HFE_RAT
ID HFE_RAT Reviewed; 360 AA.
AC O35799; O35175;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Hereditary hemochromatosis protein homolog;
DE AltName: Full=RT1-CAFE;
DE Flags: Precursor;
GN Name=Hfe;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Banasch M.W., Schaefer H., Schmidt W.E.;
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 42-303.
RC TISSUE=Small intestine;
RA Sawada-Hirai R., Rothenberg B.E.;
RL Submitted (JUN-1997) 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; AJ001517; CAA04799.1; -; mRNA.
DR EMBL; AF008587; AAB86597.1; -; mRNA.
DR RefSeq; NP_445753.1; NM_053301.4.
DR AlphaFoldDB; O35799; -.
DR SMR; O35799; -.
DR STRING; 10116.ENSRNOP00000022881; -.
DR GlyGen; O35799; 4 sites.
DR PaxDb; O35799; -.
DR Ensembl; ENSRNOT00000022809; ENSRNOP00000022809; ENSRNOG00000016967.
DR GeneID; 29199; -.
DR KEGG; rno:29199; -.
DR UCSC; RGD:2793; rat.
DR CTD; 3077; -.
DR RGD; 2793; Hfe.
DR eggNOG; KOG1745; Eukaryota.
DR HOGENOM; CLU_047501_0_2_1; -.
DR InParanoid; O35799; -.
DR OMA; KGWEHMF; -.
DR OrthoDB; 912212at2759; -.
DR PhylomeDB; O35799; -.
DR TreeFam; TF336617; -.
DR Reactome; R-RNO-917977; Transferrin endocytosis and recycling.
DR PRO; PR:O35799; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000016967; Expressed in liver and 20 other tissues.
DR ExpressionAtlas; O35799; baseline and differential.
DR Genevisible; O35799; RN.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0045178; C:basal part of cell; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005769; C:early endosome; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:1990712; C:HFE-transferrin receptor complex; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0055037; C:recycling endosome; ISO:RGD.
DR GO; GO:1990357; C:terminal web; IDA:RGD.
DR GO; GO:0030881; F:beta-2-microglobulin binding; ISO:RGD.
DR GO; GO:0039706; F:co-receptor binding; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:1990459; F:transferrin receptor binding; ISO:RGD.
DR GO; GO:0006953; P:acute-phase response; IEP:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; ISO:RGD.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:RGD.
DR GO; GO:0071281; P:cellular response to iron ion; ISO:RGD.
DR GO; GO:0010106; P:cellular response to iron ion starvation; IEP:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0042446; P:hormone biosynthetic process; ISO:RGD.
DR GO; GO:0055072; P:iron ion homeostasis; IEP:RGD.
DR GO; GO:0098711; P:iron ion import across plasma membrane; IEA:InterPro.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; ISO:RGD.
DR GO; GO:1904283; P:negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I; ISO:RGD.
DR GO; GO:2001186; P:negative regulation of CD8-positive, alpha-beta T cell activation; ISO:RGD.
DR GO; GO:1900121; P:negative regulation of receptor binding; ISO:RGD.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; ISO:RGD.
DR GO; GO:0002626; P:negative regulation of T cell antigen processing and presentation; IEA:InterPro.
DR GO; GO:0002725; P:negative regulation of T cell cytokine production; ISO:RGD.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:1904434; P:positive regulation of ferrous iron binding; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; ISO:RGD.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:RGD.
DR GO; GO:1900122; P:positive regulation of receptor binding; ISO:RGD.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISO:RGD.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; ISO:RGD.
DR GO; GO:1904437; P:positive regulation of transferrin receptor binding; ISO:RGD.
DR GO; GO:0034756; P:regulation of iron ion transport; ISO:RGD.
DR GO; GO:2000008; P:regulation of protein localization to cell surface; ISO:RGD.
DR GO; GO:0010039; P:response to iron ion; ISO:RGD.
DR GO; GO:1990641; P:response to iron ion starvation; IEP:RGD.
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; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..360
FT /note="Hereditary hemochromatosis protein homolog"
FT /id="PRO_0000018895"
FT TOPO_DOM 26..319
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q30201"
FT TRANSMEM 320..340
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 341..360
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q30201"
FT DOMAIN 220..309
FT /note="Ig-like C1-type"
FT REGION 26..127
FT /note="Alpha-1"
FT REGION 128..218
FT /note="Alpha-2"
FT REGION 219..310
FT /note="Alpha-3"
FT REGION 311..319
FT /note="Connecting peptide"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 137..200
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 238..295
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 198
FT /note="R -> K (in Ref. 2; AAB86597)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 360 AA; 40988 MW; CC819834EE3240B3 CRC64;
MDRSAGLPVR LLLLLLLLLL WSVAPQALRP GSHSLRYLFM GASKPDLGLP FFEALGYVDD
QLFVSYNHES RRAEPRAPWI LGQTSSQLWL QLSQSLKGWD YMFIVDFWTI MGNYNHSKVT
KLRVVPESHI LQVILGCEVH EDNSTSGFWK YGYDGQDHLE FCPKTLNWSA AEPRAWATKM
EWEEHRIRAR QSRDYLQRDC PQQLKQVLEL QRGVLGQQVP TLVKVTRHWA STGTSLRCQA
LNFFPQNITM RWLKDSQPLD AKDVNPENVL PNGDGTYQGW LTLAVAPGEE TRFSCQVEHP
GLDQPLTATW EPSRSQDMII GIISGITICA IFFVGILILV LRKRKVSGGT MGDYVLTECE
