Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRGFOI7)

DOT Name Serine/threonine-protein phosphatase 2A activator (PTPA)
Synonyms
EC 5.2.1.8; PP2A, subunit B', PR53 isoform; Phosphotyrosyl phosphatase activator; PTPA; Serine/threonine-protein phosphatase 2A regulatory subunit 4; Serine/threonine-protein phosphatase 2A regulatory subunit B'
Gene Name PTPA
Related Disease
Autoimmune disease ( )
Bipolar disorder ( )
Ovarian cancer ( )
Pancreatic cancer ( )
Adult glioblastoma ( )
Adult T-cell leukemia/lymphoma ( )
Alzheimer disease ( )
Amyotrophic lateral sclerosis ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Cardiac failure ( )
Cardiovascular disease ( )
Cervical carcinoma ( )
Chronic obstructive pulmonary disease ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Gastric neoplasm ( )
Head-neck squamous cell carcinoma ( )
Hereditary diffuse gastric adenocarcinoma ( )
High blood pressure ( )
Hypersomnia ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Medulloblastoma ( )
Multiple sclerosis ( )
Neuroblastoma ( )
Non-insulin dependent diabetes ( )
Osteosarcoma ( )
Parkinson disease ( )
Prostate cancer ( )
Prostate carcinoma ( )
Small lymphocytic lymphoma ( )
Tauopathy ( )
Carcinoma ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
leukaemia ( )
Stomach cancer ( )
Melanoma ( )
Acute monocytic leukemia ( )
Acute myelogenous leukaemia ( )
Asthma ( )
Colon cancer ( )
Colon carcinoma ( )
Endometrial cancer ( )
Systemic lupus erythematosus ( )
UniProt ID
PTPA_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
2G62; 2HV6; 2HV7; 2IXM; 4LAC; 4NY3
EC Number
5.2.1.8
Pfam ID
PF03095
Sequence
MAEGERQPPPDSSEEAPPATQNFIIPKKEIHTVPDMGKWKRSQAYADYIGFILTLNEGVK
GKKLTFEYRVSEMWNEVHEEKEQAAKQSVSCDECIPLPRAGHCAPSEAIEKLVALLNTLD
RWIDETPPVDQPSRFGNKAYRTWYAKLDEEAENLVATVVPTHLAAAVPEVAVYLKESVGN
STRIDYGTGHEAAFAAFLCCLCKIGVLRVDDQIAIVFKVFNRYLEVMRKLQKTYRMEPAG
SQGVWGLDDFQFLPFIWGSSQLIDHPYLEPRHFVDEKAVNENHKDYMFLECILFITEMKT
GPFAEHSNQLWNISAVPSWSKVNQGLIRMYKAECLEKFPVIQHFKFGSLLPIHPVTSG
Function
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Acts as a regulatory subunit for serine/threonine-protein phosphatase 2A (PP2A) modulating its activity or substrate specificity, probably by inducing a conformational change in the catalytic subunit, a proposed direct target of the PPIase. Can reactivate inactive phosphatase PP2A-phosphatase methylesterase complexes (PP2A(i)) in presence of ATP and Mg(2+). Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is involved in apoptosis; the function appears to be independent from PP2A.
Tissue Specificity Widely expressed.
