TFR1_HUMAN
ID TFR1_HUMAN Reviewed; 760 AA.
AC P02786; D3DXB0; Q1HE24; Q59G55; Q9UCN0; Q9UCU5; Q9UDF9; Q9UK21;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 253.
DE RecName: Full=Transferrin receptor protein 1;
DE Short=TR;
DE Short=TfR;
DE Short=TfR1;
DE Short=Trfr;
DE AltName: Full=T9;
DE AltName: Full=p90;
DE AltName: CD_antigen=CD71;
DE Contains:
DE RecName: Full=Transferrin receptor protein 1, serum form;
DE Short=sTfR;
GN Name=TFRC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-142.
RX PubMed=6090955; DOI=10.1038/311675b0;
RA Schneider C., Owen M.J., Banville D., Williams J.G.;
RT "Primary structure of human transferrin receptor deduced from the mRNA
RT sequence.";
RL Nature 311:675-678(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-142.
RX PubMed=6094009; DOI=10.1016/0092-8674(84)90004-7;
RA McClelland A., Kuhn L.C., Ruddle F.H.;
RT "The human transferrin receptor gene: genomic organization, and the
RT complete primary structure of the receptor deduced from a cDNA sequence.";
RL Cell 39:267-274(1984).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=9358047; DOI=10.1016/s0378-1119(97)00356-9;
RA Evans P., Kemp J.;
RT "Exon/intron structure of the human transferrin receptor gene.";
RL Gene 199:123-131(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RA Wheeler D.L.;
RT "Molecular and evolutionary studies of the transferrin receptor.";
RL Thesis (1999), University of Iowa, United States.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [9]
RP PROTEIN SEQUENCE OF 101-119 (STFR).
RX PubMed=2229063; DOI=10.1016/s0021-9258(17)30627-0;
RA Shih Y.J., Baynes R.D., Hudson B.G., Flowers C.H., Skikne B.S., Cook J.D.;
RT "Serum transferrin receptor is a truncated form of tissue receptor.";
RL J. Biol. Chem. 265:19077-19081(1990).
RN [10]
RP PROTEIN SEQUENCE OF 101-123 (STFR), AND CHARACTERIZATION.
RC TISSUE=Erythroleukemia;
RX PubMed=1871153; DOI=10.3181/00379727-197-43276;
RA Baynes R.D., Shih Y.J., Hudson B.G., Cook J.D.;
RT "Characterization of transferrin receptor released by K562 erythroleukemia
RT cells.";
RL Proc. Soc. Exp. Biol. Med. 197:416-423(1991).
RN [11]
RP PROTEIN SEQUENCE OF 288-302; 694-708 AND 721-730.
RC TISSUE=Prostatic carcinoma;
RX PubMed=7864799; DOI=10.1042/bj3060129;
RA Coppolino M., Migliorini M., Argraves W.S., Dedhar S.;
RT "Identification of a novel form of the alpha 3 integrin subunit: covalent
RT association with transferrin receptor.";
RL Biochem. J. 306:129-134(1995).
RN [12]
RP PROTEIN SEQUENCE OF 680-696.
RX PubMed=1380674; DOI=10.1038/358764a0;
RA Chicz R.M., Urban R.G., Lane W.S., Gorga J.C., Stern L.J., Vignali D.A.A.,
RA Strominger J.L.;
RT "Predominant naturally processed peptides bound to HLA-DR1 are derived from
RT MHC-related molecules and are heterogeneous in size.";
RL Nature 358:764-768(1992).
RN [13]
RP FUNCTION.
RX PubMed=3568132; DOI=10.1016/0092-8674(87)90295-9;
RA Rothenberger S., Iacopetta B.J., Kuhn L.C.;
RT "Endocytosis of the transferrin receptor requires the cytoplasmic domain
RT but not its phosphorylation site.";
RL Cell 49:423-431(1987).
RN [14]
RP PALMITOYLATION AT CYS-62 AND CYS-67, AND INTERCHAIN DISULFIDE BOND AT
RP CYS-89 AND CYS-98.
RX PubMed=3582362; DOI=10.1002/j.1460-2075.1987.tb04758.x;
RA Jing S., Trowbridge I.S.;
RT "Identification of the intermolecular disulfide bonds of the human
RT transferrin receptor and its lipid-attachment site.";
RL EMBO J. 6:327-331(1987).
RN [15]
RP MUTAGENESIS OF CYSTEINE RESIDUES INVOLVED IN INTERMOLECULAR BONDS.
RX PubMed=2507316; DOI=10.1002/j.1460-2075.1989.tb08347.x;
RA Alvarez E., Girones N., Davis R.J.;
RT "Intermolecular disulfide bonds are not required for the expression of the
RT dimeric state and functional activity of the transferrin receptor.";
RL EMBO J. 8:2231-2240(1989).
RN [16]
RP MUTAGENESIS OF TYR-20.
RX PubMed=2327986; DOI=10.1042/bj2670031;
RA Alvarez E., Girones N., Davis R.J.;
RT "A point mutation in the cytoplasmic domain of the transferrin receptor
RT inhibits endocytosis.";
RL Biochem. J. 267:31-35(1990).
