Affinage

HAMP

Hepcidin · UniProt P81172

Length
84 aa
Mass
9.4 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HAMP encodes hepcidin, a 25-residue, four-disulfide-bonded peptide isolated from human blood ultrafiltrate that displays direct antimicrobial activity and is expressed predominantly in liver (PMID:11034317). Beyond this innate-immune role, hepcidin is the central effector controlling systemic iron distribution: in hepcidin-deficient mice, ferroportin protein rises in duodenum and spleen while the iron-import machinery DMT1 and Dcytb are hyperinduced, and silencing duodenal Dmt1 corrects the resulting iron overload, establishing that hepcidin restrains dietary iron absorption by acting on these iron-transport proteins (PMID:22241739, PMID:34063414). HAMP transcription integrates multiple inputs converging on hepatocyte promoter elements: the BMP-SMAD axis, in which hemojuvelin serves as a major matriptase-2 (TMPRSS6) substrate driving Hamp expression (PMID:19751239) and which is suppressed by GDF11 through SMURF1/ERK1/2-mediated reduction of phospho-SMAD1/5/8 (PMID:31418854); a STAT site mediating basal and IL-6-inducible activity (PMID:17689119); and dedicated transcription factors including GATA-4/6 (antagonized by FOG proteins) (PMID:21971825) and the iron- and erythropoiesis-responsive ATOH8, which acts both through promoter E-boxes and through BMP signaling (PMID:24236640). Hepcidin output is further tuned post-transcriptionally—saturated fatty acids stabilize HAMP mRNA via a 3'-UTR AU-rich element bound by PKC-activated HuR (PMID:26304124)—and epigenetically through promoter DNA methylation, which suppresses expression in iron-deficient and post-surgical states (PMID:31839527, PMID:29501389). Loss-of-function HAMP mutations—including cysteine substitutions that disrupt disulfide bonds, premature stop codons, frameshifts, and a 5'-UTR upstream-AUG mutation—abolish detectable hepcidin protein and cause juvenile hemochromatosis, while heterozygous variants co-inherited with HFE C282Y produce digenic adult-onset iron overload (PMID:12915468, PMID:15198949, PMID:15024747, PMID:22297252).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2000 High

    Established the molecular identity of HAMP's product—a disulfide-rich peptide with antimicrobial activity—before its iron-regulatory role was known, defining the protein at the biochemical level.

    Evidence Mass-spectrometric isolation from human blood ultrafiltrate and radial diffusion antimicrobial assays with synthetic peptide

    PMID:11034317

    Open questions at the time
    • Did not connect the peptide to iron homeostasis
    • Physiological relevance of antimicrobial activity versus hormonal function not resolved
  2. 2003 Medium

    Answered whether HAMP variation contributes to human iron-overload disease by showing HAMP mutations act as digenic modifiers of HFE-associated hemochromatosis.

    Evidence Sequencing of HAMP in hemochromatosis families and cohorts with genotype-phenotype correlation against population controls

    PMID:12915468 PMID:14670915

    Open questions at the time
    • Did not establish hepcidin protein levels in carriers
    • Mechanism by which heterozygous loss synergizes with HFE not dissected
  3. 2004 Medium

    Linked specific structural and regulatory HAMP lesions to absent hepcidin protein, demonstrating that disulfide integrity and correct translation initiation are required for a functional hormone.

    Evidence Sequencing of disulfide-disrupting cysteine mutations and a 5'-UTR upstream-AUG mutation, with hepcidin protein assays in urine and clinical phenotyping in juvenile hemochromatosis families

    PMID:15024747 PMID:15099344 PMID:15198949

    Open questions at the time
    • No structural model of the disulfide-bonded active conformation provided
    • Quantitative relationship between residual hepcidin and disease severity not defined
  4. 2007 Medium

    Mapped the functional cis-elements of the HAMP promoter, identifying a STAT site as critical for basal and IL-6-inducible transcription.

    Evidence Luciferase reporter assays with promoter mutagenesis comparing human HAMP and murine Hamp constructs

    PMID:17689119

    Open questions at the time
    • Did not identify the full set of trans-acting factors at the STAT site
    • Species differences in promoter architecture left unresolved
  5. 2009 High

    Placed HAMP regulation within a defined upstream pathway by establishing hemojuvelin as a major matriptase-2 substrate controlling Hamp expression.

    Evidence Hfe2/Tmprss6 double-knockout mice with Hamp expression and serum/liver iron quantification

    PMID:19751239

    Open questions at the time
    • Did not resolve the direct biochemical cleavage event on hemojuvelin
    • How the pathway scales hepcidin output to iron load not quantified
  6. 2011 Medium

    Expanded the transcription-factor repertoire controlling HAMP by identifying GATA-4/6 activation (suppressed by FOG) and USF binding at promoter elements.