KEGG Pathway
Insulin resistance (hsa04931 )
Diabetic cardiomyopathy (hsa05415 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autoimmune disease DISORMTM Definitive Biomarker [1]
Bipolar disorder DISAM7J2 Definitive Altered Expression [2]
Ovarian cancer DISZJHAP Definitive Biomarker [3]
Pancreatic cancer DISJC981 Definitive Biomarker [4]
Adult glioblastoma DISVP4LU Strong Altered Expression [5]
Adult T-cell leukemia/lymphoma DIS882XU Strong Biomarker [6]
Alzheimer disease DISF8S70 Strong Altered Expression [7]
Amyotrophic lateral sclerosis DISF7HVM Strong Biomarker [8]
Bone osteosarcoma DIST1004 Strong Biomarker [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Breast carcinoma DIS2UE88 Strong Biomarker [10]
Cardiac failure DISDC067 Strong Altered Expression [11]
Cardiovascular disease DIS2IQDX Strong Biomarker [12]
Cervical carcinoma DIST4S00 Strong Altered Expression [13]
Chronic obstructive pulmonary disease DISQCIRF Strong Altered Expression [14]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [15]
Congestive heart failure DIS32MEA Strong Altered Expression [11]
Gastric neoplasm DISOKN4Y Strong Biomarker [16]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [17]
Hereditary diffuse gastric adenocarcinoma DISUIBYS Strong Biomarker [16]
High blood pressure DISY2OHH Strong Altered Expression [18]
Hypersomnia DISKYOM6 Strong Genetic Variation [19]
Lung adenocarcinoma DISD51WR Strong Biomarker [20]
Lung cancer DISCM4YA Strong Biomarker [21]
Lung carcinoma DISTR26C Strong Biomarker [21]
Medulloblastoma DISZD2ZL Strong Altered Expression [22]
Multiple sclerosis DISB2WZI Strong Biomarker [23]
Neuroblastoma DISVZBI4 Strong Altered Expression [24]
Non-insulin dependent diabetes DISK1O5Z Strong Biomarker [25]
Osteosarcoma DISLQ7E2 Strong Biomarker [9]
Parkinson disease DISQVHKL Strong Biomarker [26]
Prostate cancer DISF190Y Strong Biomarker [27]
Prostate carcinoma DISMJPLE Strong Biomarker [27]
Small lymphocytic lymphoma DIS30POX Strong Posttranslational Modification [28]
Tauopathy DISY2IPA Strong Biomarker [29]
Carcinoma DISH9F1N moderate Biomarker [30]
Gastric cancer DISXGOUK moderate Altered Expression [31]
Glioblastoma multiforme DISK8246 moderate Biomarker [32]
leukaemia DISS7D1V moderate Biomarker [33]
Stomach cancer DISKIJSX moderate Altered Expression [31]
Melanoma DIS1RRCY Disputed Altered Expression [34]
Acute monocytic leukemia DIS28NEL Limited Genetic Variation [35]
Acute myelogenous leukaemia DISCSPTN Limited Altered Expression [36]
Asthma DISW9QNS Limited Biomarker [37]
Colon cancer DISVC52G Limited Biomarker [38]
Colon carcinoma DISJYKUO Limited Biomarker [38]
Endometrial cancer DISW0LMR Limited Genetic Variation [39]
Systemic lupus erythematosus DISI1SZ7 Limited Biomarker [1]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [40]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [41]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [42]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [43]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [44]
Selenium DM25CGV Approved Selenium increases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [45]
Azacitidine DMTA5OE Approved Azacitidine increases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [46]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [45]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [47]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [48]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Serine/threonine-protein phosphatase 2A activator (PTPA). [49]
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⏷ Show the Full List of 11 Drug(s)

References

1 Phosphatase PP2A is essential for T(H)17 differentiation.Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):982-987. doi: 10.1073/pnas.1807484116. Epub 2018 Dec 28.
2 NNMT Silencing Activates Tumor Suppressor PP2A, Inactivates Oncogenic STKs, and Inhibits Tumor Forming Ability.Clin Cancer Res. 2017 May 1;23(9):2325-2334. doi: 10.1158/1078-0432.CCR-16-1323. Epub 2016 Nov 3.
3 Mouse model for probing tumor suppressor activity of protein phosphatase 2A in diverse signaling pathways.Cell Cycle. 2012 Feb 1;11(3):451-9. doi: 10.4161/cc.11.3.19057. Epub 2012 Feb 1.
4 PR55 Subunit of Protein Phosphatase 2A Supports the Tumorigenic and Metastatic Potential of Pancreatic Cancer Cells by Sustaining Hyperactive Oncogenic Signaling.Cancer Res. 2016 Apr 15;76(8):2243-2253. doi: 10.1158/0008-5472.CAN-15-2119. Epub 2016 Feb 18.
5 Downregulation of protein phosphatase 2A by apolipoprotein E: Implications for Alzheimer's disease.Mol Cell Neurosci. 2017 Sep;83:83-91. doi: 10.1016/j.mcn.2017.07.002. Epub 2017 Jul 15.
6 Novel PRMT5-mediated arginine methylations of HSP90A are essential for maintenance of HSP90A function in NDRG2(low) ATL and various cancer cells.Biochim Biophys Acta Mol Cell Res. 2020 Feb;1867(2):118615. doi: 10.1016/j.bbamcr.2019.118615. Epub 2019 Nov 22.