RN [17]
RP INTERNALIZATION SEQUENCE, AND MUTAGENESIS OF TYR-20.
RX PubMed=2298808; DOI=10.1083/jcb.110.2.283;
RA Jing S., Spencer T., Miller K., Hopkins C., Trowbridge I.S.;
RT "Role of the human transferrin receptor cytoplasmic domain in endocytosis:
RT localization of a specific signal sequence for internalization.";
RL J. Cell Biol. 110:283-294(1990).
RN [18]
RP GLYCOSYLATION AT THR-104.
RX PubMed=1421756; DOI=10.1093/glycob/2.4.345;
RA Do S.-I., Cummings R.D.;
RT "Presence of O-linked oligosaccharide on a threonine residue in the human
RT transferrin receptor.";
RL Glycobiology 2:345-353(1992).
RN [19]
RP GLYCOSYLATION AT THR-104.
RX PubMed=1421757; DOI=10.1093/glycob/2.4.355;
RA Hayes G.R., Enns C.A., Lucas J.J.;
RT "Identification of the O-linked glycosylation site of the human transferrin
RT receptor.";
RL Glycobiology 2:355-359(1992).
RN [20]
RP MUTAGENESIS OF 20-TYR--PHE-23; TYR-20; THR-21 AND PHE-23.
RX PubMed=8408022; DOI=10.1016/s0021-9258(20)80596-1;
RA Collawn J.F., Lai A., Domingo D.L., Fitch M., Hatton S., Trowbridge I.S.;
RT "YTRF is the conserved internalization signal of the transferrin receptor,
RT and a second YTRF signal at position 31-34 enhances endocytosis.";
RL J. Biol. Chem. 268:21686-21692(1993).
RN [21]
RP GLYCOSYLATION AT ASN-727, AND STRUCTURE OF CARBOHYDRATES ON ASN-727.
RX PubMed=7780197; DOI=10.1093/glycob/5.2.227;
RA Hayes G.R., Williams A., Costello C.E., Enns C.A., Lucas J.J.;
RT "The critical glycosylation site of human transferrin receptor contains a
RT high-mannose oligosaccharide.";
RL Glycobiology 5:227-232(1995).
RN [22]
RP IDENTIFICATION OF LIGAND-BINDING DOMAIN.
RX PubMed=8631371; DOI=10.1111/j.1432-1033.1996.0009u.x;
RA Buchegger F., Trowbridge I.S., Liu L.F., White S., Collawn J.F.;
RT "Functional analysis of human/chicken transferrin receptor chimeras
RT indicates that the carboxy-terminal region is important for ligand
RT binding.";
RL Eur. J. Biochem. 235:9-17(1996).
RN [23]
RP MUTAGENESIS OF ARG-646; GLY-647 AND ASP-648.
RX PubMed=10377239; DOI=10.1042/bj3410011;
RA Dubljevic V., Sali A., Goding J.W.;
RT "A conserved RGD (Arg-Gly-Asp) motif in the transferrin receptor is
RT required for binding to transferrin.";
RL Biochem. J. 341:11-14(1999).
RN [24]
RP MUTAGENESIS.
RX PubMed=11800564; DOI=10.1006/jmbi.2001.5048;
RA West A.P. Jr., Giannetti A.M., Herr A.B., Bennett M.J., Nangiana J.S.,
RA Pierce J.R., Weiner L.P., Snow P.M., Bjorkman P.J.;
RT "Mutational analysis of the transferrin receptor reveals overlapping HFE
RT and transferrin binding sites.";
RL J. Mol. Biol. 313:385-397(2001).
RN [25]
RP INTERACTION WITH SH3BP4.
RX PubMed=16325581; DOI=10.1016/j.cell.2005.10.021;
RA Tosoni D., Puri C., Confalonieri S., Salcini A.E., De Camilli P.,
RA Tacchetti C., Di Fiore P.P.;
RT "TTP specifically regulates the internalization of the transferrin
RT receptor.";
RL Cell 123:875-888(2005).
RN [26]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-251.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [28]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J.,
RA Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S.,
RA Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [29]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH MACHUPO VIRUS PROTEIN
RP GLYCOPROTEIN COMPLEX.
RX PubMed=17287727; DOI=10.1038/nature05539;
RA Radoshitzky S.R., Abraham J., Spiropoulou C.F., Kuhn J.H., Nguyen D.,
RA Li W., Nagel J., Schmidt P.J., Nunberg J.H., Andrews N.C., Farzan M.,
RA Choe H.;
RT "Transferrin receptor 1 is a cellular receptor for New World haemorrhagic
RT fever arenaviruses.";
RL Nature 446:92-96(2007).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [31]
RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH GUANARITO VIRUS
RP GLYCOPROTEIN COMPLEX, INTERACTION WITH JUNIN VIRUS GLYCOPROTEIN COMPLEX,
RP AND INTERACTION WITH MACHUPO VIRUS GLYCOPROTEIN COMPLEX.
