Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT9RT5N)

DOT Name Mediator of RNA polymerase II transcription subunit 19 (MED19)
Synonyms Lung cancer metastasis-related protein 1; Mediator complex subunit 19
Gene Name MED19
Related Disease
Bladder transitional cell carcinoma ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Colorectal carcinoma ( )
DICER1-related tumor predisposition ( )
Gastric cancer ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Lung adenocarcinoma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Pancreatic cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Smith-Lemli-Opitz syndrome ( )
Stomach cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Juvenile myoclonic epilepsy ( )
Lung cancer ( )
Lung carcinoma ( )
Non-insulin dependent diabetes ( )
Advanced cancer ( )
Amyotrophic lateral sclerosis ( )
Breast cancer ( )
Breast carcinoma ( )
Chromosomal disorder ( )
Epithelial ovarian cancer ( )
Melanoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Rett syndrome ( )
Small lymphocytic lymphoma ( )
UniProt ID
MED19_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
7EMF; 7ENA; 7ENC; 7ENJ; 7LBM; 7NVR; 8GXQ; 8GXS
Pfam ID
PF10278
Sequence
MENFTALFGAQADPPPPPTALGFGPGKPPPPPPPPAGGGPGTAPPPTAATAPPGADKSGA
GCGPFYLMRELPGSTELTGSTNLITHYNLEQAYNKFCGKKVKEKLSNFLPDLPGMIDLPG
SHDNSSLRSLIEKPPILSSSFNPITGTMLAGFRLHTGPLPEQCRLMHIQPPKKKNKHKHK
QSRTQDPVPPETPSDSDHKKKKKKKEEDPDRKRKKKEKKKKKNRHSPDHPGMGSSQASSS
SSLR
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.
Reactome Pathway
Transcriptional regulation of white adipocyte differentiation (R-HSA-381340 )
PPARA activates gene expression (R-HSA-1989781 )

Molecular Interaction Atlas (MIA) of This DOT

37 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bladder transitional cell carcinoma DISNL46A Definitive Biomarker [1]
Bladder cancer DISUHNM0 Strong Biomarker [2]
Bone osteosarcoma DIST1004 Strong Biomarker [3]
Cervical cancer DISFSHPF Strong Biomarker [4]
Cervical carcinoma DIST4S00 Strong Biomarker [4]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [5]
DICER1-related tumor predisposition DISHCY33 Strong Biomarker [6]
Gastric cancer DISXGOUK Strong Biomarker [7]
Hepatitis C virus infection DISQ0M8R Strong Altered Expression [8]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [9]
Lung adenocarcinoma DISD51WR Strong Biomarker [10]
Metastatic malignant neoplasm DIS86UK6 Strong Biomarker [11]
Neoplasm DISZKGEW Strong Biomarker [12]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [13]
Osteosarcoma DISLQ7E2 Strong Biomarker [3]
Pancreatic cancer DISJC981 Strong Biomarker [14]
Prostate cancer DISF190Y Strong Biomarker [15]
Prostate carcinoma DISMJPLE Strong Biomarker [15]
Smith-Lemli-Opitz syndrome DISX9ZUA Strong Genetic Variation [16]
Stomach cancer DISKIJSX Strong Biomarker [7]
Urinary bladder cancer DISDV4T7 Strong Biomarker [2]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [2]
Juvenile myoclonic epilepsy DISYXV1N moderate Biomarker [17]
Lung cancer DISCM4YA moderate Biomarker [18]
Lung carcinoma DISTR26C moderate Biomarker [18]
Non-insulin dependent diabetes DISK1O5Z Disputed Genetic Variation [19]
Advanced cancer DISAT1Z9 Limited Biomarker [20]
Amyotrophic lateral sclerosis DISF7HVM Limited Genetic Variation [21]
Breast cancer DIS7DPX1 Limited Biomarker [22]
Breast carcinoma DIS2UE88 Limited Biomarker [22]
Chromosomal disorder DISM5BB5 Limited Biomarker [23]
Epithelial ovarian cancer DIS56MH2 Limited Biomarker [24]
Melanoma DIS1RRCY Limited Altered Expression [25]
Ovarian cancer DISZJHAP Limited Biomarker [24]
Ovarian neoplasm DISEAFTY Limited Biomarker [24]
Rett syndrome DISGG5UV Limited Biomarker [26]
Small lymphocytic lymphoma DIS30POX Limited Genetic Variation [23]
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⏷ Show the Full List of 37 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 19 (MED19). [27]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Mediator of RNA polymerase II transcription subunit 19 (MED19). [31]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Mediator of RNA polymerase II transcription subunit 19 (MED19). [31]
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4 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 19 (MED19). [28]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Mediator of RNA polymerase II transcription subunit 19 (MED19). [29]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Mediator of RNA polymerase II transcription subunit 19 (MED19). [30]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Mediator of RNA polymerase II transcription subunit 19 (MED19). [32]
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References

