HFE_MOUSE
ID HFE_MOUSE Reviewed; 359 AA.
AC P70387; Q14AQ5; Q5SZ90; Q9D754;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Hereditary hemochromatosis protein homolog;
DE Flags: Precursor;
GN Name=Hfe; Synonyms=Mr2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=9396865; DOI=10.1007/s002510050344;
RA Riegert P., Gilfillan S., Nanda I., Schmid M., Bahram S.;
RT "The mouse HFE gene.";
RL Immunogenetics 47:174-177(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Lung;
RA Hashimoto K.;
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 37-211.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=9020055; DOI=10.1006/bbrc.1996.5889;
RA Hashimoto K., Hirai M., Kurosawa Y.;
RT "Identification of a mouse homolog for the human hereditary
RT haemochromatosis candidate gene.";
RL Biochem. Biophys. Res. Commun. 230:35-39(1997).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 79-359.
RC STRAIN=129;
RA Albig W., Drabent B., Doenecke D.;
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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; AF007558; AAC03447.1; -; Genomic_DNA.
DR EMBL; U66849; AAB07525.1; -; mRNA.
DR EMBL; AK009581; BAB26373.1; -; mRNA.
DR EMBL; AK150697; BAE29776.1; -; mRNA.
DR EMBL; AL590388; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466561; EDL32544.1; -; Genomic_DNA.
DR EMBL; BC116744; AAI16745.1; -; mRNA.
DR EMBL; BC116746; AAI16747.1; -; mRNA.
DR EMBL; Y12650; CAA73197.1; -; Genomic_DNA.
DR EMBL; U80604; AAB51504.1; -; Genomic_DNA.
DR CCDS; CCDS26360.1; -.
DR PIR; JC5382; JC5382.
DR RefSeq; NP_001334422.1; NM_001347493.1.
DR RefSeq; NP_034554.2; NM_010424.5.
DR AlphaFoldDB; P70387; -.
DR SMR; P70387; -.
DR BioGRID; 200285; 1.
DR STRING; 10090.ENSMUSP00000089298; -.
DR GlyGen; P70387; 4 sites.
DR iPTMnet; P70387; -.
DR PhosphoSitePlus; P70387; -.
DR MaxQB; P70387; -.
DR PaxDb; P70387; -.
DR PeptideAtlas; P70387; -.
DR PRIDE; P70387; -.
DR ProteomicsDB; 269661; -.
DR Antibodypedia; 2221; 347 antibodies from 32 providers.
DR DNASU; 15216; -.
DR Ensembl; ENSMUST00000091706; ENSMUSP00000089298; ENSMUSG00000006611.
DR GeneID; 15216; -.
DR KEGG; mmu:15216; -.
DR UCSC; uc007pup.1; mouse.
DR CTD; 3077; -.
DR MGI; MGI:109191; Hfe.
DR VEuPathDB; HostDB:ENSMUSG00000006611; -.
DR eggNOG; KOG1745; Eukaryota.
DR GeneTree; ENSGT01040000240396; -.
DR HOGENOM; CLU_047501_0_2_1; -.
DR InParanoid; P70387; -.
DR OMA; KGWEHMF; -.
DR OrthoDB; 912212at2759; -.
DR PhylomeDB; P70387; -.
DR TreeFam; TF336617; -.
DR Reactome; R-MMU-917977; Transferrin endocytosis and recycling.
DR BioGRID-ORCS; 15216; 2 hits in 78 CRISPR screens.
DR PRO; PR:P70387; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P70387; protein.
DR Bgee; ENSMUSG00000006611; Expressed in choroid plexus epithelium and 178 other tissues.
DR ExpressionAtlas; P70387; baseline and differential.
DR Genevisible; P70387; MM.
DR GO; GO:0045177; C:apical part of cell; ISO:MGI.
DR GO; GO:0045178; C:basal part of cell; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:1990712; C:HFE-transferrin receptor complex; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0055037; C:recycling endosome; ISO:MGI.
DR GO; GO:1990357; C:terminal web; ISO:MGI.
