Model of transmembrane organization and regulation of the NHE1 exchanger. Transmembrane domains IV and IX (in red) are involved in the sensitivity of amiloride and its derivates. Numbers in the C-terminus domain indicate amino acid number in the structure. It is thought that intracellular H+ activates amino acids 445 and 446 in the transmembrane domain. Green arrows indicate sites of activation by different kinases while red arrows indicate sites of negative regulation by kinases or PP2. 14-3-3: 14-3-3 protein, CAII: carbonic anhydrase II, CaM-A and CaM-B: calcium-calmodulin A and B, CHP: calcineurin B homolog protein, ERK1/2: extracellular signal-related kinase, ERM: ezrin, radixin, and moesin, NIK: Nck-interacting kinase, : ribosomal protein S6 kinase, p160ROCK: p160-Rho-associated kinase, PIP2: phosphatidylinositol 4,5-bisphosphate, PKB: protein kinase B, and PP2: protein phosphatase 2.
