Pathways & interactions
DEZ orphan receptor (IPR002258)
Short name: DEZorph_rcpt
- G protein-coupled receptor, rhodopsin-like (IPR000276)
- DEZ orphan receptor (IPR002258)
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].
Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. A novel GPCR has been isolated from a cDNA derived from the cell line NH15-CA2 and a cDNA library from adult mouse brain [PMID: 9144535]. The amino acid sequence of the receptor, DEZ, shows closest resemblance to neuropeptide and chemoattractant receptors, with highest similarity to the orphan receptor GPR-1. In situ hybridisation experiments indicate that dez is differentially regulated during development, with prominent expression in developing osseous and cartilaginous tissue [PMID: 9144535]. It is also detectable in adult parathyroid glands, suggesting a possible function in bone metabolism.
- PR01126 (DEZORPHANR)