DR GO; GO:0030881; F:beta-2-microglobulin binding; ISO:MGI.
DR GO; GO:0039706; F:co-receptor binding; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:1990459; F:transferrin receptor binding; IPI:BHF-UCL.
DR GO; GO:0006953; P:acute-phase response; IEA:Ensembl.
DR GO; GO:0030509; P:BMP signaling pathway; ISO:MGI.
DR GO; GO:0006879; P:cellular iron ion homeostasis; ISO:MGI.
DR GO; GO:0071281; P:cellular response to iron ion; ISO:MGI.
DR GO; GO:0010106; P:cellular response to iron ion starvation; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0042446; P:hormone biosynthetic process; IMP:MGI.
DR GO; GO:0055072; P:iron ion homeostasis; IMP:MGI.
DR GO; GO:0098711; P:iron ion import across plasma membrane; IEA:InterPro.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; IMP:MGI.
DR GO; GO:1904283; P:negative regulation of antigen processing and presentation of endogenous peptide antigen via MHC class I; ISO:MGI.
DR GO; GO:2001186; P:negative regulation of CD8-positive, alpha-beta T cell activation; ISO:MGI.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IC:BHF-UCL.
DR GO; GO:1900121; P:negative regulation of receptor binding; ISO:MGI.
DR GO; GO:2000272; P:negative regulation of signaling receptor activity; ISO:MGI.
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:MGI.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:1904434; P:positive regulation of ferrous iron binding; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:MGI.
DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; ISO:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:MGI.
DR GO; GO:1900122; P:positive regulation of receptor binding; ISO:MGI.
DR GO; GO:0048260; P:positive regulation of receptor-mediated endocytosis; ISO:MGI.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; ISO:MGI.
DR GO; GO:1904437; P:positive regulation of transferrin receptor binding; ISO:MGI.
DR GO; GO:0034756; P:regulation of iron ion transport; ISO:MGI.
DR GO; GO:2000008; P:regulation of protein localization to cell surface; ISO:MGI.
DR GO; GO:0010039; P:response to iron ion; ISO:MGI.
DR GO; GO:1990641; P:response to iron ion starvation; IBA:GO_Central.
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 1: Evidence at protein 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..24
FT /evidence="ECO:0000255"
FT CHAIN 25..359
FT /note="Hereditary hemochromatosis protein homolog"
FT /id="PRO_0000018894"
FT TOPO_DOM 25..318
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q30201"
FT TRANSMEM 319..339
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 340..359
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q30201"
FT DOMAIN 219..308
FT /note="Ig-like C1-type"
FT REGION 25..126
FT /note="Alpha-1"
FT REGION 127..217
FT /note="Alpha-2"
FT REGION 218..309
FT /note="Alpha-3"
FT REGION 310..318
FT /note="Connecting peptide"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 246
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 136..199
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 237..294
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 327
FT /note="V -> I (in Ref. 1; AAC03447, 2; AAB07525, 6;
FT AAI16745/AAI16747 and 8; CAA73197)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 359 AA; 40534 MW; 586657B7F9FF20B4 CRC64;
MSLSAGLPVR PLLLLLLLLW SVAPQALPPR SHSLRYLFMG ASEPDLGLPL FEARGYVDDQ
LFVSYNHESR RAEPRAPWIL EQTSSQLWLH LSQSLKGWDY MFIVDFWTIM GNYNHSKVTK
LGVVSESHIL QVVLGCEVHE DNSTSGFWRY GYDGQDHLEF CPKTLNWSAA EPGAWATKVE
WDEHKIRAKQ NRDYLEKDCP EQLKRLLELG RGVLGQQVPT LVKVTRHWAS TGTSLRCQAL
DFFPQNITMR WLKDNQPLDA KDVNPEKVLP NGDETYQGWL TLAVAPGDET RFTCQVEHPG
LDQPLTASWE PLQSQAMIIG IISGVTVCAI FLVGILFLIL RKRKASGGTM GGYVLTDCE