RX PubMed=18268337; DOI=10.1073/pnas.0709254105;
RA Radoshitzky S.R., Kuhn J.H., Spiropoulou C.F., Albarino C.G., Nguyen D.P.,
RA Salazar-Bravo J., Dorfman T., Lee A.S., Wang E., Ross S.R., Choe H.,
RA Farzan M.;
RT "Receptor determinants of zoonotic transmission of New World hemorrhagic
RT fever arenaviruses.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:2664-2669(2008).
RN [32]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-251 AND ASN-727.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [33]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-251.
RC TISSUE=Leukemic T-cell;
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 [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-20, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [36]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [39]
RP FUNCTION, AND STEAROYLATION.
RX PubMed=26214738; DOI=10.1038/nature14601;
RA Senyilmaz D., Virtue S., Xu X., Tan C.Y., Griffin J.L., Miller A.K.,
RA Vidal-Puig A., Teleman A.A.;
RT "Regulation of mitochondrial morphology and function by stearoylation of
RT TFR1.";
RL Nature 525:124-128(2015).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [41]
RP ELECTRON MICROSCOPY, AND PHOSPHORYLATION AT SER-24.
RX PubMed=9782058; DOI=10.1016/s0969-2126(98)00124-5;
RA Fuchs H., Luecken W., Tauber R., Engel A.;
RT "Structural model of phospholipid-reconstituted human transferrin receptor
RT derived by electron microscopy.";
RL Structure 6:1235-1243(1998).
RN [42]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 121-760, AND GLYCOSYLATION AT
RP ASN-251; ASN-317 AND ASN-727.
RX PubMed=10531064; DOI=10.1126/science.286.5440.779;
RA Lawrence C.M., Ray S., Babyonyshev M., Galluser R., Borhani D.W.,
RA Harrison S.C.;
RT "Crystal structure of the ectodomain of human transferrin receptor.";
RL Science 286:779-782(1999).
RN [43]
RP VARIANT SER-142.
RX PubMed=11702220; DOI=10.1007/s004390100599;
RA Douabin-Gicquel V., Soriano N., Ferran H., Wojcik F., Palierne E.,
RA Tamim S., Jovelin T., McKie A.T., Le Gall J.-Y., David V., Mosser J.;
RT "Identification of 96 single nucleotide polymorphisms in eight genes
RT involved in iron metabolism: efficiency of bioinformatic extraction
RT compared with a systematic sequencing approach.";
RL Hum. Genet. 109:393-401(2001).
RN [44]
RP INVOLVEMENT IN IMD46, VARIANT IMD46 HIS-20, CHARACTERIZATION OF VARIANT
RP IMD46 HIS-20, FUNCTION, AND INTERACTION WITH STEAP3.
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 (PubMed:26214738). 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). A second ligand, the heditary hemochromatosis protein HFE,
CC competes for binding with transferrin for an overlapping C-terminal
CC binding site. Positively regulates T and B cell proliferation through
CC iron uptake (PubMed:26642240). Acts as a lipid sensor that regulates
CC mitochondrial fusion by regulating activation of the JNK pathway
CC (PubMed:26214738). When dietary levels of stearate (C18:0) are low,
CC promotes activation of the JNK pathway, resulting in HUWE1-mediated
CC ubiquitination and subsequent degradation of the mitofusin MFN2 and
CC inhibition of mitochondrial fusion (PubMed:26214738). When dietary
CC levels of stearate (C18:0) are high, TFRC stearoylation inhibits
CC activation of the JNK pathway and thus degradation of the mitofusin
CC MFN2 (PubMed:26214738). {ECO:0000250, ECO:0000269|PubMed:26214738,
CC ECO:0000269|PubMed:26642240, ECO:0000269|PubMed:3568132}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for new-world
CC arenaviruses: Guanarito, Junin and Machupo virus.
CC {ECO:0000269|PubMed:17287727, ECO:0000269|PubMed:18268337}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Binds one transferrin or HFE
CC molecule per subunit. Binds the HLA class II histocompatibility
CC antigen, DR1. Interacts with SH3BP3. Interacts with STEAP3; facilitates
CC TFRC endocytosis in erythroid precursor cells (PubMed:26642240).
CC {ECO:0000269|PubMed:16325581, ECO:0000269|PubMed:26642240}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Guanarito, Junin and
CC Machupo arenavirus glycoprotein complex (PubMed:17287727,
CC PubMed:18268337). {ECO:0000269|PubMed:17287727,
CC ECO:0000269|PubMed:18268337}.
