Introduction of P2RY6
P2RY6 is encoded by the P2RY6 gene. It belongs to the G-protein-coupled receptor (GPCR) family which is the largest family of membrane proteins in the human genome and the richest source of drug targets for the academia and pharmaceutic industry. It is one of the eight subtypes of P2Y G protein-coupled receptors, which are activated to UDP, UTP, and ADP, but are not activated by ATP. Like other receptors of the GPCR family, P2RY6 possesses seven transmembrane domains and the N terminal region contains an asparagine liked glycosylation sites, the C terminal region has two phosphorylation sites.
|Basic Information of P2RY6|
|Protein Name||P2Y purinoceptor 6|
|Organism||Homo sapiens (Human)|
Function of P2RY6 Membrane Protein
P2RY6 is activated by diphospho-nucleotides. UDP and UTP are the endogenous ligands for P2RY6, and UDP is about 100 fold more potent than UTP. On the tissular level, P2RY6 is expressed in many kinds of tissues widely, including spleen, brain, thymus, heart, blood vessels and placenta. On the cellular level, P2RY6 is distributed in various types of cells, including immune cells, intestinal epithelial cells, vascular endothelial cells, and microglia. The interaction between the released UTP from damaged cells and P2RY6 can trigger the phagocytosis of microglia, and P2RY6 is reported to be involved in neurodegenerative diseases by regulation the microglia associated processes. On the other side, P2RY6 plays a vital role to modulate immune inflammation by regulating the release of interleukin-8 from macrophages and monocytes. So, targeting P2RY6 could be a promising way to treat the microglia activation related diseases, neurodegenerative diseases, and inflammatory diseases.
Fig.1 Schematic overview of signaling pathway of P2RY6 receptor. (Quintas, 2014)
Application of P2RY6 Membrane Protein in Literature
This article reviews that P2RY6 is involved in regulating the release of interleukin-8 from macrocytes and monocytes. At the same time, the authors in this article summarize the relationship between P2RY6 and microglia and propose that P2RY6 might be a promising drug target to treat the neuroinflammation in CNS.
This article indicates that the P2RY6 may be a promising therapeutic drug target for the treatment of monosodium urate associated inflammatory diseases because both P2RY6 antisense oligonucleotide and P2RY6 specific antagonist can inhibit the release of interleukin-8, interleukin-1α, and interleukin-6 from human THP-1 cells.
This article suggests that the P2RY6 may represent a potential target to develop a therapy to treat the colorectal carcinogenesis because P2RY6 knockout mice show a reduced number of colorectal tumors with smaller tumors volumes.
The authors in this article propose that the blocking of P2RY6 may be a novel treatment for controlling persistent storage symptoms in obstructed patients because the activation of P2RY6 can increase the release of mucosal adenosine triphosphate in patients.
This article reports that the activation of P2RY6 is involved in the controlling excessive astrogliosis in neuronal disease because the release of no induced by microglial P2RY6 can activate the astroglial apoptosis chronically.
P2RY6 Preparation Options
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