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P81172 (HEPC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. Hepcidin-25
    Short name=Hepc25
  2. Hepcidin-20
    Short name=Hepc20
Gene names
Name:HAMP
Synonyms:HEPC, LEAP1
ORF Names:UNQ487/PRO1003
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length84 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Seems to act as a signaling molecule involved in the maintenance of iron homeostasis. Seems to be required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages By similarity. Ref.2

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. Ref.2

Subcellular location

Secreted.

Tissue specificity

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. Ref.2

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15

Sequence similarities

Belongs to the hepcidin family.

Mass spectrometry

Molecular mass is 2789.8 Da from positions 60 - 84. Determined by MALDI. Ref.2

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Propeptide25 – 5430
PRO_0000013378
Peptide60 – 8425Hepcidin-25 Ref.1 Ref.2
PRO_0000013379
Peptide65 – 8420Hepcidin-20
PRO_0000013380

Amino acid modifications

Disulfide bond66 ↔ 82 Ref.9 Ref.10
Disulfide bond69 ↔ 72 Ref.9 Ref.10
Disulfide bond70 ↔ 78 Ref.9 Ref.10
Disulfide bond73 ↔ 81 Ref.9 Ref.10

Natural variations

Natural variant591R → G in HFE2B. Ref.14
VAR_042512
Natural variant701C → R in HFE2B. Ref.13
VAR_042513
Natural variant711G → D in HFE2B. Ref.11 Ref.12 Ref.14
Corresponds to variant rs104894696 [ dbSNP | Ensembl ].
VAR_026648
Natural variant781C → Y in HFE2B. Ref.15
VAR_042514

Experimental info

Sequence conflict311T → M in AAK14912. Ref.3

Secondary structure

..... 84
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P81172 [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 5F8DCA23D19D29F7

FASTA849,408
        10         20         30         40         50         60 
MALSSQIWAA CLLLLLLLAS LTSGSVFPQQ TGQLAELQPQ DRAGARASWM PMFQRRRRRD 

        70         80 
THFPICIFCC GCCHRSKCGM CCKT 

« Hide

References

« Hide 'large scale' references
[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, FUNCTION, 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]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"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.
[10]"Hepcidin revisited, disulfide connectivity, dynamics, and structure."
Jordan J.B., Poppe L., Haniu M., Arvedson T., Syed R., Li V., Kohno H., Kim H., Schnier P.D., Harvey T.S., Miranda L.P., Cheetham J., Sasu B.J.
J. Biol. Chem. 284:24155-24167(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 60-84, DISULFIDE BONDS.
[11]"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.
[12]"Digenic inheritance of mutations in HAMP and HFE results in different types of haemochromatosis."
Merryweather-Clarke A.T., Cadet E., Bomford A., Capron D., Viprakasit V., Miller A., McHugh P.J., Chapman R.W., Pointon J.J., Wimhurst V.L., Livesey K.J., Tanphaichitr V., Rochette J., Robson K.J.
Hum. Mol. Genet. 12:2241-2247(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HFE2B ASP-71.
[13]"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.
[14]"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.
[15]"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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_066998.1. NM_021175.2.
UniGeneHs.8821.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M4ENMR-A65-84[»]
1M4FNMR-A60-84[»]
2KEFNMR-A60-84[»]
3H0TX-ray1.89C60-84[»]
ProteinModelPortalP81172.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121776. 2 interactions.
IntActP81172. 2 interactions.
STRING9606.ENSP00000222304.

Protein family/group databases

TCDB8.A.37.1.2. the hepcidin (hepcidin) family.

Polymorphism databases

DMDM10720397.

Proteomic databases

PaxDbP81172.
PRIDEP81172.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000222304; ENSP00000222304; ENSG00000105697.
ENST00000598398; ENSP00000471894; ENSG00000105697.
GeneID57817.
KEGGhsa:57817.
UCSCuc002nyw.3. human.

Organism-specific databases

CTD57817.
GeneCardsGC19P035777.
HGNCHGNC:15598. HAMP.
MIM606464. gene.
613313. phenotype.
neXtProtNX_P81172.
Orphanet79230. Hemochromatosis type 2.
PharmGKBPA29182.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG45549.
HOGENOMHOG000008666.
HOVERGENHBG003716.
InParanoidP81172.
OMAPICIFCC.
OrthoDBEOG7N8ZZ3.
PhylomeDBP81172.
TreeFamTF330932.

Gene expression databases

ArrayExpressP81172.
BgeeP81172.
CleanExHS_HAMP.
GenevestigatorP81172.

Family and domain databases

InterProIPR010500. Hepcidin.
[Graphical view]
PfamPF06446. Hepcidin. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP81172.
GeneWikiHAMP.
GenomeRNAi57817.
NextBio64762.
PROP81172.
SOURCESearch...

Entry information

Entry nameHEPC_HUMAN
AccessionPrimary (citable) accession number: P81172
Secondary accession number(s): Q1HE14, Q9BY68
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: December 1, 2000
Last modified: April 16, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM