Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV8WT2L)

• DOT Name: Mitochondrial Rho GTPase 2 (RHOT2)
• Synonyms: MIRO-2; hMiro-2; EC 3.6.5.-; Ras homolog gene family member T2
• Gene Name: RHOT2
• Related Disease:
  Adenocarcinoma
  Autism
  Cardiac disease
  Stroke
• UniProt ID: MIRO2_HUMAN
• PDB ID: 5KUT
• EC Number: 3.6.5.-
• Pfam ID: PF08355 ; PF08356 ; PF00071
• Sequence:
  MRRDVRILLLGEAQVGKTSLILSLVGEEFPEEVPPRAEEITIPADVTPEKVPTHIVDYSE
  AEQTDEELREEIHKANVVCVVYDVSEEATIEKIRTKWIPLVNGGTTQGPRVPIILVGNKS
  DLRSGSSMEAVLPIMSQFPEIETCVECSAKNLRNISELFYYAQKAVLHPTAPLYDPEAKQ
  LRPACAQALTRIFRLSDQDLDQALSDEELNAFQKSCFGHPLAPQALEDVKTVVCRNVAGG
  VREDRLTLDGFLFLNTLFIQRGRHETTWTILRRFGYSDALELTADYLSPLIHVPPGCSTE
  LNHLGYQFVQRVFEKHDQDRDGALSPVELQSLFSVFPAAPWGPELPRTVRTEAGRLPLHG
  YLCQWTLVTYLDVRSCLGHLGYLGYPTLCEQDQAHAITVTREKRLDQEKGQTQRSVLLCK
  VVGARGVGKSAFLQAFLGRGLGHQDTREQPPGYAIDTVQVNGQEKYLILCEVGTDGLLAT
  SLDATCDVACLMFDGSDPKSFAHCASVYKHHYMDGQTPCLFVSSKADLPEGVAVSGPSPA
  EFCRKHRLPAPVPFSCAGPAEPSTTIFTQLATMAAFPHLVHAELHPSSFWLRGLLGVVGA
  AVAAVLSFSLYRVLVKSQ
• Function: Mitochondrial GTPase involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution.
• Tissue Specificity: Ubiquitously expressed. Highly expressed in heart, liver, skeletal muscle, kidney and pancreas.
• KEGG Pathway: Mitophagy - animal (hsa04137)
• Reactome Pathway: RHOT2 GTPase cycle (R-HSA-9013419)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Autism	DISV4V1Z	Strong	Biomarker	[2]
Cardiac disease	DISVO1I5	Strong	Biomarker	[3]
Stroke	DISX6UHX	Limited	Biomarker	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Mitochondrial Rho GTPase 2 (RHOT2) affects the response to substance of Paclitaxel.	[13]

3 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 Mitochondrial Rho GTPase 2 (RHOT2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Mitochondrial Rho GTPase 2 (RHOT2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Mitochondrial Rho GTPase 2 (RHOT2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial Rho GTPase 2 (RHOT2).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mitochondrial Rho GTPase 2 (RHOT2).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mitochondrial Rho GTPase 2 (RHOT2).	[8]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Mitochondrial Rho GTPase 2 (RHOT2).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Mitochondrial Rho GTPase 2 (RHOT2).	[10]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Mitochondrial Rho GTPase 2 (RHOT2).	[8]

References

• [1] Frequent occurrence of Ha-rasl allelic deletion in human ovarian adenocarcinomas.Tumori. 1991 Feb 28;77(1):16-20. doi: 10.1177/030089169107700104.
• [2] High-throughput screening and classification of chemicals and their effects on neuronal gene expression using RASL-seq.Sci Rep. 2019 Mar 14;9(1):4529. doi: 10.1038/s41598-019-39016-5.
• [3] Miro2 Regulates Inter-Mitochondrial Communication in the Heart and Protects Against TAC-Induced Cardiac Dysfunction.Circ Res. 2019 Sep 27;125(8):728-743. doi: 10.1161/CIRCRESAHA.119.315432. Epub 2019 Aug 28.
• [4] Preserving Mitochondrial Structure and Motility Promotes Recovery of White Matter After Ischemia.Neuromolecular Med. 2019 Dec;21(4):484-492. doi: 10.1007/s12017-019-08550-w. Epub 2019 May 31.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] 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.
• [12] 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.
• [13] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.