Function: 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. Ref.11 Ref.15 Ref.18
Subunit structure: Oligomer
By similarity. Interacts with calmodulin and TESC. Interacts (via the juxtamembrane region of the cytoplasmic C-terminus domain) with CHP1; the interaction occurs at the plasma membrane in a calcium-dependent manner. Interacts with CHP2; the interaction occurs in a calcium-dependent manner. Ref.10 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.25
Subcellular location: Membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein
By similarity. Cell membrane; Multi-pass membrane protein. Note: Colocalizes with CHP1 at the reticulum endoplasmic
By similarity. Colocalizes with CHP1 and CHP2 at the plasma membrane. Ref.14 Ref.18 Ref.25
Tissue specificity: Kidney and intestine.
Post-translational modification: O-glycosylated. Ref.9Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1
By similarity.
Miscellaneous: 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.
Sequence similarities: Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family. [View classification]
Caution: 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 Ref.17 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.Although Ref.17 report that CHP1 and TESC bind to SLC9A1 at different sites, studies with rat SLC9A1 show that they bind at the same C-terminal site.
Biophysicochemical propertiespH dependence:Fully active at acidic pHs, the antiporter is virtually turned off at neutral pH.
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