NrampDMT1

NrampDMT1 refers to the divalent metal transporter 1, a member of the natural resistance-associated macrophage protein (NRAMP) family of metal ion transporters. It is encoded in humans by the SLC11A2 gene and is commonly called DMT1 (divalent metal transporter 1) or NRAMP2. DMT1 is broadly expressed and plays a central role in cellular uptake and distribution of divalent metals, especially iron.

DMT1 localizes to the apical membrane of intestinal enterocytes where it mediates uptake of dietary Fe2+ after reduction of Fe3+ by ferric reductases. It is also present on endosomal membranes of most cell types, where it transports Fe2+ released from transferrin into the cytosol during transferrin receptor–mediated iron uptake. In addition to iron, DMT1 transports other divalent metals, including Mn2+, Zn2+, Co2+, and, with lower affinity, Cd2+.

The transport is proton-coupled, leveraging the proton gradient to drive uptake of divalent metal ions. DMT1 activity is regulated in part by cellular iron status through iron-responsive elements in its mRNA, enabling coordinated control of iron uptake with systemic needs. Different tissue-specific isoforms arise from alternative transcription and splicing, leading to localization differences (endosomal vs plasma membrane) and regulatory nuances.

Clinically, defects in DMT1/SLC11A2 can impair iron absorption or intracellular iron handling, producing iron deficiency symptoms. Mouse models lacking DMT1 exhibit severe microcytic anemia due to impaired intestinal iron uptake and disrupted iron delivery to developing tissues. The NRAMP family also includes Nramp1 (SLC11A1), which functions in macrophage phagosomes to influence intracellular pathogen resistance.