UniProtKB - P81172 (HEPC_HUMAN)
Hepcidin
HAMP
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/SLC40A1, leading to the retention of iron in iron-exporting cells and decreased flow of iron into plasma (PubMed:22682227, PubMed:29237594, PubMed:32814342).
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).
4 PublicationsHas 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 PublicationsGO - Molecular functioni
- copper ion binding Source: Ensembl
- hormone activity Source: BHF-UCL
- iron ion transmembrane transporter 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 another organism Source: UniProtKB
- liver regeneration Source: Ensembl
- multicellular organismal iron ion homeostasis Source: BHF-UCL
- myeloid cell homeostasis Source: Ensembl
- negative regulation of bone resorption Source: Ensembl
- negative regulation of inflammatory response Source: Ensembl
- negative regulation of intestinal absorption Source: BHF-UCL
- negative regulation of ion transmembrane transporter activity Source: BHF-UCL
- negative regulation of iron export across plasma membrane Source: BHF-UCL
- negative regulation of iron ion transmembrane transport Source: GO_Central
- negative regulation of iron ion transmembrane transporter activity Source: BHF-UCL
- 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 cellular protein catabolic process Source: Ensembl
- positive regulation of macrophage activation 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
- positive regulation of transcription by RNA polymerase II Source: Ensembl
- receptor signaling pathway via JAK-STAT Source: Ensembl
- 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 function | Antibiotic, Antimicrobial, Fungicide, Hormone |
Enzyme and pathway databases
PathwayCommonsi | P81172 |
SignaLinki | P81172 |
SIGNORi | P81172 |
Protein family/group databases
TCDBi | 8.A.37.1.2, the hepcidin (hepcidin) family |
Names & Taxonomyi
Protein namesi | Recommended name: HepcidinCuratedAlternative name(s): Liver-expressed antimicrobial peptide 1 Short name: LEAP-1 Putative liver tumor regressor Short name: PLTR Cleaved into the following 2 chains: |
Gene namesi | ORF Names:UNQ487/PRO1003 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:15598, HAMP |
MIMi | 606464, gene |
neXtProti | NX_P81172 |
VEuPathDBi | HostDB:ENSG00000105697 |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: UniProtKB
- extracellular space Source: UniProtKB
Nucleus
- nucleus Source: Ensembl
Other locations
- apical cortex Source: Ensembl
- intercalated disc Source: Ensembl
Keywords - Cellular componenti
SecretedPathology & Biotechi
Involvement in diseasei
Hemochromatosis 2B (HFE2B)5 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_042512 | 59 | R → G in HFE2B. 1 PublicationCorresponds to variant dbSNP:rs779021719EnsemblClinVar. | 1 | |
Natural variantiVAR_042513 | 70 | C → R in HFE2B. 1 PublicationCorresponds to variant dbSNP:rs1374259518EnsemblClinVar. | 1 | |
Natural variantiVAR_026648 | 71 | G → D in HFE2B. 3 PublicationsCorresponds to variant dbSNP:rs104894696EnsemblClinVar. | 1 | |
Natural variantiVAR_042514 | 78 | C → Y in HFE2B. 1 PublicationCorresponds to variant dbSNP:rs1462013476Ensembl. | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 57817 |
GeneReviewsi | HAMP |
MalaCardsi | HAMP |
MIMi | 613313, phenotype |
OpenTargetsi | ENSG00000105697 |
Orphaneti | 79230, Hemochromatosis type 2 |
PharmGKBi | PA29182 |
Miscellaneous databases
Pharosi | P81172, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3989381 |
DrugBanki | DB13257, Ferrous sulfate anhydrous |
Genetic variation databases
BioMutai | HAMP |
DMDMi | 10720397 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 24 | Sequence analysisAdd BLAST | 24 | |
PropeptideiPRO_0000013378 | 25 – 54 | Add BLAST | 30 | |
PeptideiPRO_0000013379 | 60 – 84 | Hepcidin-25Add BLAST | 25 | |
PeptideiPRO_0000013380 | 65 – 84 | Hepcidin-20Add BLAST | 20 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 66 ↔ 82 | 1 Publication | ||
Disulfide bondi | 69 ↔ 72 | 1 Publication | ||
Disulfide bondi | 70 ↔ 78 | 1 Publication | ||
Disulfide bondi | 73 ↔ 81 | 1 Publication |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bondProteomic databases
jPOSTi | P81172 |
MassIVEi | P81172 |
PaxDbi | P81172 |
PeptideAtlasi | P81172 |
PRIDEi | P81172 |
ProteomicsDBi | 57692 |
PTM databases
PhosphoSitePlusi | P81172 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000105697, Expressed in anatomical system and 209 other tissues |
Genevisiblei | P81172, HS |
Organism-specific databases
HPAi | ENSG00000105697, Tissue enriched (liver) |
Interactioni
Subunit structurei
Interacts with SLC40A1; this interaction promotes SLC40A1 rapid ubiquitination.