CC -!- INTERACTION:
CC P02786; P02768: ALB; NbExp=2; IntAct=EBI-355727, EBI-714423;
CC P02786; Q13520: AQP6; NbExp=3; IntAct=EBI-355727, EBI-13059134;
CC P02786; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-355727, EBI-11343438;
CC P02786; P07307-3: ASGR2; NbExp=3; IntAct=EBI-355727, EBI-12808270;
CC P02786; Q96HA4-2: C1orf159; NbExp=3; IntAct=EBI-355727, EBI-17586094;
CC P02786; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-355727, EBI-6942903;
CC P02786; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-355727, EBI-18304435;
CC P02786; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-355727, EBI-18938272;
CC P02786; P02794: FTH1; NbExp=2; IntAct=EBI-355727, EBI-713259;
CC P02786; O00258: GET1; NbExp=3; IntAct=EBI-355727, EBI-18908258;
CC P02786; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-355727, EBI-13345167;
CC P02786; Q30201: HFE; NbExp=3; IntAct=EBI-355727, EBI-1028850;
CC P02786; Q30201-1: HFE; NbExp=3; IntAct=EBI-355727, EBI-15489346;
CC P02786; P31937: HIBADH; NbExp=3; IntAct=EBI-355727, EBI-11427100;
CC P02786; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-355727, EBI-2820517;
CC P02786; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-355727, EBI-11956541;
CC P02786; O14880: MGST3; NbExp=3; IntAct=EBI-355727, EBI-724754;
CC P02786; O75459: PAGE1; NbExp=3; IntAct=EBI-355727, EBI-2559100;
CC P02786; Q86WH2: RASSF3; NbExp=3; IntAct=EBI-355727, EBI-2845202;
CC P02786; Q8NC24: RELL2; NbExp=3; IntAct=EBI-355727, EBI-10269209;
CC P02786; Q96TC7: RMDN3; NbExp=3; IntAct=EBI-355727, EBI-1056589;
CC P02786; O43765: SGTA; NbExp=6; IntAct=EBI-355727, EBI-347996;
CC P02786; Q9P0V3: SH3BP4; NbExp=6; IntAct=EBI-355727, EBI-1049513;
CC P02786; Q14973: SLC10A1; NbExp=3; IntAct=EBI-355727, EBI-3923031;
CC P02786; P54219-3: SLC18A1; NbExp=3; IntAct=EBI-355727, EBI-17595455;
CC P02786; P02787: TF; NbExp=11; IntAct=EBI-355727, EBI-714319;
CC P02786; P02786: TFRC; NbExp=4; IntAct=EBI-355727, EBI-355727;
CC P02786; A5K736: PVX_094255; Xeno; NbExp=12; IntAct=EBI-355727, EBI-20622076;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17081065};
CC Single-pass type II membrane protein {ECO:0000269|PubMed:17081065}.
CC Melanosome {ECO:0000269|PubMed:17081065}. Note=Identified by mass
CC spectrometry in melanosome fractions from stage I to stage IV.
CC {ECO:0000269|PubMed:17081065}.
CC -!- SUBCELLULAR LOCATION: [Transferrin receptor protein 1, serum form]:
CC Secreted {ECO:0000269|PubMed:17081065}.
CC -!- INDUCTION: Regulated by cellular iron levels through binding of the
CC iron regulatory proteins, IRP1 and IRP2, to iron-responsive elements in
CC the 3'-UTR. Up-regulated upon mitogenic stimulation.
CC -!- PTM: Stearoylated by ZDHHC6 which inhibits TFRC-mediated activation of
CC the JNK pathway and promotes mitochondrial fragmentation
CC (PubMed:26214738). Stearoylation does not affect iron uptake
CC (PubMed:26214738). {ECO:0000269|PubMed:26214738}.
CC -!- PTM: N- and O-glycosylated, phosphorylated and palmitoylated. The serum
CC form is only glycosylated. {ECO:0000269|PubMed:1421756,
CC ECO:0000269|PubMed:1421757, ECO:0000269|PubMed:16335952,
CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19349973,
CC ECO:0000269|PubMed:3582362}.
CC -!- PTM: Proteolytically cleaved on Arg-100 to produce the soluble serum
CC form (sTfR).
CC -!- PTM: Palmitoylated on both Cys-62 and Cys-67. Cys-62 seems to be the
CC major site of palmitoylation. {ECO:0000269|PubMed:3582362}.
CC -!- DISEASE: Immunodeficiency 46 (IMD46) [MIM:616740]: An autosomal
CC recessive primary immunodeficiency disorder characterized by early-
CC onset chronic diarrhea, recurrent infections, hypo- or
CC agammaglobulinemia, normal lymphocyte counts, intermittent neutropenia,
CC and intermittent thrombocytopenia. {ECO:0000269|PubMed:26642240}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: Serum transferrin receptor (sTfR) is used as a means of
CC detecting erythropoietin (EPO) misuse by athletes and as a diagnostic
CC test for anemia resulting from a number of conditions including
CC rheumatoid arthritis, pregnancy, irritable bowel syndrome and in HIV
CC patients.
CC -!- MISCELLANEOUS: Canine and feline parvoviruses bind human and feline
CC transferrin receptors and use these receptors to enter and infect
CC cells.
CC -!- SIMILARITY: Belongs to the peptidase M28 family. M28B subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92491.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TFRCID259ch3q29.html";
CC ---------------------------------------------------------------------------
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DR EMBL; X01060; CAA25527.1; -; mRNA.
