Alignment of the heptahelical domain of hCaSR, hmGlu2, rmGlu1, rmGlu5, and hTAS1R3. Transmembrane segments (TM) are shown in bold. Intra- and extracellular loops are marked by ICL and ECL, respectively. Amino acids that influence allosteric modulator activity in hCaSR, hmGlu2, rmGlu1 and 5 are marked in grey. Positions that alter the response of the sweet receptor to lactisole, cyclamate, or NHDC are shown in red. Asterisks indicate residues involved in receptor activation by NHDC (orange) or cyclamate (blue). Green asteriks denote residues mediating sensitivity of the receptor to lactisole.