TFR1_CRIGR
ID TFR1_CRIGR Reviewed; 757 AA.
AC Q07891;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-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 Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
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 [2]
RP PRELIMINARY PARTIAL NUCLEOTIDE SEQUENCE.
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).
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 -!- 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; L19142; AAA03576.1; -; mRNA.
DR PIR; A48592; A48592.
DR RefSeq; NP_001233748.1; NM_001246819.1.
DR AlphaFoldDB; Q07891; -.
DR SMR; Q07891; -.
DR STRING; 10029.NP_001233748.1; -.
DR MEROPS; M28.972; -.
DR GeneID; 100689395; -.
DR KEGG; cge:100689395; -.
DR CTD; 7037; -.
DR eggNOG; KOG2195; Eukaryota.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055037; C:recycling endosome; IDA:MGI.
DR GO; GO:0004998; F:transferrin receptor activity; ISS:UniProtKB.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IEA:InterPro.
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; Signal-anchor;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..757
FT /note="Transferrin receptor protein 1"
FT /id="PRO_0000174130"
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..757
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 220..310
FT /note="PA"
FT REGION 1..67
FT /note="Mediates interaction with SH3BP4"
FT /evidence="ECO:0000250"
FT REGION 566..757
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 643..645
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 67
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 103
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 248
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 314
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 719
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 724
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT DISULFID 89
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT DISULFID 97
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT CONFLICT 20
FT /note="Y -> T (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 757 AA; 85081 MW; A6E6D1B8BB57C2EE CRC64;
MMDQARSAIS NLFGGEPLSY TRFSLARQVD GDNSHVEMKL AVDEEENTDN NMKASVRKHR
RLNGRLCFGT IAVVIFFLIG FMIGYLGYCK RTEQKDCVRL AETETGNSEI IQEENIPQSS
RLYWADLKKL LSEKLDAIEF TDTIKQLSQT SREAGSQKDE NLAYYIENQF RDFKLSKVWR
DEHYVKIQVK GSAAQNAVTI INVNGDSDLV ENPGGYVAYS KATTVSGKLI HANFGTKKDF
EDLKYPVNGS LVIVRAGKIT FAEKVANAQS FNAIGVLIYM DQTKFPVVEA ELSLFGHAHL
GTGDPYTPGF PSFNHTQFPP SQSSGLPSIP VQTISRKAAE KLFQNMETNC PPSWNTDSLC
KLESSQGINV NLSVNNVLKE TRILNIFGVI KGFEEPDRYI VVGAQRDAWG PGAAKSSVGT
GLLLKLAQAF SDMVSRGGFK PSRSIIFASW SAGDFGAVGA TEWLEGYLSS LHLKAFTYIN
LDKVVLGTRN FKVSASPLLY TLIEKTMQDV RHPIDGKPLY RDSNWISKVE DLSLDNAAFP
FLAYSGIPAV SFWFCENEDY PYLDTNLDTY EKLIQKVPQL NKMVRAAAEV AGQFIIKLTH
DIELNLDYDM YNNKILSFVK ELNQFRADIK AMGLSLQWLY SARGDFFRAT SRLTTDFHNA
EKTNRFVVRE INNRIMKVEY HFLSPYVSPR ESPFRHIFWG SGSHTLTALV ENLKLRQKNS
SAFNETLFRN QLALATWTIQ GVANALSGDI WDIDNEF
