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P81172

- HEPC_HUMAN

UniProt

P81172 - HEPC_HUMAN

Protein

Hepcidin

Gene

HAMP

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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 - Biological processi

    1. cellular iron ion homeostasis Source: Ensembl
    2. defense response to bacterium Source: UniProtKB-KW
    3. defense response to fungus Source: UniProtKB-KW
    4. immune response Source: UniProtKB
    5. killing of cells of other organism Source: UniProtKB-KW

    Keywords - Molecular functioni

    Antibiotic, Antimicrobial, Fungicide, Hormone

    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
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:15598. HAMP.

    Subcellular locationi

    GO - Cellular componenti

    1. apical cortex Source: Ensembl
    2. extracellular region Source: UniProtKB

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Hemochromatosis 2B (HFE2B) [MIM:613313]: A 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.5 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti59 – 591R → G in HFE2B. 1 Publication
    VAR_042512
    Natural varianti70 – 701C → R in HFE2B. 1 Publication
    VAR_042513
    Natural varianti71 – 711G → D in HFE2B. 3 Publications
    Corresponds to variant rs104894696 [ dbSNP | Ensembl ].
    VAR_026648
    Natural varianti78 – 781C → Y in HFE2B. 1 Publication
    VAR_042514

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi613313. phenotype.
    Orphaneti79230. Hemochromatosis type 2.
    PharmGKBiPA29182.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2424Sequence AnalysisAdd
    BLAST
    Propeptidei25 – 5430PRO_0000013378Add
    BLAST
    Peptidei60 – 8425Hepcidin-25PRO_0000013379Add
    BLAST
    Peptidei65 – 8420Hepcidin-20PRO_0000013380Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    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.
    PRIDEiP81172.

    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

    ArrayExpressiP81172.
    BgeeiP81172.
    CleanExiHS_HAMP.
    GenevestigatoriP81172.

    Interactioni

    Protein-protein interaction databases

    BioGridi121776. 2 interactions.
    IntActiP81172. 2 interactions.
    STRINGi9606.ENSP00000222304.

    Structurei

    Secondary structure

    1
    84
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi66 – 716
    Beta strandi76 – 827

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1M4ENMR-A65-84[»]
    1M4FNMR-A60-84[»]
    2KEFNMR-A60-84[»]
    3H0TX-ray1.89C60-84[»]
    ProteinModelPortaliP81172.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP81172.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the hepcidin family.Curated

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG45549.
    HOGENOMiHOG000008666.
    HOVERGENiHBG003716.
    InParanoidiP81172.
    OMAiGARAGWT.
    OrthoDBiEOG7N8ZZ3.
    PhylomeDBiP81172.
    TreeFamiTF330932.

    Family and domain databases

    InterProiIPR010500. Hepcidin.
    [Graphical view]
    PfamiPF06446. Hepcidin. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P81172-1 [UniParc]FASTAAdd to Basket

    « Hide

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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti31 – 311T → M in AAK14912. 1 PublicationCurated

    Mass spectrometryi

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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti59 – 591R → G in HFE2B. 1 Publication
    VAR_042512
    Natural varianti70 – 701C → R in HFE2B. 1 Publication
    VAR_042513
    Natural varianti71 – 711G → D in HFE2B. 3 Publications
    Corresponds to variant rs104894696 [ dbSNP | Ensembl ].
    VAR_026648
    Natural varianti78 – 781C → Y in HFE2B. 1 Publication
    VAR_042514

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_021175.2.
    UniGeneiHs.8821.

    Genome annotation databases

    EnsembliENST00000222304; ENSP00000222304; ENSG00000105697.
    ENST00000598398; ENSP00000471894; ENSG00000105697.
    GeneIDi57817.
    KEGGihsa:57817.
    UCSCiuc002nyw.3. human.

    Polymorphism databases

    DMDMi10720397.

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Hepcidin entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_021175.2.
    UniGenei Hs.8821.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali P81172.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 121776. 2 interactions.
    IntActi P81172. 2 interactions.
    STRINGi 9606.ENSP00000222304.

    Protein family/group databases

    TCDBi 8.A.37.1.2. the hepcidin (hepcidin) family.

    Polymorphism databases

    DMDMi 10720397.

    Proteomic databases

    PaxDbi P81172.
    PRIDEi P81172.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000222304 ; ENSP00000222304 ; ENSG00000105697 .
    ENST00000598398 ; ENSP00000471894 ; ENSG00000105697 .
    GeneIDi 57817.
    KEGGi hsa:57817.
    UCSCi uc002nyw.3. human.

