2.A.134. The 3 TMS Na+/H+ antiporter, NhaM (NhaM) Family
NhaM proteins are transmembrane proteins composed of about 103 amino acid residues that function as Na+(Li+, K+)/H+ antiporters (Shao et al. 2020). These antiporters are the smallest of known Na+/H+ antiporters, and thus have been designated as NhaM to represent the minimal Na+/H+antiporter. Phylogenetic analysis and protein alignments have been reported. NhaM is assembled with parallel protomers into a homo-oligomer, and oligomerization is vital for the function of this antiporter. This implies that NhaM may adopt and require an oligomer for its normal function to create a similar X-shaped structure corresponding to that of the NhaA fold (Shao et al. 2020). Many of the NhaM homologues appear (based on hydrdopathy plots) to have 4 TMSs, often in a 2 + 2 TMS topology. This suggests either that a trimeric structure may be functional (assuming a 12 TMS topology, or if a tetramer is the active form, that it may have 16 TMSs. These proteins predominat in Firmcutes although homologs outside of this phylum have been detected, assuming that their annotated organismal assignments are correct.