Ferroportin

Ferroportin-1 also known as solute carrier family 40 member 1 (SLC40A1) or iron-regulated transporter 1 is a is_associated_with::protein that in humans is encoded by the SLC40A1 is_associated_with::gene. Ferroportin is a is_associated_with::transmembrane protein that transports is_associated_with::iron from the inside of a cell to the outside of it.

Structure
Ferroportin-1 consists of 571 is_associated_with::amino acid residues, with a highly conserved is_associated_with::histidine at residue position 32. When mutated, lower activity in its iron transport role is observed.

Tissue distribution
Ferroportin is found on the surface of cells that store or transport iron, including:
 * is_associated_with::Enterocytes in the is_associated_with::duodenum
 * is_associated_with::Hepatocytes
 * is_associated_with::Macrophages of the is_associated_with::reticuloendothelial system.
 * is_associated_with::Adipocytes

Role in development
Ferroportin-1 plays an important role in is_associated_with::neural tube closure and is_associated_with::forebrain patterning.

Mouse embyros lacking the Scl40a1 gene are aborted before is_associated_with::gastrulation occurs, proving that the Fpn1 protein encoded is necessary and essential for normal embryonic development. Fpn1 is expressed in the is_associated_with::syncytiotrophoblast cells in the placenta and visceral endoderm of mice at E7.5. Further, several retrospective studies have noted an increased incidence of is_associated_with::spina bifida occurring after low maternal intake of iron during embryonic and fetal development.

A recent study examining the consequences of several different mutations of the Slc40a1 mouse gene concluded that several serious neural tube and patterning defects were produced as a result, including spina bifida, is_associated_with::exencephaly, and forebrain truncations, among others. Given the findings of studies to date, there appears to be significant evidence that intact iron transport mechanisms are critical to normal neural tube closure. Furthermore, other experiments have suggested that Fpn1 product and activity is required along the entire anterior-posterior axis of the animal to ensure proper closure of the neural tube.

Role in iron metabolism
Ferroportin is inhibited by is_associated_with::hepcidin, which binds to ferroportin and internalises it within the cell. This results in the retention of iron within enterocytes, hepatocytes, and macrophages with a consequent reduction in iron levels within the blood serum. This is especially significant with enterocytes which, when shed at the end of their lifespan, results in significant iron loss.

This is part of the mechanism that causes is_associated_with::anaemia of chronic disease; hepcidin is released from the liver in response to inflammatory cytokines, namely is_associated_with::interleukin-6, which results in an increased hepcidin concentration and a consequent decrease in plasma iron levels.

The ferroportin expression is also regulated by the IRP regulatory mechanism. If the iron concentration is too low, the IRP concentration increases, thus inhibiting the ferroportin translation. The ferroportin translation is also regulated by the micro RNA miR-485-3p.

Clinical significance
Mutations in the ferroportin gene are known to cause an autosomal dominant form of iron overload known as Type IV Haemochromatosis or Ferroportin Disease. The effects of the mutations are generally not severe but a spectrum of clinical outcomes are seen with different mutations. Ferroportin is also associated with is_associated_with::African iron overload. Ferroportin and is_associated_with::hepcidin are critical proteins for the regulation of systemic is_associated_with::iron homeostasis. Both ferroportin and hepcidin are expressed in cultured human breast epithelial cells and hepcidin regulates ferroportin in these cells. Transfection of breast cancer cells with ferroportin significantly reduces their growth after orthotopic implantation in the mouse mammary fat pad. Ferroportin is a pivotal protein in breast biology and a strong and independent predictor of prognosis in breast cancer.