P2RY12 Membrane Protein Introduction

Introduction of P2RY12

P2RY12, also known as purinergic receptor P2RY12, purinergic receptor P2Y12, purinergic receptor P2Y, P2Y(AC), P2Y(12)R, HORK3, BDPLT8, putative G-protein coupled receptor, G-protein coupled receptor SP1999, Gi-coupled ADP receptor HORK3, is a member of G-protein coupled receptors (GPCR) family, which has some receptor subtypes with different pharmacological selectivity. It is a 39.4 kDa molecule and in humans, encoded on the chromosome 3q25.1. Initially, the P2RY12 gene is reported that contains at least 2 exons, in charge of coding for 342 amino acid all length protein and separated by a 1,700 bp intron, localized upstream of the ATG codon. There are two transcript variants coding for the same isoform that have been identified for the P2RY12 gene.

Basic Information of P2RY12
Protein Name P2Y purinoceptor 12
Gene Name P2RY12
Aliases P2Y12, ADP-glucose receptor, ADPG-R, P2T(AC), P2Y(AC), P2Y(cyc), P2Y12 platelet ADP receptor, P2Y(ADP), SP1999
Organism Homo sapiens (Human)
UniProt ID Q9H244
Transmembrane Times 7
Length (aa) 342

Function of P2RY12 Membrane Protein

This receptor is found abundantly expressed in human platelets and smooth muscle, as well as spinal cords and numerous brain regions. It participates in the platelet aggregation and becomes a promising target for the clinical treatment of thromboembolism as well as other clotting disorders. Moreover, expressed sequence tags (ESTs) for P2RY12 have been isolated from B-cell, brain, eye, embryo, prostate, along with kidney and colon carcinoma libraries. Here, P2RY12, P2RY1, and P2X1 are three known ADP receptor subtypes on platelets. And ADP is secreted from red blood cells, damaged vessels, and platelets stimulated by other agonists. ADP can bind to P2RY1 to exert the platelet aggregation and to P2RY12, which amplifies the platelet aggregation. Furthermore, continued ADP-induced platelet aggregation demands the coactivation of both P2RY1 and P2RY12. P2RY12 receptor functions by inhibiting adenylyl cyclase through a Gi protein and enhances dense granule secretion, procoagulant activity, along with platelet aggregation. Without sustained activation of this receptor, aggregated platelets would disaggregate.

Structure of P2RY12 protein.Fig.1 Structure of P2RY12 protein.

Application of P2RY12 Membrane Protein in Literature

  1. Tarantini G., et al. Efficacy and safety of potent platelet P2Y12 receptor inhibitors in elderly versus nonelderly patients with acute coronary syndrome: A systematic review and meta-analysis. Am Heart J. 2018, 195,78-85. PubMed ID: 29224649

    The effect of more potent P2Y12 inhibitors in contrast to clopidogrel on efficacy as well as safety end points was consistent in younger and elderly patients. And data in this review implied that these P2Y12 inhibitors should not be withheld from eligible patients solely due to advanced age.

  2. Mundell S.J., et al. Receptor homodimerization plays a critical role in a novel dominant negative P2RY12 variant identified in a family with severe bleeding. J Thromb Haemost. 2018, 116(1),44-53. PubMed ID: 29117459

    Proline played a critical role in P2Y12R ligand binding and signal defects and the homodimer formation of P2Y12R was important for the function and signaling of receptor. The new dominant negative variant confirmed the significant effect of R265 in EL3 in the P2Y12R functional integrity and suggested pathologic heterodimer formation might underlie this family bleeding phenotype.

  3. Sumitani M., et al. Association between polymorphisms in the purinergic P2Y12 receptor gene and severity of both cancer pain and postoperative pain. Pain Med. 2018, 19(2),348-354. PubMed ID: 28472364

    Polymorphisms of the P2RY12 gene possibly predicted individual differences both in cancer and postoperative pain severity; this may be caused by functional alteration of nociceptive neurons via the neuron-glia interaction.

  4. Taghizadeh M., et al. Effects of endurance training on hsa-miR-223, P2RY12 receptor expression and platelet function in type 2 diabetic patients. Clin Hemorheol Microcirc. 2018, 68(4),391-399. PubMed ID: 29526844

    Short-term endurance training did not induce the downregulation of P2RY12 and upregulation of hsa-miR-223, while it had a positive influence on glycemic indices, platelet functions, physical fitness, together with body composition in female T2DM patients.

  5. Li J.L., et al. Association between P2RY12 gene polymorphisms and adverse clinical events in coronary artery disease patients treated with clopidogrel: A systematic review and meta-analysis. Gene. 2018, 657,69-80. PubMed ID: 29510176

    P2RY12 gene polymorphisms may correlate with higher risk of composite ischemic situations, stent thrombosis, unstable angina, and non-fatal myocardial infarction. However, there was no significant effect found on bleeding, mortality, and target vessel revascularization.

P2RY12 Preparation Options

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  1. Degn M, et al. (2017). Rare missense mutations in P2RY12 in narcolepsy with cataplexy. Brain. 140(6), 1657-1668.

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