This entry includes the SLC41A family members mostly from eukaryotes and archaea. Some proteins are from bacteria. The SLC41A family of divalent cation transporters includes SLC41A1, SLC41A2 and SLC41A3 and MgtE [, , , ]. MgtE, the SLC41A1 orthologue found in prokaryotes, consists of a homodimer architecture with five transmembrane domains at the C terminus and the cytosolic domains at the N terminus. Structural and functional analyses showed MgtE conserved acidic side-chains play a key role as part of its selectivity filter [, ]. In humans, SLC41A1 is a Na+/Mg2+ ion exchanger that acts as a predominant Mg2+ efflux system at the plasma membrane. The transporter activity is driven by the inwardly directed electrochemical gradient for Na+ ions, thus directly depends on the extracellular Na+ ion concentration set by the Na+/K+ pump. In this way, it generates circadian cellular Mg2+ fluxes that feed back to regulate clock-controlled gene expression and metabolism and facilitate higher energetic demands during the day. This protein is located in the cell membrane [, ]. Its expression level has been linked to diverse disorders such as preeclampsia in pregnant woman, nephronophthisis, Parkinson's disease and bone mass loss. Hence, it has been suggested this protein might be a great therapeutic target [, , , ]. Mouse SLC41A2 has been shown to transport Mg2+ and a range of other divalent cations: Ba2+, Ni2+, Co2+, Fe2+, or Mn2+, but not Ca2+, Zn2+, or Cu2+ [].
