ID   HFE_DICBI               Reviewed;         348 AA.
AC   Q9GL43; Q9GK81;
DT   25-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   25-MAY-2022, entry version 78.
DE   RecName: Full=Hereditary hemochromatosis protein homolog;
DE   Flags: Precursor;
GN   Name=HFE;
OS   Diceros bicornis (Black rhinoceros).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Perissodactyla; Rhinocerotidae; Diceros.
OX   NCBI_TaxID=9805;
RN   [1]
RP   NUCLEOTIDE SEQUENCE.
RA   West C.J., Worley M., Beutler E.;
RT   "Rhinoceros HFE polymorphisms.";
RL   Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Binds to transferrin receptor (TFR) and reduces its affinity
CC       for iron-loaded transferrin. {ECO:0000250|UniProtKB:Q30201}.
CC   -!- SUBUNIT: Binds TFR through the extracellular domain in a pH-dependent
CC       manner. {ECO:0000250|UniProtKB:Q30201}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q30201};
CC       Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q30201}.
CC   -!- SIMILARITY: Belongs to the MHC class I family. {ECO:0000305}.
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DR   EMBL; AY007542; AAG23702.1; -; mRNA.
DR   EMBL; AF301592; AAG39940.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q9GL43; -.
DR   SMR; Q9GL43; -.
DR   GO; GO:1990712; C:HFE-transferrin receptor complex; IEA:InterPro.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:1990459; F:transferrin receptor binding; IEA:InterPro.
DR   GO; GO:0098711; P:iron ion import across plasma membrane; IEA:InterPro.
DR   GO; GO:0002626; P:negative regulation of T cell antigen processing and presentation; IEA:InterPro.
DR   Gene3D; 2.60.40.10; -; 1.
DR   Gene3D; 3.30.500.10; -; 1.
DR   InterPro; IPR031092; HFE.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003006; Ig/MHC_CS.
DR   InterPro; IPR003597; Ig_C1-set.
DR   InterPro; IPR011161; MHC_I-like_Ag-recog.
DR   InterPro; IPR037055; MHC_I-like_Ag-recog_sf.
DR   InterPro; IPR011162; MHC_I/II-like_Ag-recog.
DR   InterPro; IPR001039; MHC_I_a_a1/a2.
DR   PANTHER; PTHR16675:SF172; PTHR16675:SF172; 1.
DR   Pfam; PF07654; C1-set; 1.
DR   Pfam; PF00129; MHC_I; 1.
DR   PRINTS; PR01638; MHCCLASSI.
DR   SMART; SM00407; IGc1; 1.
DR   SUPFAM; SSF48726; SSF48726; 1.
DR   SUPFAM; SSF54452; SSF54452; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   PROSITE; PS00290; IG_MHC; 1.
PE   2: Evidence at transcript level;
KW   Cell membrane; Disulfide bond; Glycoprotein; Ion transport; Iron;
KW   Iron transport; Membrane; Signal; Transmembrane; Transmembrane helix;
KW   Transport.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000250"
FT   CHAIN           23..348
FT                   /note="Hereditary hemochromatosis protein homolog"
FT                   /id="PRO_0000018890"
FT   TOPO_DOM        23..306
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:Q30201"
FT   TRANSMEM        307..330
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        331..348
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q30201"
FT   DOMAIN          207..296
FT                   /note="Ig-like C1-type"
FT   REGION          23..114
FT                   /note="Alpha-1"
FT   REGION          115..205
FT                   /note="Alpha-2"
FT   REGION          206..297
FT                   /note="Alpha-3"
FT   REGION          298..306
FT                   /note="Connecting peptide"
FT   CARBOHYD        110
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        130
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        124..187
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   DISULFID        225..282
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ   SEQUENCE   348 AA;  39818 MW;  4D95E7B01E48FB90 CRC64;
     MGPRARPALF FLILLRTVAA QGRPPRSHSL RYLFMGASER DHGLPLFEAL GYVDDELFVA
     YNHESRRAES RAQWVLGEAH SQLWLQLTQS LKGWDHMFIV DFWTIMDNHN HSKESHTLQV
     ILGCEVQEDN STRGFWKYGY DGQDHLEFCP ETLDWRAAES RALTTKLEWE VNKIRAKQNR
     AYLERDCPEQ LQWLLELGRG VLDQQVPPLV KVTHHVASAV TTLRCQALNF YPQNITMRWL
     KDRKPVDVKD AESKDVLPSG DGTYQSWEAL AVPPGEEQRY TCQVEHPGLD QPLTATWEPS
     LSNTLVTGVI SGIAVCVIIF FIGILFRILR KRQASRGAMG DYVLAECE