TFR1_MOUSE
ID TFR1_MOUSE Reviewed; 763 AA.
AC Q62351; Q61560;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Transferrin receptor protein 1;
DE Short=TR;
DE Short=TfR;
DE Short=TfR1;
DE Short=Trfr;
DE AltName: CD_antigen=CD71;
GN Name=Tfrc; Synonyms=Trfr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6 X DBA/2; TISSUE=Hematopoietic;
RA Trowbridge I.S., Domingo D.L., Thomas M.L., Chain A.;
RL Submitted (JAN-1991) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-301.
RC TISSUE=Myeloma;
RX PubMed=2984291;
RA Stearne P.A., Pietersz G.A., Goding J.W.;
RT "cDNA cloning of the murine transferrin receptor: sequence of trans-
RT membrane and adjacent regions.";
RL J. Immunol. 134:3474-3479(1985).
RN [4]
RP PROTEIN SEQUENCE OF 7-19; 158-179; 196-208; 450-467 AND 736-759.
RC TISSUE=Myeloma;
RX PubMed=6092468;
RA van Driel I.R., Stearne P.A., Grego B., Simpson R.J., Goding J.W.;
RT "The receptor for transferrin on murine myeloma cells: one-step
RT purification based on its physiology, and partial amino acid sequence.";
RL J. Immunol. 133:3220-3224(1984).
RN [5]
RP FUNCTION.
RX PubMed=10192390; DOI=10.1038/7727;
RA Levy J.E., Jin O., Fujiwara Y., Kuo F., Andrews N.C.;
RT "Transferrin receptor is necessary for development of erythrocytes and the
RT nervous system.";
RL Nat. Genet. 21:396-399(1999).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-20, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-20, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [8]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-725 AND ASN-730.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP MUTAGENESIS OF TYR-20, AND FUNCTION.
RX PubMed=26642240; DOI=10.1038/ng.3465;
RA Jabara H.H., Boyden S.E., Chou J., Ramesh N., Massaad M.J., Benson H.,
RA Bainter W., Fraulino D., Rahimov F., Sieff C., Liu Z.J., Alshemmari S.H.,
RA Al-Ramadi B.K., Al-Dhekri H., Arnaout R., Abu-Shukair M., Vatsayan A.,
RA Silver E., Ahuja S., Davies E.G., Sola-Visner M., Ohsumi T.K.,
RA Andrews N.C., Notarangelo L.D., Fleming M.D., Al-Herz W., Kunkel L.M.,
RA Geha R.S.;
RT "A missense mutation in TFRC, encoding transferrin receptor 1, causes
RT combined immunodeficiency.";
RL Nat. Genet. 48:74-78(2016).
CC -!- FUNCTION: Cellular uptake of iron occurs via receptor-mediated
CC endocytosis of ligand-occupied transferrin receptor into specialized
CC endosomes (By similarity). Endosomal acidification leads to iron
CC release. The apotransferrin-receptor complex is then recycled to the
CC cell surface with a return to neutral pH and the concomitant loss of
CC affinity of apotransferrin for its receptor. Transferrin receptor is
CC necessary for development of erythrocytes and the nervous system (By
CC similarity). Upon stimulation, positively regulates T and B cell
CC proliferation through iron uptake (PubMed:26642240). Acts as a lipid
CC sensor that regulates mitochondrial fusion by regulating activation of
CC the JNK pathway (By similarity). When dietary levels of stearate
CC (C18:0) are low, promotes activation of the JNK pathway, resulting in
CC HUWE1-mediated ubiquitination and subsequent degradation of the
CC mitofusin MFN2 and inhibition of mitochondrial fusion (By similarity).
CC When dietary levels of stearate (C18:0) are high, TFRC stearoylation
CC inhibits activation of the JNK pathway and thus degradation of the
CC mitofusin MFN2 (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:10192390, ECO:0000269|PubMed:26642240}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Binds one transferrin molecule
CC per subunit. Interacts with SH3BP4 (By similarity). Interacts with
CC STEAP3; facilitates TFRC endocytosis in erythroid precursor cells (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P02786}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P02786};
CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:P02786}.
CC Melanosome {ECO:0000250|UniProtKB:P02786}.
CC -!- PTM: Stearoylated by ZDHHC6 which inhibits TFRC-mediated activation of
CC the JNK pathway and promotes mitochondrial fragmentation (By
CC similarity). Stearoylation does not affect iron uptake (By similarity).
CC {ECO:0000250|UniProtKB:P02786}.
