Na(+)/H(+) antiporter that extrudes sodium in exchange for external protons (PubMed:2839489, PubMed:1645730, PubMed:8383669, PubMed:8019504, PubMed:7737413, PubMed:23836890). Plays an important role in the regulation of intracellular pH, cellular Na(+) content and cell volume (PubMed:33129932). Catalyzes the exchange of 2 H(+) per Na(+) (PubMed:8383669, PubMed:23836890). This stoichiometry applies at both neutral and alkaline pH values (PubMed:8383669). In addition, can also transport lithium and is involved in lithium detoxification (PubMed:8019504, PubMed:7737413, PubMed:22915592, PubMed:27021484). Binding of the Li(+) and H(+) ligands to NhaA is coupled and antagonistic (PubMed:27021484). 2 H(+)(out) + Na(+)(in) = 2 H(+)(in) + Na(+)(out) 2 H(+)(out) + Li(+)(in) = 2 H(+)(in) + Li(+)(out) Activity is regulated by pH (PubMed:1645730, PubMed:23836890, PubMed:10455127, PubMed:14604993). Active at alkaline pH (PubMed:1645730, PubMed:23836890, PubMed:10455127, PubMed:14604993). Activity is strongly down-regulated below pH 6.5 and a dramatic increase in activity is observed upon increase of the pH from 6.5 to 8.5 (PubMed:1645730). Monomer (PubMed:17635927). Homodimer (PubMed:11258962, PubMed:17635927, PubMed:15988517, PubMed:19396973, PubMed:25422503). Under routine stress conditions, the monomeric form is fully functional (PubMed:17635927, PubMed:23836890). However, the dimeric form is much more efficient in conferring growth resistance under extreme stress conditions (PubMed:17635927). Expression is induced by Na(+) and Li(+). The Na(+)-dependent enhancement of expression is augmented by alkalinization. Displays a non-canonical transmembrane assembly, which is termed the NhaA fold. A unique assembly of two pairs of short helices connected by crossed, extended chains creates a balanced electrostatic environment for the binding of the substrate ions (PubMed:15988517). Is organized into two functional regions: the pH sensor region, a cluster of amino-acyl side chains involved in pH regulation, and a catalytic region containing the ion-binding site located approximately 9 Angstroms apart from the pH sensor region (PubMed:33129932). Shows two different conformational changes in response to pH and substrate ions (PubMed:19396973, PubMed:22694117). The first change is induced by a rise in pH from 6 to 7 and marks the transition to the pH-activated state (PubMed:19396973). The second conformational change is induced by the substrate ions Na(+) and Li(+) at pH above 7 (PubMed:19396973). This movement would cause a charge imbalance at the ion-binding site that may trigger the release of the substrate ion and open a periplasmic exit channel (PubMed:19396973). The transport mechanism may involve Asp-163 switching between forming a salt bridge with Lys-300 and interacting with the proton and/or sodium ion (PubMed:25422503, PubMed:27708266, PubMed:28330875). The salt bridge may stabilize the conformation (PubMed:28330875). Mutant lacking this gene can grow in the presence of 0.1 M LiCl, but not in the presence of 0.6 M LiCl. Belongs to the NhaA Na(+)/H(+) (TC 2.A.33) antiporter family.