Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR1T8E9)

DOT Name Transcription factor AP-2-beta (TFAP2B)
Synonyms AP2-beta; Activating enhancer-binding protein 2-beta
Gene Name TFAP2B
Related Disease
Char syndrome ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid tumor ( )
Advanced cancer ( )
Alcohol dependence ( )
Amoebiasis ( )
Breast carcinoma ( )
Breast neoplasm ( )
Depression ( )
Ductal breast carcinoma in situ ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Glaucoma/ocular hypertension ( )
Hepatocellular carcinoma ( )
Hereditary glaucoma ( )
Holt-Oram syndrome ( )
Intestinal amebiasis ( )
Lung adenocarcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Lung neoplasm ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Non-small-cell lung cancer ( )
Polydactyly ( )
Renal cell carcinoma ( )
Retinoblastoma ( )
Sleep disorder ( )
Juvenile myoclonic epilepsy ( )
Obesity ( )
Rhabdomyosarcoma ( )
Tetralogy of fallot ( )
Obsolete familial patent arterial duct ( )
Breast cancer ( )
Central diabetes insipidus ( )
Congenital heart disease ( )
Coronary atherosclerosis ( )
Coronary heart disease ( )
Myopia ( )
Neuroblastoma ( )
Sensorineural hearing loss disorder ( )
Urolithiasis ( )
UniProt ID
AP2B_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
8J0Q
Pfam ID
PF03299
Sequence
MHSPPRDQAAIMLWKLVENVKYEDIYEDRHDGVPSHSSRLSQLGSVSQGPYSSAPPLSHT
PSSDFQPPYFPPPYQPLPYHQSQDPYSHVNDPYSLNPLHQPQQHPWGQRQRQEVGSEAGS
LLPQPRAALPQLSGLDPRRDYHSVRRPDVLLHSAHHGLDAGMGDSLSLHGLGHPGMEDVQ
SVEDANNSGMNLLDQSVIKKVPVPPKSVTSLMMNKDGFLGGMSVNTGEVFCSVPGRLSLL
SSTSKYKVTVGEVQRRLSPPECLNASLLGGVLRRAKSKNGGRSLRERLEKIGLNLPAGRR
KAANVTLLTSLVEGEAVHLARDFGYICETEFPAKAVSEYLNRQHTDPSDLHSRKNMLLAT
KQLCKEFTDLLAQDRTPIGNSRPSPILEPGIQSCLTHFSLITHGFGAPAICAALTALQNY
LTEALKGMDKMFLNNTTTNRHTSGEGPGSKTGDKEEKHRK
Function
Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-beta appears to be required for normal face and limb development and for proper terminal differentiation and function of renal tubular epithelia.
Reactome Pathway
Negative regulation of activity of TFAP2 (AP-2) family transcription factors (R-HSA-8866904 )
Activation of the TFAP2 (AP-2) family of transcription factors (R-HSA-8866907 )
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors (R-HSA-8866910 )
SUMOylation of transcription factors (R-HSA-3232118 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Char syndrome DISCCXBU Definitive Autosomal dominant [1]
Thyroid cancer DIS3VLDH Definitive Altered Expression [2]
Thyroid gland carcinoma DISMNGZ0 Definitive Altered Expression [2]
Thyroid tumor DISLVKMD Definitive Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Biomarker [3]
Alcohol dependence DIS4ZSCO Strong Genetic Variation [4]
Amoebiasis DISAJWJL Strong Genetic Variation [5]
Breast carcinoma DIS2UE88 Strong Biomarker [6]
Breast neoplasm DISNGJLM Strong Altered Expression [7]
Depression DIS3XJ69 Strong Genetic Variation [8]
Ductal breast carcinoma in situ DISLCJY7 Strong Biomarker [6]
Endometrial cancer DISW0LMR Strong Altered Expression [9]
Endometrial carcinoma DISXR5CY Strong Biomarker [9]
Glaucoma/ocular hypertension DISLBXBY Strong Altered Expression [10]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [11]
Hereditary glaucoma DISJYSR1 Strong Altered Expression [10]
Holt-Oram syndrome DISBNDZ2 Strong Biomarker [12]
Intestinal amebiasis DIS0IHMD Strong Genetic Variation [5]
Lung adenocarcinoma DISD51WR Strong Altered Expression [13]
Lung cancer DISCM4YA Strong Biomarker [13]
Lung carcinoma DISTR26C Strong Biomarker [13]
Lung neoplasm DISVARNB Strong Altered Expression [14]
Neoplasm DISZKGEW Strong Altered Expression [2]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [15]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [13]
Polydactyly DIS25BMZ Strong Biomarker [16]
Renal cell carcinoma DISQZ2X8 Strong Altered Expression [17]
Retinoblastoma DISVPNPB Strong Posttranslational Modification [18]
Sleep disorder DIS3JP1U Strong Biomarker [19]
Juvenile myoclonic epilepsy DISYXV1N moderate Biomarker [20]
Obesity DIS47Y1K moderate Genetic Variation [21]
Rhabdomyosarcoma DISNR7MS moderate Biomarker [22]