DR EMBL; M11507; AAA61153.1; -; mRNA.
DR EMBL; AF187320; AAF04564.1; -; Genomic_DNA.
DR EMBL; AB209254; BAD92491.1; ALT_INIT; mRNA.
DR EMBL; DQ496099; ABF47088.1; -; Genomic_DNA.
DR EMBL; CH471191; EAW53670.1; -; Genomic_DNA.
DR EMBL; CH471191; EAW53673.1; -; Genomic_DNA.
DR EMBL; BC001188; AAH01188.1; -; mRNA.
DR CCDS; CCDS3312.1; -.
DR PIR; A93343; JXHU.
DR RefSeq; NP_001121620.1; NM_001128148.2.
DR RefSeq; NP_001300894.1; NM_001313965.1.
DR RefSeq; NP_001300895.1; NM_001313966.1.
DR RefSeq; NP_003225.2; NM_003234.3.
DR PDB; 1CX8; X-ray; 3.20 A; A/B/C/D/E/F/G/H=122-760.
DR PDB; 1DE4; X-ray; 2.80 A; C/F/I=121-760.
DR PDB; 1SUV; EM; 7.50 A; A/B=122-760.
DR PDB; 2NSU; EM; 27.00 A; A/B=122-760.
DR PDB; 3KAS; X-ray; 2.40 A; A=121-760.
DR PDB; 3S9L; X-ray; 3.22 A; A/B=120-760.
DR PDB; 3S9M; X-ray; 3.32 A; A/B=120-760.
DR PDB; 3S9N; X-ray; 3.25 A; A/B=120-760.
DR PDB; 6D03; EM; 3.68 A; A/B=121-760.
DR PDB; 6D04; EM; 3.74 A; A/B=121-760.
DR PDB; 6D05; EM; 3.80 A; A/B=121-760.
DR PDB; 6GSR; EM; 5.50 A; Ab/Aq=121-760.
DR PDB; 6H5I; EM; 3.90 A; Ab/Aq=121-760.
DR PDB; 6OKD; X-ray; 1.85 A; A/B=121-760.
DR PDB; 6W3H; X-ray; 3.38 A; C/D=296-326.
DR PDB; 6WRV; X-ray; 2.47 A; A/B/E=121-759.
DR PDB; 6WRW; X-ray; 2.84 A; A/B=121-760.
DR PDB; 6WRX; X-ray; 3.07 A; A/B=121-760.
DR PDB; 6Y76; X-ray; 1.98 A; A/B=197-378.
DR PDBsum; 1CX8; -.
DR PDBsum; 1DE4; -.
DR PDBsum; 1SUV; -.
DR PDBsum; 2NSU; -.
DR PDBsum; 3KAS; -.
DR PDBsum; 3S9L; -.
DR PDBsum; 3S9M; -.
DR PDBsum; 3S9N; -.
DR PDBsum; 6D03; -.
DR PDBsum; 6D04; -.
DR PDBsum; 6D05; -.
DR PDBsum; 6GSR; -.
DR PDBsum; 6H5I; -.
DR PDBsum; 6OKD; -.
DR PDBsum; 6W3H; -.
DR PDBsum; 6WRV; -.
DR PDBsum; 6WRW; -.
DR PDBsum; 6WRX; -.
DR PDBsum; 6Y76; -.
DR AlphaFoldDB; P02786; -.
DR SMR; P02786; -.
DR BioGRID; 112895; 442.
DR CORUM; P02786; -.
DR DIP; DIP-2736N; -.
DR ELM; P02786; -.
DR IntAct; P02786; 135.
DR MINT; P02786; -.
DR STRING; 9606.ENSP00000353224; -.
DR ChEMBL; CHEMBL3712860; -.
DR DrugBank; DB13949; Ferric cation.
DR DrugBank; DB15617; Ferric derisomaltose.
DR DrugBank; DB14490; Ferrous ascorbate.
DR DrugBank; DB14491; Ferrous fumarate.
DR DrugBank; DB14488; Ferrous gluconate.
DR DrugBank; DB14501; Ferrous glycine sulfate.
DR DrugBank; DB14489; Ferrous succinate.
DR DrugBank; DB13257; Ferrous sulfate anhydrous.
DR DrugBank; DB01592; Iron.
DR DrugBank; DB14520; Tetraferric tricitrate decahydrate.
DR MEROPS; M28.972; -.
DR TCDB; 9.B.229.1.1; the transferrin receptor, cd71, (tfr) family.
DR GlyConnect; 607; 36 N-Linked glycans (5 sites), 5 O-Linked glycans (1 site).
DR GlyGen; P02786; 11 sites, 46 N-linked glycans (7 sites), 11 O-linked glycans (2 sites).
DR iPTMnet; P02786; -.
DR MetOSite; P02786; -.
DR PhosphoSitePlus; P02786; -.
DR SwissPalm; P02786; -.
DR BioMuta; TFRC; -.
DR DMDM; 108935939; -.
DR CPTAC; non-CPTAC-2704; -.
