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hepcidin antimicrobial peptide; liver-expressed antimicrobial peptide; LEAP-1; putative liver tumor regressor; PLTR [Contains: Hepcidin-25 (Hepc25); Hepcidin-20 (Hepc20)] (HAMP, HEPC, LEAP1, UNQ487/PRO1003)

Function: 1) signaling molecule involved in maintenance of iron homeostasis 2) in conjunction with HFE, regulates both a) intestinal iron absorption b) iron storage in macrophages 3) inhibits ferroportin, iron export protein (transporter) in plasma membrane of enterocytes & hepatocytes thus inhibiting both iron absorption by enterocytes & iron release by hepatocytes 4) antimicrobial activity a) E. coli > S. epidermidis, S.aureus & group B streptococcus b) active against fungus C. albicans c) No activity against P. aeruginosa Compartment: secreted, secreted into the urine Expression: 1) highest expression in liver & to a lesser extent in heart, brain 2) low levels in lung, tonsils, salivary gland, trachea, prostate gland, adrenal gland, thyroid gland 3) secreted into the plasma & urine 4) low plasma iron &/or low iron stores inhibit release of hepcidin into plasma Pathology: 1) defects in HAMP are the cause of hemochromatosis type 2B 2) hepcidin is released from the liver in response to IL6, thus contributing to diminished iron transport during anemia of chronic inflammation 3) increased plasma hepcidin levels in older patients may be associated with anemia of chronic inflammation [6] Pharmacology: - targeting hepcidin-ferroportin interaction may provide a strategy to treat anemia of chronic disease [7] Laboratory: - hepcidin in serum/plasma - pro-hepcidin in serum/plasma

General

secreted protein

Properties

SIZE: MW = 9 kD entity length = 84 aa COMPARTMENT: extracellular compartment MOTIF: signal sequence {1-24} cysteine residue {C66} MODIFICATION: cysteine residue {C72} cysteine residue {C69} MODIFICATION: cysteine residue {C82} cysteine residue {C70} MODIFICATION: cysteine residue {C81} cysteine residue {C72} MODIFICATION: cysteine residue {C66} cysteine residue {C73} MODIFICATION: cysteine residue {C78} cysteine residue {C78} MODIFICATION: cysteine residue {C73} cysteine residue {C81} MODIFICATION: cysteine residue {C70} cysteine residue {C82} MODIFICATION: cysteine residue {C69}

Database Correlations

OMIM correlations MORBIDMAP 606464 UniProt P81172 Pfam PF06446

References

  1. UniProt :accession P81172
  2. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=HAMP
  3. Medical Knowledge Self Assessment Program (MKSAP) 16, American College of Physicians, Philadelphia 2012
  4. Babitt JL, Lin HY Molecular mechanisms of hepcidin regulation: implications for the anemia of CKD. Am J Kidney Dis. 2010 Apr;55(4):726-41 PMID: 20189278
  5. Nemeth E, Ganz T. The role of hepcidin in iron metabolism. Acta Haematol. 2009;122(2-3):78-86 PMID: 19907144 - Nemeth E, Tuttle MS, Powelson J, Vaughn MB et al Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004 Dec 17;306(5704):2090-3. Epub 2004 Oct 28. PMID: 15514116
  6. Ferrucci L, Semba RD, Guralnik JM et al Proinflammatory state, hepcidin, and anemia in older persons. Blood. 2010 May 6;115(18):3810-6. PMID: 20081092
  7. Sun CC, Vaja V, Babitt JL, Lin HY. Targeting the hepcidin-ferroportin axis to develop new treatment strategies for anemia of chronic disease and anemia of inflammation. Am J Hematol. 2012 Apr;87(4):392-400. Review. PMID: 22290531