Fig. 1

Proposed topology of the thiazide-sensitive Na-Cl co-transporter. The NCC is a protein composed of a central hydrophobic domain containing 12 transmembrane regions (see from right to left) interconnected by six extracellular handles and five cytoplasmic handles. The glycosylation is present on the large extracellular loop between the 7th and 8th membrane-spanning segment, which is essential in trafficking proteins to the cell surface. Also, the central hydrophobic domain is flanked by a short amino-terminal domain (NH₂) and a long carboxyl-terminal domain (COOH), which are located inside the cell [27, 28]. Figure adapted from Gamba G [29].