Na+/hydrogen exchanger 4 (Na+/H+ exchanger 4, NHE-4, solute carrier family 9 member 4, SLC9A4, NHE4)

Function: - role in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions - major H⁺ extruding system driven by the inward Na⁺ chemical gradient - plays an important role in signal transduction - may play a specialized role in the kidney in rectifying cell volume in response to extreme fluctuations of hyperosmolar-stimulated cell shrinkage - relatively amiloride & ethylisopropylamiloride (EIPA) insensitive - can be activated under conditions of hyperosmolar-induced cell shrinkage in a sustained intracellular acidification- dependence manner - activated by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) in a sustained intracellular acidification-dependence manner - affects K⁺/proton exchange as well as Na⁺/proton & Li⁺/proton exchange - in basolateral cell membrane, participates in homeostatic control of intracellular pH, & may play a role in proton extrusion in order to achieve transepithelial HCO₃^- secretion - an apical cell membrane may be involved in mediating Na⁺ absorption - requires for normal levels of gastric acid secretion, secretory membrane development, parietal cell maturation &/or differentiation & at least secondarily for chief cell differentiation (putative) - may be phosphorylated (putative) Structure: - belongs to the Na⁺/H⁺ exchanger (TC 2.A.36.5.1) family - number, localization & denomination of hydrophobic domains in the Na⁺/H⁺ exchangers vary among authors Compartment: - membrane - apical cell membrane, basolateral cell membran - found in zymogen granule membranes (putative)

General

glycoprotein solute carrier family 9 (SLC9, SLC9A) transmembrane 10 protein

Properties

SIZE: entity length = 798 aa MW = 90 kD COMPARTMENT: cellular membrane MOTIF: cytoplasmic domain {1-94} MOTIF: A (M1) hydrophobic {14-28} B (M2) hydrophobic {70-90} transmembrane domain {95-115} exoplasmic loop {116-127} transmembrane domain {128-148} cytoplasmic loop {149-154} transmembrane domain {155-175} exoplasmic loop {176-196} transmembrane domain {197-217} cytoplasmic loop {218-226} transmembrane domain {227-247} exoplasmic loop {248-270} transmembrane domain {271-291} cytoplasmic loop {292-304} transmembrane domain {305-325} exoplasmic loop {326-356} MOTIF: N-glycosylation site {N342} transmembrane domain {357-373} cytoplasmic loop {374-384} transmembrane domain {385-405} exoplasmic loop {406-450} MOTIF: L, hydrophobic {421-441} transmembrane domain {451-471} cytoplasmic domain {472-798}

Database Correlations

OMIM 600531 UniProt Q6AI14 Pfam PF00999 Entrez Gene 6552

References

UniProt :accession Q6AI14