7 Crocin-protected malathion-induced spatial memory deficits by inhibiting TAU protein hyperphosphorylation and antiapoptotic effects.Nutr Neurosci. 2020 Mar;23(3):221-236. doi: 10.1080/1028415X.2018.1492772. Epub 2019 Feb 21.
8 Alzheimer disease and amyotrophic lateral sclerosis: an etiopathogenic connection.Acta Neuropathol. 2014 Feb;127(2):243-56. doi: 10.1007/s00401-013-1175-9. Epub 2013 Oct 18.
9 MicroRNA-221 promotes cisplatin resistance in osteosarcoma cells by targeting PPP2R2A.Biosci Rep. 2019 Jul 10;39(7):BSR20190198. doi: 10.1042/BSR20190198. Print 2019 Jul 31.
10 Dephosphorylation of Girdin by PP2A inhibits breast cancer metastasis.Biochem Biophys Res Commun. 2019 May 21;513(1):28-34. doi: 10.1016/j.bbrc.2019.03.167. Epub 2019 Mar 29.
11 PR65A phosphorylation regulates PP2A complex signaling.PLoS One. 2014 Jan 21;9(1):e85000. doi: 10.1371/journal.pone.0085000. eCollection 2014.
12 A Review of Cardiovascular Toxicity of Microcystins.Toxins (Basel). 2019 Aug 30;11(9):507. doi: 10.3390/toxins11090507.
13 PP2A Inhibits Cervical Cancer Cell Migration by Dephosphorylation of p-JNK, p-p38 and the p-ERK/MAPK Signaling Pathway.Curr Med Sci. 2018 Feb;38(1):115-123. doi: 10.1007/s11596-018-1854-9. Epub 2018 Mar 15.
14 Protein Phosphatase 2A Reduces Cigarette Smoke-induced Cathepsin S and Loss of Lung Function.Am J Respir Crit Care Med. 2019 Jul 1;200(1):51-62. doi: 10.1164/rccm.201808-1518OC.
15 Analysis of Potential Alterations Affecting SETBP1 as a Novel Contributing Mechanism to Inhibit PP2A in Colorectal Cancer Patients.World J Surg. 2018 Nov;42(11):3771-3778. doi: 10.1007/s00268-018-4684-9.
16 A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
17 SET protein accumulation prevents cell death in head and neck squamous cell carcinoma through regulation of redox state and autophagy.Biochim Biophys Acta Mol Cell Res. 2019 Apr;1866(4):623-637. doi: 10.1016/j.bbamcr.2019.01.005. Epub 2019 Jan 16.
18 The regulatory role of dopamine receptor D1 on PP2A via SUMO-1 modification.Eur Rev Med Pharmacol Sci. 2017 Jul;21(14):3270-3276.
19 A variant at 9q34.11 is associated with HLA-DQB1*06:02negative essential hypersomnia.J Hum Genet. 2018 Dec;63(12):1259-1267. doi: 10.1038/s10038-018-0518-8. Epub 2018 Sep 28.
20 Direct activation of PP2A for the treatment of tyrosine kinase inhibitor-resistant lung adenocarcinoma.JCI Insight. 2019 Feb 21;4(4):e125693. doi: 10.1172/jci.insight.125693. eCollection 2019 Feb 21.
21 Metformin Inhibit Lung Cancer Cell Growth and Invasion in Vitro as Well as Tumor Formation in Vivo Partially by Activating PP2A.Med Sci Monit. 2019 Jan 29;25:836-846. doi: 10.12659/MSM.912059.
22 p53 Function Is Compromised by Inhibitor 2 of Phosphatase 2A in Sonic Hedgehog Medulloblastoma.Mol Cancer Res. 2019 Jan;17(1):186-198. doi: 10.1158/1541-7786.MCR-18-0485. Epub 2018 Sep 17.
23 Synthesis and Biological Evaluation of FTY720 (Fingolimod) Derivatives with Aromatic Head Group as Anticancer Agents.Chem Pharm Bull (Tokyo). 2018;66(10):1015-1018. doi: 10.1248/cpb.c18-00065.
