KiSS-1 peptide receptor (IPR008103)
Short name: KiSS_1_rcpt
Overlapping homologous superfamilies
- G protein-coupled receptor, rhodopsin-like (IPR000276)
- KiSS-1 peptide receptor (IPR008103)
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].
The metastasis suppressor gene KiSS-1 encodes a number of RFamide-related peptides, the largest of which, metastin, contains 54 amino acids. An orphan G protein-coupled receptor, GPR54, has been identified as a receptor for these peptides [PMID: 11385580]. GPR54 is highly expressed in placenta, pituitary, pancreas and spinal cord. Binding of KiSS-1-encoded peptides to the receptor results in coupling to the Gq pathway, stimulating calcium mobilisation, phosphatidylinositol hydrolysis, arachidonic acid release, ERK and p38 MAP kinase phosphorylation and stress fibre formation. It also inhibits cell proliferation. The distribution of GPR54, together with the finding that administration of KiSS-1 peptides in rat stimulates oxytocin secretion, suggests a role in regulation of endocrine function.
- PR01728 (KISS1RECEPTR)