P2Y purinoceptor 12

Function

Receptor for ADP and ATP coupled to G proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, P2Y12_rcpt

Functional cluster

MFS & Drug-Efflux Transporters

Experimental structures · PDB · 5

• 4NTJ X-ray 2.62A
• 4PXZ X-ray 2.50A
• 4PY0 X-ray 3.10A
• 7PP1 X-ray 2.78A
• 7XXI EM 3.00A

A predicted model is available from AlphaFold.

Gene Ontology · 31

• GO:0044298 cell body membrane
• GO:0031253 cell projection membrane
• GO:0009986 cell surface
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0001609 G protein-coupled adenosine receptor activity
• GO:0001621 G protein-coupled ADP receptor activity
• GO:0045028 G protein-coupled purinergic nucleotide receptor activity
• GO:0005085 guanyl-nucleotide exchange factor activity
• GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• GO:0019722 calcium-mediated signaling
• GO:0030030 cell projection organization
• GO:0071318 cellular response to ATP
• GO:0021801 cerebral cortex radial glia-guided migration
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0007599 hemostasis
• GO:0030032 lamellipodium assembly
• GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
• GO:0030168 platelet activation
• GO:0070527 platelet aggregation
• GO:0033630 positive regulation of cell adhesion mediated by integrin
• GO:0050921 positive regulation of chemotaxis
• GO:0033626 positive regulation of integrin activation by cell surface receptor linked signal transduction
• GO:1904141 positive regulation of microglial cell migration
• GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• GO:1900029 positive regulation of ruffle assembly
• GO:0050920 regulation of chemotaxis
• GO:1904139 regulation of microglial cell migration
• GO:0048678 response to axon injury
• GO:0006930 substrate-dependent cell migration, cell extension
• GO:0150063 visual system development

Disease associations

• platelet-type bleeding disorder 8 MONDO:0012354

Drugs targeting this protein · 13

• CLOPIDOGREL BISULFATE antagonist
• CANGRELOR TETRASODIUM antagonist
• PRASUGREL HYDROCHLORIDE antagonist
• TICLOPIDINE HYDROCHLORIDE antagonist
• ELINOGREL antagonist
• REGRELOR DISODIUM antagonist
• CANGRELOR inhibitor
• TICAGRELOR negative allosteric modulator
• SELATOGREL antagonist
• CLOPIDOGREL BESILATE antagonist
• CLOPIDOGREL HYDROCHLORIDE antagonist
• PRASUGREL BESYLATE antagonist
• CLOPIDOGREL HYDROBROMIDE antagonist

Related proteins · sequence + function similarity

• P2Y purinoceptor 12 1.00
• P2Y purinoceptor 12 0.99
• P2Y purinoceptor 12 0.99
• P2Y purinoceptor 14 0.97
• P2Y purinoceptor 14 0.97
• P2Y purinoceptor 14 0.97
• P2Y purinoceptor 14 0.96
• G protein-coupled receptor 87 0.95
• G protein-coupled receptor 87 0.95
• P2Y purinoceptor 13 0.94
• P2Y purinoceptor 13 0.94
• G protein-coupled receptor 171 0.93

Co-cited proteins · studied together in the literature

• P2Y purinoceptor 12 1 shared papers
• Putative vomeronasal receptor-like protein 4 1 shared papers
• Probable G protein-coupled receptor 160 1 shared papers
• Probable G protein-coupled receptor 152 1 shared papers
• Cysteinyl leukotriene receptor 2 1 shared papers
• Probable G protein-coupled receptor 148 1 shared papers
• Putative G protein-coupled receptor GPR32P1 1 shared papers
• Probable G protein-coupled receptor 174 1 shared papers
• Oxoeicosanoid receptor 1 1 shared papers
• GPI ethanolamine phosphate transferase 3, catalytic subunit 1 shared papers
• Transmembrane protein 171 1 shared papers
• Probable G protein-coupled receptor 82 1 shared papers

Literature · 9 cited papers

• Identification of a new dysfunctional platelet P2Y12 receptor variant associated with bleeding diathesis. Blood · 2015
• Agonist-bound structure of the human P2Y12 receptor. Nature · 2014
• Structure of the human P2Y12 receptor in complex with an antithrombotic drug. Nature · 2014
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding. Proc. Natl. Acad. Sci. U.S.A. · 2003
• Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett. · 2002
• Molecular cloning of the platelet P2T(AC) ADP receptor: pharmacological comparison with another ADP receptor, the P2Y1 receptor. Mol. Pharmacol. · 2001
• Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature · 2001
• ADP is the cognate ligand for the orphan G protein-coupled receptor SP1999. J. Biol. Chem. · 2001