P2Y12

P2RY12
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4NTJ, 4PXZ, 4PY0
Identifiers
Aliases	P2RY12, ADPG-R, BDPLT8, HORK3, P2T(AC), P2Y(12)R, P2Y(AC), P2Y(ADP), P2Y(cyc), P2Y12, SP1999, purinergic receptor P2Y12
External IDs	OMIM: 600515; MGI: 1918089; HomoloGene: 11260; GeneCards: P2RY12; OMA:P2RY12 - orthologs
Gene location (Human)
Chr.	Chromosome 3 (human)
End	151,384,753 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	59,170,292 bp
RNA expression pattern
	Top expressed in
	inferior ganglion of vagus nerve; ; superior vestibular nucleus; ; ventral tegmental area; ; subthalamic nucleus; ; Brodmann area 46; ; monocyte; ; corpus callosum; ; spinal ganglia; ; spinal cord; ; testicle;
	Top expressed in
	globus pallidus; ; blood; ; lumbar subsegment of spinal cord; ; superior frontal gyrus; ; primary visual cortex; ; dentate gyrus of hippocampal formation granule cell; ; morula; ; optic nerve; ; olfactory tubercle; ; Region I of hippocampus proper;
	More reference expression data
	n/a
Gene ontology
Molecular function	G protein-coupled adenosine receptor activity; G protein-coupled receptor activity; guanyl-nucleotide exchange factor activity; G protein-coupled purinergic nucleotide receptor activity; signal transducer activity; G protein-coupled ADP receptor activity;
Cellular component	integral component of membrane; membrane; plasma membrane; integral component of plasma membrane; cell surface; basal plasma membrane; mitochondrion; caveola; intrinsic component of membrane; external side of plasma membrane;
Biological process	hemostasis; G protein-coupled adenosine receptor signaling pathway; regulation of calcium ion transport; adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; protein kinase B signaling; adenylate cyclase-modulating G protein-coupled receptor signaling pathway; negative regulation of cell differentiation; substrate-dependent cell migration, cell extension; cellular response to organic cyclic compound; negative regulation of norepinephrine secretion; G protein-coupled purinergic nucleotide receptor signaling pathway; regulation of microglial cell migration; cell projection organization; calcium ion transmembrane transport; positive regulation of ion transport; potassium ion transmembrane transport; cellular response to ATP; platelet aggregation; glial cell migration; signal transduction; blood coagulation; platelet activation; G protein-coupled receptor signaling pathway; regulation of molecular function;
	Sources:Amigo / QuickGO
Orthologs
	64805
	70839
	ENSG00000169313
	ENSMUSG00000036353
	Q9H244
	Q9CPV9
	NM_176876; NM_022788
	NM_027571; NM_001357007; NM_001357008; NM_001357010
	NP_073625; NP_795345
	NP_081847; NP_001343936; NP_001343937; NP_001343939
	Wikidata
View/Edit Human	View/Edit Mouse

In the field of purinergic signaling, the P2Y₁₂ protein is found mainly but not exclusively on the surface of blood platelets, and is an important regulator in blood clotting.^[5]

P2Y₁₂ belongs to the G_i class of a group of G protein-coupled (GPCR) purinergic receptors^[6] and is a chemoreceptor for adenosine diphosphate (ADP).^[7]^[8] This P2Y receptor family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. The P2Y12 receptor is involved in platelet aggregation and is thus a biological target for the treatment of thromboembolisms and other clotting disorders. Two transcript variants encoding the same isoform have been identified for this gene.^[9]

Clinical significance

The drugs clopidogrel (Plavix), prasugrel (Efient, Effient), ticagrelor (Brilinta), and cangrelor (Kengreal) bind to this receptor and are marketed as antiplatelet agents.^[7]

P2Y₁₂ inhibitors do not change the risk of death when given as a pretreatment prior to routine percutaneous coronary intervention (PCI) in people who have had a non-ST-elevation myocardial infarction (NSTEMI). Though, a P2Y12 inhibitor in addition to aspirin should be administered for up to 12 months to most patients with non-ST-elevation acute coronary syndrome. They do however increase the risk of bleeding and decrease the risk of further cardiovascular problems. Thus their routine use in this context is of questionable value.^[10]

