TFR1_PIG
ID TFR1_PIG Reviewed; 768 AA.
AC Q8HZV3;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 108.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Small intestine;
RX PubMed=16130451; DOI=10.1111/j.1439-0388.2005.00490.x;
RA Python P., Jorg H., Neuenschwander S., Asai-Coakwell M., Hagger C.,
RA Burgi E., Bertschinger H.U., Stranzinger G., Vogeli P.;
RT "Inheritance of the F4ab, F4ac and F4ad E. coli receptors in swine and
RT examination of four candidate genes for F4acR.";
RL J. Anim. Breed. Genet. 122:5-14(2005).
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 SH3BP3. Interacts with STEAP3; facilitates TFRC endocytosis in
CC erythroid precursor cells (By similarity). {ECO:0000250,
CC 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; AF416763; AAN09749.1; -; mRNA.
DR RefSeq; NP_999166.1; NM_214001.1.
DR AlphaFoldDB; Q8HZV3; -.
DR SMR; Q8HZV3; -.
DR STRING; 9823.ENSSSCP00000029501; -.
DR MEROPS; M28.972; -.
DR PaxDb; Q8HZV3; -.
DR PeptideAtlas; Q8HZV3; -.
DR PRIDE; Q8HZV3; -.
DR Ensembl; ENSSSCT00000012960; ENSSSCP00000012619; ENSSSCG00000011848.
DR Ensembl; ENSSSCT00005038577; ENSSSCP00005023673; ENSSSCG00005024344.
DR Ensembl; ENSSSCT00005038600; ENSSSCP00005023689; ENSSSCG00005024344.
DR Ensembl; ENSSSCT00005038626; ENSSSCP00005023711; ENSSSCG00005024344.
DR Ensembl; ENSSSCT00005038807; ENSSSCP00005023845; ENSSSCG00005024344.
DR Ensembl; ENSSSCT00005038830; ENSSSCP00005023862; ENSSSCG00005024344.
DR Ensembl; ENSSSCT00005038866; ENSSSCP00005023875; ENSSSCG00005024344.
DR Ensembl; ENSSSCT00015094782; ENSSSCP00015038877; ENSSSCG00015069917.
DR Ensembl; ENSSSCT00025040290; ENSSSCP00025017146; ENSSSCG00025029620.
DR Ensembl; ENSSSCT00040042676; ENSSSCP00040017879; ENSSSCG00040031412.
DR Ensembl; ENSSSCT00045017888; ENSSSCP00045012318; ENSSSCG00045010359.
DR Ensembl; ENSSSCT00050086561; ENSSSCP00050037146; ENSSSCG00050063573.
DR Ensembl; ENSSSCT00055011713; ENSSSCP00055009275; ENSSSCG00055005971.
DR Ensembl; ENSSSCT00065003468; ENSSSCP00065001260; ENSSSCG00065002628.
DR Ensembl; ENSSSCT00070023963; ENSSSCP00070019815; ENSSSCG00070011774.
DR Ensembl; ENSSSCT00070023968; ENSSSCP00070019819; ENSSSCG00070011774.
DR Ensembl; ENSSSCT00070023975; ENSSSCP00070019827; ENSSSCG00070011774.
DR Ensembl; ENSSSCT00070023978; ENSSSCP00070019830; ENSSSCG00070011774.
DR Ensembl; ENSSSCT00070023989; ENSSSCP00070019840; ENSSSCG00070011774.
DR Ensembl; ENSSSCT00070024000; ENSSSCP00070019851; ENSSSCG00070011774.
DR Ensembl; ENSSSCT00070024010; ENSSSCP00070019860; ENSSSCG00070011774.
DR GeneID; 397062; -.
DR KEGG; ssc:397062; -.
DR CTD; 7037; -.
DR VGNC; VGNC:93925; TFRC.
DR eggNOG; KOG2195; Eukaryota.
DR GeneTree; ENSGT01030000234598; -.
DR InParanoid; Q8HZV3; -.
DR OrthoDB; 804230at2759; -.
DR Proteomes; UP000008227; Chromosome 13.
DR Proteomes; UP000314985; Chromosome 13.
DR Bgee; ENSSSCG00000011848; Expressed in heart left ventricle and 45 other tissues.
DR ExpressionAtlas; Q8HZV3; baseline and differential.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
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:0006826; P:iron ion transport; IBA:GO_Central.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:0045830; P:positive regulation of isotype switching; ISS:UniProtKB.
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..768
FT /note="Transferrin receptor protein 1"
FT /id="PRO_0000237616"
FT TOPO_DOM 1..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 90..768
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 231..321
FT /note="PA"
FT REGION 1..70
FT /note="Mediates interaction with SH3BP4"
FT /evidence="ECO:0000250"
FT REGION 577..768
FT /note="Ligand-binding"
FT /evidence="ECO:0000250"
FT MOTIF 20..23
FT /note="Endocytosis signal"
FT MOTIF 61..64
FT /note="Stop-transfer sequence"
FT MOTIF 654..656
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: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 70
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 325
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 730
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 735
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT DISULFID 92
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 101
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 768 AA; 86122 MW; 55B15CEFA2F4D1CF CRC64;
MMDQARSAFS SLFGGEPLSY TRFSLARQVD GDNSHVEMKL AADEEENVDS NTRSNHIGVA
KPKRLNGYVC YGIIAVITFF LIGFMIGYLA YCKRVESKTD CKTLVPTEPS ETEETETFEA
ENFPQTPRLF WADLKILLSK GLDTTDFTRT IKMLNEDYAP REAGSQKDES LGFFIENQFR
EFKLSKVWHD EHFVKIQVKG SNAENSVTLV NTDSNSLVYP VESPEGYVAY SKATTVTGKL
IFANFGTKKD FEDLKMPVNG SLVIVRAGKI TFAEKVANAQ SLDAIGVLIY MDRANFPIIN
ADVPVFGHAH LGTGDPYTPG FPSFNHTQFP PSQSSGLPNI PVQTISRAGA EKLFGNMEQD
CPLTWRTDFP CKLVSSPSKN VKLTVNNVLK EIKILNIFGV IKGFEEPDRY VIVGAQRDAW
GPGAAKSSVG TSLLLNLAQI LSDMVIKGQF KPSRSIVFAS WSAGDFGAIG ATEWLEGYLS
SLHLKAFTYI NLDKAVLGTS NFKVSASPLL YSLIEKMMQD VKNPVTGQSL YRDSNWINKV
EKLSFDDAAF PFLAYSGIPA VSFCFCEDTD YPYLGTTMDT YDVLSKRVPQ LNRMARAAAE
VAGHLVIKLT IDFELNLNYE MYNDKILSFV REMNQFRVDI REMGLSLQWL YSARGDFFRA
TSRLTSDYRN VETRDKFVMR EINDRIMKVE YHFLSPYVSP RESPFRHIFW GSGSHTLSAL
VEHLKLRQKN SSAFNQTLLK NQLALATWTI QGAANALSGD IWDIDNEF
