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Details on Person UniProt:P02786 TFRC

Class:Id	ReferenceGeneProduct:65925
_chainChangeLog	chain:1-760 added on Sat February 7 2015;chain:101-760 added on Sat February 7 2015
_displayName	UniProt:P02786 TFRC
_timestamp	2026-02-20 22:50:05
chain	chain:1-760 chain:101-760
checksum	C886F14000D90154
comment	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).FUNCTION (Microbial infection) Acts as a receptor for new-world arenaviruses: Guanarito, Junin and Machupo virus.FUNCTION (Microbial infection) Acts as a host entry factor for rabies virus that hijacks the endocytosis of TFRC to enter cells.FUNCTION (Microbial infection) Acts as a host entry factor for SARS-CoV, MERS-CoV and SARS-CoV-2 viruses that hijack the endocytosis of TFRC to enter cells.FUNCTION (Microbial infection) Acts as a receptor for Plasmodium vivax.SUBUNIT Homodimer; disulfide-linked. Binds one transferrin or HFE molecule per subunit. Binds the HLA class II histocompatibility antigen, DR1. Interacts with SH3BP3. Interacts with STEAP3; facilitates TFRC endocytosis in erythroid precursor cells (PubMed:26642240). Interacts with GRM2 (PubMed:36779763). Interacts with SNX32; the interaction is involved in intracellular trafficking of the receptor (PubMed:37158588).SUBUNIT (Microbial infection) Interacts with Guanarito, Junin and Machupo arenavirus glycoprotein complex (PubMed:17287727, PubMed:18268337).SUBUNIT (Microbial infection) Interacts with rabies virus protein G.SUBUNIT (Microbial infection) Interacts with SARS-CoV-2 spike protein S.SUBUNIT (Microbial infection) Interacts with Plasmodium vivax RBP2b; the interaction mediates parasite invasion into human reticulocytes.INTERACTION Identified by mass spectrometry in melanosome fractions from stage I to stage IV.SUBCELLULAR LOCATION Regulated by cellular iron levels through binding of the iron regulatory proteins, IRP1 and IRP2, to iron-responsive elements in the 3'-UTR. Up-regulated upon mitogenic stimulation.PTM 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).PTM N- and O-glycosylated, phosphorylated and palmitoylated. The serum form is only glycosylated.PTM Proteolytically cleaved on Arg-100 to produce the soluble serum form (sTfR).PTM Palmitoylated on both Cys-62 and Cys-67. Cys-62 seems to be the major site of palmitoylation.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Serum transferrin receptor (sTfR) is used as a means of detecting erythropoietin (EPO) misuse by athletes and as a diagnostic test for anemia resulting from a number of conditions including rheumatoid arthritis, pregnancy, irritable bowel syndrome and in HIV patients.MISCELLANEOUS Canine and feline parvoviruses bind human and feline transferrin receptors and use these receptors to enter and infect cells.SIMILARITY Belongs to the peptidase M28 family. M28B subfamily.
description	recommendedName: Transferrin receptor protein 1 shortName: TR shortName: TfR shortName evidence="31 32"TfR1 shortName: Trfr alternativeName: T9 alternativeName: fullName evidence="31 32"Transferrin receptor 1 alternativeName: p90 cdAntigenName evidence="31"CD71/cdAntigenName component recommendedName: Transferrin receptor protein 1, serum form shortName: sTfR /component
geneName	TFRC
identifier	P02786
isSequenceChanged	FALSE
keyword	3D-structure Cell membrane Direct protein sequencing Disease variant Disulfide bond Endocytosis Glycoprotein Host cell receptor for virus entry Host-virus interaction Lipoprotein Malaria Membrane Palmitate Phosphoprotein Proteomics identification Receptor Reference proteome Secreted Signal-anchor Transducer Transmembrane Transmembrane helix
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
name	TFRC
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:9003279] ENSEMBL:ENSG00000072274 TFRC [Homo sapiens]
secondaryIdentifier	TFR1_HUMAN D3DXB0 Q1HE24 Q59G55 Q9UCN0 Q9UCU5 Q9UDF9 Q9UK21
sequenceLength	760
species	[Species:48887] Homo sapiens
(referenceEntity)	[EntityWithAccessionedSequence:434196] TFRC(1-760) [cytoplasmic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:434330] TFRC(1-760) [Golgi membrane] [Homo sapiens] [EntityWithAccessionedSequence:917983] TFRC(1-760) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:8869124] TFRC(1-760) [clathrin-coated endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:8961829] TFRC(1-760) [endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:9986825] TFRC [endoplasmic reticulum membrane] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P02786 TFRC (65925)