3 PublicationsGO - Molecular functioni
- hormone activity Source: BHF-UCL
- signaling receptor binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 121776, 3 interactors |
IntActi | P81172, 2 interactors |
STRINGi | 9606.ENSP00000471894 |
Miscellaneous databases
RNActi | P81172, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P81172 |
SMRi | P81172 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P81172 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | ENOG502T0FU, Eukaryota |
GeneTreei | ENSGT00390000003154 |
HOGENOMi | CLU_2557737_0_0_1 |
InParanoidi | P81172 |
OMAi | PICLFCC |
OrthoDBi | 1623838at2759 |
PhylomeDBi | P81172 |
TreeFami | TF330932 |
Family and domain databases
InterProi | View protein in InterPro IPR010500, Hepcidin |
PANTHERi | PTHR16877, PTHR16877, 1 hit |
Pfami | View protein in Pfam PF06446, Hepcidin, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MALSSQIWAA CLLLLLLLAS LTSGSVFPQQ TGQLAELQPQ DRAGARASWM
60 70 80
PMFQRRRRRD THFPICIFCC GCCHRSKCGM CCKT
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 31 | T → M in AAK14912 (Ref. 3) Curated | 1 |
Mass spectrometryi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_042512 | 59 | R → G in HFE2B. 1 PublicationCorresponds to variant dbSNP:rs779021719EnsemblClinVar. | 1 | |
Natural variantiVAR_042513 | 70 | C → R in HFE2B. 1 PublicationCorresponds to variant dbSNP:rs1374259518EnsemblClinVar. | 1 | |
Natural variantiVAR_026648 | 71 | G → D in HFE2B. 3 PublicationsCorresponds to variant dbSNP:rs104894696EnsemblClinVar. | 1 | |
Natural variantiVAR_042514 | 78 | C → Y in HFE2B. 1 PublicationCorresponds to variant dbSNP:rs1462013476Ensembl. | 1 |
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 |
CCDSi | CCDS12454.1 |
RefSeqi | NP_066998.1, NM_021175.3 |
Genome annotation databases
Ensembli | ENST00000222304.5; ENSP00000222304.2; ENSG00000105697.9 ENST00000598398.5; ENSP00000471894.1; ENSG00000105697.9 |
GeneIDi | 57817 |
KEGGi | hsa:57817 |
MANE-Selecti | ENST00000222304.5; ENSP00000222304.2; NM_021175.4; NP_066998.1 |
UCSCi | uc002nyw.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Hepcidin entry |
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 |
CCDSi | CCDS12454.1 |
RefSeqi | NP_066998.1, NM_021175.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1M4E | NMR | - | A | 65-84 | [»] | |
1M4F | NMR | - | A | 60-84 | [»] | |
2KEF | NMR | - | A | 60-84 | [»] | |
3H0T | X-ray | 1.89 | C | 60-84 | [»] | |
4QAE | X-ray | 2.10 | P/Q/R/S/T/U | 60-84 | [»] | |
6WBV | electron microscopy | 2.50 | B | 60-84 | [»] | |
AlphaFoldDBi | P81172 | |||||
SMRi | P81172 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121776, 3 interactors |
IntActi | P81172, 2 interactors |
STRINGi | 9606.ENSP00000471894 |
Chemistry databases
ChEMBLi | CHEMBL3989381 |
DrugBanki | DB13257, Ferrous sulfate anhydrous |
Protein family/group databases
TCDBi | 8.A.37.1.2, the hepcidin (hepcidin) family |
PTM databases
PhosphoSitePlusi | P81172 |
Genetic variation databases
BioMutai | HAMP |
DMDMi | 10720397 |
Proteomic databases
jPOSTi | P81172 |
MassIVEi | P81172 |
PaxDbi | P81172 |
PeptideAtlasi | P81172 |
PRIDEi | P81172 |
ProteomicsDBi | 57692 |
Protocols and materials databases
ABCDi | P81172, 4 sequenced antibodies |
Antibodypediai | 29325, 435 antibodies from 30 providers |
DNASUi | 57817 |
Genome annotation databases
Ensembli | ENST00000222304.5; ENSP00000222304.2; ENSG00000105697.9 ENST00000598398.5; ENSP00000471894.1; ENSG00000105697.9 |
GeneIDi | 57817 |
KEGGi | hsa:57817 |
MANE-Selecti | ENST00000222304.5; ENSP00000222304.2; NM_021175.4; NP_066998.1 |
UCSCi | uc002nyw.4, human |
Organism-specific databases
CTDi | 57817 |
DisGeNETi | 57817 |
GeneCardsi | HAMP |
GeneReviewsi | HAMP |
HGNCi | HGNC:15598, HAMP |
HPAi | ENSG00000105697, Tissue enriched (liver) |
MalaCardsi | HAMP |
MIMi | 606464, gene 613313, phenotype |
neXtProti | NX_P81172 |
OpenTargetsi | ENSG00000105697 |
Orphaneti | 79230, Hemochromatosis type 2 |
PharmGKBi | PA29182 |
VEuPathDBi | HostDB:ENSG00000105697 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502T0FU, Eukaryota |
GeneTreei | ENSGT00390000003154 |
HOGENOMi | CLU_2557737_0_0_1 |
InParanoidi | P81172 |
OMAi | PICLFCC |
OrthoDBi | 1623838at2759 |
PhylomeDBi | P81172 |
TreeFami | TF330932 |
Enzyme and pathway databases
PathwayCommonsi | P81172 |
SignaLinki | P81172 |
SIGNORi | P81172 |
Miscellaneous databases
BioGRID-ORCSi | 57817, 313 hits in 1077 CRISPR screens |
EvolutionaryTracei | P81172 |
GeneWikii | HAMP |
GenomeRNAii | 57817 |
Pharosi | P81172, Tbio |
PROi | PR:P81172 |
RNActi | P81172, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000105697, Expressed in anatomical system and 209 other tissues |
Genevisiblei | P81172, HS |
Family and domain databases
InterProi | View protein in InterPro IPR010500, Hepcidin |
PANTHERi | PTHR16877, PTHR16877, 1 hit |
Pfami | View protein in Pfam PF06446, Hepcidin, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | HEPC_HUMAN | |
Accessioni | P81172Primary (citable) accession number: P81172 Secondary accession number(s): Q1HE14, Q9BY68 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | December 1, 2000 | |
Last modified: | May 25, 2022 | |
This is version 190 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families