2.A.55.2.3
Macrophage and intestinal divalent cation (Mn²⁺ > Fe²⁺):H⁺ antiporter (catalyzes divalent cation efflux and regulates cation homeostasis), NRAMP1, scavenger receptor-BI (SR-BI) or Slc11a2.  (Techau et al., 2007). The C-terminal cytoplasmic PDZ-interacting domain and the C-terminal transmembrane domains are both necessary for HDL signaling. Direct binding of cholesterol to the C-terminal transmembrane domain has been demonstrated (Assanasen et al. 2005). Thus, HDL signaling requires cholesterol binding and efflux as well as the C-terminal domains of SR-BI; thus, SR-BI serves as a cholesterol sensor on the plasma membrane. The G212V mutation leads to microcytic anemia and liver iron overload (Bardou-Jacquet et al., 2011). Multiple targeting motifs direct NRAMP1 into lysosomes (Cheng and Wang, 2012). The structure and topology has been studied revealing a symmetric but inversely oriented arrangement (Li et al., 2012). Structural modeling and molecular dynamics simulations of the caprine and bovine orthologs led to mechanistic predictions (Triantaphyllopoulos et al. 2019). Leishmania infection triggers hepcidin-mediated proteasomal degradation of Nramp1 to increase phagolysosomal iron availability (Banerjee and Datta 2020). It may also transport, or play a role in transport, of α- and β-carotene as well as cyptoxanthine, lutein, lycopene (Reboul 2013).