Details of Drug Off-Target (DOT)

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

• DOT Name: Mediator of RNA polymerase II transcription subunit 31 (MED31)
• Synonyms: Mediator complex subunit 31; Mediator complex subunit SOH1; hSOH1
• Gene Name: MED31
• Related Disease:
  Advanced cancer
  Bone osteosarcoma
  Osteosarcoma
• UniProt ID: MED31_HUMAN
• PDB ID: 7EMF; 7ENA; 7ENC; 7ENJ; 7LBM; 7NVR; 8GXQ; 8GXS
• Pfam ID: PF05669
• Sequence:
  MAAAVAMETDDAGNRLRFQLELEFVQCLANPNYLNFLAQRGYFKDKAFVNYLKYLLYWKD
  PEYAKYLKYPQCLHMLELLQYEHFRKELVNAQCAKFIDEQQILHWQHYSRKRMRLQQALA
  EQQQQNNTSGK
• 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:
  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
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Bone osteosarcoma	DIST1004	moderate	Biomarker	[2]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[2]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Mediator of RNA polymerase II transcription subunit 31 (MED31).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mediator of RNA polymerase II transcription subunit 31 (MED31).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mediator of RNA polymerase II transcription subunit 31 (MED31).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mediator of RNA polymerase II transcription subunit 31 (MED31).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mediator of RNA polymerase II transcription subunit 31 (MED31).	[7]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Mediator of RNA polymerase II transcription subunit 31 (MED31).	[8]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Mediator of RNA polymerase II transcription subunit 31 (MED31).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Mediator of RNA polymerase II transcription subunit 31 (MED31).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Mediator of RNA polymerase II transcription subunit 31 (MED31).	[11]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mediator of RNA polymerase II transcription subunit 31 (MED31).	[9]

References

• [1] Gene expression profile of the whole Mediator complex in human osteosarcoma and normal osteoblasts.Med Oncol. 2013 Dec;30(4):739. doi: 10.1007/s12032-013-0739-9. Epub 2013 Oct 8.
• [2] MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31.Oncol Rep. 2014 Sep;32(3):1249-56. doi: 10.3892/or.2014.3274. Epub 2014 Jun 20.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [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] 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.
• [8] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [9] 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.
• [10] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.