Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ8S1PL)

DOT Name Tensin-1 (TNS1)
Synonyms EC 3.1.3.-
Gene Name TNS1
Related Disease
Acute megakaryoblastic leukemia ( )
Asthma ( )
Breast carcinoma ( )
Cleft palate ( )
Colorectal carcinoma ( )
Endometriosis ( )
Isolated cleft palate ( )
Seasonal allergic rhinitis ( )
Coronary heart disease ( )
Chronic obstructive pulmonary disease ( )
Leiomyosarcoma ( )
UniProt ID
TENS1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.1.3.-
Pfam ID
PF00130 ; PF08416 ; PF10409 ; PF00017
Sequence
MTWICLSCMLWPEDLEAPKTHRFKVKTFKKVKPCGICRQVITQEGCTCKVCSFSCHRKCQ
AKVAAPCVPPSNHELVPITTENAPKNVVDKGEGASRGGNTRKSLEDNGSTRVTPSVQPHL
QPIRNMSVSRTMEDSCELDLVYVTERIIAVSFPSTANEENFRSNLREVAQMLKSKHGGNY
LLFNLSERRPDITKLHAKVLEFGWPDLHTPALEKICSICKAMDTWLNADPHNVVVLHNKG
NRGRIGVVIAAYMHYSNISASADQALDRFAMKRFYEDKIVPIGQPSQRRYVHYFSGLLSG
SIKMNNKPLFLHHVIMHGIPNFESKGGCRPFLRIYQAMQPVYTSGIYNIPGDSQTSVCIT
IEPGLLLKGDILLKCYHKKFRSPARDVIFRVQFHTCAIHDLGVVFGKEDLDDAFKDDRFP
EYGKVEFVFSYGPEKIQGMEHLENGPSVSVDYNTSDPLIRWDSYDNFSGHRDDGMEEVVG
HTQGPLDGSLYAKVKKKDSLHGSTGAVNATRPTLSATPNHVEHTLSVSSDSGNSTASTKT
DKTDEPVPGASSATAALSPQEKRELDRLLSGFGLEREKQGAMYHTQHLRSRPAGGSAVPS
SGRHVVPAQVHVNGGALASERETDILDDELPNQDGHSAGSMGTLSSLDGVTNTSEGGYPE
ALSPLTNGLDKSYPMEPMVNGGGYPYESASRAGPAHAGHTAPMRPSYSAQEGLAGYQREG
PHPAWPQPVTTSHYAHDPSGMFRSQSFSEAEPQLPPAPVRGGSSREAVQRGLNSWQQQQQ
QQQQPRPPPRQQERAHLESLVASRPSPQPLAETPIPSLPEFPRAASQQEIEQSIETLNML
MLDLEPASAAAPLHKSQSVPGAWPGASPLSSQPLSGSSRQSHPLTQSRSGYIPSGHSLGT
PEPAPRASLESVPPGRSYSPYDYQPCLAGPNQDFHSKSPASSSLPAFLPTTHSPPGPQQP
PASLPGLTAQPLLSPKEATSDPSRTPEEEPLNLEGLVAHRVAGVQAREKQPAEPPAPLRR
RAASDGQYENQSPEATSPRSPGVRSPVQCVSPELALTIALNPGGRPKEPHLHSYKEAFEE
MEGTSPSSPPPSGVRSPPGLAKTPLSALGLKPHNPADILLHPTGEPRSYVESVARTAVAG
PRAQDSEPKSFSAPATQAYGHEIPLRNGTLGGSFVSPSPLSTSSPILSADSTSVGSFPSG
ESSDQGPRTPTQPLLESGFRSGSLGQPSPSAQRNYQSSSPLPTVGSSYSSPDYSLQHFSS
SPESQARAQFSVAGVHTVPGSPQARHRTVGTNTPPSPGFGWRAINPSMAAPSSPSLSHHQ
MMGPPGTGFHGSTVSSPQSSAATTPGSPSLCRHPAGVYQVSGLHNKVATTPGSPSLGRHP
GAHQGNLASGLHSNAIASPGSPSLGRHLGGSGSVVPGSPCLDRHVAYGGYSTPEDRRPTL
SRQSSASGYQAPSTPSFPVSPAYYPGLSSPATSPSPDSAAFRQGSPTPALPEKRRMSVGD
RAGSLPNYATINGKVSSPVASGMSSPSGGSTVSFSHTLPDFSKYSMPDNSPETRAKVKFV
QDTSKYWYKPEISREQAIALLKDQEPGAFIIRDSHSFRGAYGLAMKVSSPPPTIMQQNKK
GDMTHELVRHFLIETGPRGVKLKGCPNEPNFGSLSALVYQHSIIPLALPCKLVIPNRDPT
DESKDSSGPANSTADLLKQGAACNVLFVNSVDMESLTGPQAISKATSETLAADPTPAATI
VHFKVSAQGITLTDNQRKLFFRRHYPLNTVTFCDLDPQERKWMKTEGGAPAKLFGFVARK
QGSTTDNACHLFAELDPNQPASAIVNFVSKVMLNAGQKR
Function
May act as a protein phosphatase and/or a lipid phosphatase (Probable). Involved in fibrillar adhesion formation. Essential for myofibroblast differentiation and myofibroblast-mediated extracellular matrix deposition. Enhances RHOA activation in the presence of DLC1. Plays a role in cell polarization and migration. May be involved in cartilage development and in linking signal transduction pathways to the cytoskeleton.
Tissue Specificity In the lung, detected in the alveolar septa (at protein level) . Ubiquitous .