    Evidence Promoter deletion/mutagenesis, luciferase reporters, EMSA/ChIP in Huh7 cells; USF1/2 co-transfection reporter assays in HepG2

    PMID:21143959 PMID:21971825

    Open questions at the time
    • Physiological signals upstream of GATA/USF engagement not defined
    • Relative contribution versus BMP-SMAD and STAT inputs unquantified
  7. 2012 Medium

    Demonstrated the downstream consequence of hepcidin loss—dysregulation of the iron-transport machinery—and showed partial hepcidin-independent compensation.

    Evidence Hamp-/- mice on iron-deficient diet with qPCR and Western blot for ferroportin, DMT1, Dcytb; LC-MS/MS confirmation of absent hepcidin in a p.R75X patient

    PMID:22241739 PMID:22297252

    Open questions at the time
    • Nature of hepcidin-independent compensatory mechanisms not identified
    • Single-patient protein confirmation for the nonsense mutation
  8. 2013 Medium

    Connected erythropoietic and iron status to HAMP transcription through ATOH8, and proposed a nuclear autoregulatory role for prohepcidin at the STAT3 promoter site.

    Evidence ChIP, promoter reporter/mutagenesis and in vivo hypoxia/EPO models for ATOH8; immunofluorescence localization and reporter gain/loss-of-function for prohepcidin in WRL68 cells; Caulis Spatholobi pSMAD experiments

    PMID:23390933 PMID:23700338 PMID:24236640

    Open questions at the time
    • Prohepcidin nuclear autoregulation rests on a single lab without reciprocal validation
    • Physiological extent of prohepcidin feedback in vivo unknown
  9. 2015 High

    Established that HAMP is regulated post-transcriptionally, defining a saturated-fatty-acid-responsive HuR/ARE mRNA-stabilization mechanism distinct from promoter control.

    Evidence Actinomycin D chase, 3'-UTR ARE reporter and mutagenesis, HuR siRNA, PKC inhibitors and HuR-HAMP mRNA binding assays

    PMID:26304124

    Open questions at the time
    • In vivo relevance of fatty-acid-driven stabilization to systemic iron not established
    • Interplay with transcriptional inputs not integrated
  10. 2019 Medium

    Added epigenetic and growth-factor layers to HAMP control: HDAC3-dependent transcription-factor recruitment, GDF11-driven BMP-SMAD suppression, and promoter methylation responsive to systemic iron state.

    Evidence ChIP and HDAC3 inhibition; GDF11 administration with SMAD/SMURF1/ERK1/2 dissection in mice and hepatocytes; MassARRAY methylation and reporter assays in surgical and Kawasaki-disease models

    PMID:29501389 PMID:30328580 PMID:31418854 PMID:31839527

    Open questions at the time
    • How these layers are coordinated with canonical BMP/STAT signaling unresolved
    • Causal hierarchy among methylation, HDAC3, and transcription factors not ordered
  11. 2021 Medium

    Validated DMT1 as a therapeutically actionable downstream node of hepcidin deficiency, showing its silencing corrects HAMP-loss iron overload.

    Evidence Oral Dmt1 siRNA via lipid nanoparticles plus dietary iron restriction in Hamp-KO mice with 59Fe absorption and iron measurements

    PMID:34063414

    Open questions at the time
    • Long-term efficacy and ferroportin-axis effects not assessed
    • Generalizability to human HAMP-related hemochromatosis untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse transcriptional (BMP-SMAD, STAT, GATA, ATOH8, USF, HDAC3), post-transcriptional (HuR/ARE), and epigenetic (DNA methylation) inputs are quantitatively integrated to set hepcidin output—and the structural basis of the disulfide-bonded active peptide—remains unresolved.
  • No unified model weighting the relative inputs to HAMP transcription
  • No experimental structure of the mature peptide bound to ferroportin
  • Tissue-specific regulation (e.g. kidney HIF-1α) not integrated with hepatic control

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0090729 toxin activity 1
Localization
GO:0005576 extracellular region 1 GO:0005634 nucleus 1
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-168256 Immune System 1
Partners
ATOH8ELAVL1FPN1GATA4GATA6HJVSERPINA1TMPRSS6

