Retinal pigment epithelium GPCR (IPR001793)

Short name: RPE_GPCR

Overlapping homologous superfamilies


Family relationships


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].

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 [PMID: 2111655, PMID: 2830256, PMID: 8386361].

Retinal pigment epithelium (RPE) hosts a putative GPCR. The RPE-retinal GPCR (RGR) covalently binds all-trans- and 11-cis-retinal after reduction by sodium borohydride [PMID: 7947717]. All-trans-retinal is bound preferentially over the 11-cis isomer. The human sequence is 86% identical to that of bovine RGR [PMID: 7947717, PMID: 8258527], and a lysine residue, analogous to the retinaldehyde attachment site of rhodopsin, is conserved in TM domain 7 [PMID: 7947717]. The human gene, whose structure is distinct from that of the visual pigment genes, spans 14.8 kb and is split into 7 exons [PMID: 7947717]. This suggests that the rgr gene represents the earliest independent branch of the vertebrate opsin gene family [PMID: 7947717]. Since the RGR gene product preferentially binds all-trans-retinal, it is thought that one of its functions may be to catalyse isomerisation of the chromophore by a retinochrome-like mechanism [PMID: 7947717].

GO terms

Biological Process

GO:0007186 G protein-coupled receptor signaling pathway
GO:0007602 phototransduction
GO:0007601 visual perception

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.