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Function

Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (PubMed:26214738). 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). A second ligand, the hereditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. 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 (PubMed:26214738). 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 (PubMed:26214738). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (PubMed:26214738). Mediates uptake of NICOL1 into fibroblasts where it may regulate extracellular matrix production (By similarity).

(Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus.

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

Target type

Proteins

Primary research area

Oncology

Molecular weight

84871Da

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