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 HAMP/LEAP-1 (hepcidin) is a 25-residue peptide containing four disulfide bonds (novel disulfide motif) isolated from human blood ultrafiltrate, with antimicrobial activity against Gram-positive bacteria (Bacillus megaterium, B. subtilis, Micrococcus luteus, Staphylococcus carnosus), Gram-negative Neisseria cinerea, and yeast Saccharomyces cerevisiae in radial diffusion assays; expression is predominantly hepatic. Mass spectrometric isolation from blood ultrafiltrate; radial diffusion antimicrobial assay with synthetic peptide; expression analysis FEBS letters High 11034317
2003 Heterozygous loss-of-function mutations in HAMP (frameshift Met50del IVS2+1(-G) and missense G71D) co-inherited with HFE C282Y mutation cause digenic hereditary hemochromatosis with iron overload severity corresponding to HAMP mutation severity, establishing HAMP as a modifier of HFE-associated iron homeostasis. Genetic sequencing of HAMP in hemochromatosis families; genotype-phenotype correlation; control chromosome analysis Human molecular genetics Medium 12915468
2003 Heterozygous HAMP mutations (pR59G, pG71D, pR56X) increase phenotypic iron overload expression in HFE pC282Y/pC282Y homozygous patients, and heterozygous mutations in both HFE and HAMP can lead to adult-onset iron overload in a digenic inheritance model. Cohort sequencing; iron indices comparison; population control analysis Blood Medium 14670915
2004 A mutation in the 5'-UTR of HAMP creates a new upstream initiation codon in a Kozak context, causing ribosomes to select the mutant codon for translation, resulting in non-detectable hepcidin protein in urine and juvenile hemochromatosis; this directly links translational regulation to hepcidin production and iron overload. Sequencing of HAMP 5'-UTR; hepcidin protein detection in urine; clinical phenotyping; phlebotomy response Blood Medium 15198949
2004 The HAMP mutation C78T (p.C78T/C70R in mature peptide) disrupts one of the four intramolecular disulfide bonds present in hepcidin, supporting that these conserved cysteines are critical for hepcidin structure and function, with loss causing severe hereditary hemochromatosis. HAMP gene sequencing; structural analysis of conserved cysteines; clinical phenotype characterization Human mutation Medium 15024747
2004 Homozygosity for HAMP mutation C78T (p.C78T), which disrupts a conserved cysteine critical for disulfide bonding, causes juvenile hemochromatosis in a consanguineous family, confirming that the conserved cysteines are required for active hepcidin function. Direct sequencing of HAMP; clinical phenotype assessment in consanguineous family Clinical genetics Medium 15099344
2007 The HAMP gene promoter contains functional regulatory elements including a STAT site (nt -148 to -130) important for basal level expression in humans, and AP-1, E-box, and TIEG motifs do not play a critical role in IL-6 or BMP-9 induced responses in murine Hamp1; the human HAMP STAT site is important for both basal and IL-6-inducible promoter activity. Luciferase reporter assays with promoter mutagenesis; comparison of human HAMP vs. murine Hamp1/Hamp2 promoter constructs in reporter gene assays Blood cells, molecules & diseases Medium 17689119
2009 Genetic epistasis in mice lacking both hemojuvelin (HFE2) and matriptase-2 (TMPRSS6) shows low Hamp expression and iron overload, demonstrating that hemojuvelin is a major substrate for matriptase-2 in activating Hamp expression, and that the two pathways converge on hepcidin regulation. Double knockout mouse generation; Hamp expression measurement; serum and liver iron quantification British journal of haematology High 19751239
