Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL8PP6V)

DOT Name	Testin (TES)
Synonyms	TESS
Gene Name	TES
Related Disease	Adult glioblastoma ( ) Allergic asthma ( ) B-cell lymphoma ( ) Depression ( ) Endometrial cancer ( ) Endometrial carcinoma ( ) Glioblastoma multiforme ( ) leukaemia ( ) Leukemia ( ) Lung cancer ( ) Lung carcinoma ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Prostate cancer ( ) Prostate carcinoma ( ) Prostate neoplasm ( ) Psoriasis ( ) Seasonal allergic rhinitis ( ) Cardiovascular disease ( ) Gastric cancer ( ) Melanoma ( ) Stomach cancer ( ) Acute lymphocytic leukaemia ( ) Advanced cancer ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Breast cancer ( ) Breast carcinoma ( ) Childhood kidney Wilms tumor ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) Ductal breast carcinoma in situ ( ) Epithelial ovarian cancer ( ) Invasive ductal breast carcinoma ( ) Leiomyoma ( ) Nasopharyngeal carcinoma ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Pneumocystis pneumonia ( ) Uterine fibroids ( ) Wilms tumor ( )
UniProt ID	TES_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2IYB; 2XQN
Pfam ID	PF00412 ; PF06297
Sequence	MDLENKVKKMGLGHEQGFGAPCLKCKEKCEGFELHFWRKICRNCKCGQEEHDVLLSNEED RKVGKLFEDTKYTTLIAKLKSDGIPMYKRNVMILTNPVAAKKNVSINTVTYEWAPPVQNQ ALARQYMQMLPKEKQPVAGSEGAQYRKKQLAKQLPAHDQDPSKCHELSPREVKEMEQFVK KYKSEALGVGDVKLPCEMDAQGPKQMNIPGGDRSTPAAVGAMEDKSAEHKRTQYSCYCCK LSMKEGDPAIYAERAGYDKLWHPACFVCSTCHELLVDMIYFWKNEKLYCGRHYCDSEKPR CAGCDELIFSNEYTQAENQNWHLKHFCCFDCDSILAGEIYVMVNDKPVCKPCYVKNHAVV CQGCHNAIDPEVQRVTYNNFSWHASTECFLCSCCSKCLIGQKFMPVEGMVFCSVECKKRM S
Function	Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. Plays a role in the regulation of cell proliferation. May act as a tumor suppressor. Inhibits tumor cell growth.
Tissue Specificity	Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adult glioblastoma	DISVP4LU	Definitive	Biomarker	[1]
Allergic asthma	DISHF0H3	Strong	Biomarker	[2]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[3]
Depression	DIS3XJ69	Strong	Genetic Variation	[4]
Endometrial cancer	DISW0LMR	Strong	Posttranslational Modification	[5]
Endometrial carcinoma	DISXR5CY	Strong	Posttranslational Modification	[5]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
leukaemia	DISS7D1V	Strong	Biomarker	[6]
Leukemia	DISNAKFL	Strong	Biomarker	[6]
Lung cancer	DISCM4YA	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Biomarker	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[7]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[9]
Prostate carcinoma	DISMJPLE	Strong	Genetic Variation	[9]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[10]
Psoriasis	DIS59VMN	Strong	Biomarker	[11]
Seasonal allergic rhinitis	DIS58KQX	Strong	Biomarker	[2]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[12]
Gastric cancer	DISXGOUK	moderate	Biomarker	[8]
Melanoma	DIS1RRCY	moderate	Biomarker	[13]
Stomach cancer	DISKIJSX	moderate	Biomarker	[8]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Altered Expression	[14]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[7]
Arteriosclerosis	DISK5QGC	Limited	Biomarker	[15]
Atherosclerosis	DISMN9J3	Limited	Biomarker	[15]
Breast cancer	DIS7DPX1	Limited	Biomarker	[16]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[16]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Biomarker	[17]
Coronary atherosclerosis	DISKNDYU	Limited	Biomarker	[15]
Coronary heart disease	DIS5OIP1	Limited	Altered Expression	[15]
Ductal breast carcinoma in situ	DISLCJY7	Limited	Altered Expression	[18]
Epithelial ovarian cancer	DIS56MH2	Limited	Posttranslational Modification	[19]
Invasive ductal breast carcinoma	DIS43J58	Limited	Altered Expression	[18]
Leiomyoma	DISLDDFN	Limited	Altered Expression	[20]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[21]
Ovarian cancer	DISZJHAP	Limited	Posttranslational Modification	[19]
Ovarian neoplasm	DISEAFTY	Limited	Posttranslational Modification	[19]
Pneumocystis pneumonia	DISFSOM3	Limited	Biomarker	[22]
Uterine fibroids	DISBZRMJ	Limited	Altered Expression	[20]
Wilms tumor	DISB6T16	Limited	Biomarker	[17]
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Molecular Interaction Atlas (MIA)

MIA Detail

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 decreases the methylation of Testin (TES).	[23]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Testin (TES).	[40]
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22 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Testin (TES).	[24]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Testin (TES).	[25]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Testin (TES).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Testin (TES).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Testin (TES).	[28]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Testin (TES).	[29]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Testin (TES).	[30]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Testin (TES).	[31]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Testin (TES).	[32]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Testin (TES).	[33]
Marinol	DM70IK5	Approved	Marinol increases the expression of Testin (TES).	[34]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Testin (TES).	[32]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Testin (TES).	[35]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Testin (TES).	[36]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Testin (TES).	[32]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Testin (TES).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Testin (TES).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Testin (TES).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Testin (TES).	[41]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Testin (TES).	[42]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Testin (TES).	[43]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride increases the expression of Testin (TES).	[44]
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⏷ Show the Full List of 22 Drug(s)

