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P2Y11 receptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 327

Nomenclature: P2Y11 receptor

Family: P2Y receptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 374 19p13.2 P2RY11 purinergic receptor P2Y11 4
Previous and Unofficial Names Click here for help
purinergic receptor P2Y, G-protein coupled, 11
Database Links Click here for help
Specialist databases
GPCRDB p2y11_human (Hs)
Other databases
ChEMBL Target CHEMBL4867 (Hs)
Ensembl Gene ENSG00000244165 (Hs)
Entrez Gene 5032 (Hs)
Human Protein Atlas ENSG00000244165 (Hs)
KEGG Gene hsa:5032 (Hs)
OMIM 602697 (Hs)
Orphanet ORPHA371321 (Hs)
Pharos Q96G91 (Hs)
RefSeq Nucleotide NM_002566 (Hs)
RefSeq Protein NP_002557 (Hs)
UniProtKB Q96G91 (Hs)
Wikipedia P2RY11 (Hs)
Natural/Endogenous Ligands Click here for help
ATP
uridine triphosphate
Potency order of endogenous ligands (Human)
ATP>ADP

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AR-C67085 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 8.5 pEC50 2,6
⤷ pEC50 8.5 [2,6]
NF546 Small molecule or natural product Hs Full agonist 6.3 pEC50 14
⤷ pEC50 6.3 [14]
ATPγS Small molecule or natural product Click here for species-specific activity table Hs Full agonist 4.9 – 5.5 pEC50 6
⤷ pEC50 4.9 – 5.5 [6]
uridine triphosphate Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 5.2 pEC50 22
⤷ pEC50 5.2 [22]
BzATP Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.0 – 5.1 pEC50 6
⤷ pEC50 5.0 – 5.1 [6]
dATP Small molecule or natural product Ligand has a PDB structure Hs Full agonist 4.8 – 5.0 pEC50 6
⤷ pEC50 4.8 – 5.0 [6]
ATP Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 4.2 – 5.6 pEC50 6,10,22
⤷ pEC50 4.2 – 5.6 [6,10,22]
ADPβS Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 3.8 – 4.5 pEC50 6
⤷ pEC50 3.8 – 4.5 [6]
2MeSATP Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 3.7 – 4.3 pEC50 6
⤷ pEC50 3.7 – 4.3 [6]
NAADP Small molecule or natural product Click here for species-specific activity table Hs Full agonist - - 16
⤷ [16]
NAD Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist - - 17
⤷ [17]
Agonist Comments
Reference [6] EC50 values are found using cAMP and/or IP3 functional assays.
Reference [22] EC50 values are found using Ca2+ functional assays.
In 1321N1 cells transfected with the human P2Y11, β-NAD+ and NAAD+ increase intracellular production of IP3 and cyclic AMP followed by elevation of Ca2+ in a concentration range of 1-100 μM [16-17]. Two new iso-lantherans have been isolated from a marine Australian sponge and represent a promising new structural type for the development of P2Y11 receptor agonists [8].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
NF157 Small molecule or natural product Hs Antagonist 7.3 pKi 20
⤷ pKi 7.3 [20]
NF340 Small molecule or natural product Hs Antagonist 7.3 – 7.7 pEC50 25
⤷ pEC50 7.3 – 7.7 [25]
NF340 Small molecule or natural product Hs Antagonist 6.4 – 7.1 pIC50 14
⤷ pIC50 6.4 – 7.1 [14]
suramin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.8 – 6.0 pIC50 6
⤷ pIC50 4.8 – 6.0 [6]
reactive blue-2 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.0 pIC50 6
⤷ pIC50 5.0 [6]
Antagonist Comments
Reference [6] IC50 values are found using IP3 and/or cAMP functional assays.
Immunopharmacology Comments
The P2Y11 receptor has been identified as a molecular target for the development of anti-inflammatory/immunosuppressive therapeutics [9]. P2Y11 stimulation induces an anti-inflammatory effect in human dendritic cells [3].
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References:  18
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
References:  6,18
Tissue Distribution Click here for help
Platelets
Species:  Human
Technique:  RT-PCR
References:  16
Brain: Parahippocampal gyrus, putamen, nucleus accumbens, striatum > caudate nucleus, cingulate gyrus, cerebellum, amygdala > globus pallidus, hippocampus, hypothalamus, superior frontal gyrus, thalamus > locus coeruleus, medulla oblongata, substantia nigra > medial frontal gyrus > spinal cord.
Species:  Human
Technique:  RT-PCR.
References:  15