2010 Severe iron deficiency blunts the hepatic Hamp/hepcidin transcriptional response to lipopolysaccharide-induced inflammation, and also reduces IL-6 and TNF-α production, suggesting iron is required for a full acute-phase hepcidin response; iron chelation in HuH7 cells blunts hepcidin response to IL-6 directly. Animal dietary model (iron-deficient rats + LPS); qRT-PCR for Hamp and cytokine mRNAs; ELISA for serum cytokines; cell culture experiments with iron chelators Haematologica Medium 20511664
2011 GATA-4 and GATA-6 transcription factors bind to a GATA regulatory element (-TTATCT- at positions -103/-98) in the HAMP promoter and transactivate hepcidin expression in hepatocytes; FOG (Friend of GATA) proteins 1 and 2 suppress this GATA-mediated transactivation of HAMP. HAMP promoter 5'-deletion analysis; site-directed mutagenesis of GATA-RE; luciferase reporter assays in Huh7 cells; EMSA/ChIP for GATA protein binding Journal of molecular endocrinology Medium 21971825
2012 In Hamp knockout mice fed an iron-deficient diet, ferroportin protein expression increases in duodenum and spleen while decreasing in liver, and Dcytb and DMT1 mRNAs are more strongly induced than in controls, demonstrating that hepcidin regulates iron transport machinery (ferroportin, DMT1, Dcytb) and that hepcidin-independent mechanisms can partially compensate for iron homeostasis. Hamp-/- mouse model; dietary iron restriction; qPCR for iron-related gene mRNAs; Western blot for protein expression European journal of nutrition Medium 22241739
2012 A novel HAMP mutation p.R75X (homozygous) abolishes detectable hepcidin protein in serum and urine (by LC-MS/MS), directly linking this premature stop codon to complete absence of hepcidin and consequent juvenile hemochromatosis. Direct HAMP gene sequencing; LC-MS/MS protein detection in serum and urine Blood cells, molecules & diseases Medium 22297252
2013 ATOH8 transcription factor activates HAMP transcription by directly binding to E-box regions in the HAMP promoter (confirmed by ChIP) and also indirectly through BMP signaling (increased pSMAD1,5,8); liver Atoh8 levels are reduced by conditions increasing erythropoietic activity (hypoxia, hemolytic anemia, EPO treatment) and increased by holo-transferrin, positioning ATOH8 as a novel iron- and erythropoiesis-responsive transcriptional regulator of HAMP. ChIP assay for ATOH8 binding to HAMP promoter E-box; HAMP promoter activity reporter assay; promoter mutation analysis; pSMAD1,5,8 measurement; in vivo mouse models (hypoxia, phlebotomy, EPO) British journal of haematology High 24236640
2013 Prohepcidin (the HAMP precursor) localizes to the nucleus of hepatocytes and specifically binds the STAT3 site in the HAMP promoter, reducing HAMP promoter activity when overexpressed; decreasing prohepcidin increases promoter activity; binding partner α-1 antitrypsin competes with this autoregulatory function, suggesting a novel negative autoregulatory feedback loop. Indirect immunofluorescence and mCherry tagging (subcellular localization); DNA-binding assay (STAT3 site); luciferase reporter assays with prohepcidin overexpression/knockdown in WRL68 cells The Biochemical journal Medium 23390933
2015 Saturated fatty acids (palmitic acid, stearic acid) upregulate HAMP mRNA through post-transcriptional stabilization via the 3'-UTR AU-rich element (ARE), not through promoter activation; the ARE-binding protein HuR is required, as its siRNA knockdown abolishes the effect; PKC-mediated phosphorylation drives HuR nucleo-cytoplasmic shuttling and binding to HAMP mRNA. RT-PCR; actinomycin D transcription block; 3'-UTR reporter assays; ARE mutagenesis; HuR siRNA knockdown; PKC inhibitors; HuR-HAMP mRNA binding assay The Journal of biological chemistry High 26304124
2010 The HAMP c.-582A>G promoter variant decreases transcriptional activity by 20% in HepG2 cells when co-transfected with USF1 and by 12-14% with USF2, identifying USF transcription factors as regulators of HAMP promoter activity through this element. Luciferase reporter assay with HAMP promoter variants co-transfected with USF1/USF2 expression plasmids BMC genetics Medium 21143959
