P2RY4

Pyrimidinergic receptor P2Y, G-protein coupled, 4

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2B6Q

Identifiers

Symbols

P2RY4 ; NRU; P2P; P2Y4; UNR

External IDs

OMIM: 300038 MGI: 1926594 HomoloGene: 20568 IUPHAR: 325 ChEMBL: 2123 GeneCards: P2RY4 Gene

Gene ontology
Molecular function	• ATP binding • uridine nucleotide receptor activity • G-protein coupled purinergic nucleotide receptor activity • UTP-activated nucleotide receptor activity
Cellular component	• cytosol • plasma membrane • integral component of plasma membrane • basolateral plasma membrane • apical plasma membrane
Biological process	• phospholipase C-activating G-protein coupled receptor signaling pathway • positive regulation of cytosolic calcium ion concentration • transepithelial chloride transport • G-protein coupled purinergic nucleotide receptor signaling pathway • cellular response to prostaglandin E stimulus
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr X:
70.26 – 70.26 Mb

Chr X:
100.59 – 100.59 Mb

PubMed search

P2Y purinoceptor 4 is a protein that in humans is encoded by the P2RY4 gene.^[1]^[2]

The product of this gene, P2Y₄, belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is responsive to uridine nucleotides, partially responsive to ATP, and not responsive to ADP.^[2]

References

↑ Communi D, Pirotton S, Parmentier M, Boeynaems JM (Feb 1996). "Cloning and functional expression of a human uridine nucleotide receptor". J Biol Chem 270 (52): 30849–52. doi:10.1074/jbc.270.52.30849. PMID 8537336.
1 2 "Entrez Gene: P2RY4 pyrimidinergic receptor P2Y, G-protein coupled, 4".

External links

"P2Y Receptors: P2Y₄". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

Nguyen T, Erb L, Weisman GA, et al. (1996). "Cloning, expression, and chromosomal localization of the human uridine nucleotide receptor gene.". J. Biol. Chem. 270 (52): 30845–8. doi:10.1074/jbc.270.52.30845. PMID 8537335.
Stam NJ, Klomp J, Van de Heuvel N, Olijve W (1996). "Molecular cloning and characterization of a novel orphan receptor (P2P) expressed in human pancreas that shows high structural homology to the P2U purinoceptor.". FEBS Lett. 384 (3): 260–4. doi:10.1016/0014-5793(96)00321-3. PMID 8617367.
Nicholas RA, Watt WC, Lazarowski ER, et al. (1996). "Uridine nucleotide selectivity of three phospholipase C-activating P2 receptors: identification of a UDP-selective, a UTP-selective, and an ATP- and UTP-specific receptor.". Mol. Pharmacol. 50 (2): 224–9. PMID 8700127.
Maier R, Glatz A, Mosbacher J, Bilbe G (1997). "Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y receptor subtype expression in bone and brain tissues.". Biochem. Biophys. Res. Commun. 237 (2): 297–302. doi:10.1006/bbrc.1997.7135. PMID 9268704.
Jin J, Dasari VR, Sistare FD, Kunapuli SP (1998). "Distribution of P2Y receptor subtypes on haematopoietic cells.". Br. J. Pharmacol. 123 (5): 789–94. doi:10.1038/sj.bjp.0701665. PMC 1565225. PMID 9535005.
Brinson AE, Harden TK (2001). "Differential regulation of the uridine nucleotide-activated P2Y4 and P2Y6 receptors. SER-333 and SER-334 in the carboxyl terminus are involved in agonist-dependent phosphorylation desensitization and internalization of the P2Y4 receptor.". J. Biol. Chem. 276 (15): 11939–48. doi:10.1074/jbc.M009909200. PMID 11114308.
Suarez-Huerta N, Pouillon V, Boeynaems J, Robaye B (2001). "Molecular cloning and characterization of the mouse P2Y4 nucleotide receptor.". Eur. J. Pharmacol. 416 (3): 197–202. doi:10.1016/S0014-2999(01)00875-5. PMID 11290369.
Moore DJ, Chambers JK, Wahlin JP, et al. (2001). "Expression pattern of human P2Y receptor subtypes: a quantitative reverse transcription-polymerase chain reaction study.". Biochim. Biophys. Acta 1521 (1-3): 107–19. doi:10.1016/S0167-4781(01)00291-3. PMID 11690642.
Idzko M, Dichmann S, Ferrari D, et al. (2002). "Nucleotides induce chemotaxis and actin polymerization in immature but not mature human dendritic cells via activation of pertussis toxin-sensitive P2y receptors.". Blood 100 (3): 925–32. doi:10.1182/blood.V100.3.925. PMID 12130504.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Burrell HE, Bowler WB, Gallagher JA, Sharpe GR (2003). "Human keratinocytes express multiple P2Y-receptors: evidence for functional P2Y1, P2Y2, and P2Y4 receptors.". J. Invest. Dermatol. 120 (3): 440–7. doi:10.1046/j.1523-1747.2003.12050.x. PMID 12603858.
Kim SG, Soltysiak KA, Gao ZG, et al. (2003). "Tumor necrosis factor alpha-induced apoptosis in astrocytes is prevented by the activation of P2Y6, but not P2Y4 nucleotide receptors.". Biochem. Pharmacol. 65 (6): 923–31. doi:10.1016/S0006-2952(02)01614-3. PMC 3402349. PMID 12623123.
Herold CL, Qi AD, Harden TK, Nicholas RA (2004). "Agonist versus antagonist action of ATP at the P2Y4 receptor is determined by the second extracellular loop.". J. Biol. Chem. 279 (12): 11456–64. doi:10.1074/jbc.M301734200. PMC 1821344. PMID 14670966.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Cavaliere F, Nestola V, Amadio S, et al. (2005). "The metabotropic P2Y4 receptor participates in the commitment to differentiation and cell death of human neuroblastoma SH-SY5Y cells.". Neurobiol. Dis. 18 (1): 100–9. doi:10.1016/j.nbd.2004.09.001. PMID 15649700.
Ross MT, Grafham DV, Coffey AJ, et al. (2005). "The DNA sequence of the human X chromosome.". Nature 434 (7031): 325–37. doi:10.1038/nature03440. PMC 2665286. PMID 15772651.

