TFRC
Description
The TFRC (transferrin receptor) is a protein-coding gene located on chromosome 3.
Transferrin receptor protein 1 (TfR1), also known as Cluster of Differentiation 71 (CD71), is a protein that in humans is encoded by the TFRC gene. TfR1 is required for iron import from transferrin into cells by endocytosis. TfR1 is a transmembrane glycoprotein composed of two disulfide-linked monomers joined by two disulfide bonds. Each monomer binds one holo-transferrin molecule creating an iron-Tf-TfR complex which enters the cell by endocytosis. TfR1 as a potential new target in cases of human leukemia & lymphoma. InatherYs, in Évry, France, developed a candidate drug, INA01 antibody (anti-CD71) that showed efficacy in pre-clinical studies in the therapy of two incurable orphan oncohematological diseases: the adult T cell leukemia (ATLL) caused by HTLV-1 and the Mantle cell lymphoma (MCL). TfR1 expressed on the endothelial cells of the blood-brain barrier (BBB) is used also in preclinical research to allow the delivery of large molecules including antibodies into the brain. Some of the TfR1 targeting antibodies have been shown to cross the blood-brain barrier, without interfering with the uptake of iron. Amongst those are the mouse anti rat-TfR antibody OX26 and the rat anti mouse-TfR antibody 8D3. The affinity of the antibody-TfR interaction seems to be important determining the success of transcytotic transport over endothelial cells of the BBB. Monovalent TfR interaction favors BBB transport due to altered intracellular sorting pathways.
The TFRC gene encodes the transferrin receptor protein 1 (TfR1), which plays a crucial role in iron uptake by cells. TfR1 binds to transferrin, a protein that carries iron in the blood, and facilitates its internalization through endocytosis. Within specialized endosomes, the acidic environment triggers the release of iron from transferrin. The now iron-free transferrin (apotransferrin) remains bound to TfR1 and is recycled back to the cell surface. This process is essential for maintaining cellular iron levels and is vital for the development of red blood cells and the nervous system. Additionally, TfR1 interacts with the hereditary hemochromatosis protein HFE, competing for binding with transferrin. This interaction has implications for iron regulation and potentially for the development of iron overload disorders. Furthermore, TfR1 functions as a lipid sensor, influencing mitochondrial fusion by modulating the activity of the JNK pathway. When dietary stearate levels are low, TFRC activates the JNK pathway, leading to the degradation of the mitofusin MFN2 protein and consequently inhibiting mitochondrial fusion. Conversely, when stearate levels are high, TFRC undergoes stearoylation, suppressing JNK pathway activation and preventing MFN2 degradation, ultimately promoting mitochondrial fusion.
TFRC is also known as CD71, IMD46, T9, TFR, TFR1, TR, TRFR, p90.
