Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLBR20R)

DOT Name P2X purinoceptor 5 (P2RX5)
Synonyms P2X5; ATP receptor; Purinergic receptor
Gene Name P2RX5
Related Disease
Autosomal recessive polycystic kidney disease ( )
Mood disorder ( )
Pulmonary disease ( )
Alzheimer disease ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Bone osteosarcoma ( )
Brain neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Bronchopulmonary dysplasia ( )
Cardiac failure ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Depression ( )
Graft-versus-host disease ( )
Head-neck squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
Inflammatory bowel disease ( )
leukaemia ( )
Leukemia ( )
Lung cancer ( )
Lung carcinoma ( )
Major depressive disorder ( )
Multiple sclerosis ( )
Narcolepsy ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Parkinson disease ( )
Prostate cancer ( )
Prostate carcinoma ( )
Rheumatoid arthritis ( )
Schizophrenia ( )
Systemic lupus erythematosus ( )
Acute myelogenous leukaemia ( )
Carcinoma ( )
Chronic obstructive pulmonary disease ( )
Colon cancer ( )
Colon carcinoma ( )
Type-1/2 diabetes ( )
Adenocarcinoma ( )
Bipolar disorder ( )
Neuralgia ( )
Neuroblastoma ( )
UniProt ID
P2RX5_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00864
Sequence
MGQAGCKGLCLSLFDYKTEKYVIAKNKKVGLLYRLLQASILAYLVVWVFLIKKGYQDVDT
SLQSAVITKVKGVAFTNTSDLGQRIWDVADYVIPAQGENVFFVVTNLIVTPNQRQNVCAE
NEGIPDGACSKDSDCHAGEAVTAGNGVKTGRCLRRENLARGTCEIFAWCPLETSSRPEEP
FLKEAEDFTIFIKNHIRFPKFNFSKSNVMDVKDRSFLKSCHFGPKNHYCPIFRLGSVIRW
AGSDFQDIALEGGVIGINIEWNCDLDKAASECHPHYSFSRLDNKLSKSVSSGYNFRFARY
YRDAAGVEFRTLMKAYGIRFDVMVNGKGAFFCDLVLIYLIKKREFYRDKKYEEVRGLEDS
SQEAEDEASGLGLSEQLTSGPGLLGMPEQQELQEPPEAKRGSSSQKGNGSVCPQLLEPHR
ST
Function Receptor for ATP that acts as a ligand-gated ion channel.
Tissue Specificity Expressed at high levels in brain and immune system.
KEGG Pathway
Calcium sig.ling pathway (hsa04020 )
Neuroactive ligand-receptor interaction (hsa04080 )
Reactome Pathway
Platelet homeostasis (R-HSA-418346 )
Elevation of cytosolic Ca2+ levels (R-HSA-139853 )

Molecular Interaction Atlas (MIA) of This DOT

47 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]
Pulmonary disease DIS6060I Definitive Biomarker [3]
Alzheimer disease DISF8S70 Strong Genetic Variation [4]
Arteriosclerosis DISK5QGC Strong Biomarker [5]
Atherosclerosis DISMN9J3 Strong Biomarker [5]
Bone osteosarcoma DIST1004 Strong Biomarker [6]
Brain neoplasm DISY3EKS Strong Biomarker [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Biomarker [8]
Breast neoplasm DISNGJLM Strong Biomarker [9]
Bronchopulmonary dysplasia DISO0BY5 Strong Biomarker [10]
Cardiac failure DISDC067 Strong Altered Expression [11]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [12]
Congestive heart failure DIS32MEA Strong Altered Expression [11]
Depression DIS3XJ69 Strong Genetic Variation [10]
Graft-versus-host disease DIS0QADF Strong Biomarker [13]
Head-neck squamous cell carcinoma DISF7P24 Strong Altered Expression [14]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [15]
Inflammatory bowel disease DISGN23E Strong Biomarker [16]
leukaemia DISS7D1V Strong Altered Expression [17]
Leukemia DISNAKFL Strong Altered Expression [17]
Lung cancer DISCM4YA Strong Genetic Variation [18]
Lung carcinoma DISTR26C Strong Genetic Variation [18]
Major depressive disorder DIS4CL3X Strong Biomarker [10]
Multiple sclerosis DISB2WZI Strong Altered Expression [19]
Narcolepsy DISLCNLI Strong Genetic Variation [20]
Neoplasm DISZKGEW Strong Altered Expression [21]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [22]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [23]
Osteosarcoma DISLQ7E2 Strong Biomarker [6]
Parkinson disease DISQVHKL Strong Altered Expression [24]
Prostate cancer DISF190Y Strong Altered Expression [21]
Prostate carcinoma DISMJPLE Strong Altered Expression [21]
Rheumatoid arthritis DISTSB4J Strong Biomarker [25]
Schizophrenia DISSRV2N Strong Genetic Variation [26]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [25]
Acute myelogenous leukaemia DISCSPTN moderate Biomarker [13]
Carcinoma DISH9F1N moderate Biomarker [27]
Chronic obstructive pulmonary disease DISQCIRF moderate Biomarker [28]
Colon cancer DISVC52G moderate Biomarker [29]
Colon carcinoma DISJYKUO moderate Biomarker [29]
Type-1/2 diabetes DISIUHAP Disputed Biomarker [30]
Adenocarcinoma DIS3IHTY Limited Biomarker [31]
Bipolar disorder DISAM7J2 Limited Biomarker [32]
Neuralgia DISWO58J Limited Biomarker [33]
Neuroblastoma DISVZBI4 Limited Altered Expression [34]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
1 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 5 (P2RX5). [35]
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14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of P2X purinoceptor 5 (P2RX5). [36]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of P2X purinoceptor 5 (P2RX5). [37]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of P2X purinoceptor 5 (P2RX5). [38]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of P2X purinoceptor 5 (P2RX5). [39]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of P2X purinoceptor 5 (P2RX5). [40]
Estradiol DMUNTE3 Approved Estradiol increases the expression of P2X purinoceptor 5 (P2RX5). [41]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of P2X purinoceptor 5 (P2RX5). [42]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of P2X purinoceptor 5 (P2RX5). [43]
Tamibarotene DM3G74J Phase 3 Tamibarotene increases the expression of P2X purinoceptor 5 (P2RX5). [44]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of P2X purinoceptor 5 (P2RX5). [45]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of P2X purinoceptor 5 (P2RX5). [46]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of P2X purinoceptor 5 (P2RX5). [47]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of P2X purinoceptor 5 (P2RX5). [42]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of P2X purinoceptor 5 (P2RX5). [48]
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⏷ Show the Full List of 14 Drug(s)

