number of different mutations of the F8 gene have been found so far, including point mutations, gene deletion, insertion, nonsense mutations, splicing mutations, etc. These mutations often lead to the development of hemophilia A or B. Additionally, factor VIII is regulated by several other proteins and pathways, including von Willebrand factor (VWF). Patients with von Willebrand disease (VWD) with VWF severely low or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to F8, may have reduced F8 levels secondary to their VWD.

Fig1. Secreted factor VIII protein from cancer cell lines is bioactive. Graphical representation of the measurement of FVIII antigen.

Bioapplications of F8

In hemophilia studies using AAV (adeno-associated virus) for treatment, it has been found that AAV vectors carrying F8 or F9 genes can produce functional FIX or F8 proteins under the control of liver promoters. Or using gene-editing technology to repair mutations in the F8 gene could also treat hemophilia A.

Case Study 1: Maitreyee Sharma, 2016

Fig1. Intrinsic tenase complex (ITC), in the presence or absence of phospholipid and alkylated daboxin P (indicated by *).

Case Study 2: Victor Tse, 2024

Fig2. A representative agarose RNA gel showing the effects on splicing by various HA-causing variants in a panel of F8 exon-16 splicing reporters.

F8 has several biochemical functions, for example, copper ion binding,oxidoreductase activity,protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by F8 itself. We selected most functions F8 had, and list some proteins which have the same functions with F8. You can find most of the proteins on our site.

F8 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with F8 here. Most of them are supplied by our site. Hope this information will be useful for your research of F8.

kv312_human;EIF1B;CALR;GGA1;UBQLN1;MAP1LC3A