| Description: |
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [, , ].Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. A novel GPCR (GPR4) from the critical myotonic dystrophy (DM) region on chromosome 19q13.3 has been sequenced [, ]. The gene is intronless and contain an open reading frame encoding a protein of 362amino acids. Two isoforms of GPR4 are expressed in humans, differing in their 3'untranslated region as a result of the use of alternate polyadenylation signals. GPR4 iswidely expressed, with higher levels in kidney, heart, and especially lung []. Sequenceanalysis suggests that GPR4 is a peptide receptor; it shares strongest similarity withpurinergic receptors and receptors for angiotensin II, platelet activating factor, thrombinand bradykinin [, ]. |
