Na+/H+ antiporter 1 (Na+/H+ antiporter amiloride-sensitive, solute carrier family 9 member 1, SLC9A1, NHE1, APNH1)

Function

• role in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions
• major proton extruding system driven by inward Na+ chemical gradient
• role in signal transduction
• interacts with tescalcin, CHP & CHP2
• phosphorylated upon DNA damage, probably by ATM or ATR
• phosphorylation may increase activity at neutral pH thus alkalinizing cytoplasm

Kinetic parameters:

• pH dependence:
  • fully active at acidic pHs
  • antiporter is virtually turned off at neutral pH;

Structure

• belongs to the Na(+)/H(+) exchanger (TC 2.A.36.5.1) family
• O-glycosylated
• region between transmembrane regions M4 & M5 & between M6 & M7 (also termed intracellular loops IL2 & IL4, respectively) seem to be localized at least in part in the membrane
• hydrophobic region H10 is proposed to be located within the membrane

Compartment

membrane

Alternative splicing

named isoforms=2

Expression

• kidney, intestine
• inhibited by amiloride & 5-amino-substituted derivatives
• 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

More general terms

• transmembrane 12 protein
• Na+/H+ antiporter
• phosphoprotein
• glycoprotein
• solute carrier family 9 (SLC9, SLC9A)

Database

• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6548
• OMIM: https://mirror.omim.org/entry/107310
• UniProt: http://www.uniprot.org/uniprot/P19634.html