P2Y purinoceptor 12

Details

Name
P2Y purinoceptor 12
Synonyms
  • ADP-glucose receptor
  • ADPG-R
  • HORK3
  • P2T(AC)
  • P2Y(AC)
  • P2Y(ADP)
  • P2Y(cyc)
  • P2Y12
  • P2Y12 platelet ADP receptor
  • SP1999
Gene Name
P2RY12
Organism
Humans
Amino acid sequence
>lcl|BSEQ0009940|P2Y purinoceptor 12
MQAVDNLTSAPGNTSLCTRDYKITQVLFPLLYTVLFFVGLITNGLAMRIFFQIRSKSNFI
IFLKNTVISDLLMILTFPFKILSDAKLGTGPLRTFVCQVTSVIFYFTMYISISFLGLITI
DRYQKTTRPFKTSNPKNLLGAKILSVVIWAFMFLLSLPNMILTNRQPRDKNVKKCSFLKS
EFGLVWHEIVNYICQVIFWINFLIVIVCYTLITKELYRSYVRTRGVGKVPRKKVNVKVFI
IIAVFFICFVPFHFARIPYTLSQTRDVFDCTAENTLFYVKESTLWLTSLNACLDPFIYFF
LCKSFRNSLISMLKCPNSATSLSQDNRKKEQDGGDPNEETPM
Number of residues
342
Molecular Weight
39438.355
Theoretical pI
9.99
GO Classification
Functions
ADP receptor activity / G-protein coupled adenosine receptor activity / guanyl-nucleotide exchange factor activity
Processes
adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway / blood coagulation / calcium ion transmembrane transport / cellular response to ATP / G-protein coupled purinergic nucleotide receptor signaling pathway / G-protein coupled receptor signaling pathway / glial cell migration / hemostasis / negative regulation of cell differentiation / negative regulation of norepinephrine secretion / platelet activation / platelet aggregation / positive regulation of GTPase activity / positive regulation of ion transport / potassium ion transmembrane transport / protein kinase B signaling / regulation of calcium ion transport / regulation of microglial cell migration / substrate-dependent cell migration, cell extension
Components
basal plasma membrane / caveola / cell surface / external side of plasma membrane / integral component of plasma membrane / intrinsic component of membrane / mitochondrion / plasma membrane
General Function
Guanyl-nucleotide exchange factor activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
28-50 62-82 98-118 143-162 186-207 234-259 279-298
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0009941|P2Y purinoceptor 12 (P2RY12)
ATGCAAGCCGTCGACAACCTCACCTCTGCGCCTGGTAACACCAGTCTGTGCACCAGAGAC
TACAAAATCACCCAGGTCCTCTTCCCACTGCTCTACACTGTCCTGTTTTTTGTTGGACTT
ATCACAAATGGCCTGGCGATGAGGATTTTCTTTCAAATCCGGAGTAAATCAAACTTTATT
ATTTTTCTTAAGAACACAGTCATTTCTGATCTTCTCATGATTCTGACTTTTCCATTCAAA
ATTCTTAGTGATGCCAAACTGGGAACAGGACCACTGAGAACTTTTGTGTGTCAAGTTACC
TCCGTCATATTTTATTTCACAATGTATATCAGTATTTCATTCCTGGGACTGATAACTATC
GATCGCTACCAGAAGACCACCAGGCCATTTAAAACATCCAACCCCAAAAATCTCTTGGGG
GCTAAGATTCTCTCTGTTGTCATCTGGGCATTCATGTTCTTACTCTCTTTGCCTAACATG
ATTCTGACCAACAGGCAGCCGAGAGACAAGAATGTGAAGAAATGCTCTTTCCTTAAATCA
GAGTTCGGTCTAGTCTGGCATGAAATAGTAAATTACATCTGTCAAGTCATTTTCTGGATT
AATTTCTTAATTGTTATTGTATGTTATACACTCATTACAAAAGAACTGTACCGGTCATAC
GTAAGAACGAGGGGTGTAGGTAAAGTCCCCAGGAAAAAGGTGAACGTCAAAGTTTTCATT
ATCATTGCTGTATTCTTTATTTGTTTTGTTCCTTTCCATTTTGCCCGAATTCCTTACACC
CTGAGCCAAACCCGGGATGTCTTTGACTGCACTGCTGAAAATACTCTGTTCTATGTGAAA
GAGAGCACTCTGTGGTTAACTTCCTTAAATGCATGCCTGGATCCGTTCATCTATTTTTTC
CTTTGCAAGTCCTTCAGAAATTCCTTGATAAGTATGCTGAAGTGCCCCAATTCTGCAACA
TCTCTGTCCCAGGACAATAGGAAAAAAGAACAGGATGGTGGTGACCCAAATGAAGAGACT
CCAATGTAA
Chromosome Location
3
Locus
3q24-q25
External Identifiers
ResourceLink
UniProtKB IDQ9H244
UniProtKB Entry NameP2Y12_HUMAN
GenBank Protein ID12083902
GenBank Gene IDAF313449
GenAtlas IDP2RY12
HGNC IDHGNC:18124
General References
  1. Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB: Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature. 2001 Jan 11;409(6817):202-7. [PubMed:11196645]
  2. Zhang FL, Luo L, Gustafson E, Lachowicz J, Smith M, Qiao X, Liu YH, Chen G, Pramanik B, Laz TM, Palmer K, Bayne M, Monsma FJ Jr: ADP is the cognate ligand for the orphan G protein-coupled receptor SP1999. J Biol Chem. 2001 Mar 16;276(11):8608-15. Epub 2000 Dec 4. [PubMed:11104774]
  3. Takasaki J, Kamohara M, Saito T, Matsumoto M, Matsumoto S, Ohishi T, Soga T, Matsushime H, Furuichi K: Molecular cloning of the platelet P2T(AC) ADP receptor: pharmacological comparison with another ADP receptor, the P2Y(1) receptor. Mol Pharmacol. 2001 Sep;60(3):432-9. [PubMed:11502873]
  4. Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S: Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett. 2002 Jun 5;520(1-3):97-101. [PubMed:12044878]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  6. Zhang K, Zhang J, Gao ZG, Zhang D, Zhu L, Han GW, Moss SM, Paoletta S, Kiselev E, Lu W, Fenalti G, Zhang W, Muller CE, Yang H, Jiang H, Cherezov V, Katritch V, Jacobson KA, Stevens RC, Wu B, Zhao Q: Structure of the human P2Y12 receptor in complex with an antithrombotic drug. Nature. 2014 May 1;509(7498):115-8. doi: 10.1038/nature13083. Epub 2014 Mar 23. [PubMed:24670650]
  7. Zhang J, Zhang K, Gao ZG, Paoletta S, Zhang D, Han GW, Li T, Ma L, Zhang W, Muller CE, Yang H, Jiang H, Cherezov V, Katritch V, Jacobson KA, Stevens RC, Wu B, Zhao Q: Agonist-bound structure of the human P2Y12 receptor. Nature. 2014 May 1;509(7498):119-22. doi: 10.1038/nature13288. [PubMed:24784220]
  8. Cattaneo M, Zighetti ML, Lombardi R, Martinez C, Lecchi A, Conley PB, Ware J, Ruggeri ZM: 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 Feb 18;100(4):1978-83. Epub 2003 Feb 10. [PubMed:12578987]
  9. Lecchi A, Razzari C, Paoletta S, Dupuis A, Nakamura L, Ohlmann P, Gachet C, Jacobson KA, Zieger B, Cattaneo M: Identification of a new dysfunctional platelet P2Y12 receptor variant associated with bleeding diathesis. Blood. 2015 Feb 5;125(6):1006-13. doi: 10.1182/blood-2013-07-517896. Epub 2014 Nov 26. [PubMed:25428217]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00208TiclopidineapprovedyesantagonistDetails
DB00758ClopidogrelapprovedyesantagonistDetails
DB01240EpoprostenolapprovedyesagonistDetails
DB00374Treprostinilapproved, investigationalyesagonistDetails
DB06209PrasugrelapprovedyesantagonistDetails
DB06350ElinogrelinvestigationalunknownDetails
DB06441CangrelorapprovedyesinhibitorDetails
DB08816TicagrelorapprovedyesinhibitorDetails
DB05553RegrelorinvestigationalunknownantagonistDetails
DB01069Promethazineapproved, investigationalunknowninhibitorDetails