GeneID: 177

Description:
The HAMP gene encodes hepcidin, a major regulator of iron homeostasis. Hepcidin is a 2.7 kDa (25 amino acids) hormone peptide synthesized and secreted by hepatocytes in the liver. It is mainly found free in circulation except for weak binding to albumin and α2-macroglobulin. It is filtered by the kidneys and excreted in urine. Hepcidin is generated from an 84-amino-acid preproprotein composed of an N-terminal 24-amino-acid signal sequence, a 35-amino-acid proregion with a consensus furin cleavage site, and the C-terminal mature 25-amino-acid peptide. Preprohepcidin is cleaved to a 60-amino-acid prohepcidin, an intermediate product with no known function other than being a precursor of the mature peptide, which is further cleaved by furin to give rise to hepcidin. Two smaller isoforms of 20- and 22-amino-acids have been found. All three forms are detected in urine, while hepcidin-25 is also found in blood plasma and is the only form to participate in the regulation of iron metabolism. Hepcidin consists of eight cysteine residues connected by disulphide bonds, forming a β-hairpin structure with a rare vicinal bond at the hairpin turn, which possibly has a functional role. Hepcidin controls the level of circulating iron by acting on the iron exporter ferroportin to reduce dietery iron absorption from the duodenum, the release of stored iron from hepatocytes, and the delivery of recycled iron from macrophages. Hepcidin also exhibits antimicrobial activity against bacteria and fungi. The BMP/SMAD signalling pathway is involved in the regulation of hepcidin transcription. Mutations in this gene cause hemochromatosis type 2B, also known as juvenile hemochromatosis, a disease caused by severe iron overload that results in cardiomyopathy, cirrhosis, and endocrine failure.

Synonyms: HEPC , HFE2B , LEAP-1 , LEAP1

Comments:
N/A

Number of entries/variants: 1

1. Collins JF, Wessling-Resnick M, Knutson MD, Hepcidin regulation of iron transport., J. Nutr. , 138(11), 2284-8, 2008 PubMed
2. Kwapisz J, Slomka A, Zekanowska E, Hepcidin and Its Role in Iron Homeostasis., EJIFCC , 20(2), 124-8, 2009 PubMed
3. Ganz T, Hepcidin and iron regulation, 10 years later., Blood , 117(17), 4425-33, 2011 PubMed
4. Ganz T, Systemic iron homeostasis., Physiol. Rev. , 93(4), 1721-41, 2013 PubMed