P2Y purinoceptor 12, member of the class A family of seven-transmembrane G protein-coupled receptors
The P2Y12 receptor (P2Y12R) is found predominantly on the surface of blood platelets and is activated by adenosine diphosphate (ADP). P2Y12R plays an important role in the regulation of blood clotting and belongs to the G(i) class of the P2Y family of purinergic G protein-coupled receptors. P2Y receptor family is composed of eight subtypes, which are activated by naturally occurring extracellular nucleotides such as ATP, ADP, UTP, UDP, and UDP-sugars. These eight receptors are ubiquitous in human tissues and can be further classified into two subfamilies based on sequence homology and second messenger coupling: a subfamily of five P2Y1-like receptors (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11Rs) that are coupled to G(q) protein to activate phospholipase C (PLC) and a second subfamily of three P2Y12-like receptors (P2Y12, P2YR13, and P2Y14Rs) that are coupled to G(i) protein to inhibit adenylate cyclase. Several cloned subtypes, such as P2Y3, P2Y5 and P2Y7-10, are not functional mammalian nucleotide receptors. The native agonists for P2Y receptors are: ATP (P2Y2, P2Y12), ADP (P2Y1, P2Y12 and P2Y13), UTP (P2Y2, P2Y4), UDP (P2Y6, P2Y14), and UDP-sugars (P2Y14).
Feature 1:ligand binding site [chemical binding site]
Evidence:
Comment:based on the binding of human P2Y12 receptor to full agonist 2-methylthio-adenosine-5'-diphosphate (2MeSADP, a close analogue of endogenous agonist ADP)
Structure:4PXZ: Human P2Y12 receptor binds full agonist 2MeSADP, a close analogue of ADP; contacts at 4A
Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracellular surface of its receptor.
Jiyao W et al.(2023). "The conserved domain database in 2023.",