Natural resistance-associated macrophage proteins ( NRAMPs)are members of the metal ion (Mn2+-iron) transporter family (TC# 2.A.55) . The NRAMP family is a member of the large APC Superfamily of secondary carriers. Homologues of this family are found in various yeasts, plants, animals, archaea, and Gram-negative and Gram-positive bacteria termed  "natural resistance-associated" macrophage proteins because one of the animal homologues plays a role in resistance to intracellular bacterial pathogens such as Salmonella enterica serovar Typhimurium, Leishmania donovani and Mycobacterium bovis. The natural history of SLC11 genes in vertebrates has been discussed by Neves et al. (2011). Proposed to be a distant member of the APC Superfamily, several human pathologies may result from defects in NRAMP-dependent Fe2+ or Mn2+ transport, including iron overload, neurodegenerative diseases and innate susceptibility to infectious diseases. NRAMP2 Humans and rodents possess two distinct NRAMPs . The broad specificity NRAMP2 (DMT1) , which transports a range of divalent metal cations , transports Fe2+ and H+ with a 1:1 stoichiometry and apparent affinities of 6 μm and about 1 μm, respectively. Variable H+:Fe2+ stoichiometry has also been reported. The order of substrate preference for NRAMP2 is: NRAMP1 In contrast to the widely expressed NRAMP2, NRAMP1 is expressed primarily in macrophages and monocytes and appears to have a preference for Mn2+ rather than Fe2+. NRAMP1 (TC# 2.A.55.2.3) has been reported to function by metal:H+ antiport. 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 homologues which exhibit extremely high selectivity for Mn2+ over Fe2+, Zn2+ and other divalent cations. Regulation of these transporters in bacteria can occur through Fur, OxyR, and most commonly a DtxR homolog, MntR.
Natural resistance-associated macrophage proteins ( Nramps), also known as metal ion (Mn2+-iron) transporters (TC# 2.A.55) , are a family of metal transport proteins found throughout all domains of life. Taking on an eleven-helix LeuT fold, the Nramp family is a member of the large APC Superfamily of secondary carriers. They transport a variety of transition metals such as manganese, cadmium, and manganese using an alternating access mechanism characteristic of secondary transporters. The name "natural resistance-associated" macrophage proteins arises from the role in resistance of intracellular bacterial pathogens played by some animal homologs. Several human pathologies may result from defects in Nramp-dependent Fe2+ or Mn2+ transport, including iron overload, neurodegenerative diseases and innate susceptibility to infectious diseases. Human homologs Humans and rodents possess two distinct Nramp proteins . The broad specificity NRAMP2 (DMT1) transports a range of divalent metal cations . Studies have shown that it transports Fe2+ and H+ with a 1:1 stoichiometry and apparent affinities of 6 μm and about 1 μm, respectively. Variable H+:Fe2+ stoichiometry has also been reported. The order of substrate preference for NRAMP2 is: In contrast to the widely expressed NRAMP2, NRAMP1 is expressed primarily in macrophages and monocytes and appears to have a preference for Mn2+ rather than Fe2+. NRAMP1 (TC# 2.A.55.2.3) has been reported to function by metal:H+ antiport. 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. Regulation of these transporters in bacteria can occur through Fur, OxyR, and most commonly a DtxR homolog, MntR.
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