TFR1_RAT
ID TFR1_RAT Reviewed; 761 AA.
AC Q99376; G3V679;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 2.
DT 03-AUG-2022, entry version 149.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1] {ECO:0000312|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000312|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0000312|EMBL:EDM11405.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000312|EMBL:EDM11405.1};
RA Mural R.J., Li P.W., Adams M.D., Amanatides P.G., Baden-Tillson H.,
RA Barnstead M., Chin S.H., Dew I., Evans C.A., Ferriera S., Flanigan M.,
RA Fosler C., Glodek A., Gu Z., Holt R.A., Jennings D., Kraft C.L., Lu F.,
RA Nguyen T., Nusskern D.R., Pfannkoch C.M., Sitter C., Sutton G.G.,
RA Venter J.C., Wang Z., Woodage T., Zheng X.H., Zhong F.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 140-761.
RC TISSUE=Testis;
RX PubMed=2126342; DOI=10.1210/mend-4-4-531;
RA Roberts K.P., Griswold M.D.;
RT "Characterization of rat transferrin receptor cDNA: the regulation of
RT transferrin receptor mRNA in testes and in Sertoli cells in culture.";
RL Mol. Endocrinol. 4:531-542(1990).
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). Positively regulates T and B cell proliferation through
CC iron uptake (By similarity). Acts as a lipid sensor that regulates
CC mitochondrial fusion by regulating activation of the JNK pathway (By
CC similarity). When dietary levels of stearate (C18:0) are low, promotes
CC activation of the JNK pathway, resulting in HUWE1-mediated
CC ubiquitination and subsequent degradation of the mitofusin MFN2 and
CC inhibition of mitochondrial fusion (By similarity). When dietary levels
CC of stearate (C18:0) are high, TFRC stearoylation inhibits activation of
CC the JNK pathway and thus degradation of the mitofusin MFN2 (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:P02786}.
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 -!- INTERACTION:
CC Q99376; Q9BRI3: SLC30A2; Xeno; NbExp=3; IntAct=EBI-2112551, EBI-8644112;
CC Q99376; O14863: SLC30A4; Xeno; NbExp=5; IntAct=EBI-2112551, EBI-13918058;
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 -!- TISSUE SPECIFICITY: In testis, expressed in Sertoli cells, peritubular
CC myoid cells and in germinal cells. Highest levels in Sertoli cells.
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; AC136847; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473967; EDM11405.1; -; Genomic_DNA.
DR EMBL; M58040; AAA42273.1; -; mRNA.
DR PIR; A34549; A34549.
DR RefSeq; NP_073203.1; NM_022712.1.
DR RefSeq; XP_006248524.1; XM_006248462.3.
DR RefSeq; XP_006248525.1; XM_006248463.3.
DR AlphaFoldDB; Q99376; -.
DR SMR; Q99376; -.
DR IntAct; Q99376; 8.
DR MINT; Q99376; -.
DR STRING; 10116.ENSRNOP00000002407; -.
DR MEROPS; M28.972; -.
DR GlyGen; Q99376; 5 sites.
DR PhosphoSitePlus; Q99376; -.
DR jPOST; Q99376; -.
DR PaxDb; Q99376; -.
DR PeptideAtlas; Q99376; -.
DR PRIDE; Q99376; -.
DR ABCD; Q99376; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000002407; ENSRNOP00000002407; ENSRNOG00000001766.
DR GeneID; 64678; -.
DR KEGG; rno:64678; -.
DR UCSC; RGD:70488; rat.
DR CTD; 7037; -.
DR RGD; 70488; Tfrc.
DR eggNOG; KOG2195; Eukaryota.
DR GeneTree; ENSGT01030000234598; -.
DR HOGENOM; CLU_005688_5_0_1; -.
DR InParanoid; Q99376; -.
DR OMA; VMRVEYY; -.
DR OrthoDB; 804230at2759; -.
DR PhylomeDB; Q99376; -.
DR TreeFam; TF312981; -.
DR Reactome; R-RNO-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013026; RHOB GTPase cycle.
DR Reactome; R-RNO-9013106; RHOC GTPase cycle.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR Reactome; R-RNO-9013406; RHOQ GTPase cycle.
DR Reactome; R-RNO-9013407; RHOH GTPase cycle.
DR Reactome; R-RNO-9013408; RHOG GTPase cycle.
DR Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR Reactome; R-RNO-917977; Transferrin endocytosis and recycling.
DR Reactome; R-RNO-9696270; RND2 GTPase cycle.
DR Reactome; R-RNO-9696273; RND1 GTPase cycle.
DR PRO; PR:Q99376; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Proteomes; UP000234681; Chromosome 11.
DR Bgee; ENSRNOG00000001766; Expressed in quadriceps femoris and 20 other tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:RGD.
