Fig. 2. Predicted membrane topology of a sodium/proton exchanger (NHE). NHEs are proposed to contain 12 transmembrane domains (N-domain) with varying regulatory elements in the carboxy termini. The N-domain is sufficient for transporting proton in exchange for Na⁺, whereas the carboxy cytoplasmic region determines several regulatory aspects of the exchanger. Vertebrate NHE1, modeled after Wakabayashi et al. (2000), is shown. CHP, PIP₂ and CaM refer to schematic locations of domains implicated in calcineurin-homologous protein-binding, phosphatidyl inositide-binding and Ca²⁺/calmodulin-binding, respectively, in vertebrate NHE1. Aedes NHE3 possesses a nearly superimposable secondary structure (Pullikuth et al., submitted).