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 27-MAR-2024, entry version 170. 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}. 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; 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 GlyCosmos; O35799; 4 sites, No reported glycans. DR GlyGen; O35799; 4 sites. DR PhosphoSitePlus; O35799; -. DR PaxDb; 10116-ENSRNOP00000022881; -. DR Ensembl; ENSRNOT00000022809.7; ENSRNOP00000022809.4; ENSRNOG00000016967.8. DR Ensembl; ENSRNOT00055008711; ENSRNOP00055006610; ENSRNOG00055005418. DR Ensembl; ENSRNOT00060023995; ENSRNOP00060019117; ENSRNOG00060014012. DR Ensembl; ENSRNOT00065036291; ENSRNOP00065029247; ENSRNOG00065021338. DR GeneID; 29199; -. DR KEGG; rno:29199; -. DR UCSC; RGD:2793; rat. DR AGR; RGD:2793; -. DR CTD; 3077; -. DR RGD; 2793; Hfe. DR eggNOG; KOG1745; Eukaryota. DR GeneTree; ENSGT01100000263517; -. DR HOGENOM; CLU_047501_0_2_1; -. DR InParanoid; O35799; -. DR OMA; KGWEHMF; -. DR OrthoDB; 3840485at2759; -. 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 cell types or tissues. DR ExpressionAtlas; O35799; baseline and differential. 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:0048471; C:perinuclear region of cytoplasm; ISO: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:0002486; P:antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent; IBA:GO_Central. DR GO; GO:0002476; P:antigen processing and presentation of endogenous peptide antigen via MHC class Ib; IBA:GO_Central. DR GO; GO:0030509; P:BMP signaling pathway; 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:0006879; P:intracellular iron ion homeostasis; ISO:RGD. DR GO; GO:0006826; P:iron ion transport; IEA:UniProtKB-KW. DR GO; GO:0097421; P:liver regeneration; IEP:RGD. DR GO; GO:0060586; P:multicellular organismal-level iron ion homeostasis; IEP: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:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD. 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:0010628; P:positive regulation of gene expression; ISO:RGD. DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; ISO:RGD. DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISO:RGD. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:RGD. DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IBA:GO_Central. 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; Immunoglobulins; 1. DR Gene3D; 3.30.500.10; MHC class I-like antigen recognition-like; 1. 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; HEREDITARY HEMOCHROMATOSIS PROTEIN; 1. DR PANTHER; PTHR16675; MHC CLASS I-RELATED; 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; Immunoglobulin; 1. DR SUPFAM; SSF54452; MHC antigen-recognition domain; 1. DR PROSITE; PS50835; IG_LIKE; 1. DR PROSITE; PS00290; IG_MHC; 1. DR Genevisible; O35799; RN. 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 //