Ferroportin

3006153945ENSG00000138449ENSMUSG00000025993Q9NP59Q9JHI9NM_014585NM_016917NP_055400NP_058613 Ferroportin-1, also known as solute carrier family 40 member 1 (SLC40A1) or iron-regulated transporter 1 (IREG1), is a protein that in humans is encoded by the SLC40A1 gene, and is part of the Ferroportin (Fpn) Family (TC# 2.A.100). Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of the cell. Ferroportin is the only known iron exporter. After dietary iron is absorbed into the cells of the small intestine, ferroportin allows that iron to be transported out of those cells and into the bloodstream. Fpn also mediates the efflux of iron recycled from macrophages resident in the spleen and liver. Ferroportin is regulated by hepcidin, a hormone produced by the liver; hepcidin binds to Fpn and limits its iron-efflux activity, thereby reducing iron delivery to the blood plasma. Therefore, the interaction between Fpn and hepcidin controls systemic iron homeostasis. Members of the ferroportin family consist of 400-800 amino acid residues, with a highly conserved histidine at residue position 32 (H32), and exhibit 8-12 putative transmembrane domains. Human Fpn consists of 571 amino acid residues. When H32 is mutated in mice, iron transport activity is impaired. Recent crystal structures generated from a bacterial homologue of ferroportin (from Bdellovibrio bacteriovorus) revealed that the Fpn structure resembles that of major facilitator superfamily (MFS) transporters. The prospective substrate binding site is located at the interface between the N-terminal and C-terminal halves of the protein, and is alternately accessible from either side of the cell membrane, consistent with MFS transporters. Ferroportin-mediated iron efflux is calcium-activated; studies of human Fpn expressed in Xenopus laevis oocytes demonstrated that calcium is a required cofactor for Fpn, but that Fpn does not transport calcium. Thus, Fpn does not function as an iron/calcium antiporter. The thermodynamic driving force for Fpn remains unknown. In addition to iron, ferroportin has been shown to transport cobalt & zinc, as well as nickel. Ferroportin may also function as a manganese exporter. Ferroportin is found on the basolateral membranes of intestinal epithelia of mammals, including: