P2Y purinoceptor 12

Basic Information
Short Name	P2Y12, ADPG-R
UNP ID	Q9H244
Organism	Homo sapiens
Cys Site	Cys17, Cys270
Family/Domain	7 transmembrane receptor (rhodopsin family), G-protein coupled receptor 1 family]
Known Ligand	Ligand list
Function Type	G-protein coupled receptor

Summary

Protein Function

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. P2Y12 belongs to the Gi class of a group of G protein-coupled (GPCR) purinergic receptors and is a chemoreceptor for adenosine diphosphate (ADP). The P2Y family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is involved in platelet aggregation, and is a potential target for the treatment of thromboembolisms and other clotting disorders.
The drugs clopidogrel (Plavix), prasugrel (Efient, Effient) ticagrelor (Brilinta) and cangrelor (Kengreal) bind to this receptor and are marketed as antiplatelet agents. P2Y12 inhibitors do not change the risk of death when given to people who have had a NSTEMI. They do however increase the risk of bleeding and decrease the risk of further cardiovascular problems. Thus their routine use is of questionable value. (From Wikipedia)
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. (From Uniprot)

Cys Function & Property

Cys17 and Cys270 are located at the extracellular regions of P2Y12, and could form disulfide bond

P2Y12 topology (PMID: 30302530)

• Hydrophobic property:

• SASA：

Cys17: 26.597 A^2

Cys270: 44.767 A^2

Protein Sequence

MQAVDNLTSA PGNTSLCTRD YKITQVLFPL LYTVLFFVGL ITNGLAMRIF
FQIRSKSNFI IFLKNTVISD LLMILTFPFK ILSDAKLGTG PLRTFVCQVT
SVIFYFTMYI SISFLGLITI DRYQKTTRPF KTSNPKNLLG AKILSVVIWA
FMFLLSLPNM ILTNRQPRDK NVKKCSFLKS EFGLVWHEIV NYICQVIFWI
NFLIVIVCYT LITKELYRSY VRTRGVGKVP RKKVNVKVFI IIAVFFICFV
PFHFARIPYT LSQTRDVFDC TAENTLFYVK ESTLWLTSLN ACLDPFIYFF
LCKSFRNSLI SMLKCPNSAT SLSQDNRKKE QDGGDPNEET PM

Structural Information

• Known structure with covalent ligand:
  

Unknown

• Protein structure:

Related Pathway

• Platelet activation
  

Experimental Evidence

Cys-directed Mutation

Reference

1. Ding Z, Kim S, Dorsam R T, et al. Inactivation of the human P2Y₁₂ receptor by thiol reagents requires interaction with both extracellular cysteine residues, Cys17 and Cys270[J]. Blood, 2003, 101(10): 3908-3914. 12560222