2019 GDF11 suppresses hepatic HAMP expression in vivo and in vitro by decreasing BMP-SMAD signaling, enhancing SMAD ubiquitin regulatory factor 1 (SMURF1) expression, and activating ERK1/2 signaling; ERK1/2 activation is required for GDF11/SMURF1-mediated BMP-SMAD suppression and HAMP inhibition. Exogenous GDF11 administration in mice and hepatocyte cultures; SMAD phosphorylation measurement; SMURF1 expression; ERK1/2 inhibition experiments; phlebotomy and EPO mouse models British journal of haematology Medium 31418854
2019 Downregulation of HAMP (hepcidin) in hepatocellular carcinoma cells promotes proliferation and migration through activation of the CDK1/STAT3 pathway, as confirmed by Western blotting showing that reduced HAMP activates CDK1/STAT3 signaling. HAMP knockdown/overexpression in SMMC-7721 and HepG2 cells; EdU proliferation assay; Transwell migration assay; flow cytometry; Western blot for CDK1/STAT3; GSEA Diagnostics Low 31052210
2018 HDAC3 modulates binding of transcription factors C/EBPα, HIF1α, and STAT3 to the LEAP-1/HAMP promoter, and HDAC3 inhibition upregulates HAMP (LEAP-1) expression in hepatocytes, identifying an epigenetic mechanism controlling hepcidin transcription. ChIP assay for transcription factor binding to HAMP promoter; microarray and qRT-PCR; HDAC3 inhibitor treatment in Huh7 cells and mouse model Virologica Sinica Medium 30328580
2021 In Hamp knockout mice (model of type 2B hereditary hemochromatosis), oral delivery of Dmt1 siRNA combined with dietary iron restriction suppressed duodenal Dmt1 mRNA by ~50% and reduced serum and liver non-heme iron by ~60% and >85%, demonstrating that DMT1 upregulation is a functional consequence of hepcidin deficiency and that silencing DMT1 can correct iron overload caused by HAMP loss. Hamp KO mouse model; oral siRNA delivery via ginger-derived lipid nanoparticles; qPCR for Dmt1; serum and liver iron measurement; 59Fe absorption assay Nutrients Medium 34063414
2011 HIF-1α stabilization (via PHD inhibition by EGCG) induces Hamp expression in rat kidney, establishing that HIF-1α can positively regulate hepcidin transcription in the kidney (in contrast to its role in the liver where it represses hepcidin). In vivo EGCG dosing in rats; HIF-1α stabilization confirmed by Western blot; PHD inhibition assay; Hamp qPCR; in vitro Hep3B cell assay with EGCG Biochemical and biophysical research communications Low 22138393
2019 DNA methylation of the Hamp promoter region is significantly elevated after Roux-en-Y gastric bypass surgery in rats, correlating with decreased Hamp mRNA and HEPCIDIN-25 protein, establishing that promoter methylation suppresses Hamp expression in response to post-surgical iron deficiency. RNA-seq; qPCR; ELISA for hepcidin-25; MassARRAY EpiTYPER DNA methylation quantification at Hamp promoter CpG sites Surgery for obesity and related diseases Medium 31839527
2018 HAMP promoter hypomethylation (at CpG sites cg23677000 and cg04085447) upregulates hepcidin expression in Kawasaki disease patients; IVIG treatment restores methylation; luciferase reporter assays confirmed that methylation of these target CpG sites decreases HAMP gene expression. Illumina HumanMethylation450 BeadChip; pyrosequencing for validation; luciferase reporter assay with methylated/unmethylated constructs; ELISA for plasma hepcidin Journal of molecular and cellular cardiology Medium 29501389
2013 The extract of Caulis Spatholobi inhibits HAMP expression in Huh7 cells by reducing phosphorylated SMAD1/5/8 levels (by 80%), with stronger inhibition of BMP6-induced than IL-6-induced HAMP expression; in vivo in mice it decreases hepatic HAMP expression by 60% and reduces hepatic iron concentration. Cell-based HAMP expression assay; pSMAD1/5/8 Western blot; BMP6 and IL-6 stimulation; in vivo mouse feeding experiment with hepatic HAMP qPCR and iron measurement The Journal of nutrition Medium 23700338

