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  • The SLC4 family of bicarbon...
    Romero, Michael F.; Chen, An-Ping; Parker, Mark D.; Boron, Walter F.

    Molecular aspects of medicine, April-June 2013, 2013 Apr-Jun, 2013-4-00, 20130401, Volume: 34, Issue: 2-3
    Journal Article

    The SLC4 family consists of 10 genes (SLC4A1–5; SLC4A7–11). All encode integral membrane proteins with very similar hydropathy plots—consistent with 10–14 transmembrane segments. Nine SLC4 members encode proteins that transport HCO3- (or a related species, such as CO32-) across the plasma membrane. Functionally, eight of these proteins fall into two major groups: three Cl–HCO3 exchangers (AE1–3) and five Na+-coupled HCO3- transporters (NBCe1, NBCe2, NBCn1, NBCn2, NDCBE). Two of the Na+-coupled transporters (NBCe1, NBCe2) are electrogenic; the other three Na+-coupled HCO3- transporters and all three AEs are electroneutral. In addition, two other SLC4 members (AE4, SLC4A9 and BTR1, SLC4A11) do not yet have a firmly established function. Most, though not all, SLC4 members are functionally inhibited by 4,4′-diisothiocyanatostilbene-2,2′-disulfonate (DIDS). SLC4 proteins play important roles many modes of acid–base homeostasis: the carriage of CO2 by erythrocytes, the transport of H+ or HCO3- by several epithelia, as well as the regulation of cell volume and intracellular pH.