TFR1_CANLF
ID TFR1_CANLF Reviewed; 770 AA.
AC Q9GLD3;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 25-MAY-2022, entry version 128.
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11264378; DOI=10.1128/jvi.75.8.3896-3902.2001;
RA Parker J.S.L., Murphy W.J., Wang D., O'Brien S.J., Parrish C.R.;
RT "Canine and feline parvoviruses can use human or feline transferrin
RT receptors to bind, enter, and infect cells.";
RL J. Virol. 75:3896-3902(2001).
RN [2]
RP INTERACTION WITH CANINE PARVOVIRUS CAPSID PROTEINS.
RX PubMed=19656887; DOI=10.1128/jvi.00295-09;
RA Harbison C.E., Lyi S.M., Weichert W.S., Parrish C.R.;
RT "Early steps in cell infection by parvoviruses: host-specific differences
RT in cell receptor binding but similar endosomal trafficking.";
RL J. Virol. 83:10504-10514(2009).
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 -!- DOMAIN: The YTRF endocytosis motif engages the clathrin-mediated
CC endocytic machinery through adapter protein-2.
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 -!- 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}.
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DR EMBL; AF297626; AAG24850.1; -; mRNA.
DR RefSeq; NP_001003111.1; NM_001003111.1.
DR AlphaFoldDB; Q9GLD3; -.
DR SMR; Q9GLD3; -.
DR STRING; 9612.ENSCAFP00000019067; -.
DR MEROPS; M28.972; -.
DR PaxDb; Q9GLD3; -.
DR GeneID; 403703; -.
DR KEGG; cfa:403703; -.
DR CTD; 7037; -.
DR eggNOG; KOG2195; Eukaryota.
DR InParanoid; Q9GLD3; -.
DR OrthoDB; 804230at2759; -.
DR Proteomes; UP000002254; Unplaced.
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: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 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Endocytosis; Glycoprotein;
KW Host-virus interaction; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Receptor; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..770
FT /note="Transferrin receptor protein 1"
FT /id="PRO_0000174129"
FT TOPO_DOM 1..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..90
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 91..770
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 233..323
FT /note="PA"
FT REGION 1..70
FT /note="Mediates interaction with SH3BP4"
FT /evidence="ECO:0000250"
FT REGION 102..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 579..770
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 656..658
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 65
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 70
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 107
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 261
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 384
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 732
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 737
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 770 AA; 86649 MW; 871F8320A1E1345A CRC64;
MMDQARSAFS TLFGGEPLSY TRFSLARQVD GDNSHVEMKL AADEEENVDN NMRGNHASVP
KPKRCNGFIC YGTIAVVLFF LIGFMIGYLG YCKRVEPKAG CERPTGTEAL GTERTEPSET
EEYFPETPSR LFWTDLKTML SERLSNTDFT NTMRWLNENS YVPREAGSQK DESLALLIEN
RFREFQLSKS WRDEHFVEIQ VKSSNAQNTV TIVDMESDLV YLAESPEGYV AYSKATTVTG
RLVHVNFGTK KDFENLKSPV NGSLVIARAG KITFAEKVAN AQSYNALGVL IYMDQARFPI
VNARIPFFGH AHLGTGDPYT PGFPSFNHTQ FPPSQSSGLP SIPVQTISRA AAEKLFENME
GDCPSAWEID PSCRLETSSN KNVNLTVNNV LKEIRIFNVF GVIKGFEEPD RYVVIGAQRD
AWGPGAAKSS VGTALLLELA RIFSDMVLKG GFKPSRSIVF ASWSAGDFGA IGATEWLEGY
LSSLHLKAFT YINLDKAILG TSNFKVSASP LLYSLLEKTM KDVKHPITGQ SLYRDSNWIN
KVEKLSLDNA AFPFLAYSGI PAVSFCFCED TDYPYLGTTM DLYENLNQKI PQLNKMARGA
AEVAGQLIMK LTYDLELNLN YEMYNDRILS FVRDMNQFRT DIKEMGLNLQ WLYSARGDFF
RATSRLTTDY KNAERTNRFV MREINDRIMK VEHNFLSPYV SPRDSPFRHI FWGSGSHTLP
ALVEHLKLRQ KNKSAFNETL LRNQLALATW TIQGAANALS GDIWDIDNEF
