Subclasses within structural class 2
| Code | Subclass | Examples | |
|---|---|---|---|
| 2.1 | “Rhodopsin” subclass | ||
| The vast majority of seven transmembrane domain, G protein-coupled receptors are included in this subclass4-a | 2.1 | ADR | |
| 2.2 | Secretin receptor subclass | ||
| This is the second largest subclass and | 2.2 | SEC | |
| comprises receptors for calcitonin, CGRP, corticotropin-releasing factor, gastric inhibitory peptide, glucagon, glucagon-like peptide, growth hormone releasing factor, PACAP, parathyroid hormone, secretin and vasoactive intestinal peptide | 2.2 | CGRP | |
| 2.3 | Metabotropic glutamate/GABAB receptor subclass | 2.3 | GLU |
(G protein-coupled receptors)
The subclasses shown have been classified according to their protein sequences so that within a subclass all receptor types share significant similarity (i.e., ≥20% sequence identity) throughout the predicted hydrophobic transmembrane domains (Kolakowski, 1994; see also the G protein-Coupled Receptor Database at www.gcrdb.ulthscsa.edu).
↵4-a From the strict structural viewpoint, Class 2.1 is not homogeneous. All its members comprise a seven-transmembrane amino acid chain, but in a very few, the active receptor is formed from this by a proteolytic cleavage. The first described was the thrombin receptor (2.1.THR), in which the agonist thrombin specifically cleaves the receptor chain to liberate a new N-terminal segment and activate the receptor (Vu et al., 1991). Others are the thyrotropin receptor (2.1.TSH), where a peptidase produces two extracellular chains (Misrahi et al., 1994), and other protease-activated receptors where the natural agonist is an unidentified trypsin-like protease (Nystedt et al., 1995; Ishihara et al., 1997).