| A 20-aa peptide sequence within the cytoplasmic, C-terminus of human NBC2. Bicarbonate, along with CO2, is the major pH buffer of biological fluids. A great majority of HCO3- reabsorption occurs via trans-cellular coupling of the luminal Na-H+-exchanger 3 and Na+-H+-ATPase with the basolateral Na+-HCO3- cotransporters (NBC). Several related proteins constitute the emerging NBC family (NBC1-3) of membrane cotransporters that are found in a variety of epithelial and non-epithelial tissues, and may be tissue specific. Physiologically, NBC is electrogenic, Na+ and HCO3- dependent, Cl- independent, and inhibited by stilbenes (DIDS and SITS). The NBC family of proteins are 30-35% related to anion exchangers (AE2 and AE3, SLC4A1-SLC4A3) and display the same protein topology: (a) At least 10 TM domains with both the N and C-termini predicted to be intracellular, (b) presence of a large, glycosylated, extracellular loop between TM5 and TM6, and (c) the lysine residues are conserved at predicted DIDS-reactive sites. NBC2 (PSLC4A6, human 1018 aa), initially isolated from retina, is only 53% identical to NBC1. It is widely expressed in retinal, testis, spleen, colon, small intestine, ovary, thymus, prostate, skeletal muscle, heat, kidney, stomach, and bone marrow. It appears to be absent in pancreas and liver. |