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

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Adhesion	ADGRG (1 2 3 4 5 6 7)

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

Purinergics

Receptor
(ligands)

P0
(adenine)

Agonists: 8-Aminoadenine
Adenine

P1
(adenosine)

Agonists: 2-(1-Hexynyl)-N-methyladenosine
2-Cl-IB-MECA
2'-MeCCPA
4'-O-β-D-Glucosyl-9-O-(6''-deoxysaccharosyl)olivil
5'-N-ethylcarboxamidoadenosine
Adenosine
ADP
AMP
Apadenoson
ATL-146e
ATP
BAY 60–6583
Binodenoson
Capadenoson
CCPA
CGS-21680
CP-532,903
Evodenoson
GR 79236
LUF-5835
LUF-5845
N⁶-Cyclopentyladenosine
Neladenoson dalanate
Piclidenoson
Regadenoson
SDZ WAG 994
Selodenoson
Sonedenoson
Tecadenoson
UK-432,097

P2
(nucleotide)

P2X (ATP)	Agonists: 2-Me-SATP α,β-Me-ATP Adenosine ADP AMP Ap4A Ap5A ATP ATPγS BzATP Cibacron blue CTP D-β,γ-Me-ATP GTP HT-AMP Ivermectin L-β,γ-Me-ATP MRS-2219 PAPET-ATP UTP Zinc Antagonists: 5-BDBD A-317491 A-438079 A-740003 A-804598 A-839977 AF-353 AZ-10606120 AZ-11645373 BBG Calcium Calmidazolium Chelerythrine Copper Emodin (Rheum officinale) Evans Blue GW-791343 HMA Ip5I isoPPADS JNJ-47965567 KN-04 KN-62 Magnesium MRS-2159 NF-023 NF-110 NF-157 NF-279 NF-449 Oxidized-ATP Phenol Red Phenolphthalein PPADS PPNDS PSB-12062 Puerarin (Radix puerariae) Purotoxin 1 RB-2 Ro 0437626 Ro 51 RO-3 Sodium ferulate (Angelica sinensis, Ligusticum wallichii) Suramin TC-P 262 Tetramethylpyrazine (ligustrazine) (Ligusticum wallichii) TNP-ATP Zinc

P2Y	Agonists: 2-Me-SADP 2-Me-SATP 2-Thio-UTP 5-Br-UDP 5-OMe-UDP α,β-Me-ATP Adenosine ADP ADPβS Ap3A AR-C 67085MX ATP ATPγS CTP dATP Denufosol Diquafosol IDP ITP INS-365 INS-37217 MRS-2365 MRS-2690 MRS-2693 MRS-2768 MRS-2957 MRS-4062 NF-546 PAPET-ATP PSB-0474 PSB-1114 UDP UDPβS UDP-galactose UDP-glucose UDP-N-acetylglucosamine Up3U UTP UTPγS Antagonists: 2-Me-SAMP A3P5PS AMPαS Ap4A AR-C 66096 AR-C 67085MX AR-C 69931MX AR-C 118925XX ATP BzATP C1330-7 Cangrelor Clopidrogel Elinogrel Ip5I MRS-2179 MRS-2211 MRS-2279 MRS-2395 MRS-2500 MRS-2578 NF-157 NF-340 PIT PPADS Prasugrel PSB-0739 RB-2 Regrelor Suramin Ticagrelor Ticlopidine UDP

Transporter
(blockers)

CNTs	6-Hydroxy-7-methoxyflavone Adenosine dMeThPmR Estradiol KGO-2142 KGO-2173 MeThPmR Phloridzin Progesterone

ENTs	Barbiturates Benzodiazepines Cilostazol Dilazep Dipyridamole Estradiol Ethanol Hexobendine NBMPR Pentoxifylline Progesterone Propentofylline

PMAT	Decynium-22

Enzyme
(inhibitors)

XO	Allopurinol Amflutizole Benzbromarone Caffeic acid Cinnamaldehyde Cinnamomum osmophloeum Febuxostat Myo-inositol Kaempferol Myricetin Niraxostat Oxypurinol Phytic acid Pistacia integerrima Propolis Quercetin Tisopurine Topiroxostat

Others	Aminopterin Azathioprine Methotrexate Mycophenolic acid Pemetrexed Pralatrexate Many others

Others

Others: Chrysophanol (rhubarb)

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P2RY4

See also

References

External links

Further reading