Family

OGR1 sphingosylphosphorylcholine receptor (IPR005389)

Short name: OGR1_rcpt

Family relationships

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].

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].

Sphingosylphosphorylcholine (SPC) is produced from degradation of sphingomyelin and regulates many diverse cellular functions, such as: proliferation, growth inhibition, smooth muscle contraction and wound healing. It is also thought to play a role in the cardiovascular system and potently activates inwardly rectifying K+ channels, suggesting a possible role in regulation of heart rate.

The orphan receptor OGR1 has been identified as a high affinity receptor for SPC [PMID: 10806476]. OGR1 is expressed in ovarian cancer cell lines and also in spleen, testis, small intestine, peripheral blood leukocytes, brain, heart, lung, placenta and kidney. Expression has not been found in thymus, prostate, ovary, colon, liver, skeletal muscle or pancreas [PMID: 8661159]. Upon activation by SPC, OGR1 couples to both Gi proteins, causing increases in intracellular calcium, and Gq proteins, to activate MAP kinases, inhibiting proliferation. SPC also causes regulation of ion channel activity, binding of activator protein-1 to DNA, and expression of cell adhesion molecule-1 and interleukin-6 [PMID: 10806476].

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway

Molecular Function

No terms assigned in this category.

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PRINTS
CDD