Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO9O6HS)

• DOT Name: Calcium uptake protein 3, mitochondrial (MICU3)
• Synonyms: EF-hand domain-containing family member A2
• Gene Name: MICU3
• UniProt ID: MICU3_HUMAN
• PDB ID: 6AGI; 6AGJ
• Pfam ID: PF13499
• Sequence:
  MAALRRLLWPPPRVSPPLCAHQPLLGPWGRPAVTTLGLPGRPFSSREDEERAVAEAAWRR
  RRRWGELSVAAAAGGGLVGLVCYQLYGDPRAGSPATGRPSKSAATEPEDPPRGRGMLPIP
  VAAAKETVAIGRTDIEDLDLYATSRERRFRLFASIECEGQLFMTPYDFILAVTTDEPKVA
  KTWKSLSKQELNQMLAETPPVWKGSSKLFRNLKEKGVISYTEYLFLLCILTKPHAGFRIA
  FNMFDTDGNEMVDKKEFLVLQEIFRKKNEKREIKGDEEKRAMLRLQLYGYHSPTNSVLKT
  DAEELVSRSYWDTLRRNTSQALFSDLAERADDITSLVTDTTLLVHFFGKKGKAELNFEDF
  YRFMDNLQTEVLEIEFLSYSNGMNTISEEDFAHILLRYTNVENTSVFLENVRYSIPEEKG
  ITFDEFRSFFQFLNNLEDFAIALNMYNFASRSIGQDEFKRAVYVATGLKFSPHLVNTVFK
  IFDVDKDDQLSYKEFIGIMKDRLHRGFRGYKTVQKYPTFKSCLKKELHSR
• Function: May play a role in mitochondrial calcium uptake.
• Reactome Pathway:
  Processing of SMDT1 (R-HSA-8949664)
  Mitochondrial calcium ion transport (R-HSA-8949215)

Molecular Interaction Atlas (MIA) 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 Calcium uptake protein 3, mitochondrial (MICU3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Calcium uptake protein 3, mitochondrial (MICU3).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Calcium uptake protein 3, mitochondrial (MICU3).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Calcium uptake protein 3, mitochondrial (MICU3).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Calcium uptake protein 3, mitochondrial (MICU3).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Calcium uptake protein 3, mitochondrial (MICU3).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Calcium uptake protein 3, mitochondrial (MICU3).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Calcium uptake protein 3, mitochondrial (MICU3).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Calcium uptake protein 3, mitochondrial (MICU3).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Calcium uptake protein 3, mitochondrial (MICU3).	[10]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [9] 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.
• [10] 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.