G protein-coupled receptor 37 orphan (IPR003909)
Short name: GPR37_orph
Overlapping homologous superfamilies
- G protein-coupled receptor, rhodopsin-like (IPR000276)
- G protein-coupled receptor 37 orphan (IPR003909)
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. GPR37 was isolated from a set of human brain frontal lobe expressed sequence tags. The GPR37 genomic sequence was subsequently mapped to chromosome 7. A putative orthologue, 83% identical to the human form in terms of predicted amino acid sequence, has since been identified in the mouse genome and mapped to chromosome 6. Northern blot analyses revealed a highly expressed 3.8kb mRNA and a less abundant 8kb mRNA in both human and mouse brain. The 3.8kb mRNA was also less abundantly expressed in human liver and placenta, and a further 3kb mRNA was found in mouse testis [PMID: 9799598].
- PR01421 (GPR37ORPHANR)