Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0LF34A)

DOT Name P2X purinoceptor 2 (P2RX2)
Synonyms P2X2; ATP receptor; Purinergic receptor
Gene Name P2RX2
Related Disease
Autosomal recessive polycystic kidney disease ( )
Mood disorder ( )
Alzheimer disease ( )
Arrhythmia ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Autosomal dominant nonsyndromic hearing loss 41 ( )
Brain neoplasm ( )
Bronchopulmonary dysplasia ( )
Carcinoma ( )
Cardiac failure ( )
Congestive heart failure ( )
Cystic fibrosis ( )
Dengue ( )
Depression ( )
Epilepsy ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Head-neck squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
Hyperglycemia ( )
Influenza ( )
Lung cancer ( )
Lung carcinoma ( )
Major depressive disorder ( )
Multiple sclerosis ( )
Myeloid leukaemia ( )
Narcolepsy ( )
Neoplasm ( )
Neuralgia ( )
Non-insulin dependent diabetes ( )
Parkinson disease ( )
Pulmonary fibrosis ( )
Pulmonary tuberculosis ( )
Rheumatoid arthritis ( )
Schizophrenia ( )
Status epilepticus seizure ( )
Systemic lupus erythematosus ( )
Vascular disease ( )
Acute graft versus host disease ( )
Chronic obstructive pulmonary disease ( )
Nonsyndromic genetic hearing loss ( )
Autosomal dominant nonsyndromic hearing loss ( )
Pulmonary disease ( )
Advanced cancer ( )
Amyotrophic lateral sclerosis ( )
Bipolar disorder ( )
Hepatitis ( )
Intellectual disability ( )
Neuroblastoma ( )
Periodontitis ( )
UniProt ID
P2RX2_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00864
Sequence
MAAAQPKYPAGATARRLARGCWSALWDYETPKVIVVRNRRLGVLYRAVQLLILLYFVWYV
FIVQKSYQESETGPESSIITKVKGITTSEHKVWDVEEYVKPPEGGSVFSIITRVEATHSQ
TQGTCPESIRVHNATCLSDADCVAGELDMLGNGLRTGRCVPYYQGPSKTCEVFGWCPVED
GASVSQFLGTMAPNFTILIKNSIHYPKFHFSKGNIADRTDGYLKRCTFHEASDLYCPIFK
LGFIVEKAGESFTELAHKGGVIGVIINWDCDLDLPASECNPKYSFRRLDPKHVPASSGYN
FRFAKYYKINGTTTRTLIKAYGIRIDVIVHGQAGKFSLIPTIINLATALTSVGVGSFLCD
WILLTFMNKNKVYSHKKFDKVCTPSHPSGSWPVTLARVLGQAPPEPGHRSEDQHPSPPSG
QEGQQGAECGPAFPPLRPCPISAPSEQMVDTPASEPAQASTPTDPKGLAQL
Function
Ion channel gated by extracellular ATP involved in a variety of cellular responses, such as excitatory postsynaptic responses in sensory neurons, neuromuscular junctions (NMJ) formation, hearing, perception of taste and peristalsis. In the inner ear, regulates sound transduction and auditory neurotransmission, outer hair cell electromotility, inner ear gap junctions, and K(+) recycling. Mediates synaptic transmission between neurons and from neurons to smooth muscle.
KEGG Pathway
Calcium sig.ling pathway (hsa04020 )
Neuroactive ligand-receptor interaction (hsa04080 )
Taste transduction (hsa04742 )
Reactome Pathway
Platelet homeostasis (R-HSA-418346 )
Elevation of cytosolic Ca2+ levels (R-HSA-139853 )

Molecular Interaction Atlas (MIA) of This DOT

51 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal recessive polycystic kidney disease DISPUS40 Definitive Altered Expression [1]
Mood disorder DISLVMWO Definitive Genetic Variation [2]
Alzheimer disease DISF8S70 Strong Genetic Variation [3]
Arrhythmia DISFF2NI Strong Altered Expression [4]
Arteriosclerosis DISK5QGC Strong Biomarker [5]
Atherosclerosis DISMN9J3 Strong Biomarker [5]
Autosomal dominant nonsyndromic hearing loss 41 DIS6YOSV Strong Autosomal dominant [6]
Brain neoplasm DISY3EKS Strong Biomarker [7]
Bronchopulmonary dysplasia DISO0BY5 Strong Biomarker [8]
Carcinoma DISH9F1N Strong Biomarker [9]
Cardiac failure DISDC067 Strong Altered Expression [4]
Congestive heart failure DIS32MEA Strong Altered Expression [4]
Cystic fibrosis DIS2OK1Q Strong Altered Expression [10]
Dengue DISKH221 Strong Biomarker [11]
Depression DIS3XJ69 Strong Genetic Variation [8]
Epilepsy DISBB28L Strong Biomarker [12]
Head and neck cancer DISBPSQZ Strong Altered Expression [13]
Head and neck carcinoma DISOU1DS Strong Altered Expression [13]
Head-neck squamous cell carcinoma DISF7P24 Strong Altered Expression [13]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [14]
Hyperglycemia DIS0BZB5 Strong Biomarker [15]
Influenza DIS3PNU3 Strong Biomarker [16]
Lung cancer DISCM4YA Strong Genetic Variation [17]
Lung carcinoma DISTR26C Strong Genetic Variation [17]
Major depressive disorder DIS4CL3X Strong Biomarker [8]
Multiple sclerosis DISB2WZI Strong Altered Expression [18]
Myeloid leukaemia DISMN944 Strong Biomarker [19]
Narcolepsy DISLCNLI Strong Genetic Variation [20]
Neoplasm DISZKGEW Strong Biomarker [21]
Neuralgia DISWO58J Strong Biomarker [22]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [23]
Parkinson disease DISQVHKL Strong Altered Expression [24]
Pulmonary fibrosis DISQKVLA Strong Biomarker [25]
Pulmonary tuberculosis DIS6FLUM Strong Biomarker [26]
Rheumatoid arthritis DISTSB4J Strong Biomarker [27]
Schizophrenia DISSRV2N Strong Genetic Variation [28]
Status epilepticus seizure DISY3BIC Strong Biomarker [29]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [27]
Vascular disease DISVS67S Strong Biomarker [30]
Acute graft versus host disease DIS8KLVM moderate Altered Expression [31]
Chronic obstructive pulmonary disease DISQCIRF moderate Biomarker [32]
Nonsyndromic genetic hearing loss DISZX61P Moderate Autosomal dominant [33]
Autosomal dominant nonsyndromic hearing loss DISYC1G0 Supportive Autosomal dominant [6]
Pulmonary disease DIS6060I Disputed Biomarker [25]
Advanced cancer DISAT1Z9 Limited Altered Expression [34]
Amyotrophic lateral sclerosis DISF7HVM Limited Biomarker [35]
Bipolar disorder DISAM7J2 Limited Biomarker [36]
Hepatitis DISXXX35 Limited Biomarker [37]
Intellectual disability DISMBNXP Limited Biomarker [38]
Neuroblastoma DISVZBI4 Limited Altered Expression [39]
Periodontitis DISI9JOI Limited Biomarker [40]
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⏷ Show the Full List of 51 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of P2X purinoceptor 2 (P2RX2). [41]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of P2X purinoceptor 2 (P2RX2). [44]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of P2X purinoceptor 2 (P2RX2). [42]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of P2X purinoceptor 2 (P2RX2). [43]
QUERCITRIN DM1DH96 Investigative QUERCITRIN increases the expression of P2X purinoceptor 2 (P2RX2). [45]
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References

1 Characterization of purinergic receptor expression in ARPKD cystic epithelia.Purinergic Signal. 2018 Dec;14(4):485-497. doi: 10.1007/s11302-018-9632-5. Epub 2018 Nov 11.
2 The P2RX7 polymorphism rs2230912 is associated with depression: A meta-analysis.Prog Neuropsychopharmacol Biol Psychiatry. 2018 Mar 2;82:272-277. doi: 10.1016/j.pnpbp.2017.11.003. Epub 2017 Nov 7.
3 Theobromine-Induced Changes in A1 Purinergic Receptor Gene Expression and Distribution in a Rat Brain Alzheimer's Disease Model.J Alzheimers Dis. 2017;55(3):1273-1283. doi: 10.3233/JAD-160569.