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS letters 986 11034317
2006 The HAMP domain structure implies helix rotation in transmembrane signaling. Cell 324 16959572
2003 Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis. Human molecular genetics 191 12915468
2010 Signaling mechanisms of HAMP domains in chemoreceptors and sensor kinases. Annual review of microbiology 157 20690824
2003 HAMP as a modifier gene that increases the phenotypic expression of the HFE pC282Y homozygous genotype. Blood 124 14670915
2009 Mutational analyses of HAMP helices suggest a dynamic bundle model of input-output signalling in chemoreceptors. Molecular microbiology 116 19656294
2010 Structure of concatenated HAMP domains provides a mechanism for signal transduction. Structure (London, England : 1993) 107 20399181
2011 The mechanisms of HAMP-mediated signaling in transmembrane receptors. Structure (London, England : 1993) 83 21397188
2011 Biphasic control logic of HAMP domain signalling in the Escherichia coli serine chemoreceptor. Molecular microbiology 81 21306449
2010 Comprehensive analysis of HAMP domains: implications for transmembrane signal transduction. Journal of molecular biology 79 20184894
2007 Structure of the conserved HAMP domain in an intact, membrane-bound chemoreceptor: a disulfide mapping study. Biochemistry 78 17994770
1996 Isolation and expression in Escherichia coli of hepB and hepC, genes coding for the glycosaminoglycan-degrading enzymes heparinase II and heparinase III, respectively, from Flavobacterium heparinum. Applied and environmental microbiology 76 8702264
2003 Mutational analysis of a conserved signal-transducing element: the HAMP linker of the Escherichia coli nitrate sensor NarX. Journal of bacteriology 72 12486044
2008 Role of HAMP domains in chemotaxis signaling by bacterial chemoreceptors. Proceedings of the National Academy of Sciences of the United States of America 67 18940922
2007 Aer on the inside looking out: paradigm for a PAS-HAMP role in sensing oxygen, redox and energy. Molecular microbiology 64 17824925
2003 Probing conservation of HAMP linker structure and signal transduction mechanism through analysis of hybrid sensor kinases. Journal of bacteriology 62 12897007
2008 Mutational analysis of the connector segment in the HAMP domain of Tsr, the Escherichia coli serine chemoreceptor. Journal of bacteriology 58 18621896
2010 Interactions among HAMP domain repeats act as an osmosensing molecular switch in group III hybrid histidine kinases from fungi. The Journal of biological chemistry 57 20164185
2013 HAMP domain conformers that propagate opposite signals in bacterial chemoreceptors. PLoS biology 53 23424282
2010 Severe iron deficiency blunts the response of the iron regulatory gene Hamp and pro-inflammatory cytokines to lipopolysaccharide. Haematologica 52 20511664
2009 Suppression of the hepcidin-encoding gene Hamp permits iron overload in mice lacking both hemojuvelin and matriptase-2/TMPRSS6. British journal of haematology 52 19751239
2005 Structural analysis of a HAMP domain: the linker region of the phototransducer in complex with sensory rhodopsin II. The Journal of biological chemistry 52 16157581
2004 Severe hemochromatosis in a Portuguese family associated with a new mutation in the 5'-UTR of the HAMP gene. Blood 51 15198949
2009 The S helix mediates signal transmission as a HAMP domain coiled-coil extension in the NarX nitrate sensor from Escherichia coli K-12. Journal of bacteriology 46 19966007
2006 Loss- and gain-of-function mutations in the F1-HAMP region of the Escherichia coli aerotaxis transducer Aer. Journal of bacteriology 46 16672601
2008 Structure-function relationships in the HAMP and proximal signaling domains of the aerotaxis receptor Aer. Journal of bacteriology 45 18203838
2013 Molecular cloning and expression analysis of liver-expressed antimicrobial peptide 1 (LEAP-1) and LEAP-2 genes in the blunt snout bream (Megalobrama amblycephala). Fish & shellfish immunology 43 23748217
2010 PAS/poly-HAMP signalling in Aer-2, a soluble haem-based sensor. Molecular microbiology 39 21255112
2004 A homozygous HAMP mutation in a multiply consanguineous family with pseudo-dominant juvenile hemochromatosis. Clinical genetics 37 15099344
2015 HAMP Domain Rotation and Tilting Movements Associated with Signal Transduction in the PhoQ Sensor Kinase. mBio 36 26015499
2004 The effect of HAMP domains on class IIIb adenylyl cyclases from Mycobacterium tuberculosis. European journal of biochemistry 36 15182360
2012 Architecture of the soluble receptor Aer2 indicates an in-line mechanism for PAS and HAMP domain signaling. Journal of molecular biology 34 23274111
2004 Interactions between the PAS and HAMP domains of the Escherichia coli aerotaxis receptor Aer. Journal of bacteriology 34 15489456
2014 Functional suppression of HAMP domain signaling defects in the E. coli serine chemoreceptor. Journal of molecular biology 33 25134756
2008 Salt-driven equilibrium between two conformations in the HAMP domain from Natronomonas pharaonis: the language of signal transfer? The Journal of biological chemistry 31 18697747
2022 C-reactive protein to lymphocyte count ratio is a promising novel marker in hepatitis C infection: the clear hep-c study. Revista da Associacao Medica Brasileira (1992) 30 35766701
