TFRC

This gene encodes a cell surface receptor necessary for cellular iron uptake by the process of receptor-mediated endocytosis. This receptor is required for erythropoiesis and neurologic development. Multiple alternatively spliced variants have been identified.

TFRC Gene(Protein Coding) Transferrin Receptor

Transferrin Receptor; TFR1; TRFR; P90; TFR; TR; T9;

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

Biological Process acute-phase responseSource:Ensembl
Biological Process agingSource:Ensembl
Biological Process cellular iron ion homeostasisSource:GO_Central1 Publication
Biological Process cellular response to leukemia inhibitory factorSource:Ensembl
Biological Process cellular response to xenobiotic stimulusSource:MGI1 Publication
Biological Process intracellular signal transductionSource:UniProtKB1 Publication
Biological Process iron ion transportSource:UniProtKB1 Publication
Biological Process negative regulation of apoptotic processSource:ARUK-UCL1 Publication
Biological Process negative regulation of mitochondrial fusionSource:UniProtKB1 Publication
Biological Process osteoclast differentiationSource:Ensembl
Biological Process positive regulation of B cell proliferationSource:UniProtKB1 Publication
Biological Process positive regulation of bone resorptionSource:Ensembl
Biological Process positive regulation of gene expressionSource:ARUK-UCL1 Publication
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signalingSource:ARUK-UCL1 Publication
Biological Process positive regulation of isotype switchingSource:UniProtKB1 Publication
Biological Process positive regulation of NF-kappaB transcription factor activitySource:ARUK-UCL1 Publication
Biological Process positive regulation of peptidyl-serine phosphorylationSource:ARUK-UCL1 Publication
Biological Process positive regulation of protein localization to nucleusSource:ARUK-UCL1 Publication
Biological Process positive regulation of protein phosphorylationSource:ARUK-UCL1 Publication
Biological Process positive regulation of protein-containing complex assemblySource:ARUK-UCL1 Publication
Biological Process positive regulation of T cell proliferationSource:UniProtKB1 Publication
Biological Process receptor internalizationSource:UniProtKB1 Publication
Biological Process response to copper ionSource:Ensembl
Biological Process response to hypoxiaSource:Ensembl
Biological Process response to iron ionSource:Ensembl
Biological Process response to manganese ionSource:Ensembl
Biological Process response to nutrientSource:Ensembl
Biological Process response to retinoic acidSource:Ensembl
Biological Process transferrin transportSource:UniProtKB1 Publication
Biological Process transport across blood-brain barrierSource:ARUK-UCL2 Publications

Cell membrane
Melanosome
Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
Transferrin receptor protein 1, serum form
Secreted

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.

Cytoplasmic: 1-67
Helical: 68-88
Extracellular: 89-760

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.