In patients undergoing primary PCI for an ST-segment elevation myocardial infarction (STEMI), a P2Y₁₂ inhibitor should be administered as soon as possible. The use of clopidogrel in particular has been shown to improve morbidity and mortality endpoints including cardiovascular death, recurrent MI, and stroke at 30 days after PCI.^[11]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000169313 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000036353 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Dorsam RT, Kunapuli SP (Feb 2004). "Central role of the P2Y12 receptor in platelet activation". The Journal of Clinical Investigation. 113 (3): 340–5. doi:10.1172/JCI20986. PMC 324551. PMID 14755328.
^ Murugappa S, Kunapuli SP (2006). "The role of ADP receptors in platelet function". Frontiers in Bioscience. 11 (1): 1977–86. doi:10.2741/1939. PMID 16368572.
^ ^a ^b Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB (Jan 2001). "Identification of the platelet ADP receptor targeted by antithrombotic drugs". Nature. 409 (6817): 202–7. doi:10.1038/35051599. PMID 11196645.
^ Nicholas RA (Sep 2001). "Identification of the P2Y(12) receptor: a novel member of the P2Y family of receptors activated by extracellular nucleotides". Molecular Pharmacology. 60 (3): 416–20. PMID 11502870.
^ "Entrez Gene: P2RY12 purinergic receptor P2Y, G-protein coupled, 12".
^ Bellemain-Appaix A, Kerneis M, O'Connor SA, Silvain J, Cucherat M, Beygui F, Barthélémy O, Collet JP, Jacq L, Bernasconi F, Montalescot G (2014). "Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis". BMJ. 349 (aug 06 2): g6269. doi:10.1136/bmj.g6269. PMC 4208629. PMID 25954988.
^ Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Lewis BS, Murphy SA, McCabe CH, Braunwald E (Sep 2005). "Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study". JAMA. 294 (10). Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators: 1224–32. doi:10.1001/jama.294.10.1224. PMID 16143698.

External links

"P2Y Receptors: P2Y₁₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
purinoceptor+P2Y12 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000169313 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000036353 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid14755328-5] Dorsam RT, Kunapuli SP (Feb 2004). "Central role of the P2Y12 receptor in platelet activation". The Journal of Clinical Investigation. 113 (3): 340–5. doi:10.1172/JCI20986. PMC 324551. PMID 14755328.

[pmid16368572-6] Murugappa S, Kunapuli SP (2006). "The role of ADP receptors in platelet function". Frontiers in Bioscience. 11 (1): 1977–86. doi:10.2741/1939. PMID 16368572.

[pmid11196645-7] Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB (Jan 2001). "Identification of the platelet ADP receptor targeted by antithrombotic drugs". Nature. 409 (6817): 202–7. doi:10.1038/35051599. PMID 11196645.

[pmid11502870-8] Nicholas RA (Sep 2001). "Identification of the P2Y(12) receptor: a novel member of the P2Y family of receptors activated by extracellular nucleotides". Molecular Pharmacology. 60 (3): 416–20. PMID 11502870.

[entrez-9] "Entrez Gene: P2RY12 purinergic receptor P2Y, G-protein coupled, 12".

[BMJP2Y12-10] Bellemain-Appaix A, Kerneis M, O'Connor SA, Silvain J, Cucherat M, Beygui F, Barthélémy O, Collet JP, Jacq L, Bernasconi F, Montalescot G (2014). "Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis". BMJ. 349 (aug 06 2): g6269. doi:10.1136/bmj.g6269. PMC 4208629. PMID 25954988.

[JAMAP2Y12-11] Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Lewis BS, Murphy SA, McCabe CH, Braunwald E (Sep 2005). "Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study". JAMA. 294 (10). Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators: 1224–32. doi:10.1001/jama.294.10.1224. PMID 16143698.

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