Tetralogy of fallot DISMHFNW moderate Genetic Variation [23]
Obsolete familial patent arterial duct DISUZERZ Supportive Autosomal dominant [24]
Breast cancer DIS7DPX1 Disputed Biomarker [6]
Central diabetes insipidus DISJ4P9O Limited Genetic Variation [25]
Congenital heart disease DISQBA23 Limited Genetic Variation [23]
Coronary atherosclerosis DISKNDYU Limited Altered Expression [26]
Coronary heart disease DIS5OIP1 Limited Altered Expression [26]
Myopia DISK5S60 Limited Genetic Variation [27]
Neuroblastoma DISVZBI4 Limited Biomarker [28]
Sensorineural hearing loss disorder DISJV45Z Limited Genetic Variation [25]
Urolithiasis DISNFTKT Limited Genetic Variation [29]
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⏷ Show the Full List of 43 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 decreases the methylation of Transcription factor AP-2-beta (TFAP2B). [30]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Transcription factor AP-2-beta (TFAP2B). [36]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Transcription factor AP-2-beta (TFAP2B). [31]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Transcription factor AP-2-beta (TFAP2B). [32]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Transcription factor AP-2-beta (TFAP2B). [33]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Transcription factor AP-2-beta (TFAP2B). [34]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Transcription factor AP-2-beta (TFAP2B). [35]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Transcription factor AP-2-beta (TFAP2B). [34]
Belinostat DM6OC53 Phase 2 Belinostat increases the expression of Transcription factor AP-2-beta (TFAP2B). [34]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Transcription factor AP-2-beta (TFAP2B). [37]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Transcription factor AP-2-beta (TFAP2B). [38]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Transcription factor AP-2-beta (TFAP2B). [39]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of Transcription factor AP-2-beta (TFAP2B). [40]
Manganese DMKT129 Investigative Manganese increases the expression of Transcription factor AP-2-beta (TFAP2B). [41]
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⏷ Show the Full List of 12 Drug(s)

References

1 Mutations in TFAP2B cause Char syndrome, a familial form of patent ductus arteriosus. Nat Genet. 2000 May;25(1):42-6. doi: 10.1038/75578.
2 TFAP2B overexpression contributes to tumor growth and progression of thyroid cancer through the COX-2 signaling pathway.Cell Death Dis. 2019 May 21;10(6):397. doi: 10.1038/s41419-019-1600-7.
3 DHX33 Interacts with AP-2 To Regulate Bcl-2 Gene Expression and Promote Cancer Cell Survival.Mol Cell Biol. 2019 Aug 12;39(17):e00017-19. doi: 10.1128/MCB.00017-19. Print 2019 Sep 1.
4 Transcription factor AP2 beta involved in severe female alcoholism.Brain Res. 2009 Dec 11;1305 Suppl:S20-6. doi: 10.1016/j.brainres.2009.09.054. Epub 2009 Sep 22.
5 Molecular mechanisms underlying gliomas and glioblastoma pathogenesis revealed by bioinformatics analysis of microarray data.Med Oncol. 2017 Sep 26;34(11):182. doi: 10.1007/s12032-017-1043-x.
6 Lobular carcinoma in situ and invasive lobular breast cancer are characterized by enhanced expression of transcription factor AP-2.Lab Invest. 2018 Jan;98(1):117-129. doi: 10.1038/labinvest.2017.106. Epub 2017 Oct 16.
7 Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis.Clin Cancer Res. 2004 Nov 15;10(22):7621-8. doi: 10.1158/1078-0432.CCR-04-1061.
8 Transcription factor AP-2 beta genotype and psychosocial adversity in relation to adolescent depressive symptomatology.J Neural Transm (Vienna). 2009 Mar;116(3):363-70. doi: 10.1007/s00702-009-0183-3. Epub 2009 Jan 28.
9 Decreased expression of TFAP2B in endometrial cancer predicts poor prognosis: A study based on TCGA data.Gynecol Oncol. 2018 Jun;149(3):592-597. doi: 10.1016/j.ygyno.2018.03.057. Epub 2018 Mar 28.
10 Generation of a new mouse model of glaucoma characterized by reduced expression of the AP-2 and AP-2 proteins.Sci Rep. 2017 Sep 11;7(1):11140. doi: 10.1038/s41598-017-11752-6.