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute megakaryoblastic leukemia DIS0JX3M Strong Altered Expression [1]
Asthma DISW9QNS Strong Genetic Variation [2]
Breast carcinoma DIS2UE88 Strong Genetic Variation [3]
Cleft palate DIS6G5TF Strong Biomarker [4]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [5]
Endometriosis DISX1AG8 Strong Altered Expression [6]
Isolated cleft palate DISV80CD Strong Biomarker [4]
Seasonal allergic rhinitis DIS58KQX Strong Genetic Variation [2]
Coronary heart disease DIS5OIP1 moderate Genetic Variation [7]
Chronic obstructive pulmonary disease DISQCIRF Limited Genetic Variation [8]
Leiomyosarcoma DIS6COXM Limited Genetic Variation [9]
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⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Tensin-1 (TNS1). [10]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Tensin-1 (TNS1). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Tensin-1 (TNS1). [22]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Tensin-1 (TNS1). [26]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid increases the phosphorylation of Tensin-1 (TNS1). [31]
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20 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 Tensin-1 (TNS1). [11]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Tensin-1 (TNS1). [12]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Tensin-1 (TNS1). [13]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Tensin-1 (TNS1). [14]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Tensin-1 (TNS1). [15]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Tensin-1 (TNS1). [11]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Tensin-1 (TNS1). [17]
Triclosan DMZUR4N Approved Triclosan increases the expression of Tensin-1 (TNS1). [18]
Rosiglitazone DMILWZR Approved Rosiglitazone decreases the expression of Tensin-1 (TNS1). [19]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of Tensin-1 (TNS1). [20]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Tensin-1 (TNS1). [21]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Tensin-1 (TNS1). [23]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Tensin-1 (TNS1). [24]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Tensin-1 (TNS1). [25]
PMID27336223-Compound-5 DM6E50A Patented PMID27336223-Compound-5 decreases the expression of Tensin-1 (TNS1). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Tensin-1 (TNS1). [27]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Tensin-1 (TNS1). [28]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Tensin-1 (TNS1). [29]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of Tensin-1 (TNS1). [30]
Nitrobenzanthrone DMN6L70 Investigative Nitrobenzanthrone affects the expression of Tensin-1 (TNS1). [32]
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⏷ Show the Full List of 20 Drug(s)

References

1 Tensin 1 Is Essential for Myofibroblast Differentiation and Extracellular Matrix Formation.Am J Respir Cell Mol Biol. 2017 Apr;56(4):465-476. doi: 10.1165/rcmb.2016-0104OC.
2 Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.J Allergy Clin Immunol. 2014 Jun;133(6):1564-71. doi: 10.1016/j.jaci.2013.10.030. Epub 2013 Dec 31.
3 Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
4 Analysis of candidate genes on chromosome 2 in oral cleft case-parent trios from three populations.Hum Genet. 2006 Nov;120(4):501-18. doi: 10.1007/s00439-006-0235-9. Epub 2006 Sep 5.
5 Elevated transgelin/TNS1 expression is a potential biomarker in human colorectal cancer.Oncotarget. 2017 Dec 15;9(1):1107-1113. doi: 10.18632/oncotarget.23275. eCollection 2018 Jan 2.
6 Gonadotropin-releasing hormone agonist induces downregulation of tensin 1 in women with endometriosis.Acta Obstet Gynecol Scand. 2019 Feb;98(2):222-231. doi: 10.1111/aogs.13481. Epub 2018 Nov 11.
7 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
8 Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nat Genet. 2019 Mar;51(3):494-505. doi: 10.1038/s41588-018-0342-2. Epub 2019 Feb 25.
9 The differential diagnoses of uterine leiomyomas and leiomyosarcomas using DNA and RNA sequencing.Am J Obstet Gynecol. 2019 Oct;221(4):320.e1-320.e23. doi: 10.1016/j.ajog.2019.05.018. Epub 2019 May 20.
10 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.
11 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.
12 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.
13 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.
14 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
15 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
16 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
17 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
18 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
19 PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
20 The cancer chemopreventive agent resveratrol induces tensin, a cell-matrix adhesion protein with signaling and antitumor activities. Oncogene. 2005 May 5;24(20):3274-84. doi: 10.1038/sj.onc.1208485.
21 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.
22 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.
23 Highly active combination of BRD4 antagonist and histone deacetylase inhibitor against human acute myelogenous leukemia cells. Mol Cancer Ther. 2014 May;13(5):1142-54.
24 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
25 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.
26 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
27 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
28 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.
29 Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
30 Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One. 2011 Mar 24;6(3):e17728. doi: 10.1371/journal.pone.0017728.
31 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
32 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.