CC -!- PTM: N- and O-glycosylated, phosphorylated and palmitoylated.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase M28 family. M28B subfamily.
CC {ECO:0000305}.
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DR EMBL; X57349; CAA40624.1; -; mRNA.
DR EMBL; BC054522; AAH54522.1; -; mRNA.
DR EMBL; M29618; AAA37616.1; -; mRNA.
DR CCDS; CCDS28123.1; -.
DR PIR; S29548; S29548.
DR RefSeq; NP_035768.1; NM_011638.4.
DR RefSeq; XP_006522062.1; XM_006521999.3.
DR AlphaFoldDB; Q62351; -.
DR SMR; Q62351; -.
DR BioGRID; 204314; 20.
DR IntAct; Q62351; 11.
DR MINT; Q62351; -.
DR STRING; 10090.ENSMUSP00000023486; -.
DR MEROPS; M28.972; -.
DR GlyConnect; 2776; 3 N-Linked glycans (2 sites).
DR GlyGen; Q62351; 5 sites, 3 N-linked glycans (2 sites).
DR iPTMnet; Q62351; -.
DR PhosphoSitePlus; Q62351; -.
DR SwissPalm; Q62351; -.
DR EPD; Q62351; -.
DR jPOST; Q62351; -.
DR MaxQB; Q62351; -.
DR PaxDb; Q62351; -.
DR PRIDE; Q62351; -.
DR ProteomicsDB; 263168; -.
DR ABCD; Q62351; 1 sequenced antibody.
DR Antibodypedia; 4559; 2909 antibodies from 49 providers.
DR DNASU; 22042; -.
DR Ensembl; ENSMUST00000023486; ENSMUSP00000023486; ENSMUSG00000022797.
DR GeneID; 22042; -.
DR KEGG; mmu:22042; -.
DR UCSC; uc007yza.2; mouse.
DR CTD; 7037; -.
DR MGI; MGI:98822; Tfrc.
DR VEuPathDB; HostDB:ENSMUSG00000022797; -.
DR eggNOG; KOG2195; Eukaryota.
DR GeneTree; ENSGT01030000234598; -.
DR HOGENOM; CLU_005688_5_0_1; -.
DR InParanoid; Q62351; -.
DR OMA; VMRVEYY; -.
DR OrthoDB; 804230at2759; -.
DR PhylomeDB; Q62351; -.
DR TreeFam; TF312981; -.
DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-MMU-8980692; RHOA GTPase cycle.
DR Reactome; R-MMU-9013026; RHOB GTPase cycle.
DR Reactome; R-MMU-9013106; RHOC GTPase cycle.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR Reactome; R-MMU-9013404; RAC2 GTPase cycle.
DR Reactome; R-MMU-9013406; RHOQ GTPase cycle.
DR Reactome; R-MMU-9013407; RHOH GTPase cycle.
DR Reactome; R-MMU-9013408; RHOG GTPase cycle.
DR Reactome; R-MMU-9013409; RHOJ GTPase cycle.
DR Reactome; R-MMU-9013423; RAC3 GTPase cycle.
DR Reactome; R-MMU-917977; Transferrin endocytosis and recycling.
DR Reactome; R-MMU-9696270; RND2 GTPase cycle.
DR Reactome; R-MMU-9696273; RND1 GTPase cycle.
DR BioGRID-ORCS; 22042; 40 hits in 112 CRISPR screens.
DR ChiTaRS; Tfrc; mouse.
DR PRO; PR:Q62351; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q62351; protein.
DR Bgee; ENSMUSG00000022797; Expressed in placenta labyrinth and 265 other tissues.
DR ExpressionAtlas; Q62351; baseline and differential.
DR Genevisible; Q62351; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005769; C:early endosome; IDA:MGI.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0070062; C:extracellular exosome; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:1990712; C:HFE-transferrin receptor complex; IDA:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IMP:ParkinsonsUK-UCL.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0055037; C:recycling endosome; IDA:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; ISO:MGI.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:MGI.
DR GO; GO:0030544; F:Hsp70 protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005381; F:iron ion transmembrane transporter activity; TAS:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0004998; F:transferrin receptor activity; ISS:UniProtKB.
DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:MGI.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; TAS:BHF-UCL.
DR GO; GO:0071281; P:cellular response to iron ion; TAS:BHF-UCL.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0006826; P:iron ion transport; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; ISO:MGI.
DR GO; GO:0030316; P:osteoclast differentiation; IMP:DFLAT.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IDA:UniProtKB.
DR GO; GO:0045780; P:positive regulation of bone resorption; IDA:DFLAT.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0045830; P:positive regulation of isotype switching; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:UniProtKB.
DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
DR GO; GO:0046688; P:response to copper ion; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0010042; P:response to manganese ion; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0032526; P:response to retinoic acid; IEA:Ensembl.
DR GO; GO:0033572; P:transferrin transport; ISS:UniProtKB.
DR CDD; cd02128; PA_TfR; 1.
DR Gene3D; 1.20.930.40; -; 1.
DR InterPro; IPR003137; PA_domain.
DR InterPro; IPR007484; Peptidase_M28.
DR InterPro; IPR039373; Peptidase_M28B.
DR InterPro; IPR029513; TfR.
DR InterPro; IPR007365; TFR-like_dimer_dom.
DR InterPro; IPR036757; TFR-like_dimer_dom_sf.
DR InterPro; IPR037324; TfR1/2_PA.
DR PANTHER; PTHR10404; PTHR10404; 1.
DR PANTHER; PTHR10404:SF26; PTHR10404:SF26; 1.
DR Pfam; PF02225; PA; 1.
DR Pfam; PF04389; Peptidase_M28; 1.
DR Pfam; PF04253; TFR_dimer; 1.
DR SUPFAM; SSF47672; SSF47672; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Direct protein sequencing; Disulfide bond; Endocytosis;
KW Glycoprotein; Lipoprotein; Membrane; Palmitate; Phosphoprotein; Receptor;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..763
FT /note="Transferrin receptor protein 1"
FT /id="PRO_0000174133"
FT TOPO_DOM 1..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 89..763
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 225..315
FT /note="PA"
FT REGION 1..67
FT /note="Mediates interaction with SH3BP4"
FT /evidence="ECO:0000250"
FT REGION 572..763
FT /note="Ligand-binding"
FT /evidence="ECO:0000250"
FT MOTIF 20..23
FT /note="Endocytosis signal"
FT MOTIF 58..61
FT /note="Stop-transfer sequence"
FT MOTIF 649..651
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 20
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:19131326"
FT MOD_RES 21
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT LIPID 67
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 104
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 725
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 730
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT DISULFID 89
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 98
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT MUTAGEN 20
FT /note="Y->H: Negatively regulates of T and B cell
FT proliferation upon activation. Significantly increases cell
FT surface expression on T and B cells. Impairs
FT internalization."
FT /evidence="ECO:0000269|PubMed:26642240"
FT CONFLICT 25..26
FT /note="LA -> AL (in Ref. 3; AAA37616)"
FT /evidence="ECO:0000305"
FT CONFLICT 743
FT /note="W -> H (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 757
FT /note="W -> I (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 763 AA; 85731 MW; 832A148CC26CE489 CRC64;
MMDQARSAFS NLFGGEPLSY TRFSLARQVD GDNSHVEMKL AADEEENADN NMKASVRKPK
RFNGRLCFAA IALVIFFLIG FMSGYLGYCK RVEQKEECVK LAETEETDKS ETMETEDVPT
SSRLYWADLK TLLSEKLNSI EFADTIKQLS QNTYTPREAG SQKDESLAYY IENQFHEFKF
SKVWRDEHYV KIQVKSSIGQ NMVTIVQSNG NLDPVESPEG YVAFSKPTEV SGKLVHANFG
TKKDFEELSY SVNGSLVIVR AGEITFAEKV ANAQSFNAIG VLIYMDKNKF PVVEADLALF
GHAHLGTGDP YTPGFPSFNH TQFPPSQSSG LPNIPVQTIS RAAAEKLFGK MEGSCPARWN
IDSSCKLELS QNQNVKLIVK NVLKERRILN IFGVIKGYEE PDRYVVVGAQ RDALGAGVAA
KSSVGTGLLL KLAQVFSDMI SKDGFRPSRS IIFASWTAGD FGAVGATEWL EGYLSSLHLK
AFTYINLDKV VLGTSNFKVS ASPLLYTLMG KIMQDVKHPV DGKSLYRDSN WISKVEKLSF
DNAAYPFLAY SGIPAVSFCF CEDADYPYLG TRLDTYEALT QKVPQLNQMV RTAAEVAGQL
IIKLTHDVEL NLDYEMYNSK LLSFMKDLNQ FKTDIRDMGL SLQWLYSARG DYFRATSRLT
TDFHNAEKTN RFVMREINDR IMKVEYHFLS PYVSPRESPF RHIFWGSGSH TLSALVENLK
LRQKNITAFN ETLFRNQLAL ATWTIQGVAN ALSGDIWNID NEF