11 AP-2 inhibits hepatocellular carcinoma invasion and metastasis through Slug and Snail to suppress epithelial-mesenchymal transition.Theranostics. 2018 Jun 12;8(13):3707-3721. doi: 10.7150/thno.25166. eCollection 2018.
12 A heart-hand syndrome gene: Tfap2b plays a critical role in the development and remodeling of mouse ductus arteriosus and limb patterning.PLoS One. 2011;6(7):e22908. doi: 10.1371/journal.pone.0022908. Epub 2011 Jul 29.
13 TFAP2B overexpression contributes to tumor growth and a poor prognosis of human lung adenocarcinoma through modulation of ERK and VEGF/PEDF signaling.Mol Cancer. 2014 Apr 26;13:89. doi: 10.1186/1476-4598-13-89.
14 Tumor-specific activation of human telomerase reverses transcriptase promoter activity by activating enhancer-binding protein-2beta in human lung cancer cells.J Biol Chem. 2007 Sep 7;282(36):26460-70. doi: 10.1074/jbc.M610579200. Epub 2007 Jul 15.
15 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
16 Char syndrome: a new family and review of the literature emphasising the presence of symphalangism and the variable phenotype.Clin Dysmorphol. 2000 Jul;9(3):177-82. doi: 10.1097/00019605-200009030-00005.
17 Differential expression of activator protein-2 isoforms in renal cell carcinoma.Urology. 2004 Jul;64(1):162-7. doi: 10.1016/j.urology.2004.02.022.
18 AP2 transcription factor induces apoptosis in retinoblastoma cells.Genes Chromosomes Cancer. 2010 Sep;49(9):819-30. doi: 10.1002/gcc.20790.
19 Syndromic patent ductus arteriosus: evidence for haploinsufficient TFAP2B mutations and identification of a linked sleep disorder.Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2975-9. doi: 10.1073/pnas.0409852102. Epub 2005 Jan 31.
20 Mutation analyses of genes on 6p12-p11 in patients with juvenile myoclonic epilepsy.Neurosci Lett. 2006 Sep 11;405(1-2):126-31. doi: 10.1016/j.neulet.2006.06.038. Epub 2006 Jul 28.
21 Association between Transcription Factor AP-2B genotype, obesity, insulin resistance and dietary intake in a longitudinal birth cohort study.Int J Obes (Lond). 2019 Oct;43(10):2095-2106. doi: 10.1038/s41366-019-0396-y. Epub 2019 Jun 17.
22 DAX-1 Expression in Pediatric Rhabdomyosarcomas: Another Immunohistochemical Marker Useful in the Diagnosis of Translocation Positive Alveolar Rhabdomyosarcoma.PLoS One. 2015 Jul 13;10(7):e0133019. doi: 10.1371/journal.pone.0133019. eCollection 2015.
23 Analyses of GATA4, NKX2.5, and TFAP2B genes in subjects from southern China with sporadic congenital heart disease.Cardiovasc Pathol. 2013 Mar-Apr;22(2):141-5. doi: 10.1016/j.carpath.2012.07.001. Epub 2012 Sep 6.
24 Familial nonsyndromic patent ductus arteriosus caused by mutations in TFAP2B. Pediatr Cardiol. 2011 Oct;32(7):958-65. doi: 10.1007/s00246-011-0024-7. Epub 2011 Jun 4.
25 A novel missense mutation in TFAP2B associated with Char syndrome and central diabetes insipidus.Am J Med Genet A. 2019 Jul;179(7):1299-1303. doi: 10.1002/ajmg.a.61150. Epub 2019 Apr 22.
26 The transcription factor TFAP2B is associated with insulin resistance and adiposity in healthy adolescents.Obesity (Silver Spring). 2009 Sep;17(9):1762-7. doi: 10.1038/oby.2009.83. Epub 2009 Mar 26.
27 Detection and interpretation of shared genetic influences on 42 human traits.Nat Genet. 2016 Jul;48(7):709-17. doi: 10.1038/ng.3570. Epub 2016 May 16.
28 Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma.Mol Oncol. 2016 Feb;10(2):344-59. doi: 10.1016/j.molonc.2015.10.020. Epub 2015 Nov 7.
29 Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population.J Am Soc Nephrol. 2019 May;30(5):855-864. doi: 10.1681/ASN.2018090942. Epub 2019 Apr 11.
30 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.
31 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
32 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
33 Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
34 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.
35 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
36 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.
37 Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
38 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
39 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.
40 Risk assessment of parabens in a transcriptomics-based in vitro test. Chem Biol Interact. 2023 Oct 1;384:110699. doi: 10.1016/j.cbi.2023.110699. Epub 2023 Sep 9.
41 Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.