TFRC
Function
The protein expressed by the gene TFRC is involved in the cellular uptake of iron via receptor-mediated endocytosis, where the transferrin receptor, bound to its ligand, is internalized into specialized endosomes. Following endosomal acidification, iron is released, and the apotransferrin-receptor complex is recycled to the cell surface, where a return to neutral pH results in the loss of apotransferrin's affinity for its receptor. The hereditary hemochromatosis protein HFE competes with transferrin for binding at an overlapping C-terminal site. TFRC positively regulates T and B cell proliferation through iron uptake. It functions as a lipid sensor influencing mitochondrial fusion by modulating the JNK pathway activity. Low dietary levels of stearate promote JNK pathway activation, leading to HUWE1-mediated ubiquitination and degradation of the mitofusin MFN2, inhibiting mitochondrial fusion. High dietary stearate levels result in TFRC stearoylation, which inhibits JNK pathway activation and MFN2 degradation. Additionally, TFRC acts as a receptor for new-world arenaviruses, including Guanarito, Junin, and Machupo viruses. This supplementary information is collated from multiple sources and compiled automatically.
Involvement in disease
Immunodeficiency 46
IMD46
An autosomal recessive primary immunodeficiency disorder characterized by early-onset chronic diarrhea, recurrent infections, hypo- or agammaglobulinemia, normal lymphocyte counts, intermittent neutropenia, and intermittent thrombocytopenia.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Stearoylated by ZDHHC6 which inhibits TFRC-mediated activation of the JNK pathway and promotes mitochondrial fragmentation (PubMed:26214738). Stearoylation does not affect iron uptake (PubMed:26214738).
N- and O-glycosylated, phosphorylated and palmitoylated. The serum form is only glycosylated.
Proteolytically cleaved on Arg-100 to produce the soluble serum form (sTfR).
Palmitoylated on both Cys-62 and Cys-67. Cys-62 seems to be the major site of palmitoylation.
Sequence Similarities
Belongs to the peptidase M28 family. M28B subfamily.
Cellular localization
- Cell membrane
- Single-pass type II membrane protein
- Melanosome
- Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
- Transferrin receptor protein 1, serum form
- Secreted
Alternative names
CD71, Transferrin receptor protein 1, TR, TfR, TfR1, Trfr, T9, p90, TFRC