1 Med19 promotes bone metastasis and invasiveness of bladder urothelial carcinoma via bone morphogenetic protein 2.Ann Diagn Pathol. 2013 Jun;17(3):259-64. doi: 10.1016/j.anndiagpath.2012.11.004. Epub 2012 Dec 29.
2 Knockdown of mediator subunit Med19 suppresses bladder cancer cell proliferation and migration by downregulating Wnt/-catenin signalling pathway.J Cell Mol Med. 2017 Dec;21(12):3254-3263. doi: 10.1111/jcmm.13229. Epub 2017 Jun 19.
3 Inhibition of LCMR1 and ATG12 by demethylation-activated miR-570-3p is involved in the anti-metastasis effects of metformin on human osteosarcoma.Cell Death Dis. 2018 May 23;9(6):611. doi: 10.1038/s41419-018-0620-z.
4 Role and mechanism of miR-4778-3p and its targets NR2C2 and Med19 in cervical cancer radioresistance.Biochem Biophys Res Commun. 2019 Jan 1;508(1):210-216. doi: 10.1016/j.bbrc.2018.11.110. Epub 2018 Nov 23.
5 The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer.Br J Cancer. 2016 Nov 22;115(11):1367-1378. doi: 10.1038/bjc.2016.362. Epub 2016 Nov 3.
6 Macrocephaly associated with the DICER1 syndrome.Genet Med. 2017 Feb;19(2):244-248. doi: 10.1038/gim.2016.83. Epub 2016 Jul 21.
7 Med19 promotes gastric cancer progression and cellular growth.Gene. 2012 Aug 10;504(2):262-7. doi: 10.1016/j.gene.2012.04.033. Epub 2012 Apr 28.
8 Dynamic Interaction of Stress Granules, DDX3X, and IKK- Mediates Multiple Functions in Hepatitis C Virus Infection.J Virol. 2015 May;89(10):5462-77. doi: 10.1128/JVI.03197-14. Epub 2015 Mar 4.
9 The role of Med19 in the proliferation and tumorigenesis of human hepatocellular carcinoma cells.Acta Pharmacol Sin. 2011 Mar;32(3):354-60. doi: 10.1038/aps.2010.223.
10 Mammalian mediator 19 mediates H1299 lung adenocarcinoma cell clone conformation, growth, and metastasis.Asian Pac J Cancer Prev. 2012;13(8):3695-700. doi: 10.7314/apjcp.2012.13.8.3695.
11 Mediator of RNA polymerase II transcription subunit 19 promotes osteosarcoma growth and metastasis and associates with prognosis.Eur J Cancer. 2014 Apr;50(6):1125-36. doi: 10.1016/j.ejca.2014.01.030. Epub 2014 Feb 21.
12 Med19 is targeted by miR-101-3p/miR-422a and promotes breast cancer progression by regulating the EGFR/MEK/ERK signaling pathway.Cancer Lett. 2019 Mar 1;444:105-115. doi: 10.1016/j.canlet.2018.12.008. Epub 2018 Dec 21.
13 Knockdown of Med19 suppresses proliferation and enhances chemo-sensitivity to cisplatin in non-small cell lung cancer cells.Asian Pac J Cancer Prev. 2015;16(3):875-80. doi: 10.7314/apjcp.2015.16.3.875.
14 Knockdown of MED19 by short hairpin RNA-mediated gene silencing inhibits pancreatic cancer cell proliferation.Cancer Biother Radiopharm. 2011 Aug;26(4):495-501. doi: 10.1089/cbr.2010.0863.
15 Knockdown of Mediator Complex Subunit 19 Suppresses the Growth and Invasion of Prostate Cancer Cells.PLoS One. 2017 Jan 26;12(1):e0171134. doi: 10.1371/journal.pone.0171134. eCollection 2017.
16 A placebo-controlled trial of simvastatin therapy in Smith-Lemli-Opitz syndrome.Genet Med. 2017 Mar;19(3):297-305. doi: 10.1038/gim.2016.102. Epub 2016 Aug 11.
17 EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality.Genet Med. 2017 Feb;19(2):144-156. doi: 10.1038/gim.2016.86. Epub 2016 Jul 28.
18 LCMR1 interacts with DEK to suppress apoptosis in lung cancer cells.Mol Med Rep. 2017 Oct;16(4):4159-4164. doi: 10.3892/mmr.2017.7095. Epub 2017 Jul 27.
19 Personalized risk prediction for type 2 diabetes: the potential of genetic risk scores.Genet Med. 2017 Mar;19(3):322-329. doi: 10.1038/gim.2016.103. Epub 2016 Aug 11.
20 Down-regulation of mediator complex subunit 19 (Med19) induces apoptosis in human laryngocarcinoma HEp2 cells in an Apaf-1-dependent pathway.Am J Transl Res. 2017 Feb 15;9(2):755-761. eCollection 2017.
21 Genetic testing and genetic counseling for amyotrophic lateral sclerosis: an update for clinicians.Genet Med. 2017 Mar;19(3):267-274. doi: 10.1038/gim.2016.107. Epub 2016 Aug 18.
22 Med19 is involved in chemoresistance by mediating autophagy through HMGB1 in breast cancer.J Cell Biochem. 2019 Jan;120(1):507-518. doi: 10.1002/jcb.27406. Epub 2018 Aug 30.
23 Intratumoral genetic heterogeneity and number of cytogenetic aberrations provide additional prognostic significance in chronic lymphocytic leukemia.Genet Med. 2017 Feb;19(2):182-191. doi: 10.1038/gim.2016.81. Epub 2016 Jul 28.
24 Knockdown of mediator complex subunit 19 inhibits the growth of ovarian cancer.Mol Med Rep. 2012 Nov;6(5):1050-6. doi: 10.3892/mmr.2012.1065. Epub 2012 Sep 5.
25 A large-scale RNAi screen identifies LCMR1 as a critical regulator of Tspan8-mediated melanoma invasion.Oncogene. 2017 Jan 26;36(4):446-457. doi: 10.1038/onc.2016.219. Epub 2016 Jul 4.
26 Enrichment of mutations in chromatin regulators in people with Rett syndrome lacking mutations in MECP2.Genet Med. 2017 Jan;19(1):13-19. doi: 10.1038/gim.2016.42. Epub 2016 May 12.
27 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.
28 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.
29 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.
30 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
31 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.
32 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.