HEPC_MOUSE
ID HEPC_MOUSE Reviewed; 83 AA.
AC Q9EQ21;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Hepcidin;
DE Flags: Precursor;
GN Name=Hamp; Synonyms=Hamp1, Hepc, Hepc1;
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 [MRNA], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=11113132; DOI=10.1074/jbc.m008923200;
RA Pigeon C., Ilyin G., Courselaud B., Leroyer P., Turlin B., Brissot P.,
RA Loreal O.;
RT "A new mouse liver-specific gene, encoding a protein homologous to human
RT antimicrobial peptide hepcidin, is overexpressed during iron overload.";
RL J. Biol. Chem. 276:7811-7819(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=C57BL/6 X 129/Sv;
RX PubMed=11447267; DOI=10.1073/pnas.151179498;
RA Nicolas G., Bennoun M., Devaux I., Beaumont C., Grandchamp B., Kahn A.,
RA Vaulont S.;
RT "Lack of hepcidin gene expression and severe tissue iron overload in
RT upstream stimulatory factor 2 (USF2) knockout mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8780-8785(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [4]
RP INDUCTION.
RX PubMed=12370282; DOI=10.1172/jci15686;
RA Nicolas G., Chauvet C., Viatte L., Danan J.L., Bigard X., Devaux I.,
RA Beaumont C., Kahn A., Vaulont S.;
RT "The gene encoding the iron regulatory peptide hepcidin is regulated by
RT anemia, hypoxia, and inflammation.";
RL J. Clin. Invest. 110:1037-1044(2002).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12729891; DOI=10.1016/s0014-5793(03)00329-6;
RA Ilyin G., Courselaud B., Troadec M.-B., Pigeon C., Alizadeh M., Leroyer P.,
RA Brissot P., Loreal O.;
RT "Comparative analysis of mouse hepcidin 1 and 2 genes: evidence for
RT different patterns of expression and co-inducibility during iron
RT overload.";
RL FEBS Lett. 542:22-26(2003).
RN [6]
RP INDUCTION BY INFLAMMATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15124018; DOI=10.1172/jci200420945;
RA Nemeth E., Rivera S., Gabayan V., Keller C., Taudorf S., Pedersen B.K.,
RA Ganz T.;
RT "IL-6 mediates hypoferremia of inflammation by inducing the synthesis of
RT the iron regulatory hormone hepcidin.";
RL J. Clin. Invest. 113:1271-1276(2004).
RN [7]
RP FUNCTION, AND INDUCTION.
RX PubMed=24880340; DOI=10.1038/ng.2996;
RA Kautz L., Jung G., Valore E.V., Rivella S., Nemeth E., Ganz T.;
RT "Identification of erythroferrone as an erythroid regulator of iron
RT metabolism.";
RL Nat. Genet. 46:678-684(2014).
CC -!- FUNCTION: Liver-produced hormone that constitutes the main circulating
CC regulator of iron absorption and distribution across tissues. Acts by
CC promoting endocytosis and degradation of ferroportin, leading to the
CC retention of iron in iron-exporting cells and decreased flow of iron
CC into plasma. Controls the major flows of iron into plasma: absorption
CC of dietary iron in the intestine, recycling of iron by macrophages,
CC which phagocytose old erythrocytes and other cells, and mobilization of
CC stored iron from hepatocytes. {ECO:0000269|PubMed:11447267,
CC ECO:0000269|PubMed:24880340}.
CC -!- SUBUNIT: Interacts with SLC40A1; this interaction promotes SLC40A1
CC rapid ubiquitination. {ECO:0000250|UniProtKB:P81172}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11113132,
CC ECO:0000269|PubMed:15124018}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the liver and to a much lesser
CC extent in the heart. Secreted in blood (PubMed:15124018).
CC {ECO:0000269|PubMed:11113132, ECO:0000269|PubMed:12729891,
CC ECO:0000269|PubMed:15124018}.
CC -!- INDUCTION: Regulated in response to changes in circulating iron
CC concentrations, iron stores or the development of inflammation and
CC iron-restricted erythropoiesis. Down-regulated following anemia induced
CC by hemorrhage or hemolysis: down-regulation is mediated by ERFE
CC (PubMed:12370282, PubMed:24880340, PubMed:15124018). The induction of
CC upon inflammation is mediated by IL6 (PubMed:15124018).
CC {ECO:0000269|PubMed:12370282, ECO:0000269|PubMed:15124018,
CC ECO:0000269|PubMed:24880340}.
CC -!- SIMILARITY: Belongs to the hepcidin family. {ECO:0000305}.
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DR EMBL; AF297664; AAG49293.1; -; mRNA.
DR EMBL; AF503444; AAM27440.1; -; mRNA.
DR EMBL; BC021587; AAH21587.1; -; mRNA.
DR CCDS; CCDS39895.1; -.
DR RefSeq; NP_115930.1; NM_032541.2.
