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Electrogenic Na+ /HCO3 - (NBC) function has been characterized in many mammalian tissues including, kidney, pancreas, and brain. Cloning efforts identified a single cDNA, NBC/NBC1, that possesses all the functional attributes of the electrogenic Na+ /HCO3 - cotransporter. This NBC clone is related to the anion exchangers and thus forms a bicarbonate transporter superfamily. Presently two N-terminal and one C-terminal isoforms are known. All three isoforms appear to arise from the same gene and seem to have identical function. NBC antibodies have localized NBC isoforms in kidney, pancreas, brain, small intestine, colon, epididymis, eye, heart, liver, salivary glands, stomach, and testis. Functionally, NBC appears HCO3 - and Na+ selective. NBC stoichiometry in Xenopus oocytes is 1 Na+ : 2 HCO3 - , implicating a possible accessory protein interaction.