DR GO; GO:0009986; C:cell surface; IDA:ARUK-UCL.
DR GO; GO:0005905; C:clathrin-coated pit; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005769; C:early endosome; ISO:RGD.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0010008; C:endosome membrane; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0070062; C:extracellular exosome; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:1990712; C:HFE-transferrin receptor complex; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:RGD.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:CAFA.
DR GO; GO:0055037; C:recycling endosome; ISO:RGD.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:RGD.
DR GO; GO:0051087; F:chaperone binding; IPI:RGD.
DR GO; GO:0003725; F:double-stranded RNA binding; ISO:RGD.
DR GO; GO:0030544; F:Hsp70 protein binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR GO; GO:0004998; F:transferrin receptor activity; IDA:RGD.
DR GO; GO:0006953; P:acute-phase response; IEP:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0006826; P:iron ion transport; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; ISO:RGD.
DR GO; GO:0030316; P:osteoclast differentiation; ISO:RGD.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:0045780; P:positive regulation of bone resorption; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
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:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:RGD.
DR GO; GO:0042102; P:positive regulation of T cell proliferation; ISS:UniProtKB.
DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
DR GO; GO:0046688; P:response to copper ion; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0010035; P:response to inorganic substance; IEP:RGD.
DR GO; GO:0010039; P:response to iron ion; IEP:RGD.
DR GO; GO:0010042; P:response to manganese ion; IEP:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0032526; P:response to retinoic acid; IEP:RGD.
DR GO; GO:0033572; P:transferrin transport; ISO:RGD.
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; Disulfide bond; Endocytosis; Glycoprotein; Lipoprotein;
KW Membrane; Palmitate; Phosphoprotein; Receptor; Reference proteome;
KW Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..761
FT /note="Transferrin receptor protein 1"
FT /id="PRO_0000174134"
FT TOPO_DOM 1..65
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 66..86
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 87..761
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT DOMAIN 229..346
FT /note="PA"
FT /evidence="ECO:0000255"
FT REGION 1..67
FT /note="Mediates interaction with SH3BP4"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT REGION 570..761
FT /note="Ligand-binding"
FT /evidence="ECO:0000250"
FT MOTIF 20..23
FT /note="Endocytosis signal"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT MOTIF 58..61
FT /note="Stop-transfer sequence"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT MOTIF 647..649
FT /note="Cell attachment site; required for binding to
FT transferrin"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62351"
FT MOD_RES 20
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
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|UniProtKB:P02786"
FT CARBOHYD 248
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 723
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 728
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 89
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT DISULFID 98
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CONFLICT 342
FT /note="A -> P (in Ref. 3; AAA42273)"
FT /evidence="ECO:0000305"
FT CONFLICT 464
FT /note="A -> P (in Ref. 3; AAA42273)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="D -> N (in Ref. 3; AAA42273)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 761 AA; 85876 MW; 19488AD6D833249D CRC64;
MMDQARSAFS NLFGGEPLSY TRFSLARQVD GDNSHVEMKL AADEEENADS NMKASVRKPK
RFNGRLCFAT IAVVIFFLIG FMIGYLGYCK RVEQKEECVR LAEAEEADKS ENDETEYVPK
SSRLFWADLK TLLSEKLNSI EFTDIIKQLS QNTYTPREAG SQKDENLAYY IENLFHDFKF
SKVWRDEHYV KIQVKNSVSQ NLVTINSGSN IDPVEAPEGY VAFSKAGEVT GKLVHANFGT
KKDFEELNYS VNGSLVIVRA GKITFAEKVA NAQSFNAIGV LIYMDRNTFP VVEADLQFFG
HAHLGTGDPY TPGFPSFNHT QFPPSQSSGL PSIPVQTISR AAAEKLFKNM EGNCPPSWNI
DSSCKLELSQ NQNVKLTVNN VLKETRILNI FGVIKGYEEP DRYIVVGAQR DAWGPGVAKS
SVGTGLLLKL AQVFSDMISK DGFRPSRSII FASWTAGDYG AVGATEWLEG YLSSLHLKAF
TYINLDKVVL GTSNFKVSAS PLLYTLMGKI MQDVKHPIDG KYLYRDSNWI SKIEELSLDN
AAFPFLAYSG IPAVSFCFCE DEDYPYLGTK LDTYEILIQK VPQLNQMVRT AAEVAGQFII
KLTHDIELTL DYEMYNSKLL SFMKDLNQFK ADIKDMGLSL QWLYSARGDY FRATSRLTTD
FHNAEKTNRF VMREINDRIM KVEYHFLSPY VSPRESPFRH IFWGSGSHTL SALVENLRLR
QKNITAFNET LFRNQLALAT WTIQGVANAL SGDIWNIDNE F
