Na+/H+ exchanger, isoform 1 (NHE1) (IPR001970)

Short name: Na/H_exchanger_1

Family relationships


Sodium proton exchangers (NHEs) constitute a large family of integral membrane protein transporters that are responsible for the counter-transport of protons and sodium ions across lipid bilayers [PMID: 12027219, PMID: 12502567]. These proteins are found in organisms across all domains of life. In archaea, bacteria, yeast and plants, these exchangers provide increased salt tolerance by removing sodium in exchanger for extracellular protons. In mammals they participate in the regulation of cell pH, volume, and intracellular sodium concentration, as well as for the reabsorption of NaCl across renal, intestinal, and other epithelia [PMID: 16734752, PMID: 17071327, PMID: 16513813, PMID: 11187762]. Human NHE is also involved in heart disease, cell growth and in cell differentiation [PMID: 17218973]. The removal of intracellular protons in exchange for extracellular sodium effectively eliminates excess acid from actively metabolising cells. In mammalian cells, NHE activity is found in both the plasma membrane and inner mitochondrial membrane. To date, nine mammalian isoforms have been identified (designated NHE1-NHE9) [PMID: 9278382, PMID: 9507001]. These exchangers are highly-regulated (glyco)phosphoproteins, which, based on their primary structure, appear to contain 10-12 membrane-spanning regions (M) at the N terminus and a large cytoplasmic region at the C terminus. The transmembrane regions M3-M12 share identity with other members of the family. The M6 and M7 regions are highly conserved. Thus, this is thought to be the region that is involved in the transport of sodium and hydrogen ions. The cytoplasmic region has little similarity throughout the family. There is some evidence that the exchangers may exist in the cell membrane as homodimers, but little is currently known about the mechanism of their antiport [PMID: 9537504].

Na+/H+ exchanger isoform 1 (NHE1) is found in virtually all tissues and cells in mammals and is involved in numerous physiological processes, including regulation of intracellular pH, cellular volume, cytoskeletal organisation, heart disease and cancer [PMID: 17209804, PMID: 19001864, PMID: 11807182]. In epithelial cells, NHE1 is largely restricted to the basolateral membrane, which specific subcellular localisation is thought to be important to the functioning of these epithelia. NHE1 comprises two domains: an N-terminal membrane domain that functions to transport ions, and a C-terminal cytoplasmic regulatory domain that regulates the activity and mediates cytoskeletal interactions.

GO terms

Biological Process

GO:0006885 regulation of pH
GO:0006814 sodium ion transport

Molecular Function

GO:0015385 sodium:proton antiporter activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.