Conserved Site

GPCR, family 3, conserved site (IPR017979)

Short name: GPCR_3_CS

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 [PMID: 12679517]. 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 [PMID: 8170923]. 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) [PMID: 8170923, PMID: 8081729, PMID: 15914470, PMID: 18948278, PMID: 16753280]. 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 [PMID: 12679517]. 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 [PMID: 23020293].

GPCR family 3 receptors (also known as family C) are structurally similar to other GPCRs, but do not show any significant sequence similarity and thus represent a distinct group. Structurally they are composed of four elements; an N-terminal signal sequence; a large hydrophilic extracellular agonist-binding region containing several conserved cysteine residues which could be involved in disulphide bonds; a shorter region containing seven transmembrane domains; and a C-terminal cytoplasmic domain of variable length [PMID: 17266540]. Family 3 members include the metabotropic glutamate receptors, the extracellular calcium-sensing receptors, the gamma-amino-butyric acid (GABA) type B receptors, and the vomeronasal type-2 receptors [PMID: 1309649, PMID: 8255296, PMID: 10773016, PMID: 9292726]. As these receptors regulate many important physiological processes they are potentially promising targets for drug development.

This entry represents three conserved sites found in family 3 GPCR receptor proteins. The first conserved site is centred around a highly conserved hydrophobic segment in the central part of the N-terminal extracellular region; the second conserved site is centred around a cluster of six cysteines in the C-terminal part of the extracellular domain; the third conserved site is centred around the C-terminal part of the cytoplasmic loop between the fifth and sixth transmembrane domains.

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway

Molecular Function

GO:0004930 G-protein coupled receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns
PROSITE patterns
PROSITE patterns