24 Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell Survival and Tumor Growth.Transl Oncol. 2019 Jan;12(1):84-95. doi: 10.1016/j.tranon.2018.09.011. Epub 2018 Oct 1.
25 Antitumor effects of metformin via indirect inhibition of protein phosphatase 2A in patients with endometrial cancer.PLoS One. 2018 Feb 14;13(2):e0192759. doi: 10.1371/journal.pone.0192759. eCollection 2018.
26 PINK1 suppresses alpha-synuclein-induced neuronal injury: a novel mechanism in protein phosphatase 2A activation.Oncotarget. 2017 Oct 6;9(1):37-53. doi: 10.18632/oncotarget.21554. eCollection 2018 Jan 2.
27 PPP2R2A prostate cancer haploinsufficiency is associated with worse prognosis and a high vulnerability to B55/PP2A reconstitution that triggers centrosome destabilization.Oncogenesis. 2019 Dec 10;8(12):72. doi: 10.1038/s41389-019-0180-9.
28 Mitochondrial apoptosis is induced by Alkoxy phenyl-1-propanone derivatives through PP2A-mediated dephosphorylation of Bad and Foxo3A in CLL.Leukemia. 2019 May;33(5):1148-1160. doi: 10.1038/s41375-018-0288-5. Epub 2018 Oct 23.
29 Memantine mediates astrocytic activity in response to excitotoxicity induced by PP2A inhibition.Neurosci Lett. 2019 Mar 23;696:179-183. doi: 10.1016/j.neulet.2018.12.034. Epub 2018 Dec 23.
30 Protein Phosphatase 2A: More Than a Passenger in the Regulation of Epithelial Cell-Cell Junctions.Front Cell Dev Biol. 2019 Mar 6;7:30. doi: 10.3389/fcell.2019.00030. eCollection 2019.
31 CDK5 suppresses the metastasis of gastric cancer cells by interacting with and regulating PP2A.Oncol Rep. 2019 Feb;41(2):779-788. doi: 10.3892/or.2018.6860. Epub 2018 Nov 9.
32 Cucurbitacin B induces inhibitory effects via CIP2A/PP2A/Akt pathway in glioblastoma multiforme.Mol Carcinog. 2018 Jun;57(6):687-699. doi: 10.1002/mc.22789. Epub 2018 Feb 26.
33 TOPK is regulated by PP2A and BCR/ABL in leukemia and enhances cell proliferation.Int J Oncol. 2019 May;54(5):1785-1796. doi: 10.3892/ijo.2019.4740. Epub 2019 Mar 5.
34 67-kDa laminin receptor-dependent protein phosphatase 2A (PP2A) activation elicits melanoma-specific antitumor activity overcoming drug resistance.J Biol Chem. 2014 Nov 21;289(47):32671-81. doi: 10.1074/jbc.M114.604983. Epub 2014 Oct 7.
35 Novel B55-PP2A mutations in AML promote AKT T308 phosphorylation and sensitivity to AKT inhibitor-induced growth arrest.Oncotarget. 2016 Sep 20;7(38):61081-61092. doi: 10.18632/oncotarget.11209.
36 A novel FTY720 analogue targets SET-PP2A interaction and inhibits growth of acute myeloid leukemia cells without inducing cardiac toxicity.Cancer Lett. 2020 Jan 1;468:1-13. doi: 10.1016/j.canlet.2019.10.007. Epub 2019 Oct 5.
37 MID1-PP2A complex functions as new insights in human lung adenocarcinoma.J Cancer Res Clin Oncol. 2018 May;144(5):855-864. doi: 10.1007/s00432-018-2601-0. Epub 2018 Feb 15.
38 G9a governs colon cancer stem cell phenotype and chemoradioresistance through PP2A-RPA axis-mediated DNA damage response.Radiother Oncol. 2017 Sep;124(3):395-402. doi: 10.1016/j.radonc.2017.03.002. Epub 2017 Mar 25.
39 Precision Therapy for Aggressive Endometrial Cancer by Reactivation of Protein Phosphatase 2A.Cancer Res. 2019 Aug 15;79(16):4009-4010. doi: 10.1158/0008-5472.CAN-19-1938.
40 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
41 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.
42 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
43 Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
44 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
45 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
46 The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
47 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.
48 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.
49 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.