2020 Hamp Type-1 Promotes Antimicrobial Defense via Direct Microbial Killing and Regulating Iron Metabolism in Grass Carp (Ctenopharyngodon idella). Biomolecules 30 32481513
2007 The role of STAT, AP-1, E-box and TIEG motifs in the regulation of hepcidin by IL-6 and BMP-9: lessons from human HAMP and murine Hamp1 and Hamp2 gene promoters. Blood cells, molecules & diseases 29 17689119
2018 Histone Deacetylase 3 Inhibitor Suppresses Hepatitis C Virus Replication by Regulating Apo-A1 and LEAP-1 Expression. Virologica Sinica 28 30328580
2007 Structural and functional studies of the HAMP domain of EnvZ, an osmosensing transmembrane histidine kinase in Escherichia coli. The Journal of biological chemistry 28 17635923
2021 Oral Administration of Ginger-Derived Lipid Nanoparticles and Dmt1 siRNA Potentiates the Effect of Dietary Iron Restriction and Mitigates Pre-Existing Iron Overload in Hamp KO Mice. Nutrients 27 34063414
2020 Circ_0004913 Inhibits Cell Growth, Metastasis, and Glycolysis by Absorbing miR-184 to Regulate HAMP in Hepatocellular Carcinoma. Cancer biotherapy & radiopharmaceuticals 27 33021399
2013 HAMP domain structural determinants for signalling and sensory adaptation in Tsr, the Escherichia coli serine chemoreceptor. Molecular microbiology 27 24205875
2005 A liposomal formulation of doxorubicin, composed of hexadecylphosphocholine (HePC): physicochemical characterization and cytotoxic activity against human cancer cell lines. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 16271845
2018 HAMP promoter hypomethylation and increased hepcidin levels as biomarkers for Kawasaki disease. Journal of molecular and cellular cardiology 26 29501389
2011 HAMP domain-mediated signal transduction probed with a mycobacterial adenylyl cyclase as a reporter. The Journal of biological chemistry 26 22094466
2004 HAMP gene mutation c.208T>C (p.C70R) identified in an Italian patient with severe hereditary hemochromatosis. Human mutation 26 15024747
2015 Hereditary hemochromatosis type 1 phenotype modifiers in Italian patients. The controversial role of variants in HAMP, BMP2, FTL and SLC40A1 genes. Blood cells, molecules & diseases 25 25976471
2014 Light-induced switching of HAMP domain conformation and dynamics revealed by time-resolved EPR spectroscopy. FEBS letters 25 25240192
2013 Deletion of the HAMP domains from the histidine kinase CaNik1p of Candida albicans or treatment with fungicides activates the MAP kinase Hog1p in S. cerevisiae transformants. BMC microbiology 25 24044701
2011 A novel functional assay for fungal histidine kinases group III reveals the role of HAMP domains for fungicide sensitivity. Journal of biotechnology 25 21963586
2008 Conserved residues in the HAMP domain define a new family of proposed bipartite energy taxis receptors. Journal of bacteriology 25 18952801
2005 Genetic and functional characterization of the Escherichia coli BarA-UvrY two-component system: point mutations in the HAMP linker of the BarA sensor give a dominant-negative phenotype. Journal of bacteriology 25 16237014
2022 Evolutionary gain and loss of a plant pattern-recognition receptor for HAMP recognition. eLife 24 36377784
2019 HAMP Downregulation Contributes to Aggressive Hepatocellular Carcinoma via Mechanism Mediated by Cyclin4-Dependent Kinase-1/STAT3 Pathway. Diagnostics (Basel, Switzerland) 24 31052210
2010 Genetic study of the hepcidin gene (HAMP) promoter and functional analysis of the c.-582A > G variant. BMC genetics 24 21143959
2005 Genetic analysis of the HAMP domain of the Aer aerotaxis sensor localizes flavin adenine dinucleotide-binding determinants to the AS-2 helix. Journal of bacteriology 24 15601703
2014 The HAMP signal-conversion domain: static two-state or dynamic three-state? Molecular microbiology 23 24417364
2013 Screening identifies the Chinese medicinal plant Caulis Spatholobi as an effective HAMP expression inhibitor. The Journal of nutrition 23 23700338
2013 The transcription factor ATOH8 is regulated by erythropoietic activity and regulates HAMP transcription and cellular pSMAD1,5,8 levels. British journal of haematology 23 24236640
2012 HAMP domain signal relay mechanism in a sensory rhodopsin-transducer complex. The Journal of biological chemistry 23 22511775
2010 Mutational analysis of the transmembrane helix 2-HAMP domain connection in the Escherichia coli aspartate chemoreceptor tar. Journal of bacteriology 23 20870768
2015 Saturated fatty acids induce post-transcriptional regulation of HAMP mRNA via AU-rich element-binding protein, human antigen R (HuR). The Journal of biological chemistry 21 26304124
2004 The HAMP linker in histidine kinase dimeric receptors is critical for symmetric transmembrane signal transduction. The Journal of biological chemistry 20 15316026
2016 Delineating PAS-HAMP interaction surfaces and signalling-associated changes in the aerotaxis receptor Aer. Molecular microbiology 19 26713609
2013 Prohepcidin binds to the HAMP promoter and autoregulates its own expression. The Biochemical journal 19 23390933
2012 Identification of a novel mutation in the HAMP gene that causes non-detectable hepcidin molecules in a Japanese male patient with juvenile hemochromatosis. Blood cells, molecules & diseases 19 22297252
2011 Different conformations of the kinase-on and kinase-off signaling states in the Aer HAMP domain. Journal of bacteriology 19 21665965
2019 GDF11 contributes to hepatic hepcidin (HAMP) inhibition through SMURF1-mediated BMP-SMAD signalling suppression. British journal of haematology 18 31418854
