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FLASH GENE
Symbol HAMP contributors: mct/npt/pgu - updated : 15-12-2014
HGNC name hepcidin antimicrobial peptide
HGNC id 15598
DNA
TYPE functioning gene
STRUCTURE 2.64 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
text structure in mice, region of the promoter between 1.6 Kb and 1.8 Kb upstream from the start of translation is essential for the response to iron, but region between -260 bp and -1.6 Kb is not essential for the iron responsiveness of hepcidin promoter
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 430 - 84 - 2003 12663437
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   moderately
Digestiveliver   highly
Nervousbrain   moderately
Urinarykidney    
Visualeyeretina    Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Digestivehepatocyte Homo sapiens
Urinaryepithelial cell
cell lineage
cell lines
fluid/secretion blood, urine
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a hepcidin motif
  • two conserved putative binding sites for CREB3L3
  • isoforms Precursor . precursor of a 25 and a 20 AA peptides with four disulfide motifs/cystein rich domain
    HOMOLOGY
    interspecies homolog to murine Hamp1
    Homologene
    FAMILY
  • hepcidin family
  • CATEGORY immunity/defense , regulatory
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • central regulator of intestinal absorption and iron recycling by macrophages
  • type II acute phase reactant, key mediator of anemia of inflammation
  • defensin-like peptide produced by the hepatocytes in response to iron and inflammation, and is a central humoral mediator of innate immunity and host defense
  • play a key role in the regulation of iron efflux from enterocytes, macrophages, and hepatocytes
  • having iron-regulatory role in the renal tubular system (eliminated by the kidney but is also synthesized in the kidney tubular system), possibly in connection with the iron transporter divalent metal transporter-1
  • having a primary role hormonal, serving as a negative regulator of iron homeostasis
  • iron-regulatory protein that is upregulated in response to increased iron or inflammatory stimuli
  • reduces serum iron and induces iron sequestration in the reticuloendothelial macrophages
  • peptide hormone that is secreted by the liver and controls body iron homeostasis
  • regulates iron homeostasis by binding to ferroportin, an iron exporter, on the cell surface of target cells and facilitating ferroportin degradation
  • hepatic peptide hormone, negatively regulating iron efflux from the intestines into the blood
  • physiologically important peptide hormone in the regulation of iron levels in the body
  • downregulates ferroportin mRNA, thus uncovering a novel function of hepcidin in iron homeostasis
  • through an active transport mechanism, transported into RPE cells, suggesting that this peptide might have some, hitherto unrecognized, intracellular function
  • showed age and sex dependent variations that correlated with ferritin but not with serum iron and transferrin saturationb
  • HFE2 and HAMP play a critical role in retinal iron homeostasis
  • liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response
  • is a prototypical antioxidant response or cytoprotective gene within the NFE2L2 transcriptional circuitry
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • SLC40A1(to be internalized and degraded)
  • transcriptional target of TP53 (hepcidin upregulation by TP53 is part of a defence mechanism against cancer, through iron deprivation)
  • interacting with HFE and TFR2 (both HFE and TFR2 are necessary for regulation of HAMP expression)
  • TMPRSS6 is the key enzyme of iron homoeostasis modulating the expression of the liver peptide hormone HAMP
  • 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
  • BTG2 is a key player in hepatic hepcidin (HAMP) regulation via induction of Yin Yang 1 (YY1)
  • HAMP regulation is inextricably linked to the acute stress response through NFE2L2 signaling
  • cell & other
    REGULATION
    activated by TP53 (part of a defence mechanism against cancer, through iron deprivation, and induction by TP53 might be involved in the pathogenesis of anaemia accompanying cancer)
    induced by BMP2, BMP4, BMP9
    Other increased expression by binding of HFE2 to BMP6
    ASSOCIATED DISORDERS
    corresponding disease(s) HFE2B
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    inheritance of digenic mutations in HAMP and HFE results in different types of hemochromatosis
    constitutional     --low  
    deficiency leads to hemochromatosis
    constitutional     --over  
    causes anemia of inflammation
    tumoral     --low  
    in hepatocellular carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • overexpressed in mouse during iron overload
  • constitutive expression of HAMP prevents iron overload in a mouse model of hemochromatosis