TF

What is TF protein?

TF gene (transferrin) is a protein coding gene which situated on the long arm of chromosome 3 at locus 3q22. This gene encodes a glycoprotein with an approximate molecular weight of 76.5 kDa. It is thought to have been created as a result of an ancient gene duplication event that led to generation of homologous C and N-terminal domains each of which binds one ion of ferric iron. The function of this protein is to transport iron from the intestine, reticuloendothelial system, and liver parenchymal cells to all proliferating cells in the body. This protein may also have a physiologic role as granulocyte/pollen-binding protein (GPBP) involved in the removal of certain organic matter and allergens from serum. The TF protein is consisted of 698 amino acids and TF molecular weight is approximately 77.1 kDa.

What is the function of TF protein?

This is an iron-binding protein that plays a crucial role in the transport of iron in the body. It binds and transports ferric ions (Fe(III)), increasing their solubility under physiological conditions and preventing their pro-oxidant effects. In humans, transferrin is responsible for the safe transport of iron through the bloodstream and its delivery to cells that require it. Cellular uptake of iron occurs through endocytosis mediated by the transferrin receptor (TfR). Post-translational modifications of transferrin, such as phosphorylation, glycation, and oxidation, can affect its function and may contribute to the deregulation of systemic iron transport in diseases.

TF related signaling pathway

The Tf-TfR complex is internalized into the cell via clathrin-mediated endocytosis, leading to the formation of clathrin-coated vesicles. Within the acidified environment of early endosomes, iron is released from Tf, making it available for cellular use. After delivering iron, apo-transferrin (Tf without iron) is typically routed back to the cell surface via recycling endosomes through two pathways: a fast recycling route and a slower route that involves the perinuclear recycling compartment. Various methods, including microscopy, radioactivity, and surface plasmon resonance (SPR), have been used to study the Tf trafficking pathway and the cellular machinery involved.

TF related diseases

Transferrin is an iron-binding protein, which plays an important role in transporting and storing iron in the human body, and its abnormal function or imbalance is associated with a variety of diseases. Iron deficiency anemia is a common condition characterized by insufficient iron reserves in the body, resulting in the inability of red blood cells to properly synthesize hemoglobin. Multiple myeloma, on the other hand, is a malignant tumor that causes an abnormal proliferation of plasma cells in the bone marrow. In addition, some other diseases may also cause abnormal transferrin levels, such as chronic liver disease, kidney disease, inflammatory bowel disease, etc. These diseases affect the process of synthesis, secretion, or degradation of transferrins, resulting in changes in their levels.

Fig1. Schematic representation showing that holotransferrin promotes and apotransferrin prevents a form of oxidative, iron- and NMDAR-dependent neuronal death in experimental stroke. (Nuria DeGregorio-Rocasolano, 2018)

Bioapplications of TF

Recombinant human transferrin rhTF, as an important supplementary factor in cell culture medium, can provide iron source and promote the growth of mammalian cells. Levels of transferrin and its receptor (TfR1) can play a role as a biomarker for certain diseases, for example in the diagnosis and therapeutic monitoring of diseases such as anemia, neurodegenerative diseases and cancer. Transferrin can act as a drug carrier to efficiently deliver drugs into cells through its receptor-mediated endocytosis, a mechanism that has been explored for cancer therapy and brain disease treatment. The ability of rhTF to bind to CD71 receptors or other ferriferic proteins can be used to specifically label and selectively enrich CD71-positive cells. rhTF can promote cell growth, reduce cell oxidative stress and anti-apoptosis, and is suitable for damage repair, organ construction and transplantation, and can enhance the survival rate of new tissues.