2.A.55.2.2
Me²⁺ (Fe²⁺, Cd²⁺, Co²⁺):H⁺ symporter, DCT1 (Nramp2) (Splice variant isoforms serve different functions). The stoichiometry between metal ion and proton in the symport process catalyzed by DCT1 varies under different conditions due to mechanistic proton slip. A single reciprocal mutation, I144F, in TMS2 of DCT1 abolished the metal ion transport activity, increased the slip currents, and generated sodium slip currents (Nevo, 2007). A double mutation, adding F227I in TMS4 to I144F restored the uptake activity of DCT1 and reduced the slip currents. Thus, these regions are important in coupling metal ion and proton symport (Nevo, 2007).  NRAMP2 also serves as the Sindbis alpha virus receptor (Rose et al. 2011).  Three isoforms are expressed differentially in different cell types and are developmentally regulated (Ding et al. 2013).