Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTICD11V)

• DOT Name: Magnesium transporter MRS2 homolog, mitochondrial (MRS2)
• Synonyms: MRS2-like protein
• Gene Name: MRS2
• Related Disease:
  Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy
  Cerebral infarction
  Stroke
  Non-insulin dependent diabetes
  Subarachnoid hemorrhage
• UniProt ID: MRS2_HUMAN
• PDB ID: 8IP3; 8IP4; 8IP5; 8IP6; 8TUL; 8TUP
• Sequence:
  MECLRSLPCLLPRAMRLPRRTLCALALDVTSVGPPVAACGRRANLIGRSRAAQLCGPDRL
  RVAGEVHRFRTSDVSQATLASVAPVFTVTKFDKQGNVTSFERKKTELYQELGLQARDLRF
  QHVMSITVRNNRIIMRMEYLKAVITPECLLILDYRNLNLEQWLFRELPSQLSGEGQLVTY
  PLPFEFRAIEALLQYWINTLQGKLSILQPLILETLDALVDPKHSSVDRSKLHILLQNGKS
  LSELETDIKIFKESILEILDEEELLEELCVSKWSDPQVFEKSSAGIDHAEEMELLLENYY
  RLADDLSNAARELRVLIDDSQSIIFINLDSHRNVMMRLNLQLTMGTFSLSLFGLMGVAFG
  MNLESSLEEDHRIFWLITGIMFMGSGLIWRRLLSFLGRQLEAPLPPMMASLPKKTLLADR
  SMELKNSLRLDGLGSGRSILTNR
• Function: Magnesium transporter that mediates the influx of magnesium into the mitochondrial matrix. Required for normal expression of the mitochondrial respiratory complex I subunits.
• Reactome Pathway: Miscellaneous transport and binding events (R-HSA-5223345)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy	DIS93Z3E	Strong	Altered Expression	[1]
Cerebral infarction	DISR1WNP	Strong	Biomarker	[2]
Stroke	DISX6UHX	Strong	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[4]
Subarachnoid hemorrhage	DISI7I8Y	Limited	Biomarker	[5]

10 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 Magnesium transporter MRS2 homolog, mitochondrial (MRS2).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Magnesium transporter MRS2 homolog, mitochondrial (MRS2).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Magnesium transporter MRS2 homolog, mitochondrial (MRS2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Magnesium transporter MRS2 homolog, mitochondrial (MRS2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Magnesium transporter MRS2 homolog, mitochondrial (MRS2).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Magnesium transporter MRS2 homolog, mitochondrial (MRS2).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Magnesium transporter MRS2 homolog, mitochondrial (MRS2).	[12]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Magnesium transporter MRS2 homolog, mitochondrial (MRS2).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Magnesium transporter MRS2 homolog, mitochondrial (MRS2).	[14]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the expression of Magnesium transporter MRS2 homolog, mitochondrial (MRS2).	[15]

References

• [1] Vitamin D levels in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).Neurol Sci. 2017 Jul;38(7):1333-1336. doi: 10.1007/s10072-017-2900-2. Epub 2017 Apr 4.
• [2] Randomization of endovascular treatment with stent-retriever and/or thromboaspiration versus best medical therapy in acute ischemic stroke due to large vessel occlusion trial: Rationale and design.Int J Stroke. 2021 Jan;16(1):100-109. doi: 10.1177/1747493019890700. Epub 2019 Dec 2.
• [3] Effect of Baroreceptor Sensitivity on Outcomes in Patients with Acute Spontaneous Intracerebral Hemorrhage.World Neurosurg. 2018 Jan;109:e754-e760. doi: 10.1016/j.wneu.2017.10.076. Epub 2017 Oct 23.
• [4] Genetic variations in magnesium-related ion channels may affect diabetes risk among African American and Hispanic American women.J Nutr. 2015 Mar;145(3):418-24. doi: 10.3945/jn.114.203489. Epub 2015 Jan 7.
• [5] Effect of simvastatin in patients with aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis.Am J Emerg Med. 2017 Dec;35(12):1940-1945. doi: 10.1016/j.ajem.2017.09.001. Epub 2017 Sep 5.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] The contact allergen nickel triggers a unique inflammatory and proangiogenic gene expression pattern via activation of NF-kappaB and hypoxia-inducible factor-1alpha. J Immunol. 2007 Mar 1;178(5):3198-207.