Brain > pituitary > lymphocytes > spleen > intestine, macrophages > lung, stomach, adipose, pancreas > kidney, skeletal muscle, prostate, heart, placenta > foetal liver > liver, bone, cartilage.
Species:  Human
Technique:  RT-PCR.
References:  15
Functional Assays Click here for help
Measurement of IP levels in CHO cells transfected with the human P2Y11 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  IP accumulation.
References:  18
Measurement of cAMP levels in CHO cells transfected with the human P2Y11 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  cAMP accumulation.
References:  6
Measurement of IP3 levels in 1321N1 cells transfected with the P2Y11 receptor.
Species:  Human
Tissue:  1321N1 cells.
Response measured:  IP3 accumulation.
References:  6,18
Measurement of cAMP levels in 1321N1 cells transfected with the human P2Y11 receptor.
The effect of Ca2+ chelation by BAPTA and downregulation of PKC by the phorbol ester PMA on cAMP levels were tested.
The effect of PKC activation by PMA was tested.
Species:  Human
Tissue:  1321N1 cells.
Response measured:  cAMP accumulation in response to agonist.
Both BAPTA and downregulation of PKC by PMA decreased this cAMP accumulation.
PKC activation caused cAMP accumulation.
References:  18
Measurement of cAMP levels in CHO cells transfected with the human P2Y11 receptor.
The effect of Ca2+ chelation by BAPTA and downregulation of PKC by the phorbol ester PMA on cAMP levels were tested.
The effect of PKC activation by PMA was tested.
Species:  Human
Tissue:  CHO cells.
Response measured:  cAMP accumulation in response to agonist.
BAPTA had no effect on cAMP levels, while downregulation of PKC by PMA decreased cAMP accumulation.
PKC activation caused cAMP accumulation.
References:  18
Physiological Functions Click here for help
Role in maturation and migration of dendritic cells.
Species:  Human
Tissue:  Dendritic cells.
References:  13,19,23
Cell differentiation.
Species:  Human
Tissue:  Granulocytes.
References:  5
Role in platelet release of nitric oxide
Species:  Human
Tissue:  platelet
References:  12
Role in the inhibition of neutrophil apoptosis induced by ATP
Species:  Human
Tissue:  neutrophil
References:  21
Role in the positive ionotropic effects of ATP
Species:  Mouse
Tissue:  cardiomyocytes
References:  2
Role in chemotaxis of granulocytes
Species:  Human
Tissue:  granulocytes
References:  16-17
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Narcolepsy-cataplexy
Synonyms: Cataplexy and narcolepsy [Disease Ontology: DOID:9199]
Disease Ontology: DOID:9199
Orphanet: ORPHA2073
References:  11
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  According to NCBI's Single Nucleotide Polymorphism database, the P2RY11 gene contains some different single nucleotide polymorphisms, three of which are in the coding region. One of the coding region polymorphisms, (rs3745601), causes an alanine to threonine amino acid shift in residue 87 (Ala-87-Thr), near the extracellular end of transmembrane region II of the P2Y11 receptor. The Ala-87-Thr polymorphism of the P2Y11 receptor was found to be associated with acute myocardial infarction and increased level of C-reactive protein
Amino acid change:  A87T
SNP accession:  rs3745601
References:  1
Type:  Splice variants
Species:  Human
Description:  A chimeric receptor generated by the intergenic splicing between the P2Y11 receptor gene and the adjacent SSR1 gene has been identified in various human tissues.
When expressed in CHO-K1 cells this chimer appeared to have an unaltered cAMP response to ATP when compared to the wild-type P2Y11 receptor.
References:  7
General Comments
A human P2Y11 receptor homology model with two templates, bovine-rhodopsin and hP2Y1-ATP complex model, has been computed. Computational modelling and mutational analysis have shed light on the structure and ligand binding site of the receptor [24]. Although no mouse and rat orthologs have been cloned, the existence of the murine P2Y11 receptor is supported by functional data obtained in mouse cardiomyocytes (see Tissue Function table, [2]).

References

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1. Amisten S, Melander O, Wihlborg AK, Berglund G, Erlinge D. (2007) Increased risk of acute myocardial infarction and elevated levels of C-reactive protein in carriers of the Thr-87 variant of the ATP receptor P2Y11. Eur Heart J, 28 (1): 13-8. [PMID:17135283]

2. Balogh J, Wihlborg AK, Isackson H, Joshi BV, Jacobson KA, Arner A, Erlinge D. (2005) Phospholipase C and cAMP-dependent positive inotropic effects of ATP in mouse cardiomyocytes via P2Y11-like receptors. J Mol Cell Cardiol, 39 (2): 223-30. [PMID:15893764]

3. Chadet S, Ivanes F, Benoist L, Salmon-Gandonnière C, Guibon R, Velge-Roussel F, Babuty D, Baron C, Roger S, Angoulvant D. (2015) Hypoxia/Reoxygenation Inhibits P2Y11 Receptor Expression and Its Immunosuppressive Activity in Human Dendritic Cells. J Immunol, 195 (2): 651-60. [PMID:26078273]

4. Communi D, Govaerts C, Parmentier M, Boeynaems JM. (1997) Cloning of a human purinergic P2Y receptor coupled to phospholipase C and adenylyl cyclase. J Biol Chem, 272 (51): 31969-73. [PMID:9405388]

5. Communi D, Janssens R, Robaye B, Zeelis N, Boeynaems JM. (2000) Rapid up-regulation of P2Y messengers during granulocytic differentiation of HL-60 cells. FEBS Lett, 475 (1): 39-42. [PMID:10854854]

6. Communi D, Robaye B, Boeynaems JM. (1999) Pharmacological characterization of the human P2Y11 receptor. Br J Pharmacol, 128 (6): 1199-206. [PMID:10578132]

7. Communi D, Suarez-Huerta N, Dussossoy D, Savi P, Boeynaems JM. (2001) Cotranscription and intergenic splicing of human P2Y11 and SSF1 genes. J Biol Chem, 276 (19): 16561-6. [PMID:11278528]

8. Greve H, Meis S, Kassack MU, Kehraus S, Krick A, Wright AD, König GM. (2007) New iantherans from the marine sponge Ianthella quadrangulata: novel agonists of the P2Y(11) receptor. J Med Chem, 50 (23): 5600-7. [PMID:17941622]

9. Gruenbacher G, Gander H, Dobler G, Rahm A, Klaver D, Thurnher M. (2021) The human G protein-coupled ATP receptor P2Y11 is a target for anti-inflammatory strategies. Br J Pharmacol, 178 (7): 1541-1555. [PMID:33463722]

10. Jacobson KA, Jarvis MF, Williams M. (2002) Purine and pyrimidine (P2) receptors as drug targets. J Med Chem, 45 (19): 4057-93. [PMID:12213051]

11. Kornum BR, Kawashima M, Faraco J, Lin L, Rico TJ, Hesselson S, Axtell RC, Kuipers H, Weiner K, Hamacher A et al.. (2011) Common variants in P2RY11 are associated with narcolepsy. Nat Genet, 43 (1): 66-71. [PMID:21170044]

12. Magnone M, Basile G, Bruzzese D, Guida L, Signorello MG, Chothi MP, Bruzzone S, Millo E, Qi AD, Nicholas RA et al.. (2008) Adenylic dinucleotides produced by CD38 are negative endogenous modulators of platelet aggregation. J Biol Chem, 283 (36): 24460-8. [PMID:18606819]

13. Marteau F, Gonzalez NS, Communi D, Goldman M, Boeynaems JM, Communi D. (2005) Thrombospondin-1 and indoleamine 2,3-dioxygenase are major targets of extracellular ATP in human dendritic cells. Blood, 106 (12): 3860-6. [PMID:16118322]

14. Meis S, Hamacher A, Hongwiset D, Marzian C, Wiese M, Eckstein N, Royer HD, Communi D, Boeynaems JM, Hausmann R et al.. (2010) NF546 [4,4'-(carbonylbis(imino-3,1-phenylene-carbonylimino-3,1-(4-methyl-phenylene)-carbonylimino))-bis(1,3-xylene-alpha,alpha'-diphosphonic acid) tetrasodium salt] is a non-nucleotide P2Y11 agonist and stimulates release of interleukin-8 from human monocyte-derived dendritic cells. J Pharmacol Exp Ther, 332 (1): 238-47. [PMID:19815812]

15. Moore DJ, Chambers JK, Wahlin JP, Tan KB, Moore GB, Jenkins O, Emson PC, Murdock PR. (2001) Expression pattern of human P2Y receptor subtypes: a quantitative reverse transcription-polymerase chain reaction study. Biochim Biophys Acta, 1521 (1-3): 107-19. [PMID:11690642]

16. Moreschi I, Bruzzone S, Bodrato N, Usai C, Guida L, Nicholas RA, Kassack MU, Zocchi E, De Flora A. (2008) NAADP+ is an agonist of the human P2Y11 purinergic receptor. Cell Calcium, 43 (4): 344-55. [PMID:17707504]

17. Moreschi I, Bruzzone S, Nicholas RA, Fruscione F, Sturla L, Benvenuto F, Usai C, Meis S, Kassack MU, Zocchi E et al.. (2006) Extracellular NAD+ is an agonist of the human P2Y11 purinergic receptor in human granulocytes. J Biol Chem, 281 (42): 31419-29. [PMID:16926152]

18. Qi AD, Kennedy C, Harden TK, Nicholas RA. (2001) Differential coupling of the human P2Y(11) receptor to phospholipase C and adenylyl cyclase. Br J Pharmacol, 132 (1): 318-26. [PMID:11156592]

19. Schnurr M, Toy T, Stoitzner P, Cameron P, Shin A, Beecroft T, Davis ID, Cebon J, Maraskovsky E. (2003) ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y11 receptor signaling. Blood, 102 (2): 613-20. [PMID:12649135]

20. Ullmann H, Meis S, Hongwiset D, Marzian C, Wiese M, Nickel P, Communi D, Boeynaems JM, Wolf C, Hausmann R et al.. (2005) Synthesis and structure-activity relationships of suramin-derived P2Y11 receptor antagonists with nanomolar potency. J Med Chem, 48 (22): 7040-8. [PMID:16250663]

21. Vaughan KR, Stokes L, Prince LR, Marriott HM, Meis S, Kassack MU, Bingle CD, Sabroe I, Surprenant A, Whyte MK. (2007) Inhibition of neutrophil apoptosis by ATP is mediated by the P2Y11 receptor. J Immunol, 179 (12): 8544-53. [PMID:18056402]

22. White PJ, Webb TE, Boarder MR. (2003) Characterization of a Ca2+ response to both UTP and ATP at human P2Y11 receptors: evidence for agonist-specific signaling. Mol Pharmacol, 63 (6): 1356-63. [PMID:12761346]

23. Wilkin F, Duhant X, Bruyns C, Suarez-Huerta N, Boeynaems JM, Robaye B. (2001) The P2Y11 receptor mediates the ATP-induced maturation of human monocyte-derived dendritic cells. J Immunol, 166 (12): 7172-7. [PMID:11390464]

24. Zylberg J, Ecke D, Fischer B, Reiser G. (2007) Structure and ligand-binding site characteristics of the human P2Y11 nucleotide receptor deduced from computational modelling and mutational analysis. Biochem J, 405 (2): 277-86. [PMID:17338680]

25. (2006) Invited Lectures : Overviews Purinergic signalling: past, present and future. Purinergic Signal, 2 (1): 1-324. [PMID:18404494]

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