Hepcidin

Pfam_box
Symbol = Hepcidin
Name = Hepcidin


width =
caption =
Pfam= PF06446
InterPro= IPR010500
SMART=
Prosite =
SCOP = 1m4f
TCDB =
OPM family=
OPM protein= 1m4e
PDB=PDB3|1m4fA:60-84 PDB3|1m4eA:65-84

protein
Name=hepcidin antimicrobial peptide
caption=


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=

Hepcidin is a recently discovered peptide hormone produced by the liver, that appears to be the master regulator of iron homeostasis in humans and other mammals. [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" 2003;102:783-788.] PMID 12663437.] "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 [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*] . 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") [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] . Both groups were focused on the antimicrobial properties of the peptide.

Soon after this discovery, researchers discovered that hepcidin production in mice increased in conditions of iron overload as well as in inflammation. 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 inflammation came from the lab of Nancy Andrews in Boston when researchers looked at tissue from two patients with liver tumors 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 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

*
*

References