The SLC39 family of metal ion transporters

SLC39 proteins are members of the broader ZIP family of metal ion transporters found in organisms at all phylogenetic levels. Most ZIP transporters have eight predicted transmembrane domains and a similar predicted topology. Their biochemical mechanism(s) of substrate transport are not yet known. Where characterized, these proteins have been found to transport metal ions from the cell exterior or lumen of intracellular organelles into the cytoplasm. Furthermore, members of the ZIP family have been implicated in the transport of zinc, iron, and/or manganese indicating that these proteins have diverse functions. There are 14 SLC39-related proteins encoded by the human genome. Studies of SLC39A1, SLC39A2, and SLC39A4, encoding the proteins hZip1, hZip2, and hZip4, have indicated roles in zinc uptake across the plasma membrane of various cell types. Genetic studies have specifically implicated SLC39A4 in the uptake of dietary zinc into intestinal enterocytes. Mutations in SLC39A4 have been identified in patients with acrodermatitis enteropathica, a genetic disease of zinc deficiency.