Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSL49SR)

• DOT Name: Mitochondrial calcium uniporter regulator 1 (MCUR1)
• Synonyms: MCU regulator 1; Coiled-coil domain-containing protein 90A, mitochondrial
• Gene Name: MCUR1
• Related Disease: Hepatocellular carcinoma
• UniProt ID: MCUR1_HUMAN
• Pfam ID: PF07798
• Sequence:
  MDCGSVGGQRTQRLPGRQRLLFLPVGLSGRPGGSETSARRCLSALSDGLGALRPRAPAAR
  GGVSRASPLLLLLLVPSPRLAAAAPRRQLGDWERSRLGYAAPPAGRSSAWRCSPGVAAAA
  GALPQYHGPAPALVSCRRELSLSAGSLQLERKRRDFTSSGSRKLYFDTHALVCLLEDNGF
  ATQQAEIIVSALVKILEANMDIVYKDMVTKMQQEITFQQVMSQIANVKKDMIILEKSEFS
  ALRAENEKIKLELHQLKQQVMDEVIKVRTDTKLDFNLEKSRVKELYSLNEKKLLELRTEI
  VALHAQQDRALTQTDRKIETEVAGLKTMLESHKLDNIKYLAGSIFTCLTVALGFYRLWI
• Function: Key regulator of mitochondrial calcium uniporter (MCU) required for calcium entry into mitochondrion. Plays a direct role in uniporter-mediated calcium uptake via a direct interaction with MCU. Probably involved in the assembly of the membrane components of the uniporter complex (uniplex).
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Mitochondrial calcium uniporter regulator 1 (MCUR1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mitochondrial calcium uniporter regulator 1 (MCUR1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial calcium uniporter regulator 1 (MCUR1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial calcium uniporter regulator 1 (MCUR1).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mitochondrial calcium uniporter regulator 1 (MCUR1).	[2]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Mitochondrial calcium uniporter regulator 1 (MCUR1).	[6]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Mitochondrial calcium uniporter regulator 1 (MCUR1).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mitochondrial calcium uniporter regulator 1 (MCUR1).	[9]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Mitochondrial calcium uniporter regulator 1 (MCUR1).	[10]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Mitochondrial calcium uniporter regulator 1 (MCUR1).	[8]

References

• [1] MCUR1 facilitates epithelial-mesenchymal transition and metastasis via the mitochondrial calcium dependent ROS/Nrf2/Notch pathway in hepatocellular carcinoma.J Exp Clin Cancer Res. 2019 Mar 25;38(1):136. doi: 10.1186/s13046-019-1135-x.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [8] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.