DR EPD; P02786; -.
DR jPOST; P02786; -.
DR MassIVE; P02786; -.
DR MaxQB; P02786; -.
DR PaxDb; P02786; -.
DR PeptideAtlas; P02786; -.
DR PRIDE; P02786; -.
DR ProteomicsDB; 51595; -.
DR ABCD; P02786; 98 sequenced antibodies.
DR Antibodypedia; 4559; 2909 antibodies from 49 providers.
DR DNASU; 7037; -.
DR Ensembl; ENST00000360110.9; ENSP00000353224.4; ENSG00000072274.13.
DR Ensembl; ENST00000392396.7; ENSP00000376197.3; ENSG00000072274.13.
DR GeneID; 7037; -.
DR KEGG; hsa:7037; -.
DR MANE-Select; ENST00000360110.9; ENSP00000353224.4; NM_001128148.3; NP_001121620.1.
DR UCSC; uc003fvz.5; human.
DR CTD; 7037; -.
DR DisGeNET; 7037; -.
DR GeneCards; TFRC; -.
DR HGNC; HGNC:11763; TFRC.
DR HPA; ENSG00000072274; Tissue enhanced (bone).
DR MalaCards; TFRC; -.
DR MIM; 190010; gene.
DR MIM; 616740; phenotype.
DR neXtProt; NX_P02786; -.
DR OpenTargets; ENSG00000072274; -.
DR Orphanet; 476113; Combined immunodeficiency due to TFRC deficiency.
DR PharmGKB; PA36478; -.
DR VEuPathDB; HostDB:ENSG00000072274; -.
DR eggNOG; KOG2195; Eukaryota.
DR GeneTree; ENSGT01030000234598; -.
DR InParanoid; P02786; -.
DR OMA; VMRVEYY; -.
DR OrthoDB; 804230at2759; -.
DR PhylomeDB; P02786; -.
DR TreeFam; TF312981; -.
DR PathwayCommons; P02786; -.
DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-917977; Transferrin endocytosis and recycling.
DR Reactome; R-HSA-9696270; RND2 GTPase cycle.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; P02786; -.
DR SIGNOR; P02786; -.
DR BioGRID-ORCS; 7037; 551 hits in 1087 CRISPR screens.
DR ChiTaRS; TFRC; human.
DR EvolutionaryTrace; P02786; -.
DR GeneWiki; TFRC; -.
DR GenomeRNAi; 7037; -.
DR Pharos; P02786; Tbio.
DR PRO; PR:P02786; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P02786; protein.
DR Bgee; ENSG00000072274; Expressed in endothelial cell and 209 other tissues.
DR ExpressionAtlas; P02786; baseline and differential.
DR Genevisible; P02786; HS.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005905; C:clathrin-coated pit; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR GO; GO:0005769; C:early endosome; IEA:Ensembl.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0010008; C:endosome membrane; IDA:CAFA.
DR GO; GO:0009897; C:external side of plasma membrane; IGI:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:1990712; C:HFE-transferrin receptor complex; IDA:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; IGI:BHF-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:CAFA.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:Ensembl.
DR GO; GO:0051087; F:chaperone binding; IEA:Ensembl.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:MGI.
DR GO; GO:0030544; F:Hsp70 protein binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0004998; F:transferrin receptor activity; IDA:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
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; IBA:GO_Central.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:UniProtKB.
DR GO; GO:0006826; P:iron ion transport; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ARUK-UCL.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; IMP:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IDA:UniProtKB.
DR GO; GO:0045780; P:positive regulation of bone resorption; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:ARUK-UCL.
DR GO; GO:0045830; P:positive regulation of isotype switching; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:ARUK-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:ARUK-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:ARUK-UCL.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IMP:ARUK-UCL.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; IDA:UniProtKB.
DR GO; GO:0031623; P:receptor internalization; IDA: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:0010039; P:response to iron ion; 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; IDA:UniProtKB.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
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 3D-structure; Cell membrane; Direct protein sequencing; Disease variant;
KW Disulfide bond; Endocytosis; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Receptor; Reference proteome;
KW Secreted; Signal-anchor; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..760
FT /note="Transferrin receptor protein 1"
FT /id="PRO_0000174132"
FT CHAIN 101..760
FT /note="Transferrin receptor protein 1, serum form"
FT /id="PRO_0000292265"
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..760
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 223..313
FT /note="PA"
FT REGION 1..67
FT /note="Mediates interaction with SH3BP4"
FT /evidence="ECO:0000269|PubMed:16325581"
FT REGION 569..760
FT /note="Ligand-binding"
FT MOTIF 20..23
FT /note="Endocytosis signal"
FT /evidence="ECO:0000269|PubMed:2298808"
FT MOTIF 58..61
FT /note="Stop-transfer sequence"
FT /evidence="ECO:0000303|PubMed:6090955"
FT MOTIF 646..648
FT /note="Cell attachment site; required for binding to
FT transferrin"
FT SITE 100..101
FT /note="Cleavage; by trypsin; to produce soluble form"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62351"
FT MOD_RES 20
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 21
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9782058"
FT LIPID 62
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:3582362"
FT LIPID 67
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:3582362"
FT CARBOHYD 104
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:1421756,
FT ECO:0000269|PubMed:1421757"
FT /id="CAR_000072"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:10531064,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:19349973, ECO:0007744|PDB:1CX8"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:10531064,
FT ECO:0007744|PDB:1CX8"
FT CARBOHYD 727
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:10531064,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:7780197,
FT ECO:0007744|PDB:1CX8"
FT /id="CAR_000173"
FT DISULFID 89
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:3582362"
FT DISULFID 98
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:3582362"
FT VARIANT 20
FT /note="Y -> H (in IMD46; increases protein expression;
FT increases cell surface expression on T and B cells;
FT increases soluble form level; impairs receptor
FT internalization; impairs transferrin transport; impairs T
FT and B cell proliferation as well as B cell class-switching;
FT interacts with STEAP3; doesn't affect receptor
FT internalization in erythroid precursor cells;
FT dbSNP:rs863225436)"
FT /evidence="ECO:0000269|PubMed:26642240"
FT /id="VAR_076365"
FT VARIANT 142
FT /note="G -> S (in dbSNP:rs3817672)"
FT /evidence="ECO:0000269|PubMed:11702220,
FT ECO:0000269|PubMed:6090955, ECO:0000269|PubMed:6094009"
FT /id="VAR_012737"
FT VARIANT 212
FT /note="L -> V (in dbSNP:rs41301381)"
FT /id="VAR_051806"
FT VARIANT 420
FT /note="G -> S (in dbSNP:rs41295879)"
FT /id="VAR_051807"
FT VARIANT 677
FT /note="R -> H (in dbSNP:rs41298067)"
FT /id="VAR_051808"
FT MUTAGEN 9..12
FT /note="FSNL->YTRF: Only 80% as active as wild-type
FT receptor."
FT MUTAGEN 20..34
FT /note="YTRFSLARQVDGDNS->PPGYSLARQVDYTRF: No influence on
FT endocytic uptake of the receptor."
FT MUTAGEN 20..23
FT /note="YTRF->PPGY: Only 16% as active as wild-type
FT receptor."
FT /evidence="ECO:0000269|PubMed:8408022"
FT MUTAGEN 20
FT /note="Y->C: Only 35% as active as wild-type receptor."
FT /evidence="ECO:0000269|PubMed:2298808,
FT ECO:0000269|PubMed:2327986, ECO:0000269|PubMed:8408022"
FT MUTAGEN 20
FT /note="Y->G: Only 20% as active as wild-type receptor."
FT /evidence="ECO:0000269|PubMed:2298808,
FT ECO:0000269|PubMed:2327986, ECO:0000269|PubMed:8408022"
FT MUTAGEN 21
FT /note="T->F: Only 88% as active as wild-type receptor."
FT /evidence="ECO:0000269|PubMed:8408022"
FT MUTAGEN 21
FT /note="T->TA: Only 14% as active as wild-type receptor."
FT /evidence="ECO:0000269|PubMed:8408022"
FT MUTAGEN 21
FT /note="T->TAA: Only 19% as active as wild-type receptor."
FT /evidence="ECO:0000269|PubMed:8408022"
FT MUTAGEN 23
FT /note="F->Y: Only 48% as active as wild-type receptor."
FT /evidence="ECO:0000269|PubMed:8408022"
FT MUTAGEN 31..34
FT /note="GDNS->YTRF: 2-fold increase of the endocytic uptake
FT of the receptor."
FT MUTAGEN 47..50
FT /note="NADN->YTRF: 1.27-fold increase of the endocytic
FT uptake of the receptor."
FT MUTAGEN 619
FT /note="L->A: 20-fold reduced affinity for transferrin
FT receptor. No binding to HFE."
FT MUTAGEN 622
FT /note="V->A: No significant effect on binding to
FT transferrin nor HFE."
FT MUTAGEN 623
FT /note="R->A: No significant effect on binding to
FT transferrin nor HFE."
FT MUTAGEN 629
FT /note="R->A: >5-fold reduced affinity for transferrin. >10-
FT fold reduced affinity for HFE."
FT MUTAGEN 640
FT /note="Q->A: No effect on binding to transferrin. >10-fold
FT reduced affinity for HFE."
FT MUTAGEN 641
FT /note="W->A: No significant effect on binding to
FT transferrin nor HFE."
FT MUTAGEN 643
FT /note="Y->A: 20-fold reduced affinity for transferrin. No
FT binding to HFE."
FT MUTAGEN 644
FT /note="S->A: No significant effect on binding to
FT transferrin nor HFE."
FT MUTAGEN 646
FT /note="R->A,H: No binding to transferrin."
FT /evidence="ECO:0000269|PubMed:10377239"
FT MUTAGEN 646
FT /note="R->K: 5% binding to transferrin."
FT /evidence="ECO:0000269|PubMed:10377239"
FT MUTAGEN 647
FT /note="G->A: Large effect on affinity for transferrin. 4-
FT fold reduced affinity for HFE."
FT /evidence="ECO:0000269|PubMed:10377239"
FT MUTAGEN 648
FT /note="D->A: 16% binding to transferrin."
FT /evidence="ECO:0000269|PubMed:10377239"
FT MUTAGEN 648
FT /note="D->E: 57% binding to transferrin."
FT /evidence="ECO:0000269|PubMed:10377239"
FT MUTAGEN 650
FT /note="F->Q: >5-fold reduced affinity for transferrin. >10-
FT fold reduced affinity for HFE."
FT CONFLICT 104
FT /note="T -> K (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 109
FT /note="R -> V (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 123
FT /note="Y -> T (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 124..136
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 141..146
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 160..175
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 179..192
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:6W3H"
FT STRAND 199..204
FT /evidence="ECO:0007829|PDB:6OKD"
FT TURN 205..208
FT /evidence="ECO:0007829|PDB:3KAS"
FT STRAND 209..214
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:3S9L"
FT STRAND 226..230
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:6WRV"
FT HELIX 240..245
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 253..259
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:6WRV"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:6OKD"
FT TURN 285..287
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 303..306
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 308..310
FT /evidence="ECO:0007829|PDB:3S9L"
FT STRAND 311..313
FT /evidence="ECO:0007829|PDB:1CX8"
FT HELIX 317..319
FT /evidence="ECO:0007829|PDB:6WRV"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 339..346
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 355..357
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 364..367
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 372..377
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 380..393
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 396..408
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 411..413
FT /evidence="ECO:0007829|PDB:6OKD"
FT TURN 416..419
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 420..440
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 445..454
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 456..458
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 461..468
FT /evidence="ECO:0007829|PDB:6OKD"
FT TURN 469..473
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 474..476
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 478..483
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 491..498
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 500..502
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 503..510
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 512..514
FT /evidence="ECO:0007829|PDB:6WRW"
FT TURN 516..518
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 520..522
FT /evidence="ECO:0007829|PDB:3KAS"
FT HELIX 528..531
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 541..546
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 552..558
FT /evidence="ECO:0007829|PDB:6OKD"
FT TURN 564..567
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 573..579
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 583..602
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 603..606
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 613..626
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 629..634
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 640..662
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 668..678
FT /evidence="ECO:0007829|PDB:6OKD"
FT TURN 679..682
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 683..685
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 688..690
FT /evidence="ECO:0007829|PDB:3S9L"
FT TURN 692..694
FT /evidence="ECO:0007829|PDB:6OKD"
FT TURN 700..702
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 705..708
FT /evidence="ECO:0007829|PDB:3S9M"
FT HELIX 709..718
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 719..723
FT /evidence="ECO:0007829|PDB:6WRX"
FT HELIX 728..748
FT /evidence="ECO:0007829|PDB:6OKD"
FT STRAND 750..752
FT /evidence="ECO:0007829|PDB:6OKD"
FT HELIX 753..755
FT /evidence="ECO:0007829|PDB:6WRV"
SQ SEQUENCE 760 AA; 84871 MW; C886F14000D90154 CRC64;
MMDQARSAFS NLFGGEPLSY TRFSLARQVD GDNSHVEMKL AVDEEENADN NTKANVTKPK
RCSGSICYGT IAVIVFFLIG FMIGYLGYCK GVEPKTECER LAGTESPVRE EPGEDFPAAR
RLYWDDLKRK LSEKLDSTDF TGTIKLLNEN SYVPREAGSQ KDENLALYVE NQFREFKLSK
VWRDQHFVKI QVKDSAQNSV IIVDKNGRLV YLVENPGGYV AYSKAATVTG KLVHANFGTK
KDFEDLYTPV NGSIVIVRAG KITFAEKVAN AESLNAIGVL IYMDQTKFPI VNAELSFFGH
AHLGTGDPYT PGFPSFNHTQ FPPSRSSGLP NIPVQTISRA AAEKLFGNME GDCPSDWKTD
STCRMVTSES KNVKLTVSNV LKEIKILNIF GVIKGFVEPD HYVVVGAQRD AWGPGAAKSG
VGTALLLKLA QMFSDMVLKD GFQPSRSIIF ASWSAGDFGS VGATEWLEGY LSSLHLKAFT
YINLDKAVLG TSNFKVSASP LLYTLIEKTM QNVKHPVTGQ FLYQDSNWAS KVEKLTLDNA
AFPFLAYSGI PAVSFCFCED TDYPYLGTTM DTYKELIERI PELNKVARAA AEVAGQFVIK
LTHDVELNLD YERYNSQLLS FVRDLNQYRA DIKEMGLSLQ WLYSARGDFF RATSRLTTDF
GNAEKTDRFV MKKLNDRVMR VEYHFLSPYV SPKESPFRHV FWGSGSHTLP ALLENLKLRK
QNNGAFNETL FRNQLALATW TIQGAANALS GDVWDIDNEF
