Apical membrane anion-exchanger with wide epithelial distribution that plays a role as a component of the pH buffering system for maintaining acid-base homeostasis. Acts as a versatile DIDS-sensitive inorganic and organic anion transporter that mediates the uptake of monovalent anions like chloride, bicarbonate, formate and hydroxyl ion and divalent anions like sulfate and oxalate. Functions in multiple exchange modes involving pairs of these anions, which include chloride-bicarbonate, chloride-oxalate, oxalate-formate, oxalate-sulfate and chloride-formate exchange. Apical membrane chloride-bicarbonate exchanger that mediates luminal chloride absorption and bicarbonate secretion by the small intestinal brush border membrane and contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption, possibly by providing a bicarbonate import pathway. Its association with carbonic anhydrase CA2 forms a bicarbonate transport metabolon; hence maximizes the local concentration of bicarbonate at the transporter site. Mediates also intestinal chloride absorption and oxalate secretion, thereby preventing hyperoxaluria and calcium oxalate urolithiasis. Transepithelial oxalate secretion, chloride-formate, chloride-oxalate and chloride-bicarbonate transport activities in the duodenum are inhibited by PKC activation in a calcium-independent manner. The apical membrane chloride-bicarbonate exchanger provides also a major route for fluid and bicarbonate secretion into the proximal tubules of the kidney as well as into the proximal part of the interlobular pancreatic ductal tree, where it mediates electrogenic chloride-bicarbonate exchange with a chloride-bicarbonate stoichiometry of 1:2, and hence will dilute and alkalinize protein-rich acinar secretion. Mediates also the transcellular sulfate absorption and oxalate secretion across the apical membrane in the duodenum and the formate ion efflux at the apical brush border of cells in the proximal tubules of kidney. Plays a role in sperm capacitation by increasing intracellular pH. Apical membrane chloride-bicarbonate exchange activity of the pancreatic duct is inhibited by DIDS (By similarity). Apical membrane chloride-formate exchange activity in the proximal tubules of the kidney and oxalate secretion in the duodenum are inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS - an inhibitor of several anion channels and transporters). Interacts (via C-terminal cytoplasmic domain) with CA2; the interaction stimulates chloride-bicarbonate exchange activity. Interacts with SLC9A3R1 (via the PDZ domains). Interacts with SLC9A3R2 (via the PDZ domains) (By similarity). Interacts (via C-terminal domain) with PDZK1 (via C-terminal PDZ domain); the interaction induces chloride and oxalate exchange transport. Interacts with CFTR, SLC26A3 and SLC9A3R1. Interacts with AHCYL1; the interaction increases SLC26A6 activity (PubMed:23542070). Colocalized with CA2 at the surface of the cell membrane in order to form a bicarbonate transport metabolon; colocalization is reduced in phorbol myristate acetate (PMA)-induced cells (By similarity). Localized in sperm membranes. Colocalizes with CFTR at the midpiece of sperm tail. Localizes to the apical membrane brush border of epithelial cells in the proximal tubules of kidney, of enterocytes of the small intestine and of gastric parietal cells in the stomach. May be translocated from the cytosolic surface of the cell membrane to the intracellular space by PKC in phorbol myristate acetate (PMA)-induced cells. Expressed in kidney (at protein level). Highly expressed in stomach, kidney, heart and small intestine, low in the lung, liver, testis, brain, skeletal muscle and colon. Expressed in spermatogenic cells. Isoform 1 is expressed in intestine, kidney, testis, brain, muscle, heart, and stomach. Up-regulated by dietary fructose intake (at protein level). Phosphorylated on serine residues by PKC; the phosphorylation disrupts interaction with carbonic anhydrase CA2 and reduces bicarbonate transport activity in a phorbol myristate acetate (PMA)-induced manner. Mice show an important decrease in salt absorption in the intestine and failed to develop hypertension on a high-fructose diet. Show a reduction in pancreatic duct fluid and bicarbonate secretion. Show enhanced oxalate absorption in the intestine leading to hyperoxalemia and hyperoxaluria with high incidence of calcium-oxalate stones formation.