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Protein

Hepcidin

Gene

HAMP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin, leading to the retention of iron in iron-exporting cells and decreased flow of iron into plasma. Controls the major flows of iron into plasma: absorption of dietary iron in the intestine, recycling of iron by macrophages, which phagocytose old erythrocytes and other cells, and mobilization of stored iron from hepatocytes (PubMed:22306005).1 Publication
Has strong antimicrobial activity against E.coli ML35P N.cinerea and weaker against S.epidermidis, S.aureus and group b streptococcus bacteria. Active against the fungus C.albicans. No activity against P.aeruginosa (PubMed:11113131, PubMed:11034317).2 Publications

GO - Molecular functioni

  • hormone activity Source: BHF-UCL
  • iron channel inhibitor activity Source: BHF-UCL
  • signaling receptor binding Source: BHF-UCL

GO - Biological processi

  • acute-phase response Source: Ensembl
  • aging Source: Ensembl
  • antimicrobial humoral immune response mediated by antimicrobial peptide Source: UniProtKB
  • cellular iron ion homeostasis Source: BHF-UCL
  • cellular response to bile acid Source: Ensembl
  • cellular response to interleukin-6 Source: Ensembl
  • cellular response to lipopolysaccharide Source: Ensembl
  • cellular response to tumor necrosis factor Source: Ensembl
  • cellular response to X-ray Source: Ensembl
  • defense response to bacterium Source: GO_Central
  • defense response to fungus Source: UniProtKB
  • defense response to Gram-negative bacterium Source: UniProtKB
  • defense response to Gram-positive bacterium Source: UniProtKB
  • immune response Source: UniProtKB
  • killing of cells of other organism Source: UniProtKB
  • liver regeneration Source: Ensembl
  • multicellular organismal iron ion homeostasis Source: BHF-UCL
  • negative regulation of ferrous iron export Source: BHF-UCL
  • negative regulation of intestinal absorption Source: BHF-UCL
  • negative regulation of ion transmembrane transporter activity Source: BHF-UCL
  • negative regulation of iron channel activity Source: BHF-UCL
  • negative regulation of iron ion transmembrane transport Source: GO_Central
  • negative regulation of transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of cell growth involved in cardiac muscle cell development Source: Ensembl
  • positive regulation of protein polyubiquitination Source: BHF-UCL
  • positive regulation of receptor catabolic process Source: BHF-UCL
  • positive regulation of receptor internalization Source: BHF-UCL
  • response to erythropoietin Source: Ensembl
  • response to ethanol Source: Ensembl
  • response to iron ion Source: BHF-UCL
  • response to iron ion starvation Source: Ensembl
  • response to vitamin A Source: Ensembl
  • response to zinc ion Source: Ensembl

Keywordsi

Molecular functionAntibiotic, Antimicrobial, Fungicide, Hormone

Enzyme and pathway databases

SIGNORiP81172

Protein family/group databases

TCDBi8.A.37.1.2 the hepcidin (hepcidin) family

Names & Taxonomyi

Protein namesi
Recommended name:
Hepcidin
Alternative name(s):
Liver-expressed antimicrobial peptide 1
Short name:
LEAP-1
Putative liver tumor regressor
Short name:
PLTR
Cleaved into the following 2 chains:
Hepcidin-25
Short name:
Hepc25
Hepcidin-20
Short name:
Hepc20
Gene namesi
Name:HAMP
Synonyms:HEPC, LEAP1
ORF Names:UNQ487/PRO1003
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105697.7
HGNCiHGNC:15598 HAMP
MIMi606464 gene
neXtProtiNX_P81172

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Hemochromatosis 2B (HFE2B)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA juvenile form of hemochromatosis, a disorder of iron metabolism with excess deposition of iron in a variety of organs leading to their failure, bronze skin pigmentation, hepatic cirrhosis, arthropathy and diabetes. The most common symptoms of juvenile hemochromatosis at presentation are hypogonadism and cardiomyopathy.
See also OMIM:613313
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04251259R → G in HFE2B. 1 PublicationCorresponds to variant dbSNP:rs779021719EnsemblClinVar.1
Natural variantiVAR_04251370C → R in HFE2B. 1 Publication1
Natural variantiVAR_02664871G → D in HFE2B. 3 PublicationsCorresponds to variant dbSNP:rs104894696EnsemblClinVar.1
Natural variantiVAR_04251478C → Y in HFE2B. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi57817
GeneReviewsiHAMP
MalaCardsiHAMP
MIMi613313 phenotype
OpenTargetsiENSG00000105697
Orphaneti79230 Hemochromatosis type 2
PharmGKBiPA29182

