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

General

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

Properties

SIZE: MW = 91 kD entity length = 815 aa COMPARTMENT: plasma membrane MOTIF: cytoplasmic domain {1-12} transmembrane domain {13-33} exoplasmic loop {34-105} MOTIF: N-glycosylation site {N75} transmembrane domain {106-127} cytoplasmic loop {128-129} transmembrane domain {130-149} exoplasmic loop {150-154} transmembrane domain {155-174} MOTIF: Channel pore-lining {161-161} cytoplasmic loop {175-191} transmembrane domain {192-211} exoplasmic loop {212-227} transmembrane domain {228-247} cytoplasmic loop {248-256} transmembrane domain {257-276} exoplasmic loop {277-294} transmembrane domain {295-315} cytoplasmic loop {316-338} transmembrane domain {339-358} exoplasmic loop {359-410} MOTIF: Not glycosylated {370-370} H10 hydrophobic {382-402} transmembrane domain {411-430} cytoplasmic loop {431-448} transmembrane domain {449-470} exoplasmic loop {471-479} transmembrane domain {480-499} cytoplasmic domain {500-815} MOTIF: Ser phosphorylation site {S599} Ser phosphorylation site {S602} Ser phosphorylation site {S605} Ser phosphorylation site {S693} Ser phosphorylation site {S703} Ser phosphorylation site {S787} Ser phosphorylation site {S788} MISC-INFO: INHIBITOR = AMILIORIDE

Database Correlations

OMIM 107310 UniProt P19634 Pfam PF00999 Kegg hsa:6548