Tfrc
Function
Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (By similarity). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). Upon stimulation, positively regulates T and B cell proliferation through iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (By similarity). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (By similarity). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (By similarity). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (PubMed:38625739).
Post-translational modifications
Stearoylated by ZDHHC6 which inhibits TFRC-mediated activation of the JNK pathway and promotes mitochondrial fragmentation (By similarity). Stearoylation does not affect iron uptake (By similarity).
N- and O-glycosylated, phosphorylated and palmitoylated.
Sequence Similarities
Belongs to the peptidase M28 family. M28B subfamily.
Cellular localization
- Cell membrane
- Single-pass type II membrane protein
- Melanosome
Alternative names
CD71, Trfr, Tfrc, Transferrin receptor protein 1, TR, TfR, TfR1