Reactome | UniProt:P02786 TFRC

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UniProt:P02786 TFRC Show undefined attributes

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.
crossReference	[DatabaseIdentifier:12170293] PDB:6D03 [DatabaseIdentifier:12409077] RefSeq:NP_001300895.1 [DatabaseIdentifier:12409078] RefSeq:NP_003225.2 [DatabaseIdentifier:12409079] RefSeq:NP_001121620.1 [DatabaseIdentifier:12409076] RefSeq:NP_001300894.1 [DatabaseIdentifier:12284163] Pharos - Targets:P02786 [DatabaseIdentifier:12243426] PRO:P02786 [DatabaseIdentifier:12170315] PDB:9GH7 [DatabaseIdentifier:12170295] PDB:6D04 [DatabaseIdentifier:12170322] PDB:6Y76 [DatabaseIdentifier:12170325] PDB:6WRW [DatabaseIdentifier:12170326] PDB:7ZQS [DatabaseIdentifier:12170285] PDB:3S9L [DatabaseIdentifier:12170323] PDB:6WRV [DatabaseIdentifier:12168539] PDB:6GSR [DatabaseIdentifier:12170314] PDB:1CX8 [DatabaseIdentifier:12170294] PDB:6D05 [DatabaseIdentifier:12170324] PDB:6WRX [DatabaseIdentifier:12170319] PDB:3KAS [DatabaseIdentifier:12168444] PDB:6H5I [DatabaseIdentifier:12170320] PDB:1DE4 [DatabaseIdentifier:12170318] PDB:6W3H [DatabaseIdentifier:12170288] PDB:3S9N [DatabaseIdentifier:12170321] PDB:8P0Z [DatabaseIdentifier:11490436] ENSEMBL:ENSG00000072274 [DatabaseIdentifier:11596828] ENSEMBL:ENSP00000376197 [DatabaseIdentifier:11596826] ENSEMBL:ENSP00000513654 [DatabaseIdentifier:11596825] ENSEMBL:ENSP00000353224 [DatabaseIdentifier:11596827] ENSEMBL:ENSP00000513646 [DatabaseIdentifier:11719525] ENSEMBL:ENST00000698291 [DatabaseIdentifier:11719526] ENSEMBL:ENST00000392396 [DatabaseIdentifier:11719527] ENSEMBL:ENST00000360110 [DatabaseIdentifier:11719524] ENSEMBL:ENST00000698280 [DatabaseIdentifier:11779009] Guide to Pharmacology - Targets:3196 [DatabaseIdentifier:11786245] GeneCards:TFRC [DatabaseIdentifier:11801783] GlyGen:P02786 [DatabaseIdentifier:11829332] HMDB Protein:HMDBP02577 [DatabaseIdentifier:11839328] HPA:ENSG00000072274-TFRC [DatabaseIdentifier:12123843] OpenTargets:ENSG00000072274 [DatabaseIdentifier:12135034] Orphanet:TFRC [DatabaseIdentifier:12170316] PDB:2NSU [DatabaseIdentifier:12170310] PDB:1SUV [DatabaseIdentifier:12170317] PDB:6OKD [DatabaseIdentifier:12170287] PDB:3S9M
databaseName	UniProt
dbId	65925
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
displayName	UniProt:P02786 TFRC
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:9983091] Weiser, Joel, 2026-02-20
moleculeType	Protein
name	TFRC
otherIdentifier	11715477_at 11715478_a_at 11756156_s_at 16963241 207332_PM_s_at 207332_s_at 208691_PM_at 208691_at 237214_PM_at 237214_at 237215_PM_s_at 237215_s_at 2712631 2712633 2712634 2712635 2712636 2712637 2712638 2712639 2712640 2712641 2712642 2712643 2712644 2712645 2712646 2712648 2712649 2712650 2712652 2712653 2712654 2712655 2712657 2712658 2712659 2712660 2712661 2712662 2712663 2712664 2712665 2712666 2712668 2712669 2712671 2712672 2712673 2712674 2712675 2712676 2712677 2712678 2712679 2712681 2712682 2712683 2712684 2712685 2712692 37324_at 51674_at 63276_r_at 7037 8093053 89367_at AFFX-HUMTFRR/M11507_3_at AFFX-HUMTFRR/M11507_5_at AFFX-HUMTFRR/M11507_M_at A_23_P212617 A_24_P669329 GE81249 GO:0001618 GO:0001666 GO:0003013 GO:0003723 GO:0003725 GO:0004998 GO:0005515 GO:0005576 GO:0005615 GO:0005768 GO:0005769 GO:0005886 GO:0005905 GO:0006826 GO:0006879 GO:0006897 GO:0006898 GO:0006953 GO:0006954 GO:0007165 GO:0007166 GO:0007584 GO:0009897 GO:0009986 GO:0010008 GO:0010039 GO:0010042 GO:0010628 GO:0010637 GO:0016020 GO:0016192 GO:0016323 GO:0019901 GO:0030154 GO:0030316 GO:0030544 GO:0030669 GO:0030890 GO:0031334 GO:0031410 GO:0031623 GO:0032526 GO:0033572 GO:0035556 GO:0038024 GO:0042102 GO:0042470 GO:0042802 GO:0042803 GO:0043066 GO:0043123 GO:0043226 GO:0044877 GO:0045830 GO:0046688 GO:0046718 GO:0048471 GO:0051087 GO:0055037 GO:0055038 GO:0060586 GO:0070062 GO:0071466 GO:0072562 GO:0098794 GO:0098944 GO:0098978 GO:0099072 GO:0150104 GO:1900182 GO:1903561 GO:1990712 GO:1990830 HMNXSV003030758 Hs.185726.0.A1_3p_at PH_hs_0022877 TC03002155.hg X01060_at g4507456_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-917983] TFRC(1-760) [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-8961829] TFRC(1-760) [endosome membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-8869124] TFRC(1-760) [clathrin-coated endocytic vesicle membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-434196] TFRC(1-760) [cytoplasmic vesicle membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-434330] TFRC(1-760) [Golgi membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000072274] ENSEMBL:ENSG00000072274 TFRC [ReferenceDNASequence:12748996] UCSC:P02786 TFRC [ReferenceDNASequence:11355708] BioGPS Gene:7037 TFRC [ReferenceDNASequence:11401456] COSMIC - genes:TFRC TFRC [ReferenceDNASequence:11411186] CTD Gene:7037 TFRC [ReferenceDNASequence:11438782] dbSNP Gene:7037 TFRC [ReferenceDNASequence:11817877] HGNC:11763 TFRC [ReferenceDNASequence:11895168] KEGG:hsa:7037 TFRC [ReferenceDNASequence:11985497] Monarch:7037 TFRC [ReferenceDNASequence:12069590] NCBI Gene:7037 TFRC [ReferenceDNASequence:12109324] OMIM:190010 TFRC
referenceTranscript	[ReferenceRNASequence:12590780] RefSeq:NM_001313966.1 TFRC [ReferenceRNASequence:12590782] RefSeq:NM_001313965.1 TFRC [ReferenceRNASequence:12590781] RefSeq:NM_003234.4 TFRC [ReferenceRNASequence:12590779] RefSeq:NM_001128148.3 TFRC
schemaClass	ReferenceGeneProduct
secondaryIdentifier	TFR1_HUMAN D3DXB0 Q1HE24 Q59G55 Q9UCN0 Q9UCU5 Q9UDF9 Q9UK21
sequenceLength	760
species	[Species:48887] Homo sapiens
stId	uniprot:P02786
url	http://purl.uniprot.org/uniprot/P02786

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