F9

Fig1. The waterfall / cascade model of coagulation. (Allison P Wheeler, 2016)

What is F9 Protein?

F9 gene (coagulation factor IX) is a protein coding gene which situated on the long arm of chromosome X at locus Xq27. This gene encodes vitamin K-dependent coagulation factor IX that circulates in the blood as an inactive zymogen. This factor is converted to an active form by factor XIa, which excises the activation peptide and thus generates a heavy chain and a light chain held together by one or more disulfide bonds. The role of this activated factor IX in the blood coagulation cascade is to activate factor X to its active form through interactions with Ca+2 ions, membrane phospholipids, and factor VIII. Alterations of this gene, including point mutations, insertions and deletions, cause factor IX deficiency, which is a recessive X-linked disorder, also called hemophilia B or Christmas disease. The F9 protein is consisted of 461 amino acids and F9 molecular weight is approximately 51.8 kDa.

What is the Function of F9 Protein?

The protein encoded by the F9 gene circulates in the blood as an inactive zymogen that can be converted to an active form by the activation of factor XIa. Activated factor IX is able to interact with Ca2+ ions, membrane phospholipids, and factor VIII to convert factor X into its active form, thus participating in the blood clotting process. In addition, the expression of F9 gene is regulated by a variety of factors, including miRNAs, such as hsa-miR-4298, hsa-miR-1302, etc. These miRNAs can target F9 gene and thus affect its expression.

F9 Related Signaling Pathway

In terms of signal transduction, the F9 protein is associated with multiple signaling pathways. For example, abnormal expression of the F9 gene is associated with the Wnt signaling pathway, a pathway that plays an important role in various biological processes such as cell proliferation, differentiation, migration, and apoptosis. Activation of the Wnt signaling pathway can promote cell survival, proliferation, inflammatory response, and immune cell development and function. In particular, the expression of F9 gene, as a downstream target of Wnt signaling pathway, is regulated by Wnt/β-catenin signaling pathway, and the high expression of FGF9 is related to the activation of Wnt signaling pathway. In addition, the F9 protein is involved in the PI3K/Akt signaling pathway, a key signaling pathway within cells that plays a critical role in multiple biological processes, including cell growth, proliferation, metabolism, and survival. Activation of PI3K/Akt signaling pathway can promote cell proliferation and survival, and inhibit cell apoptosis.

F9 Related Diseases

The F9 protein has been linked to a range of diseases, most notably Hemophilia B, an inherited blood clotting disorder in which a mutation in the F9 gene results in defective or deficient function of factor IX, affecting normal blood clotting. In addition, abnormal expression of the F9 gene has also been associated with the development of certain cancers, such as hepatocellular carcinoma, and downregulation of F9 gene expression may be associated with tumor aggressiveness and poor prognosis. Other studies have pointed out that F9 protein may play a role in the occurrence and development of ovarian cancer, and its high expression may be related to the proliferation, invasion and metastasis of tumor cells. Therefore, abnormal function or expression of F9 protein is closely associated with blood clotting disorders and the development of certain cancers.

Bioapplications of F9

The practical application of F9 protein is mainly focused on the treatment of hemophilia B, supplementing or repairing defective clotting factor IX through gene therapy or protein replacement therapy to improve patients' clotting ability, reduce bleeding events, and improve quality of life. In addition, the study of F9 protein also involves the development of new therapeutic strategies, such as the use of gene editing technology to repair F9 gene mutations, as well as exploring its potential applications in cancer therapy, such as by targeting the Wnt/β-catenin signaling pathway to inhibit tumor growth and invasion associated with high expression of F9 protein.