7TM RECEPTORS

Overview: The completion of the Human Genome Project allowed the identification of a large family of proteins with a common motif of seven groups of 20–24 hydrophobic amino acids arranged as α helices. Approximately 800 of these seven transmembrane (7TM) receptors have been identified of which over 300 are non-olfactory receptors (see Fredriksson et al., 2003;Lagerstrom and Schioth, 2008). Subdivision on the basis of sequence homology allows the definition of rhodopsin, secretin, adhesion, glutamate and Frizzled receptor families. NC-IUPHAR recognizes Classes A, B, and C, which equate to the rhodopsin, secretin and glutamate receptor families.

The nomenclature of 7TM receptors is commonly used interchangeably with G protein-coupled receptors, although the former nomenclature allows for signalling of 7TM receptors through pathways not involving G proteins. For example, adiponectin and membrane progestin receptors appear to signal independently of G proteins and appear to reside in membranes in an inverted fashion compared with conventional 7TM receptors. Additionally, the NPR3 natriuretic peptide receptor has a single transmembrane domain structure, but appears to couple to G proteins to generate cellular responses. The 300+ non-olfactory 7TM receptors are the targets for the majority of drugs in clinical usage (Overington et al., 2006), although only a minority of these receptors are exploited therapeutically.