Protein Domain : Sodium/hydrogen exchanger 2/4 IPR001953

Type	Family
Description	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 [ , ]. 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 [, , , ]. Human NHE is also involved in heart disease, cell growth and in cell differentiation []. 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) [, ]. 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 [].This entry represents Sodium/hydrogen exchanger 2/4 (NHE-2/4) and similar proteins from vertebrates. NHE-2 is found preferentially in the gastrointestinal tract and the kidney and is also much less sensitive to the inhibitory diureticamiloride than the more ubiquitous NHE1. The targeting of NHE2 in polarised epithelial cells is controversial, some studies reporting basolateral, andothers reporting apical localisation. When transfected into mutagenised cells devoid of endogenous NHE activity, NHE2 is capable of regulating pH,cellular volume, and proliferation, in a manner similar to NHE1. In humans, NHE-2 has been related to ulcerative colitis, colon cancer and cerebral edema formation [ , , ]. NHE-4 may play a specialized role in the kidney in rectifying cell volume in response to extreme fluctuations of hyperosmolar-stimulated cell shrinkage [ ]. It Is relatively amiloride and ethylisopropylamiloride (EIPA) insensitive []. Variants of this protein have been related to eczema [].
Short Name	NHE-2/4