2.A.55.2.1
Divalent heavy metal (Fe²⁺, Zn²⁺, Mn²⁺, Cu²⁺, Cd²⁺, Co²⁺, Ni²⁺ and Pb²⁺) ion:H⁺ symporter, Nramp2 or divalent metal transporter, DMT1 = SLC11A2 (Garrick et al. 2003). A 12 TMS topology with intracellular N- and C-termini is established. Two-fold structural symmetry in the arrangement of membrane helices for TMSs 1-5 and TMSs 6-10 (conserved Slc11 hydrophobic core) is suggested (Czachorowski et al., 2009).  A conserved motif in a central flexible region of TMS1 (DPGN) binds the metal ion (Wang et al. 2011).  It is upregulated by iron deficiency and downregulated by iron loading (Nam et al. 2013).  NRAMP2 also serves as the Sindbis alpha virus receptor (Rose et al. 2011).  DMT1 interacts with the iron chaparone protein, PCBP2 (Q15366), in an iron-dependent fashion, and may be essential for iron uptake (Lane and Richardson 2014). Mutations cause a syndrome of congenital microcytic hypochromic anemia, poorly responsive to oral iron treatment, with liver iron overload associated paradoxically with normal to moderately elevated serum ferritin levels (Beaumont et al. 2006). Nigral iron accumulation and activation of NMDA receptors contribute to the neurodegeneration of dopamine neurons in Parkinson's disease, and activation of NMDA receptors participates in iron metabolism in the hippocampus (Xu et al. 2018). NMDA receptor inhibitors MK-801 and AP5 protect nigrostriatal projection systems and reduce nigral iron levels. NMDA treatment increased the expression of DMT1 and decreased the expression of the iron exporter ferroportin 1 (Fpn1) (TC# 2.A.100.1.4) (Xu et al. 2018). DMT1 cannot be a direct donor of catalytic copper because it does not have the cytosol domain present in Ctr1, which is required for copper transfer to the Cu-chaperons that assist the formation of cuproenzymes (Ilyechova et al. 2019).  Slc11a2 activity is essential for intestinal non-heme iron absorption after birth, and is also required for normal hemoglobin production during the development of erythroid precursors (Gunshin et al. 2005). May also take artemisinin (Girardi et al. 2020). Optimal conditions for Western blotting for this and other proteins requires that the sample not be boiled (Tsuji 2020). DMT1 polymorphisms affect blood lead levels of occupationally exposed individuals (Mani et al. 2021). Obese mice show defects in DMT1 function and thus iron deficiency (Zhang et al. 2024).