Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMD20XN)

DOT Name Mediator of RNA polymerase II transcription subunit 14 (MED14)
Synonyms
Activator-recruited cofactor 150 kDa component; ARC150; Cofactor required for Sp1 transcriptional activation subunit 2; CRSP complex subunit 2; Mediator complex subunit 14; RGR1 homolog; hRGR1; Thyroid hormone receptor-associated protein complex 170 kDa component; Trap170; Transcriptional coactivator CRSP150; Vitamin D3 receptor-interacting protein complex 150 kDa component; DRIP150
Gene Name MED14
Related Disease
Breast neoplasm ( )
Endometriosis ( )
Systemic lupus erythematosus ( )
UniProt ID
MED14_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7EMF; 7ENA; 7ENC; 7ENJ; 7LBM; 7NVR; 8GXQ; 8GXS
Pfam ID
PF08638
Sequence
MAPVQLENHQLVPPGGGGGGSGGPPSAPAPPPPGAAVAAAAAAAASPGYRLSTLIEFLLH
RAYSELMVLTDLLPRKSDVERKIEIVQFASRTRQLFVRLLALVKWANNAGKVEKCAMISS
FLDQQAILFVDTADRLASLARDALVHARLPSFAIPYAIDVLTTGSYPRLPTCIRDKIIPP
DPITKIEKQATLHQLNQILRHRLVTTDLPPQLANLTVANGRVKFRVEGEFEATLTVMGDD
PDVPWRLLKLEILVEDKETGDGRALVHSMQISFIHQLVQSRLFADEKPLQDMYNCLHSFC
LSLQLEVLHSQTLMLIRERWGDLVQVERYHAGKCLSLSVWNQQVLGRKTGTASVHKVTIK
IDENDVSKPLQIFHDPPLPASDSKLVERAMKIDHLSIEKLLIDSVHARAHQKLQELKAIL
RGFNANENSSIETALPALVVPILEPCGNSECLHIFVDLHSGMFQLMLYGLDQATLDDMEK
SVNDDMKRIIPWIQQLKFWLGQQRCKQSIKHLPTISSETLQLSNYSTHPIGNLSKNKLFI
KLTRLPQYYIVVEMLEVPNKPTQLSYKYYFMSVNAADREDSPAMALLLQQFKENIQDLVF
RTKTGKQTRTNAKRKLSDDPCPVESKKTKRAGEMCAFNKVLAHFVAMCDTNMPFVGLRLE
LSNLEIPHQGVQVEGDGFSHAIRLLKIPPCKGITEETQKALDRSLLDCTFRLQGRNNRTW
VAELVFANCPLNGTSTREQGPSRHVYLTYENLLSEPVGGRKVVEMFLNDWNSIARLYECV
LEFARSLPDIPAHLNIFSEVRVYNYRKLILCYGTTKGSSISIQWNSIHQKFHISLGTVGP
NSGCSNCHNTILHQLQEMFNKTPNVVQLLQVLFDTQAPLNAINKLPTVPMLGLTQRTNTA
YQCFSILPQSSTHIRLAFRNMYCIDIYCRSRGVVAIRDGAYSLFDNSKLVEGFYPAPGLK
TFLNMFVDSNQDARRRSVNEDDNPPSPIGGDMMDSLISQLQPPPQQQPFPKQPGTSGAYP
LTSPPTSYHSTVNQSPSMMHTQSPGNLHAASSPSGALRAPSPASFVPTPPPSSHGISIGP
GASFASPHGTLDPSSPYTMVSPSGRAGNWPGSPQVSGPSPAARMPGMSPANPSLHSPVPD
ASHSPRAGTSSQTMPTNMPPPRKLPQRSWAASIPTILTHSALNILLLPSPTPGLVPGLAG
SYLCSPLERFLGSVIMRRHLQRIIQQETLQLINSNEPGVIMFKTDALKCRVALSPKTNQT
LQLKVTPENAGQWKPDELQVLEKFFETRVAGPPFKANTLIAFTKLLGAPTHILRDCVHIM
KLELFPDQATQLKWNVQFCLTIPPSAPPIAPPGTPAVVLKSKMLFFLQLTQKTSVPPQEP
VSIIVPIIYDMASGTTQQADIPRQQNSSVAAPMMVSNILKRFAEMNPPRQGECTIFAAVR
DLMANLTLPPGGRP
Function
Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
Tissue Specificity Ubiquitous.
KEGG Pathway
Thyroid hormone sig.ling pathway (hsa04919 )
Reactome Pathway
Generic Transcription Pathway (R-HSA-212436 )
Transcriptional regulation of white adipocyte differentiation (R-HSA-381340 )
PPARA activates gene expression (R-HSA-1989781 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast neoplasm DISNGJLM Strong Biomarker [1]
Endometriosis DISX1AG8 Strong Biomarker [2]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [3]
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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 decreases the methylation of Mediator of RNA polymerase II transcription subunit 14 (MED14). [4]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Mediator of RNA polymerase II transcription subunit 14 (MED14). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Mediator of RNA polymerase II transcription subunit 14 (MED14). [14]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Mediator of RNA polymerase II transcription subunit 14 (MED14). [15]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Mediator of RNA polymerase II transcription subunit 14 (MED14). [16]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [7]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [9]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [10]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [11]
Marinol DM70IK5 Approved Marinol increases the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [12]
Diclofenac DMPIHLS Approved Diclofenac affects the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [11]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [13]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [7]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [17]
KOJIC ACID DMP84CS Investigative KOJIC ACID increases the expression of Mediator of RNA polymerase II transcription subunit 14 (MED14). [18]
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⏷ Show the Full List of 12 Drug(s)

References

1 Coactivation of estrogen receptor alpha (ER alpha)/Sp1 by vitamin D receptor interacting protein 150 (DRIP150).Arch Biochem Biophys. 2007 May 15;461(2):200-10. doi: 10.1016/j.abb.2006.12.030. Epub 2007 Jan 23.
2 Nuclear receptor, coregulator signaling, and chromatin remodeling pathways suggest involvement of the epigenome in the steroid hormone response of endometrium and abnormalities in endometriosis.Reprod Sci. 2012 Feb;19(2):152-62. doi: 10.1177/1933719111415546. Epub 2011 Dec 2.
3 Estradiol targets T cell signaling pathways in human systemic lupus.Clin Immunol. 2009 Dec;133(3):428-36. doi: 10.1016/j.clim.2009.09.002. Epub 2009 Sep 30.
4 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.
5 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.
6 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.
7 Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
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 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
10 The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
11 Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
12 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
13 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.
14 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
15 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.
16 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.
17 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.
18 Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.