Prolactin-releasing peptide receptor (IPR001402)

Short name: Prolrel_pep_rcpt

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].

Hypothalamic peptide hormones regulate secretion of anterior pituitary hormones, such as growth hormone, follicle stimulating hormone, luteinising hormone and thyrotropin. A novel bioactive peptide has been identified from bovine hypothalamus and found to increase prolactin secretion from the anterior pituitary [PMID: 9607765]. This peptide - prolactin-releasing peptide (PrRP) - is a member of the structurally related RF-amide family, which includes neuropeptide FF [PMID: 11030716]. The peptide exists in two forms: a 31-amino acid form and a truncated 20-amino acid form [PMID: 9607765]. PrRP has been found in the medulla oblongata, hypothalamus and pituitary, as well as in a number of other tissues. This distribution suggests the peptide may have other roles in addition to prolactin release [PMID: 10498338].

The receptor for PrRP was identified to be an orphan receptor, previously known as GPR10 [PMID: 9607765]. This receptor is expressed in the central nervous system with highest levels in the pituitary. Expression has also been detected in the cerebellum, brainstem, hypothalamus, thalamus and spinal cord in rat [PMID: 10498338]. Binding of PrRP to the receptor results in activation of extracellular signal-related kinase (ERK) in a mainly pertussis toxin sensitive manner, suggesting coupling to Gi/o proteins [PMID: 11030716]. PrRP can also cause increases in intracellular calcium and activation of c-Jun N-terminal protein kinase (JNK) in a pertussis toxin insensitive manner, indicating that the receptor can also couple to Gq proteins, depending on the cell type in which it is expressed [PMID: 11030716].

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway

Molecular Function

GO:0004983 neuropeptide Y receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

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