Polymorphism and mutation databases

BioMutaiHAMP
DMDMi10720397

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
PropeptideiPRO_000001337825 – 54Add BLAST30
PeptideiPRO_000001337960 – 84Hepcidin-25Add BLAST25
PeptideiPRO_000001338065 – 84Hepcidin-20Add BLAST20

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi66 ↔ 821 Publication
Disulfide bondi69 ↔ 721 Publication
Disulfide bondi70 ↔ 781 Publication
Disulfide bondi73 ↔ 811 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond

Proteomic databases

PaxDbiP81172
PeptideAtlasiP81172
PRIDEiP81172
ProteomicsDBi57692

Expressioni

Tissue specificityi

Highest expression in liver and to a lesser extent in heart and brain. Low levels in lung, tonsils, salivary gland, trachea, prostate gland, adrenal gland and thyroid gland. Secreted into the urine.1 Publication

Gene expression databases

BgeeiENSG00000105697
CleanExiHS_HAMP
GenevisibleiP81172 HS

Interactioni

GO - Molecular functioni

  • hormone activity Source: BHF-UCL
  • signaling receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi121776, 2 interactors
IntActiP81172, 2 interactors
STRINGi9606.ENSP00000222304

Structurei

Secondary structure

184
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi66 – 71Combined sources6
Beta strandi76 – 82Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1M4ENMR-A65-84[»]
1M4FNMR-A60-84[»]
2KEFNMR-A60-84[»]
3H0TX-ray1.89C60-84[»]
4QAEX-ray2.10P/Q/R/S/T/U60-84[»]
ProteinModelPortaliP81172
SMRiP81172
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP81172

Family & Domainsi

Sequence similaritiesi

Belongs to the hepcidin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J3JD Eukaryota
ENOG4111C2J LUCA
GeneTreeiENSGT00390000003154
HOGENOMiHOG000008666
HOVERGENiHBG003716
InParanoidiP81172
OMAiCGICCKT
OrthoDBiEOG091G1A4A
PhylomeDBiP81172
TreeFamiTF330932

Family and domain databases

InterProiView protein in InterPro
IPR010500 Hepcidin
PANTHERiPTHR16877 PTHR16877, 1 hit
PfamiView protein in Pfam
PF06446 Hepcidin, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P81172-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALSSQIWAA CLLLLLLLAS LTSGSVFPQQ TGQLAELQPQ DRAGARASWM
60 70 80
PMFQRRRRRD THFPICIFCC GCCHRSKCGM CCKT
Length:84
Mass (Da):9,408
Last modified:December 1, 2000 - v2
Checksum:i5F8DCA23D19D29F7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31T → M in AAK14912 (Ref. 3) Curated1

Mass spectrometryi

Molecular mass is 2789.8 Da from positions 60 - 84. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04251259R → G in HFE2B. 1 PublicationCorresponds to variant dbSNP:rs779021719EnsemblClinVar.1
Natural variantiVAR_04251370C → R in HFE2B. 1 Publication1
Natural variantiVAR_02664871G → D in HFE2B. 3 PublicationsCorresponds to variant dbSNP:rs104894696EnsemblClinVar.1
Natural variantiVAR_04251478C → Y in HFE2B. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF309489 mRNA Translation: AAG23966.1
AJ277280 mRNA Translation: CAC09419.1
AF131292 mRNA Translation: AAK14912.1
AY358669 mRNA Translation: AAQ89032.1
DQ496109 Genomic DNA Translation: ABF47098.1
AD000684 Genomic DNA No translation available.
BC020612 mRNA Translation: AAH20612.1
CCDSiCCDS12454.1
RefSeqiNP_066998.1, NM_021175.3
UniGeneiHs.8821

Genome annotation databases

EnsembliENST00000222304; ENSP00000222304; ENSG00000105697
ENST00000598398; ENSP00000471894; ENSG00000105697
GeneIDi57817
KEGGihsa:57817
UCSCiuc002nyw.4 human

Similar proteinsi

Entry informationi

Entry nameiHEPC_HUMAN
AccessioniPrimary (citable) accession number: P81172
Secondary accession number(s): Q1HE14, Q9BY68
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: December 1, 2000
Last modified: June 20, 2018
This is version 166 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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