Hepcidin
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215495766
2008-05-28T13:28:24Z
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{{Pfam_box
| Symbol = Hepcidin
| Name = Hepcidin
| image =
| width =
| caption =
| Pfam= PF06446
| InterPro= IPR010500
| SMART=
| Prosite =
| SCOP = 1m4f
| TCDB =
| OPM family=
| OPM protein= 1m4e
| PDB=
{{PDB3|1m4f}}A:60-84 {{PDB3|1m4e}}A:65-84
}}
{{protein
|Name=[[HAMP|hepcidin antimicrobial peptide]]
|caption=
|image=
|width=
|HGNCid=15598
|Symbol=[[HAMP]]
|AltSymbols=
|EntrezGene=57817
|OMIM=606464
|RefSeq=NM_021175
|UniProt=P81172
|PDB=
|ECnumber=
|Chromosome=19
|Arm=q
|Band=13.1
|LocusSupplementaryData=
}}
{{Protbox finish}}
'''Hepcidin''' is a recently discovered [[peptide hormone]] produced by the [[liver]], that appears to be the master regulator of [[human iron metabolism|iron homeostasis]] in humans and other [[mammal]]s.<ref>Ganz T. [http://www.bloodjournal.org/cgi/content/full/102/3/783 Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. ''[[Blood (journal)|Blood]]'' 2003;102:783-788.] PMID 12663437.</ref> ''[[HAMP]]'' is the [[gene]] that encodes for hepcidin.
==Function==
Hepcidin directly inhibits [[ferroportin]], a protein that transports iron out of cells that store it. Thus, it maintains [[iron homeostasis]].
Several mutations in hepcidin result in [[juvenile hemochromatosis]]. The majority of juvenile hemochromatosis cases are due to mutations in [[hemojuvelin]], a regulator of hepcidin production.
Hepcidin has shown fairly consistent [[antifungal]] activity. Hepcidin's [[antibacterial]] activity currently seems to be inconsistent. The current scientific evidence suggests that hepcidin is a central regulatory hormone and its main action is to regulate systemic iron homeostasis.
==History==
The peptide that would later become known as hepcidin was first reported as LEAP-1, for Liver-Expressed Antimicrobial Protein <ref>Krausse A. ''[http://insert_link_when_NBCI_works_again LEAP-1 a novel highly disulphide-bonded human peptide, exhibits antimicrobial activity]'' *note please insert citation, NCBI is down and has been for several minutes*</ref>. Independently, in a search for [[antimicrobial peptides]], researchers working in the lab of Tomas Ganz discovered a peptide associated with inflammation, and named it "hepcidin" after observing that it was produced in the liver ("hep-") and appeared to have bacteriocidal properties ("-cidin" for "killing")<ref>Park CH, Valore EV, Waring AJ, Ganz T.''[http://bloodjournal.hematologylibrary.org/cgi/ijlink?linkType=ABST&journalCode=jbc&resid=276/11/7806 Hepcidin, a Urinary Antimicrobial Peptide Synthesized in the Liver.]'' J. Biol. Chem., Vol. 276, Issue 11, 7806-7810, March 16, 2001</ref>. Both groups were focused on the antimicrobial properties of the peptide.
Soon after this discovery, researchers discovered that hepcidin production in [[mouse|mice]] increased in conditions of iron overload as well as in inflammation. [[Genetically modified organism|Genetically modified]] mice engineered to overexpress hepcidin died shortly after birth with severe iron deficiency, again suggesting a central and not redundant role in iron regulation. The first evidence that linked hepcidin to the clinical condition known as the [[anemia of chronic disease|anemia of inflammation]] came from the lab of Nancy Andrews in Boston when researchers looked at tissue from two patients with liver [[tumor]]s with a severe [[microcytic anemia]] that did not respond to iron supplementation. The tumor tissue appeared to be overproducing hepcidin, and contained large quantities of hepcidin [[messenger RNA|mRNA]]. Removing the tumors surgically cured the anemia.
Taken together, these discoveries suggested that hepcidin regulated the release of iron in the body.
==External links==
* {{cite journal |author=Camaschella C |title=Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders |journal=Blood |volume=106 |issue=12 |pages=3710–7 |year=2005 |pmid=16030190 |doi=10.1182/blood-2005-05-1857}}
* {{MeshName|hepcidin}}
[[Category:Blood]]
[[Category:Hematology]]
[[Category:Hepatology]]
[[Category:Peptide hormones]]
==References==
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{{Iron metabolism}}
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