2005 Regulatory effects of tumor necrosis factor-alpha and interleukin-6 on HAMP expression in iron loaded rat hepatocytes. Journal of hepatology 18 16221503
2020 Genetic Variability and Trajectories of DNA Methylation May Support a Role for HAMP in Patient Outcomes After Aneurysmal Subarachnoid Hemorrhage. Neurocritical care 17 31346934
2012 Regulation of iron metabolism in Hamp (-/-) mice in response to iron-deficient diet. European journal of nutrition 17 22241739
2020 The Copenhagen test and treat hepatitis C in a mobile clinic study: a protocol for an intervention study to enhance the HCV cascade of care for people who inject drugs (T'N'T HepC). BMJ open 16 33168560
2014 Intraprotein signal transduction by HAMP domains: a balancing act. International journal of medical microbiology : IJMM 16 25595022
2013 Two distinct states of the HAMP domain from sensory rhodopsin transducer observed in unbiased molecular dynamics simulations. PloS one 16 23843970
2013 The sixth HAMP domain negatively regulates the activity of the group III HHK containing seven HAMP domains. Biochemical and biophysical research communications 16 23876316
2012 Dietary fat level affects tissue iron levels but not the iron regulatory gene HAMP in rats. Nutrition research (New York, N.Y.) 16 23399663
2021 Identification of a novel mutation gene signature HAMP for cholangiocarcinoma through comprehensive TCGA and GEO data mining. International immunopharmacology 15 34426102
2018 A zipped-helix cap potentiates HAMP domain control of chemoreceptor signaling. Proceedings of the National Academy of Sciences of the United States of America 14 29581254
2017 Chlorella sp. transgenic with Scy-hepc enhancing the survival of Sparus macrocephalus and hybrid grouper challenged with Aeromonas hydrophila. Fish & shellfish immunology 14 29197618
2014 Differential role of HAMP-like linkers in regulating the functionality of the group III histidine kinase DhNik1p. The Journal of biological chemistry 14 24895133
2006 Antitumor activity of doxorubicin encapsulated in hexadecylphosphocholine (HePC) liposomes against human xenografts on Scid mice. In vivo (Athens, Greece) 14 16433041
2020 R93P Substitution in the PmrB HAMP Domain Contributes to Colistin Heteroresistance in Escherichia coli Isolates from Swine. Antimicrobial agents and chemotherapy 13 32868331
2009 Mutations in HAMP and HJV genes and their impact on expression of clinical hemochromatosis in a cohort of 100 Spanish patients homozygous for the C282Y mutation of HFE gene. Annals of hematology 13 19214511
2004 Analysis of chimeric chemoreceptors in Bacillus subtilis reveals a role for CheD in the function of the McpC HAMP domain. Journal of bacteriology 13 15317802
2023 Differences in DNA methylation of HAMP in blood cells predicts the development of type 2 diabetes. Molecular metabolism 12 37429525
2024 AlphaFold2 captures the conformational landscape of the HAMP signaling domain. Protein science : a publication of the Protein Society 11 38010737
2015 Functional dissection of HAMP domains in NIK1 ortholog from pathogenic yeast Candida lusitaniae. Gene 11 26657037
2011 Structural characterization of AS1-membrane interactions from a subset of HAMP domains. Biochimica et biophysica acta 11 21763270
2011 Friend of GATA suppresses the GATA-induced transcription of hepcidin in hepatocytes through a GATA-regulatory element in the HAMP promoter. Journal of molecular endocrinology 11 21971825
2010 Role of the HAMP domain region of sensory rhodopsin transducers in signal transduction. Biochemistry 11 21162553
2007 Signal transmission through the HtrII transducer alters the interaction of two alpha-helices in the HAMP domain. Journal of molecular biology 11 18199454
2025 An Insect Salivary Sheath Protein Triggers Plant Resistance to Insects and Pathogens as a Conserved HAMP. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10 40167256
2023 Growth-promoting effect of antimicrobial peptide Scy-hepc on mariculture large yellow croaker Larimichthys crocea and the underlying mechanism. Fish & shellfish immunology 10 36849046
2019 Hyaluronan activated-metabolism phenotype (HAMP) in pancreatic ductal adenocarcinoma. Oncotarget 10 31608136
2017 Molecular characterization of Aspergillus fumigatus TcsC, a characteristic type III hybrid histidine kinase of filamentous fungi harboring six HAMP domains. International journal of medical microbiology : IJMM 10 28527583
2017 Correlation of HAMP gene polymorphisms and expression with the susceptibility and length of hospital stays in Taiwanese children with Kawasaki disease. Oncotarget 10 28881695
2019 DNA methylation suppresses liver Hamp expression in response to iron deficiency after bariatric surgery. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery 9 31839527
2013 A Novel Isoform of the Hepatic Antimicrobial Peptide, Hepcidin (Hepc-CB1), from a Deep-Sea Fish, the Spinyjaw Greeneye Chlorophthalmus bicornis (Norman, 1939): Molecular Characterisation and Phylogeny. Probiotics and antimicrobial proteins 8 26782599
2011 Inactivation of prolyl hydroxylase domain (PHD) protein by epigallocatechin (EGCG) stabilizes hypoxia-inducible factor (HIF-1α) and induces hepcidin (Hamp) in rat kidney. Biochemical and biophysical research communications 8 22138393

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