Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY3EW73)

• DOT Name: Mapk-regulated corepressor-interacting protein 1 (MCRIP1)
• Synonyms: Granulin-2; Protein FAM195B
• Gene Name: MCRIP1
• UniProt ID: MCRI1_HUMAN
• Pfam ID: PF14799
• Sequence:
  MTSSPVSRVVYNGKRTSSPRSPPSSSEIFTPAHEENVRFIYEAWQGVERDLRGQVPGGER
  GLVEEYVEKVPNPSLKTFKPIDLSDLKRRSTQDAKKS
• Function: The phosphorylation status of MCRIP1 functions as a molecular switch to regulate epithelial-mesenchymal transition. Unphosphorylated MCRIP1 binds to and inhibits the transcriptional corepressor CTBP(s). When phosphorylated by MAPK/ERK, MCRIP1 releases CTBP(s) resulting in transcriptional silencing of the E-cadherin gene and induction of epithelial-mesenchymal transition.

Molecular Interaction Atlas (MIA) 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 increases the methylation of Mapk-regulated corepressor-interacting protein 1 (MCRIP1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Mapk-regulated corepressor-interacting protein 1 (MCRIP1).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mapk-regulated corepressor-interacting protein 1 (MCRIP1).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mapk-regulated corepressor-interacting protein 1 (MCRIP1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mapk-regulated corepressor-interacting protein 1 (MCRIP1).	[4]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Mapk-regulated corepressor-interacting protein 1 (MCRIP1).	[6]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Mapk-regulated corepressor-interacting protein 1 (MCRIP1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Mapk-regulated corepressor-interacting protein 1 (MCRIP1).	[8]

References

• [1] 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.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] 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.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] 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.
• [6] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [7] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.