The solute carrier family 4 (SLC4), also known as the bicarbonate-transporter family, includes the products of 10 human genes (SCL4A1-5; A7-11). Among them, nine SLC4 members encode these proteins that transport HCO3-, or 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). NBCe1 and NBCe2 transporters are electrogenic while the others are electroneutral. The functions of the other two SLC4 members, AE4 and SLC4A11, are not conclusively established. The SLC4 members share some similarities in hydropathy analysis, inhibition by stilbene derivatives such as DIDS, and glycosylation, but they also differ in the functional characteristics.
In mammals, the SLC4 family transporters play critical roles in several physiological processes, including the carriage of carbon dioxide from the systemic capillaries to the pulmonary capillaries, the secretion or resorption of acid-base equivalents by numerous epithelia, NaCl reabsorption by certain epithelia, the regulation of cell volume in multiple cell types, and the regulation of intracellular pH. SLC4-sequence variations are associated with pathologies of different systems, such as the circulatory system, central nervous system, digestive system, reproductive system, and the urinary system.
Here, we give an introduction of the following human SLC4 members regarding their structure, functional information, tissue distribution of the proteins, associated diseases, gene localization, etc.
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