A 20-aa peptide sequence within the cytoplasmic, N-terminus of human NBC1. Sequence is 100% conserved in mouse, rat, human and rabbit NBC1/PSLC4A4/kNBC and 75% in frog NBC1. This region is also shared 100% with pNBC/ PSLC4A5||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.||NBC1 (human, rat, mouse 1035 aa, also called NBC-1A/1B, hkNBC, rkNBC, pNBC, hhNBC, SLC4A4) was initially cloned from human Kidney. NBC1 is 30-35% identical with AEs. It is strongly expressed in the kidney and pancreas. The rat kidney NBC1 (rkNBC1; 1035 aa) is 86% identical to hkNBC1. Pancreatic NBC (pNBC/hhNBC/SLC4A5, human 1079 aa) has a unique n-terminal 85 aa sequence replacing the 41-aa in kNBC. pNBC is also more widely expressed (pancreas, thyroid, heart, and brain).

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