Anion exchange protein 3

Biological Functions
Anion exchange protein 3 (AE3) is a membrane transport protein that in humans is encoded by the SLC4A3 gene. AE3 is functionally similar to the Band 3 Cl−/HCO3− exchange protein but it is expressed primarily in brain neurons and in the heart. Like AE2 its activity is sensitive to pH. AE3 mutations have been linked to seizures.

Structural features
The cryo-EM studies on the structures of human AE3 revealed that it forms a homodimer, similar to AE1 and AE2. . AE3 is stabilized in an outward-facing conformation as its resting state, in contrast to AE2, which rests in an inward-facing conformation. This outward-facing conformation makes AE3 more vulnerable to the pan-inhibitor of anion transporters, DIDS (4,4-diisothiocyanatostilbene-2,2'-disulfonic acid). In addition to the transmembrane domain (TMD) resolved by cryo-EM, the soluble N-terminal domain (NTD) of AE3 has also been solved in a chimera consisting of the AE3 NTD and AE2 TMD.