PROSITE documentation PDOC00210

G-protein coupled receptors family 1 signature and profile

G-protein coupled receptors [1,2,3,4] (also called R7G) are an extensive group of hormones, neurotransmitters, odorants and light receptors which transduce extracellular signals by interaction with guanine nucleotide-binding (G) proteins. The receptors that are currently known to belong to this family are listed below.

• 5-hydroxytryptamine (serotonin) 1A to 1F, 2A to 2C, 4, 5A, 5B, 6 and 7 [5].
• Acetylcholine, muscarinic-type, M1 to M5.
• Adenosine A1, A2A, A2B and A3 [6].
• Adrenergic α-1A to -1C; α-2A to -2D; β-1 to -3 [7].
• Angiotensin II types I and II.
• Bombesin subtypes 3 and 4.
• Bradykinin B1 and B2.
• c3a and C5a anaphylatoxin.
• Cannabinoid CB1 and CB2.
• Chemokines C-C CC-CKR-1 to CC-CKR-8.
• Chemokines C-X-C CXC-CKR-1 to CXC-CKR-4.
• Cholecystokinin-A and cholecystokinin-B/gastrin.
• Dopamine D1 to D5 [8].
• Endothelin ET-a and ET-b [9].
• fMet-Leu-Phe (fMLP) (N-formyl peptide).
• Follicle stimulating hormone (FSH-R) [10].
• Galanin.
• Gastrin-releasing peptide (GRP-R).
• Gonadotropin-releasing hormone (GNRH-R).
• Histamine H1 and H2 (gastric receptor I).
• Lutropin-choriogonadotropic hormone (LSH-R) [10].
• Melanocortin MC1R to MC5R.
• Melatonin.
• Neuromedin B (NMB-R).
• Neuromedin K (NK-3R).
• Neuropeptide Y types 1 to 6.
• Neurotensin (NT-R).
• Octopamine (tyramine), from insects.
• Odorants [11].
• Opioids delta-, kappa- and mu-types [12].
• Oxytocin (OT-R).
• Platelet activating factor (PAF-R).
• Prostacyclin.
• Prostaglandin D2.
• Prostaglandin E2, EP1 to EP4 subtypes.
• Prostaglandin F2.
• Purinoreceptors (ATP) [13].
• Somatostatin types 1 to 5.
• Substance-K (NK-2R).
• Substance-P (NK-1R).
• Thrombin.
• Thromboxane A2.
• Thyrotropin (TSH-R) [10].
• Thyrotropin releasing factor (TRH-R).
• Vasopressin V1a, V1b and V2.
• Visual pigments (opsins and rhodopsin) [14].
• Proto-oncogene mas.
• A number of orphan receptors (whose ligand is not known) from mammals and birds.
• Caenorhabditis elegans putative receptors C06G4.5, C38C10.1, C43C3.2, T27D1.3 and ZC84.4.
• Three putative receptors encoded in the genome of cytomegalovirus: US27, US28, and UL33.
• ECRF3, a putative receptor encoded in the genome of herpesvirus saimiri.

The structure of all these receptors is thought to be identical. They have seven hydrophobic regions, each of which most probably spans the membrane. The N-terminus is located on the extracellular side of the membrane and is often glycosylated, while the C-terminus is cytoplasmic and generally phosphorylated. Three extracellular loops alternate with three intracellular loops to link the seven transmembrane regions. Most, but not all of these receptors, lack a signal peptide. The most conserved parts of these proteins are the transmembrane regions and the first two cytoplasmic loops. A conserved acidic-Arg-aromatic triplet is present in the N-terminal extremity of the second cytoplasmic loop [15] and could be implicated in the interaction with G proteins.

To detect this widespread family of proteins we have developed a pattern that contains the conserved triplet and that also spans the major part of the third transmembrane helix. We have also developed a profile that spans the seven transmembrane regions.