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P2RY4 Membrane Protein Introduction

Introduction of P2RY4

P2RY4 is encoded by the P2RY4 gene. It belongs to the G-protein-coupled receptor (GPCR) family which has proved to be the drug targets of approximately 34% of all modern medicinal drugs. It is one of the eight subtypes of G protein-coupled P2Y receptors (P2RY1, P2RY2, P2RY4, P2RY6, P2RY11, P2RY12, P2RY13, and P2RY14). P2RY4 possesses seven transmembrane alpha helices and uses uridine nucleotides as the preferred endogenous agonist. Meanwhile, P2RY4 is also known as uridine nucleotides receptor and is activated by UTP and ATP partially, but cannot be activated by UDP or ADP.

Basic Information of P2RY4
Protein Name P2Y purinoceptor 4
Gene Name P2RY4
Aliases Uridine nucleotide receptor, UNR
Organism Homo sapiens (Human)
UniProt ID P51582
Transmembrane Times 7
Length (aa) 365
Sequence MASTESSLLRSLGLSPGPGSSEVELDCWFDEDFKFILLPVSYAVVFVLGLGLNAPTLWLFIFRLRPWDAT
ATYMFHLALSDTLYVLSLPTLIYYYAAHNHWPFGTEICKFVRFLFYWNLYCSVLFLTCISVHRYLGICHP
LRALRWGRPRLAGLLCLAVWLVVAGCLVPNLFFVTTSNKGTTVLCHDTTRPEEFDHYVHFSSAVMGLLFG
VPCLVTLVCYGLMARRLYQPLPGSAQSSSRLRSLRTIAVVLTVFAVCFVPFHITRTIYYLARLLEADCRV
LNIVNVVYKVTRPLASANSCLDPVLYLLTGDKYRRQLRQLCGGGKPQPRTAASSLALVSLPEDSSCRWAA
TPQDSSCSTPRADRL

Function of P2RY4 Membrane Protein

G protein-coupled P2Y receptors family is expressed in almost all human tissues and they are of great interest as potential drug targets for many diseases, especially for neurodegenerative disorders and cardiovascular diseases. The activity of P2RY4 is mediated by uridine 5'-triphosphate (UTP) and adenosine triphosphate (ATP). P2RY4 expresses widely in the body, including central nervous system, heart, gastrointestinal tract, and skin. In the gastrointestinal tract, P2RY4 is reported to regulate the secretion of chloride. So, the P2RY4 agonists can be used as a possible target to treat the cystic fibrosis and P2RY4 antagonists are the possible targets for the treatment of diarrhea. P2RY4 also is reported to regulate the production of the amyloid precursor protein (APP) in the brain. Because the accumulation of APP in brain is associated with the development of Alzheimer’s disease, P2RY4 antagonists are possible therapeutic agents for the treatment of Alzheimer’s disease. However, no potential antagonists for P2RY4 have been reported so far, the development of selective antagonists for P2RY4 is a promising field.

Schematic representation of mechanism of P2RY4. Fig.1 Schematic representation of mechanism of P2RY4. (Paniagua-Herranz, 2017)

Application of P2RY4 Membrane Protein in Literature

  1. Lazarowski E.R., et al. Mechanisms of Release of Nucleotides and Integration of Their Action as P2X- and P2Y-Receptor Activating Molecules. Mol. Pharmacol. 2003, 64(4):785-796. PubMed ID: 14500734

    This article reviews the extracellular nucleotides and P2X- and P2Y-receptor-mediated signaling pathway in many pathophysiological processes make the antagonists for P2Y4 receptor as potentially valuable therapeutic targets.

  2. Cavaliere F., et al. Role of the metabotropic P2Y4 receptor during hypoglycemia: cross talk with the ionotropic NMDAR1 receptor. Exp. Cell Res. 2004, 300(1):149-158. PubMed ID: 15383322

    This article reveals that both P2Y4 and NMDAR1 receptor are involved in the metabolic impairment and the consequent cell death. At the same time, this article reports that P2RY4 is the first purinergic metabotropic receptor to be causal to cell death under conditions of metabolism impairment.

  3. Li HQ., et al. P2Y(4) Receptor-Mediated Pinocytosis Contributes to Amyloid Beta-Induced Self-Uptake by Microglia. Mol. Cell. Biol. 2013, 33(21):4282-4293. PubMed ID: 24001770

    Authors in this group describe that ATP functions as a “drink me” signal through activation of P2Y4 receptors for soluble amyloid beta peptide 1-42 in microglia and P2Y4 receptors might be used as a potential drug target for the treatment of Alzheimer's disease.

  4. Paniagua-Herranz L., et al. Prostaglandin E(2) Impairs P2Y(2)/P2Y(4) Receptor Signaling in Cerebellar Astrocytes via EP3 Receptors. Frontiers in Pharmacology. 2017, 8:937-952. PubMed ID: 29311938

    This article reports that PGE2 activates P2Y2/P2Y4 receptors and mediates pro or anti-inflammatory in rat cerebellar astrocytes. Inhabitation the interaction between PGE2 and P2Y signaling can impair the UTP induced intracellular calcium responses and the nucleotide elicited astrocyte migration.

  5. Horckmans M., et al. Loss of Mouse P2Y4 Nucleotide Receptor Protects against Myocardial Infarction through Endothelin-1 Downregulation. The Journal of Immunology. 2015, 194(4):1874-1885.

    This article identifies that loss of P2Y4 could bring a new therapeutic perspective for the treatment of cardiac ischemia because cardiac permeability and neutrophil infiltration are down-regulated in LPS induced inflammation P2Y4 null mice model. Meanwhile, the authors identify a new protein, ET-1, as P2Y4 target genes, which is involved and down-regulation in cardiac ischemia.

P2RY4 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-P2RY13 antibody development services.


As an innovation-driven and customer-focused company, Creative Biolabs provides a broad and integrated portfolio of services in the field of membrane protein. Our services are designed to help our worldwide customers shorten the research time and lower the cost of generation of many functional membrane proteins. Please feel free to contact us for more information.

Reference

  1. Paniagua-Herranz L., et al. (2017) Prostaglandin E(2) Impairs P2Y(2)/P2Y(4) Receptor Signaling in Cerebellar Astrocytes via EP3 Receptors. Frontiers in Pharmacology. 8:937-952.

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