P2Y purinoceptor 4 (IPR000018)

Short name: P2Y4

Overlapping homologous superfamilies


Family relationships


There are three distinct families of extracellular receptors for purine and pyrimidine nucleotides [PMID: 9364468], known as P1, P2X and P2Y purinoceptors [PMID: 19921464]. These receptors induce a wide variety of biological effects and are involved in many different cellular functions [PMID: 10629443, PMID: 20471713, PMID: 11099464]. P2X receptors are ligand-gated ion channels, whereas P1 and P2Y receptors are rhodopsin-like G protein-coupled receptors [PMID: 7724657, PMID: 8872457]. The families also differ by their method of activation: P1 receptors are preferentially activated by adenosine [PMID: 11734617], P2X via ATP [PMID: 12270951], whereas the P2Y receptors, in addition to being activated by ATP, are activated by different adenine and/or uridine nucleoside di- and triphosphates (ADP, UDP, UTP, UDP and UDP-glucose) [PMID: 16257449].

The P2Y purinoceptors currently consist of eleven subtypes: P2Y1, P2Y2, P2Y3 P2Y4, P2Y6, P2Y8, P2Y10, P2Y11, P2Y12, P2Y13 and P2Y14 [PMID: 16968944, PMID: 11004484, PMID: 9755289]. P2Y3 has, as yet, only been found in birds [PMID: 8508924], whilst the rest have been cloned in humans. The gaps in P2Y receptor numbering are due to the reclassification of some receptors that were initially associated with to the P2Y family. These include P2Y5 (now known as lysophosphatidic acid receptor 6), P2Y7 (now leukotriene B4 receptor) and P2Y9 (lysophosphatidic acid receptor 4) [PMID: 19386608, PMID: 8921391, PMID: 8702478, PMID: 12724320].

P2Y purinoceptor subtypes have different pharmacological selectivities, which overlap in some cases, for various adenosine and uridine nucleotides. They are widely expressed and are involved in platelet aggregation, vasodilation and neuromodulation, and a range of other processes, such as ion flux, differentiation, and synaptic communication [PMID: 11794691, PMID: 16914897, PMID: 16934527, PMID: 16257449]. They exert their varied biological functions based on different G-protein coupling [PMID: 11111826]. Each receptor subtype can couple to multiple G proteins, either Gi, Gq/11 or Gs, triggering the activation of diverse intracellular signalling cascades (stimulation of phospholipase C through Gq/11, stimulation of adenylyl cyclase via Gs, or ihibition of adenylyl cyclase via Gi [PMID: 18404483, PMID: 9755289]).

This entry represents P2Y4 receptor, which is expressed in the placenta, the lung, vascular smooth muscle [PMID: 11690642, PMID: 19011163, PMID: 11259526] and enteric glial cells [PMID: 19250649, PMID: 16616701]. The receptor can couple to both Gi and Gq/11. In cells stably expressing the receptor, UTP has been shown to stimulate the formation of inositol phosphates with maximal effect [PMID: 8537336, PMID: 8537335, PMID: 10779375], while ATP behaves as a partial agonist [PMID: 9647463], and ADP is almost inactive [PMID: 8537336]. In guinea pig gallbladder smooth muscle cells, P2Y4 activation is followed by phospholipase A2 and COX-1 stimulation [PMID: 18436624]. In human HaCaT keratinocytes, UTP acting on the P2Y4 receptor stimulates ERK1/2 phosphorylation, which in turn leads to IL-6 production [PMID: 17130674]. P2Y4-mediated ERK1/2 activation has also been detected in human midbrain-derived neuroprogenitor cells [PMID: 17076658]. The P2Y4 receptor has been shown to regulate chloride epithelial transport [PMID: 16056234, PMID: 12644577].

GO terms

Biological Process

GO:0007186 G protein-coupled receptor signaling pathway
GO:0030321 transepithelial chloride transport

Molecular Function

GO:0045028 G protein-coupled purinergic nucleotide receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

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