InterPro domain: IPR044880

Na/Ca2 exchangers (NCX) are membrane transporters that play an essential role in maintaining the homeostasis of cytosolic Ca2 for cell signalling. Ca2 is moved into or out of the cytosol depending on Na concentration. NCX has a symmetrical structure containing ten transmembrane helices, divided in two halves with a similar structure but opposite orientation. Based on its symmetry, NCX is able to catalyse bidirectional ion-exchange reactions. Four ion-binding sites cluster at the centre of the protein: one specific for Ca2 and three that likely bind Na. Two passageways allow for Na and Ca2 access to the central ion-binding sites from the extracellular side [ 1 , 2 ].

This superfamily entry represents the large central ion-binding region made up of 8 transmembrane helices, also known as the intracellular regulatory domain.

1. Structural insight into the ion-exchange mechanism of the sodium/calcium exchanger. Science 335, 686-90
2. Mechanism of extracellular ion exchange and binding-site occlusion in a sodium/calcium exchanger. Nat Struct Mol Biol 23, 590-599