HAX1

HAMP
Identifiers
Symbol	?
HGNC	4822
OMIM	606464
RefSeq	NM_021175
UniProt	P81172
Search for Structures Swiss-model Domains InterPro

HAMP (Hepcidin Antimicrobial Peptide) is a peptide hormone that plays a crucial role in the regulation of iron homeostasis in the human body. It is primarily produced by the liver and acts as a key regulator of iron absorption and distribution.

Structure and Function

HAMP is a small, cysteine-rich peptide consisting of 25 amino acids. It is synthesized as a preprohormone, which undergoes proteolytic cleavage to produce the active form. The mature peptide contains four disulfide bonds, which are essential for its stability and function.

Hepcidin regulates iron homeostasis by binding to the iron export protein ferroportin, which is located on the surface of enterocytes, macrophages, and hepatocytes. Upon binding, hepcidin induces the internalization and degradation of ferroportin, thereby reducing iron efflux into the bloodstream. This mechanism helps to maintain appropriate levels of iron in the body and prevents iron overload.

Regulation of HAMP Expression

The expression of HAMP is tightly regulated by several factors:

• Iron Levels: High levels of circulating iron stimulate the production of hepcidin, while low iron levels suppress it.
• Inflammation: Inflammatory cytokines, such as interleukin-6 (IL-6), can increase hepcidin expression, leading to decreased iron availability during infections or chronic inflammatory states.
• Erythropoietic Activity: Increased erythropoiesis, or red blood cell production, suppresses hepcidin expression to allow more iron to be available for hemoglobin synthesis.

Clinical Significance

Dysregulation of HAMP can lead to various iron-related disorders:

• Hereditary Hemochromatosis: A genetic disorder characterized by excessive iron absorption and accumulation, often due to mutations in the HAMP gene or related pathways.
• Anemia of Chronic Disease: A condition where increased hepcidin levels, often due to chronic inflammation, lead to reduced iron availability and anemia.
• Iron-Refractory Iron Deficiency Anemia (IRIDA): A rare genetic disorder caused by mutations in the TMPRSS6 gene, leading to inappropriate hepcidin production and iron deficiency anemia.

Research and Therapeutic Implications

HAMP is a target for therapeutic interventions in diseases of iron overload and deficiency. Modulating hepcidin levels through drugs or genetic approaches holds potential for treating conditions like hereditary hemochromatosis and anemia of chronic disease.

Also see

• Ferroportin
• Iron metabolism
• Anemia
• Hereditary hemochromatosis
• Erythropoiesis