References

1	Promoter methylation of AREG, HOXA11, hMLH1, NDRG2, NPTX2 and Tes genes in glioblastoma.J Neurooncol. 2013 Jul;113(3):441-9. doi: 10.1007/s11060-013-1133-3. Epub 2013 Apr 28.
2	Humanization of a mouse anti-human IgE antibody: a potential therapeutic for IgE-mediated allergies.Protein Eng. 1993 Nov;6(8):971-80. doi: 10.1093/protein/6.8.971.
3	MORC4, a novel member of the MORC family, is highly expressed in a subset of diffuse large B-cell lymphomas.Br J Haematol. 2007 Aug;138(4):479-86. doi: 10.1111/j.1365-2141.2007.06680.x. Epub 2007 Jun 29.
4	Screening and Stepped Care Targeting Psychological Distress in Patients With Metastatic Colorectal Cancer: The TES Cluster Randomized Trial.J Natl Compr Canc Netw. 2019 Aug 1;17(8):911-920. doi: 10.6004/jnccn.2019.7285.
5	TESTIN was commonly hypermethylated and involved in the epithelial-mesenchymal transition of endometrial cancer.APMIS. 2015 May;123(5):394-400. doi: 10.1111/apm.12361. Epub 2015 Feb 27.
6	Adenoviral transduction of TESTIN gene into breast and uterine cancer cell lines promotes apoptosis and tumor reduction in vivo.Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):806-13.
7	Testin is a tumor suppressor in non-small cell lung cancer.Oncol Rep. 2017 Feb;37(2):1027-1035. doi: 10.3892/or.2016.5316. Epub 2016 Dec 14.
8	TES functions as a Mena-dependent tumor suppressor in gastric cancer carcinogenesis and metastasis.Cancer Commun (Lond). 2019 Feb 6;39(1):3. doi: 10.1186/s40880-019-0347-y.
9	Association of testis derived transcript gene variants and prostate cancer risk.J Urol. 2007 Mar;177(3):894-8. doi: 10.1016/j.juro.2006.10.057.
10	Extensive analysis of the 7q31 region in human prostate tumors supports TES as the best candidate tumor suppressor gene.Int J Cancer. 2004 Sep 20;111(5):798-804. doi: 10.1002/ijc.20337.
11	Novel methotrexate soft nanocarrier/fractional erbium YAG laser combination for clinical treatment of plaque psoriasis.Artif Cells Nanomed Biotechnol. 2018;46(sup1):996-1002. doi: 10.1080/21691401.2018.1440236. Epub 2018 Feb 15.
12	Testin protects against cardiac hypertrophy by targeting a calcineurin-dependent signalling pathway.J Cell Mol Med. 2019 Jan;23(1):328-339. doi: 10.1111/jcmm.13934. Epub 2018 Nov 22.
13	Prognostic relevance of the expressions of CAV1 and TES genes on 7q31 in melanoma.Front Biosci (Elite Ed). 2012 Jan 1;4(5):1802-12. doi: 10.2741/501.
14	TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells.PLoS One. 2016 Mar 17;11(3):e0151341. doi: 10.1371/journal.pone.0151341. eCollection 2016.
15	Comparative gene expression analysis between coronary arteries and internal mammary arteries identifies a role for the TES gene in endothelial cell functions relevant to coronary artery disease.Hum Mol Genet. 2012 Mar 15;21(6):1364-73. doi: 10.1093/hmg/ddr574. Epub 2011 Dec 12.
16	CFP suppresses breast cancer cell growth by TES-mediated upregulation of the transcription factor DDIT3.Oncogene. 2019 Jun;38(23):4560-4573. doi: 10.1038/s41388-019-0739-0. Epub 2019 Feb 12.
17	Wilms tumor suppressor 1 (WT1) and early growth response 1 (EGR1) are regulators of STIM1 expression.J Biol Chem. 2010 Apr 2;285(14):10591-6. doi: 10.1074/jbc.M109.083493. Epub 2010 Feb 1.
18	Testin is a tumor suppressor and prognostic marker in breast cancer.Cancer Sci. 2012 Dec;103(12):2092-101. doi: 10.1111/cas.12020. Epub 2012 Oct 22.
19	Frequent hypermethylation and loss of heterozygosity of the testis derived transcript gene in ovarian cancer.Cancer Sci. 2010 May;101(5):1255-60. doi: 10.1111/j.1349-7006.2010.01497.x. Epub 2010 Jan 18.
20	Identification of a novel diagnostic gene expression signature to discriminate uterine leiomyoma from leiomyosarcoma.Exp Mol Pathol. 2019 Oct;110:104284. doi: 10.1016/j.yexmp.2019.104284. Epub 2019 Jul 10.
21	Effects of TESTIN gene expression on proliferation and migration of the 5-8F nasopharyngeal carcinoma cell line.Asian Pac J Cancer Prev. 2015;16(6):2555-9. doi: 10.7314/apjcp.2015.16.6.2555.
22	Prickle1 regulates neurite outgrowth of apical spiral ganglion neurons but not hair cell polarity in the murine cochlea.PLoS One. 2017 Aug 24;12(8):e0183773. doi: 10.1371/journal.pone.0183773. eCollection 2017.
23	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.
24	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.
25	Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
26	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.
27	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.
28	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
29	Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
30	Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
31	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.
32	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.
33	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
34	JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
35	Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
36	LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
37	Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
38	Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
39	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.
40	DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
41	From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
42	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
43	Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
44	The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.