DR AlphaFoldDB; Q9EQ21; -.
DR SMR; Q9EQ21; -.
DR STRING; 10090.ENSMUSP00000055404; -.
DR TCDB; 8.A.37.1.1; the hepcidin (hepcidin) family.
DR PhosphoSitePlus; Q9EQ21; -.
DR MaxQB; Q9EQ21; -.
DR PaxDb; Q9EQ21; -.
DR PeptideAtlas; Q9EQ21; -.
DR PRIDE; Q9EQ21; -.
DR ProteomicsDB; 269735; -.
DR Antibodypedia; 29325; 388 antibodies from 30 providers.
DR DNASU; 84506; -.
DR Ensembl; ENSMUST00000062620; ENSMUSP00000055404; ENSMUSG00000050440.
DR GeneID; 84506; -.
DR KEGG; mmu:84506; -.
DR UCSC; uc009ghf.1; mouse.
DR CTD; 57817; -.
DR MGI; MGI:1933533; Hamp.
DR VEuPathDB; HostDB:ENSMUSG00000050440; -.
DR eggNOG; ENOG502T0FU; Eukaryota.
DR GeneTree; ENSGT00390000003154; -.
DR HOGENOM; CLU_2557737_0_0_1; -.
DR InParanoid; Q9EQ21; -.
DR OMA; PICLFCC; -.
DR OrthoDB; 1623838at2759; -.
DR PhylomeDB; Q9EQ21; -.
DR TreeFam; TF330932; -.
DR BioGRID-ORCS; 84506; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Hamp; mouse.
DR PRO; PR:Q9EQ21; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9EQ21; protein.
DR Bgee; ENSMUSG00000050440; Expressed in left lobe of liver and 86 other tissues.
DR Genevisible; Q9EQ21; MM.
DR GO; GO:0045179; C:apical cortex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0014704; C:intercalated disc; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005507; F:copper ion binding; IDA:MGI.
DR GO; GO:0005179; F:hormone activity; ISO:MGI.
DR GO; GO:0097690; F:iron ion transmembrane transporter inhibitor activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; ISO:MGI.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IDA:UniProtKB.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; TAS:BHF-UCL.
DR GO; GO:0042742; P:defense response to bacterium; IDA:MGI.
DR GO; GO:0050832; P:defense response to fungus; IDA:MGI.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:MGI.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IGI:MGI.
DR GO; GO:0006954; P:inflammatory response; IGI:MGI.
DR GO; GO:0055072; P:iron ion homeostasis; IDA:MGI.
DR GO; GO:0034755; P:iron ion transmembrane transport; IGI:MGI.
DR GO; GO:0031640; P:killing of cells of another organism; ISO:MGI.
DR GO; GO:0042116; P:macrophage activation; IMP:MGI.
DR GO; GO:0060586; P:multicellular organismal iron ion homeostasis; ISO:MGI.
DR GO; GO:0002262; P:myeloid cell homeostasis; IMP:MGI.
DR GO; GO:0045779; P:negative regulation of bone resorption; IMP:MGI.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IGI:MGI.
DR GO; GO:1904479; P:negative regulation of intestinal absorption; ISO:MGI.
DR GO; GO:0032413; P:negative regulation of ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:1904039; P:negative regulation of iron export across plasma membrane; ISO:MGI.
DR GO; GO:0034760; P:negative regulation of iron ion transmembrane transport; IGI:MGI.
DR GO; GO:1904255; P:negative regulation of iron ion transmembrane transporter activity; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; ISO:MGI.
DR GO; GO:0043032; P:positive regulation of macrophage activation; IMP:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:MGI.
DR GO; GO:1902916; P:positive regulation of protein polyubiquitination; ISO:MGI.
DR GO; GO:2000646; P:positive regulation of receptor catabolic process; ISO:MGI.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0030163; P:protein catabolic process; IDA:MGI.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:MGI.
DR GO; GO:0010039; P:response to iron ion; ISO:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IGI:MGI.
DR InterPro; IPR010500; Hepcidin.
DR PANTHER; PTHR16877; PTHR16877; 1.
DR Pfam; PF06446; Hepcidin; 1.
PE 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Disulfide bond; Hormone;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..53
FT /evidence="ECO:0000255"
FT /id="PRO_0000013381"
FT PEPTIDE 59..83
FT /note="Hepcidin"
FT /id="PRO_0000013382"
FT DISULFID 65..81
FT /evidence="ECO:0000250"
FT DISULFID 68..71
FT /evidence="ECO:0000250"
FT DISULFID 69..77
FT /evidence="ECO:0000250"
FT DISULFID 72..80
FT /evidence="ECO:0000250"
SQ SEQUENCE 83 AA; 9352 MW; C76423EA46260B18 CRC64;
MALSTRTQAA CLLLLLLASL SSTTYLHQQM RQTTELQPLH GEESRADIAI PMQKRRKRDT
NFPICIFCCK CCNNSQCGIC CKT
