NRAMP

NRAMP stands for Natural Resistance-Associated Macrophage Protein, a family of conserved divalent metal ion transporters found in bacteria, plants, and animals. Members commonly move iron (Fe2+) and manganese (Mn2+) ions, and in some species broaden to other divalent metals. They are typically proton-coupled transporters with twelve transmembrane segments, enabling metal uptake or redistribution across membranes as needed by the cell.

In mammals, two main NRAMP genes are expressed. SLC11A1 encodes NRAMP1, which localizes to phagosomal membranes in macrophages and other cell types and helps regulate metal availability to intracellular pathogens, contributing to antimicrobial activity. SLC11A2 encodes NRAMP2, also known as DMT1 (divalent metal transporter 1), and functions primarily in intestinal epithelial cells to import dietary iron and to move iron from endosomal compartments; it can transport several other divalent metals as well. In plants and microbes, NRAMP homologs such as MntH in bacteria participate in uptake of Mn2+ and Fe2+ and are involved in metal homeostasis and stress responses.

Mechanistically, NRAMP transporters operate as energy-dependent, proton-coupled systems, moving divalent metals in tandem with the proton gradient. They participate in iron and manganese homeostasis, redistribution of metals during development and stress, and in host defense by restricting metal access to pathogens.

Clinical and agricultural relevance includes associations between NRAMP1 variants and susceptibility to intracellular infections in humans, as well as roles for plant NRAMPs in nutrient uptake and tolerance to metal stress.