TFR1_FELCA
ID TFR1_FELCA Reviewed; 769 AA.
AC Q9MYZ3;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 121.
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 Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
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 FELINE PANLEUKOPENIA VIRUS 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). Homodimer;
CC disulfide-linked. Binds one transferrin or HFE molecule per subunit.
CC Binds the HLA class II histocompatibility antigen, DR1. Interacts with
CC 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 -!- 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF276984; AAF81908.1; -; mRNA.
DR RefSeq; NP_001009312.1; NM_001009312.1.
DR AlphaFoldDB; Q9MYZ3; -.
DR SMR; Q9MYZ3; -.
DR STRING; 9685.ENSFCAP00000003404; -.
DR MEROPS; M28.972; -.
DR PRIDE; Q9MYZ3; -.
DR GeneID; 493880; -.
DR KEGG; fca:493880; -.
DR CTD; 7037; -.
DR eggNOG; KOG2195; Eukaryota.
DR InParanoid; Q9MYZ3; -.
DR Proteomes; UP000011712; Unplaced.
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 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..769
FT /note="Transferrin receptor protein 1"
FT /id="PRO_0000174131"
FT TOPO_DOM 1..70
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 71..91
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 92..769
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 232..322
FT /note="PA"
FT REGION 1..70
FT /note="Mediates interaction with SH3BP4"
FT /evidence="ECO:0000250"
FT REGION 578..769
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 655..657
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 107
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000250"
FT CARBOHYD 260
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 326
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P02786"
FT CARBOHYD 731
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 736
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 769 AA; 86271 MW; 47EA4FC0A18A46D7 CRC64;
MMDQARSAFS TLFGGEPLSY TRFSLARQVD GDNSHVEMKL AADEEENVDN NMRDNGASVT
KPKRFNGFIC YGTIAIILFF LIGFMIGYLG YCKRVEAKSE CERPAGTESL EVEGTEPSET
EEYFPEAPSH LFWSDLKTML SEKLSNTEFT STIRQLNENS YFPREAGSQK DESLAFFIEN
RFRELQLSKA WHDEHFVKVQ VKGSASNSVT IVGTNSGMVY LVESPEGYVA YSKAATVTGR
LVHANFGTKK DFENLNSPVN GSLVIVRAGK ITFAEKVANA ESFNAIGVLI YMDQAKFPIT
NAEIPFFGHA HLGTGDPYTP GFPSFNHTQF PPSQSSGLPN IPVQTISRAN AEKLFGNMEG
DCPSAWETDS SCRLETSRNW NVKLSVNNVL KEIRIFNVFG VIKGFEEPDH YVVVGAQRDA
WGPGAAKSSV GTALLLELAR ILSDMVLKGG FKPSRSIVFA SWSAGDFGAV GATEWLEGYL
SSLHLKAFTY INLDKAVLGT SNFKVSASPL LYSLIEKVMK DVKHPVTGQS LYRDSNWINK
VEKFSLDNAA FPFLAYSGIP AVSFCFCEDT DYPYLGTTMD VYEKLIQKVP QLNKMARAAA
EVAGQLIMKL TYDLELNLNY EMYNDKILSF VRDVSRFRAD IKEMGLNLQW LYSARGDFFR
ATSRLTTDYR NAERTNRFIM RDINDRIMRV EYHFLSPYVS PRESPFRHIF WGTGSHTLSA
LLEHLKLRQE NISAFNETLF RNQLALTTWT IQGAANALSG DIWDIDNEF
