Details of Drug Off-Target (DOT)

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

DOT Name BEN domain-containing protein 3 (BEND3)
Gene Name BEND3
Related Disease
High blood pressure ( )
UniProt ID
BEND3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
5JNO; 7W27
Pfam ID
PF10523
Sequence
MNSTEFTEDVEEVLKSITVKVETEAEDAALDCSVNSRTSEKHSVDSVLTALQDSSKRKQL
VSDGLLDSVPGVKRRRLIPEALLAGMRNRENSSPCQGNGEQAGRGRSLGNVWPGEEEPCN
DATTPSYKKPLYGISHKIMEKKNPPSGDLLNVYELFEKANASNSPSSLRLLNEPQKRDCG
STGAGTDNDPNIYFLIQKMFYMLNTLTSNMSQLHSKVDLLSLEVSRIKKQVSPTEMVAKF
QPPPEYQLTAAELKQIVDQSLSGGDLACRLLVQLFPELFSDVDFSRGCSACGFAAKRKLE
SLHLQLIRNYVEVYYPSVKDTAVWQAECLPQLNDFFSRFWAQREMEDSQPSGQVASFFEA
EQVDPGHFLDNKDQEEALSLDRSSTIASDHVVDTQDLTEFLDEASSPGEFAVFLLHRLFP
ELFDHRKLGEQYSCYGDGGKQELDPQRLQIIRNYTEIYFPDMQEEEAWLQQCAQRINDEL
EGLGLDAGSEGDPPRDDCYDSSSLPDDISVVKVEDSFEGERPGRRSKKIWLVPIDFDKLE
IPQPDFEVPGADCLLSKEQLRSIYESSLSIGNFASRLLVHLFPELFTHENLRKQYNCSGS
LGKKQLDPSRIKLIRHYVQLLYPRAKNDRVWTLEFVGKLDERCRRRDTEQRRSYQQQRKV
HVPGPECRDLTSYAINPERFREEFEGPPLPPERSSKDFCKIPLDELVVPSPDFPVPSPYL
LSDKEVREIVQQSLSVGNFAARLLVRLFPELFTAENLRLQYNHSGACNKKQLDPTRLRLI
RHYVEAVYPVEKMEEVWHYECIPSIDERCRRPNRKKCDILKKAKKVEK
Function
Transcriptional repressor which associates with the NoRC (nucleolar remodeling complex) complex and plays a key role in repressing rDNA transcription. The sumoylated form modulates the stability of the NoRC complex component BAZ2A/TIP5 by controlling its USP21-mediated deubiquitination. Binds to unmethylated major satellite DNA and is involved in the recruitment of the Polycomb repressive complex 2 (PRC2) to major satellites. Stimulates the ERCC6L translocase and ATPase activities.
Tissue Specificity Expressed at least in heart, kidney, liver, ovary and spleen, with highest levels in spleen and lowest in heart. Expressed on the surface of T-cells.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
High blood pressure DISY2OHH Limited Biomarker [1]
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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 increases the methylation of BEN domain-containing protein 3 (BEND3). [2]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of BEN domain-containing protein 3 (BEND3). [8]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of BEN domain-containing protein 3 (BEND3). [17]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 increases the phosphorylation of BEN domain-containing protein 3 (BEND3). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of BEN domain-containing protein 3 (BEND3). [20]
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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 BEN domain-containing protein 3 (BEND3). [3]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of BEN domain-containing protein 3 (BEND3). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of BEN domain-containing protein 3 (BEND3). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of BEN domain-containing protein 3 (BEND3). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of BEN domain-containing protein 3 (BEND3). [7]
Vorinostat DMWMPD4 Approved Vorinostat decreases the expression of BEN domain-containing protein 3 (BEND3). [9]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of BEN domain-containing protein 3 (BEND3). [10]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of BEN domain-containing protein 3 (BEND3). [11]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of BEN domain-containing protein 3 (BEND3). [12]
GSK2110183 DMZHB37 Phase 2 GSK2110183 decreases the expression of BEN domain-containing protein 3 (BEND3). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of BEN domain-containing protein 3 (BEND3). [14]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of BEN domain-containing protein 3 (BEND3). [15]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of BEN domain-containing protein 3 (BEND3). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of BEN domain-containing protein 3 (BEND3). [18]
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⏷ Show the Full List of 14 Drug(s)

References

1 Azelnidipine Attenuates the Oxidative and NFB Pathways in Amyloid--Stimulated Cerebral Endothelial Cells.ACS Chem Neurosci. 2019 Jan 16;10(1):209-215. doi: 10.1021/acschemneuro.8b00368. Epub 2018 Nov 8.
2 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.
3 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
4 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
5 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
6 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.
7 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
8 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.
9 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
10 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.
11 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
12 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.
13 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.
14 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.
15 Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
16 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
17 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
18 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.
19 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.
20 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.