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FLASH GENE
Symbol HFE2 contributors: mct/pgu - updated : 15-12-2015
HGNC name hemochromatosis type 2 (juvenile)
HGNC id 4887
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
4 - 2234 - 426 - 2004 14647275
  • isoform a
  • precursor
  • 3 - 2048 - 313 - 2004 14647275
  • isoform b
  • precursor
  • 3 - 1525 - 200 - 2004 14647275
  • isoform c
  • precursor
  • 2 - 1488 - 200 - 2004 14647275
  • isoform c
  • precursor
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Digestiveliver   highly Homo sapiens
     mouthtongue   
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac highly Homo sapiens
    Muscularstriatumskeletal highly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestivehepatocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal RGM domain
  • a C terminal RGM domain
  • conjugated GlycoP , LipoP
    HOMOLOGY
    interspecies ortholog to murine Hfe2
    ortholog to rattus Rgmc_predicted
    Homologene
    FAMILY
  • repulsive guidance molecule (RGM) family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
    text
  • at the subcellular level, HFE2 and TFR2 were predominantly localized to the basolateral membrane domain of hepatocytes, which renders a functional interaction of these two proteins in iron homeostasis possible
  • basic FUNCTION
  • glycosylphosphatidylinositol-linked protein potential modulator of hepcidin (HAMP) expression, playing a key role in dietary iron sensing
  • may cooperate with hepcidin to restrict iron absorption in the gut
  • interacting with NEO1 to mediate the induction of hepcidin expression
  • binding BMP6 and increasing HAMP expression presumably by acting as a BMP co-receptor
  • expression in hepatocytes plays an essential role in hepcidin expression by potentiating the BMP6-mediated signaling
  • may be a component of the signaling pathway which activates hepcidin or it may act as a modulator of hepcidin expression
  • could also represent the cellular receptor for hepcidin
  • acts as a bone morphogenetic protein coreceptor to activate hepcidin expression through a SMAD signaling pathway in hepatocytes
  • is primarily important in the liver
  • HFE2 and HAMP play a critical role in retinal iron homeostasis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism metal
    signaling
    iron metabolism
    a component
  • part of a multiprotein complex at the hepatocyte membrane involving BMP, its receptors, and NEO1
  • NEO1 likely forms a ternary complex with both TMPRSS6 and HFE2 at the plasma membrane
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HAMP (positively regulating hepcidin expression)
  • BMP coreceptor, whose enhancement of BMP signaling is important in regulating hepcidin expression and iron metabolism
  • interaction with neogenin (NEO1) resulting in iron accumulation in embryonic kidney cells
  • co-receptor for BMP6 and BMP6 and HFE2 act coordinately to induce hepcidin expression
  • interacting with BMP2, BMP4, BMPR1B, BMP6
  • TMPRSS6 regulates the levels of membrane-bound HFE2 in hepatocytes by binding to and cleaving HFE2 into an inactive soluble form that is released from cells
  • also interacts with NEO1, a ubiquitously expressed transmembrane protein with multiple functions
  • TMPRSS6 suppresses the expression of hepatic HAMP, an iron regulatory hormone, by cleaving membrane HFE2 into an inactive form
  • TMPRSS6 regulates HAMP expression by cleaving hemojuvelin (HFE2), a bone morphogenetic protein (BMP) coreceptor in the hepcidin regulatory pathway
  • HFE2 can simultaneously bind to both BMP2 and the ubiquitously expressed cell surface receptor NEO1
  • NEO1 acts as a scaffold to facilitate assembly of the HFE2·BMP·BMP receptor complex to induce hepcidin expression (
  • cell & other
    REGULATION
    inhibited by NEO1 (Neogenin inhibits HFE2 secretion and regulates BMP-induced hepcidin expression and iron homeostasis)
    ASSOCIATED DISORDERS
    corresponding disease(s) HFE2
    Susceptibility
    Variant & Polymorphism SNP modulating hemochromatosis penetrance
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • HFE2 -/- mice have severe iron overload and marked suppression of HAMP expression