    Organism-specific databases

    CTDi 57817.
    GeneCardsi GC19P035777.
    GeneReviewsi HAMP.
    HGNCi HGNC:15598. HAMP.
    MIMi 606464. gene.
    613313. phenotype.
    neXtProti NX_P81172.
    Orphaneti 79230. Hemochromatosis type 2.
    PharmGKBi PA29182.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG45549.
    HOGENOMi HOG000008666.
    HOVERGENi HBG003716.
    InParanoidi P81172.
    OMAi GARAGWT.
    OrthoDBi EOG7N8ZZ3.
    PhylomeDBi P81172.
    TreeFami TF330932.

    Miscellaneous databases

    EvolutionaryTracei P81172.
    GeneWikii HAMP.
    GenomeRNAii 57817.
    NextBioi 64762.
    PROi P81172.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P81172.
    Bgeei P81172.
    CleanExi HS_HAMP.
    Genevestigatori P81172.

    Family and domain databases

    InterProi IPR010500. Hepcidin.
    [Graphical view ]
    Pfami PF06446. Hepcidin. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Hepcidin: a urinary antimicrobial peptide synthesized in the liver."
      Park C.H., Valore E.V., Waring A.J., Ganz T.
      J. Biol. Chem. 276:7806-7810(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 60-84.
      Tissue: Liver and Urine.
    2. "LEAP-1, a novel highly disulfide-bonded human peptide exhibits antimicrobial activity."
      Krause A., Neitz S., Maegert H.-J., Schulz A., Forssmann W.-G., Schulz-Knappe P., Adermann K.
      FEBS Lett. 480:147-150(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 60-84, TISSUE SPECIFICITY, MASS SPECTROMETRY.
      Tissue: Blood and Liver.
    3. Jung J.-W., Shin W.-S., Yoon Y., Lee S.-T.
      Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. NHLBI resequencing and genotyping service (RS&G)
      Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    6. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Liver.
    8. "Chemical synthesis of beta-defensins and LEAP-1/hepcidin."
      Kluever E., Schulz A., Forssmann W.-G., Adermann K.
      J. Pept. Res. 59:241-248(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SYNTHESIS OF 60-84.
    9. Cited for: REVIEW.
    10. "The solution structure of human hepcidin, a peptide hormone with antimicrobial activity that is involved in iron uptake and hereditary hemochromatosis."
      Hunter H.N., Fulton D.B., Ganz T., Vogel H.J.
      J. Biol. Chem. 277:37597-37603(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 60-84, PRELIMINARY DISULFIDE BONDS.
    11. Cited for: X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 60-84, DISULFIDE BONDS.
    12. "Identification of new mutations of the HFE, hepcidin, and transferrin receptor 2 genes by denaturing HPLC analysis of individuals with biochemical indications of iron overload."
      Biasiotto G., Belloli S., Ruggeri G., Zanella I., Gerardi G., Corrado M., Gobbi E., Albertini A., Arosio P.
      Clin. Chem. 49:1981-1988(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HFE2B ASP-71.
    13. Cited for: VARIANT HFE2B ASP-71.
    14. "Screening hepcidin for mutations in juvenile hemochromatosis: identification of a new mutation (C70R)."
      Roetto A., Daraio F., Porporato P., Caruso R., Cox T.M., Cazzola M., Gasparini P., Piperno A., Camaschella C.
      Blood 103:2407-2409(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HFE2B ARG-70.
    15. "HAMP as a modifier gene that increases the phenotypic expression of the HFE pC282Y homozygous genotype."
      Jacolot S., Le Gac G., Scotet V., Quere I., Mura C., Ferec C.
      Blood 103:2835-2840(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS HFE2B GLY-59 AND ASP-71.
    16. "A homozygous HAMP mutation in a multiply consanguineous family with pseudo-dominant juvenile hemochromatosis."
      Delatycki M.B., Allen K.J., Gow P., MacFarlane J., Radomski C., Thompson J., Hayden M.R., Goldberg Y.P., Samuels M.E.
      Clin. Genet. 65:378-383(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT HFE2B TYR-78.

    Entry informationi

    Entry nameiHEPC_HUMAN
    AccessioniPrimary (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: October 1, 2014
    This is version 139 of the entry and version 2 of the sequence. [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

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3