Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction. Fully active at acidic pHs, the antiporter is virtually turned off at neutral pH. Oligomer (By similarity). Interacts with CALM1 in a calcium-dependent manner (PubMed:12809501, PubMed:30287853). Interacts with TESC (PubMed:11696366, PubMed:30287853, PubMed:12809501). Interacts (via the juxtamembrane region of the cytoplasmic C-terminal domain) with CHP1; the interaction occurs at the plasma membrane in a calcium-dependent manner (PubMed:8967452, PubMed:8901634, PubMed:11350981, PubMed:15035633, PubMed:17050540). Interacts with CHP2; the interaction occurs in a calcium-dependent manner (PubMed:12226101, PubMed:16710297, PubMed:21392185). Colocalizes with CHP1 at the reticulum endoplasmic (By similarity). Colocalizes with CHP1 and CHP2 at the plasma membrane. Kidney and intestine. O-glycosylated. Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1 (By similarity). The disease is caused by variants affecting the gene represented in this entry. Inhibited by amiloride and 5-amino-substituted derivatives and activated in a cooperative fashion by intracellular H(+). In quiescent cells upon growth factor stimulation, the apparent affinity for internal H(+) is increased, resulting in a persistent rise in cytoplasmic pH. Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. The region between transmembrane regions M4 and M5 and between M6 and M7 (also termed intracellular loops IL2 and IL4, respectively) seem to be localized at least in part in the membrane. The hydrophobic region H10 is proposed to be located within the membrane. Although PubMed:12809501 report that TESC-binding results in a decrease in activity, studies with rat SLC9A1 show that TESC-binding results in the maturation and accumulation of SLC9A1 at the cell surface. The interacting region with TESC is conflicting: Interaction with TESC has been reported via the juxtamembrane region of the cytoplasmic C-terminal domain, including residues 503-545 (PubMed:11696366, PubMed:30287853). In contrast, another publication has reported interaction with TESC via residues 633-815, the region of the cytoplasmic C-terminus more distal to the membrane (PubMed:12809501).