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 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.
4 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.
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 MicroRNA-381 suppresses the proliferation of osteosarcoma cells through LRH-1/Wnt/-catenin signaling pathway.Oncol Rep. 2018 Feb;39(2):589-596. doi: 10.3892/or.2017.6129. Epub 2017 Dec 4.
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 LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21.Cancer Manag Res. 2018 Aug 1;10:2389-2400. doi: 10.2147/CMAR.S162887. eCollection 2018.
9 LRH-1 controls proliferation in breast tumor cells by regulating CDKN1A gene expression.Oncogene. 2015 Aug 20;34(34):4509-18. doi: 10.1038/onc.2014.382. Epub 2014 Dec 1.
10 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.
11 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.
12 Downregulation of microRNA-30d promotes cell proliferation and invasion by targeting LRH-1 in colorectal carcinoma.Int J Mol Med. 2017 Jun;39(6):1371-1380. doi: 10.3892/ijmm.2017.2958. Epub 2017 Apr 20.
13 Myeloid leukemic progenitor cells can be specifically targeted by minor histocompatibility antigen LRH-1-reactive cytotoxic T cells.Blood. 2009 Mar 5;113(10):2312-23. doi: 10.1182/blood-2008-04-153825. Epub 2008 Dec 12.
14 P2X7 receptor and NLRP3 inflammasome activation in head and neck cancer.Oncotarget. 2017 Jul 25;8(30):48972-48982. doi: 10.18632/oncotarget.16903.
15 Regulation of liver receptor homologue-1 by DDB2 E3 ligase activity is critical for hepatic glucose metabolism.Sci Rep. 2019 Mar 28;9(1):5304. doi: 10.1038/s41598-019-41411-x.
16 LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease.Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13098-103. doi: 10.1073/pnas.0702440104. Epub 2007 Aug 1.
17 Efficient activation of LRH-1-specific CD8+ T-cell responses from transplanted leukemia patients by stimulation with P2X5 mRNA-electroporated dendritic cells.J Immunother. 2009 Jul-Aug;32(6):539-51. doi: 10.1097/CJI.0b013e3181987c22.
18 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.
19 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.
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 Nuclear Receptor LRH-1 Functions to Promote Castration-Resistant Growth of Prostate Cancer via Its Promotion of Intratumoral Androgen Biosynthesis.Cancer Res. 2018 May 1;78(9):2205-2218. doi: 10.1158/0008-5472.CAN-17-2341. Epub 2018 Feb 8.
22 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.
23 MicroRNA-381 serves as a prognostic factor and inhibits migration and invasion in non-small cell lung cancer by targeting LRH-1.Oncol Rep. 2017 Nov;38(5):3071-3077. doi: 10.3892/or.2017.5956. Epub 2017 Sep 14.
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 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.
26 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.
27 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.
28 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.
29 Liver receptor homologue 1, a novel prognostic marker in colon cancer patients.Oncol Lett. 2018 Sep;16(3):2833-2838. doi: 10.3892/ol.2018.8988. Epub 2018 Jun 18.
30 LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus.Nat Commun. 2018 Apr 16;9(1):1488. doi: 10.1038/s41467-018-03943-0.
31 Nuclear receptor liver receptor homologue 1 (LRH-1) regulates pancreatic cancer cell growth and proliferation.Proc Natl Acad Sci U S A. 2011 Oct 11;108(41):16927-31. doi: 10.1073/pnas.1112047108. Epub 2011 Sep 26.
32 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.
33 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.
34 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.
35 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.
36 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
37 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
38 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
39 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
40 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
41 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
42 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
43 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
44 Induction of class II major histocompatibility complex expression in human multiple myeloma cells by retinoid. Haematologica. 2007 Jan;92(1):115-20.
45 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
46 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
47 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
48 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.