Taking on an eleven-helix LeuT fold, the Nramp family is a member of the large APC Superfamily of secondary carriers.

[2] The name "natural resistance-associated" macrophage proteins arises from the role in resistance of intracellular bacterial pathogens played by some animal homologs.

[4] It is hypothesized that a deficiency for Mn2+ or some other metal prevents the generation of reactive oxygenic and nitrogenic compounds that are used by macrophage to combat pathogens.

This hypothesis is supported by studies on the bacterial Nramp homologs which exhibit extremely high selectivity for Mn2+ over Fe2+, Zn2+ and other divalent cations.

[5] Regulation of these transporters in bacteria can occur through Fur, OxyR, and most commonly a DtxR homolog, MntR.

Two-fold structural symmetry in the arrangement of membrane helices for TM1-5 and TM6-10 (conserved Slc2 hydrophobic core) is suggested.

All Nramp proteins have eleven to twelve transmembrane helices, the first ten of which form a canonical LeuT fold, common throughout the APC superfamily.