4 Loss of function mutation in the P2X7, a ligand-gated ion channel gene associated with hypertrophic cardiomyopathy.Purinergic Signal. 2019 Jun;15(2):205-210. doi: 10.1007/s11302-019-09660-7. Epub 2019 May 31.
5 Deletion of P2Y2 receptor reveals a role for lymphotoxin- in fatty streak formation.Vascul Pharmacol. 2016 Oct;85:11-20. doi: 10.1016/j.vph.2016.06.001. Epub 2016 Jun 26.
6 Mutation of the ATP-gated P2X(2) receptor leads to progressive hearing loss and increased susceptibility to noise. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2228-33. doi: 10.1073/pnas.1222285110. Epub 2013 Jan 23.
7 Roles of purinergic P2X(7) receptor in glioma and microglia in brain tumors.Cancer Lett. 2017 Aug 28;402:93-99. doi: 10.1016/j.canlet.2017.05.004. Epub 2017 May 20.
8 Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms.J Affect Disord. 2013 Aug 15;150(1):104-9. doi: 10.1016/j.jad.2013.02.033. Epub 2013 Apr 18.
9 Role of purinergic receptors in hepatobiliary carcinoma in Pakistani population: an approach towards proinflammatory role of P2X4 and P2X7 receptors.Purinergic Signal. 2019 Sep;15(3):367-374. doi: 10.1007/s11302-019-09675-0. Epub 2019 Aug 10.
10 Extracellular zinc and ATP restore chloride secretion across cystic fibrosis airway epithelia by triggering calcium entry.J Biol Chem. 2004 Mar 12;279(11):10720-9. doi: 10.1074/jbc.M313391200. Epub 2003 Dec 29.
11 The purinergic receptor P2X7 role in control of Dengue virus-2 infection and cytokine/chemokine production in infected human monocytes.Immunobiology. 2016 Jul;221(7):794-802. doi: 10.1016/j.imbio.2016.02.003. Epub 2016 Feb 27.
12 P2X2 and P2X4 receptor expression is regulated by a GABA(A) receptor-mediated mechanism in the gerbil hippocampus.Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):168-75. doi: 10.1016/s0169-328x(03)00260-2.
13 P2X7 receptor and NLRP3 inflammasome activation in head and neck cancer.Oncotarget. 2017 Jul 25;8(30):48972-48982. doi: 10.18632/oncotarget.16903.
14 P2X3 purinergic receptor overexpression is associated with poor recurrence-free survival in hepatocellular carcinoma patients.Oncotarget. 2015 Dec 1;6(38):41162-79. doi: 10.18632/oncotarget.6240.
15 A G(s)-coupled purinergic receptor boosts Ca(2+) influx and vascular contractility during diabetic hyperglycemia.Elife. 2019 Mar 1;8:e42214. doi: 10.7554/eLife.42214.
16 Contribution of the Purinergic Receptor P2X7 to Development of Lung Immunopathology during Influenza Virus Infection.mBio. 2017 Mar 28;8(2):e00229-17. doi: 10.1128/mBio.00229-17.
17 Correlation of P2RX7 gene rs1718125 polymorphism with postoperative fentanyl analgesia in patients with lung cancer.Medicine (Baltimore). 2019 Feb;98(7):e14445. doi: 10.1097/MD.0000000000014445.
18 The role of vitamin D and P2X7R in multiple sclerosis.J Neuroimmunol. 2019 May 15;330:159-169. doi: 10.1016/j.jneuroim.2019.03.004. Epub 2019 Mar 14.
19 Chronic treatment with P2-purinergic receptor agonists induces phenotypic modulation of the HL-60 and U937 human myelogenous leukemia cell lines.J Leukoc Biol. 1991 Aug;50(2):109-22. doi: 10.1002/jlb.50.2.109.
20 Genetic association, seasonal infections and autoimmune basis of narcolepsy.J Autoimmun. 2013 Jun;43:26-31. doi: 10.1016/j.jaut.2013.02.003. Epub 2013 Mar 13.
21 Extracellular vesicles in cancer immune responses: roles of purinergic receptors.Semin Immunopathol. 2018 Sep;40(5):465-475. doi: 10.1007/s00281-018-0706-9. Epub 2018 Sep 12.
22 P2Y(12) deficiency in mouse impairs noradrenergic system in brain, and alters anxiety-like neurobehavior and memory.Genes Brain Behav. 2019 Feb;18(2):e12458. doi: 10.1111/gbb.12458. Epub 2018 Feb 9.
23 Type 2 diabetes specifically attenuates purinergic skin vasodilatation without affecting muscarinic and nicotinic skin vasodilatation and sweating.Exp Physiol. 2018 Feb 1;103(2):212-221. doi: 10.1113/EP086694. Epub 2018 Jan 10.
24 Purinergic Signalling in Parkinson's Disease: A Multi-target System to Combat Neurodegeneration.Neurochem Res. 2019 Oct;44(10):2413-2422. doi: 10.1007/s11064-019-02798-1. Epub 2019 May 4.
25 The purinergic receptor subtype P2Y2 mediates chemotaxis of neutrophils and fibroblasts in fibrotic lung disease.Oncotarget. 2017 May 30;8(22):35962-35972. doi: 10.18632/oncotarget.16414.
26 Expression and function of the purinergic receptor P2X7 in patients with pulmonary tuberculosis.Clin Exp Immunol. 2006 Nov;146(2):253-61. doi: 10.1111/j.1365-2249.2006.03213.x.
27 Expression and function of the P2X(7) purinergic receptor in patients with systemic lupus erythematosus and rheumatoid arthritis.Hum Immunol. 2010 Aug;71(8):818-25. doi: 10.1016/j.humimm.2010.05.008. Epub 2010 May 20.
28 Variation in the purinergic P2RX(7) receptor gene and schizophrenia.Schizophr Res. 2008 Sep;104(1-3):146-52. doi: 10.1016/j.schres.2008.05.026. Epub 2008 Jul 9.
29 P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy.Cell Death Dis. 2018 May 1;9(5):546. doi: 10.1038/s41419-018-0586-x.
30 P2X7R mutation disrupts the NLRP3-mediated Th program and predicts poor cardiac allograft outcomes.J Clin Invest. 2018 Aug 1;128(8):3490-3503. doi: 10.1172/JCI94524. Epub 2018 Jul 16.
31 A Novel Function for P2Y2 in Myeloid Recipient-Derived Cells during Graft-versus-Host Disease.J Immunol. 2015 Dec 15;195(12):5795-804. doi: 10.4049/jimmunol.1501357. Epub 2015 Nov 4.
32 NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD.Eur Respir J. 2016 Jan;47(1):254-63. doi: 10.1183/13993003.02144-2014. Epub 2015 Nov 5.
33 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
34 Involvement of the P2X7 purinergic receptor in inflammation: an update of antagonists series since 2009 and their promising therapeutic potential.Curr Med Chem. 2015;22(6):713-29. doi: 10.2174/0929867322666141212120926.
35 Strong P2X4 purinergic receptor-like immunoreactivity is selectively associated with degenerating neurons in transgenic rodent models of amyotrophic lateral sclerosis.J Comp Neurol. 2008 Jan 1;506(1):75-92. doi: 10.1002/cne.21527.
36 Association between depression and the Gln460Arg polymorphism of P2RX7 gene: a dimensional approach.Am J Med Genet B Neuropsychiatr Genet. 2009 Mar 5;150B(2):295-9. doi: 10.1002/ajmg.b.30799.
37 Potentiation of hepatic stellate cell activation by extracellular ATP is dependent on P2X7R-mediated NLRP3 inflammasome activation.Pharmacol Res. 2017 Mar;117:82-93. doi: 10.1016/j.phrs.2016.11.040. Epub 2016 Dec 8.
38 12q24.33 deletion: report of a patient with intellectual disability and review of the literature.Am J Med Genet A. 2013 Jun;161A(6):1409-13. doi: 10.1002/ajmg.a.35877. Epub 2013 Apr 23.
39 The purinergic receptor P2X7 triggers alpha-secretase-dependent processing of the amyloid precursor protein.J Biol Chem. 2011 Jan 28;286(4):2596-606. doi: 10.1074/jbc.M110.200618. Epub 2010 Nov 16.
40 The purinergic receptor P2X5 contributes to bone loss in experimental periodontitis.BMB Rep. 2018 Sep;51(9):468-473. doi: 10.5483/BMBRep.2018.51.9.126.
41 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
42 Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
43 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
44 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
45 Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.