TFR1_HORSE
ID TFR1_HORSE Reviewed; 767 AA.
AC Q2V905;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 110.
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;
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wills T.L., Burnett R.C., Olver C.S.;
RT "Nucleotide sequence of the horse transferrin receptor.";
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
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 or HFE
CC molecule per subunit. Interacts with SH3BP4 (By similarity). Interacts
CC with STEAP3; facilitates TFRC endocytosis in erythroid precursor cells
CC (By 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 -!- SIMILARITY: Belongs to the peptidase M28 family. M28B subfamily.
CC {ECO:0000305}.
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DR EMBL; DQ284764; ABB91380.1; -; mRNA.
DR RefSeq; NP_001075382.1; NM_001081913.1.
DR RefSeq; XP_005601821.1; XM_005601764.2.
DR AlphaFoldDB; Q2V905; -.
DR SMR; Q2V905; -.
DR STRING; 9796.ENSECAP00000021947; -.
DR MEROPS; M28.972; -.
DR PaxDb; Q2V905; -.
DR PRIDE; Q2V905; -.
DR Ensembl; ENSECAT00000026320; ENSECAP00000021947; ENSECAG00000024267.
DR GeneID; 100034089; -.
DR KEGG; ecb:100034089; -.
DR CTD; 7037; -.
DR VGNC; VGNC:24048; TFRC.
DR GeneTree; ENSGT01030000234598; -.
DR HOGENOM; CLU_005688_5_0_1; -.
DR InParanoid; Q2V905; -.
DR OMA; VMRVEYY; -.
DR OrthoDB; 804230at2759; -.
DR TreeFam; TF312981; -.
DR Proteomes; UP000002281; Chromosome 19.
DR Bgee; ENSECAG00000024267; Expressed in bone marrow and 23 other tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IEA:Ensembl.
DR GO; GO:0010008; C:endosome membrane; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; IEA:Ensembl.
DR GO; GO:1990712; C:HFE-transferrin receptor complex; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0055037; C:recycling endosome; IEA:Ensembl.
DR GO; GO:0003725; F:double-stranded RNA binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0004998; F:transferrin receptor activity; ISS:UniProtKB.
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; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:Ensembl.
DR GO; GO:0006826; P:iron ion transport; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0010637; P:negative regulation of mitochondrial fusion; IEA:Ensembl.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:0045780; P:positive regulation of bone resorption; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IEA:Ensembl.
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: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 2: Evidence at transcript 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..767
FT /note="Transferrin receptor protein 1"
FT /id="PRO_0000237615"
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..767
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 230..320
FT /note="PA"
FT REGION 96..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 576..767
FT /note="Ligand-binding"
FT /evidence="ECO:0000250"
FT MOTIF 19..22
FT /note="Endocytosis signal"
FT MOTIF 60..63
FT /note="Stop-transfer sequence"
FT MOTIF 653..655
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 96..114
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62351"
FT MOD_RES 19
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT MOD_RES 20
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT LIPID 69
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 211
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 734
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT DISULFID 91
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 100
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 767 AA; 85517 MW; 36EEC355645ACE1A CRC64;
MDQARSAFSN LFGGAPLSYT RFSLARQVDG DNSHVEMKLA VDEEENVDNN VRSNHASLTK
PKRFNGSFCY AVIAVIIFFL IGFMIGYLGY CKRVEPKSEC GRSGDSKEIE GTEPPETEEY
FPETPSRLLW TDLRTMLSER LTATEFTNTI KRLNGNSYVP REAGSQKDES LAFFIENQFR
EFKLNKVWRD EHFVKIQVKG SNAQSSVTVV NGSGDMISLV ENPTGYVAYS KATTVTGKLV
HANFGTKEDY EALSYPVNGS LVIVRAGEIT FAQKVANAES LNAVGVLIYM DQAKFPIVNA
NLPVFGHAHL GTGDPYTPGF PSFNHTQFPP SQSSGLPNIP VQTISRAAAE ALFANMKGDC
PSSWKTDSSC RLEFPGDKNV KLTVNNELKE IRIFNVFGVI KGFEEPDRYV VIGAQRDAWG
PGAAKSSVGT ALLLELARIF SDMVSKGGFK PSRSIVFASW GAGDFGAIGA TEWLEGYLSS
LHLKAFTYIN LDKAVLGAKN FKVSASPLLY SLIEKTMQEV KHPVTGLSLY RDSNWINKVE
KLSFDNAAFP FLAYSGIPAL SFCFCEDTEY PYLGTTMDTY EVLSQNVPEL SRLTRAAAEV
AGQLLIKLSY DVELNLNYDM YNDKILSFVK DMNQFRADIK EMGLNLQWLY SARGDFFRAT
SRLTTDYKNA ERANRVVMRE INDRIMKVEY HFLSPYVSPR ESPFRHIFWG SGSHTLSALL
EHLKLRQKNS GAFNETLLRN QLALATWTIQ GAANALSGDI WDIDNEF
