X opioid receptor (IPR001420)

Short name: X_opioid_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].

The term opioid refers to a class of substance that produces its effects via the major classes of opioid receptor, termed mu, delta and kappa. The receptors are found in the CNS and certain smooth muscles: mu-opioid receptors are believed to mediate analgesia, hypothermia, respiratory depression, miosis, bradycardia, nausea, euphoria and physical dependence, beta-endorphin being the most potent endogenous ligand; delta-receptors mediate analgesia; and kappa-opioid receptors are believed to mediate analgesia, sedation, miosis and diuresis, dynorphin being the most potent endogenous ligand.

The X-receptor is closely related to opioid receptors, on grounds of both sequence and function, although it is not a typical opioid receptor [PMID: 8137918]. X-receptors are found in many regions of the brain and spinal cord, particularly limbic and hypothalamic structures. They are believed to represent a new class of opioid receptors, with a potential role in modulating various brain functions, including instinctive behaviours and emotions [PMID: 8137918].

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway

Molecular Function

GO:0001626 nociceptin receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

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