Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT76TPR2)

• DOT Name: Mitochondrial import receptor subunit TOM20 homolog (TOMM20)
• Synonyms: Mitochondrial 20 kDa outer membrane protein; Outer mitochondrial membrane receptor Tom20
• Gene Name: TOMM20
• Related Disease:
  Acute myocardial infarction
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Colorectal carcinoma
  MELAS syndrome
  Mitochondrial DNA depletion syndrome
  Neoplasm
  Neurodegeneration with brain iron accumulation 2A
  Parkinson disease
  Thyroid cancer
  Thyroid gland carcinoma
  Thyroid tumor
  Metastatic malignant neoplasm
• UniProt ID: TOM20_HUMAN
• PDB ID: 4APO; 7VBY; 7VC9
• Pfam ID: PF02064
• Sequence:
  MVGRNSAIAAGVCGALFIGYCIYFDRKRRSDPNFKNRLRERRKKQKLAKERAGLSKLPDL
  KDAEAVQKFFLEEIQLGEELLAQGEYEKGVDHLTNAIAVCGQPQQLLQVLQQTLPPPVFQ
  MLLTKLPTISQRIVSAQSLAEDDVE
• Function: Central component of the receptor complex responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with TOM22 functions as the transit peptide receptor at the surface of the mitochondrion outer membrane and facilitates the movement of preproteins into the TOM40 translocation pore. Required for the translocation across the mitochondrial outer membrane of cytochrome P450 monooxygenases.
• KEGG Pathway: Mitophagy - animal (hsa04137)
• Reactome Pathway:
  PINK1-PRKN Mediated Mitophagy (R-HSA-5205685)
  Ub-specific processing proteases (R-HSA-5689880)
  Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myocardial infarction	DISE3HTG	Strong	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Amyloidosis	DISHTAI2	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
MELAS syndrome	DIS81Z3S	Strong	Biomarker	[5]
Mitochondrial DNA depletion syndrome	DISIGZSM	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Neurodegeneration with brain iron accumulation 2A	DIS9XEBF	Strong	Biomarker	[8]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[9]
Thyroid cancer	DIS3VLDH	Strong	Biomarker	[10]
Thyroid gland carcinoma	DISMNGZ0	Strong	Biomarker	[10]
Thyroid tumor	DISLVKMD	Strong	Biomarker	[10]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[11]

11 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 Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[12]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[13]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[17]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[18]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[22]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[23]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[24]
OLEANOLIC_ACID	DMWDMJ3	Investigative	OLEANOLIC_ACID decreases the expression of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[19]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[20]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Mitochondrial import receptor subunit TOM20 homolog (TOMM20).	[21]

References

• [1] Early Aerobic Exercise Combined with Hydrogen-Rich Saline as Preconditioning Protects Myocardial Injury Induced by Acute Myocardial Infarction in Rats.Appl Biochem Biotechnol. 2019 Mar;187(3):663-676. doi: 10.1007/s12010-018-2841-0. Epub 2018 Jul 23.
• [2] TOMM20 as a potential therapeutic target of colorectal cancer.BMB Rep. 2019 Dec;52(12):712-717. doi: 10.5483/BMBRep.2019.52.12.249.
• [3] Mitochondrial Translocase of the Outer Membrane Alterations May Underlie Dysfunctional Oxidative Phosphorylation in Alzheimer's Disease.J Alzheimers Dis. 2018;61(2):793-801. doi: 10.3233/JAD-170613.
• [4] Resveratrol attenuates oxidative damage through activating mitophagy in an in vitro model of Alzheimer's disease.Toxicol Lett. 2018 Jan 5;282:100-108. doi: 10.1016/j.toxlet.2017.10.021. Epub 2017 Oct 31.
• [5] Increased number of mitochondria in capillaries distributed in stroke-like lesions of two patients with MELAS.Neuropathology. 2019 Oct;39(5):404-410. doi: 10.1111/neup.12593. Epub 2019 Aug 13.
• [6] Acute mental stress induces mitochondrial bioenergetic crisis and hyper-fission along with aberrant mitophagy in the gut mucosa in rodent model of stress-related mucosal disease.Free Radic Biol Med. 2017 Dec;113:424-438. doi: 10.1016/j.freeradbiomed.2017.10.009. Epub 2017 Oct 7.
• [7] Hodgkin lymphoma: A complex metabolic ecosystem with glycolytic reprogramming of the tumor microenvironment.Semin Oncol. 2017 Jun;44(3):218-225. doi: 10.1053/j.seminoncol.2017.10.003. Epub 2017 Oct 10.
• [8] High expression of -synuclein in damaged mitochondria with PLA2G6 dysfunction.Acta Neuropathol Commun. 2016 Mar 30;4:27. doi: 10.1186/s40478-016-0298-3.
• [9] Defective mitochondrial protein import contributes to complex I-induced mitochondrial dysfunction and neurodegeneration in Parkinson's disease.Cell Death Dis. 2018 Nov 7;9(11):1122. doi: 10.1038/s41419-018-1154-0.
• [10] Oncometabolites as biomarkers in thyroid cancer: a systematic review.Cancer Manag Res. 2019 Feb 25;11:1829-1841. doi: 10.2147/CMAR.S188661. eCollection 2019.
• [11] Tumor Metabolism in the Microenvironment of Nodal Metastasis in Oral Squamous Cell Carcinoma.Otolaryngol Head Neck Surg. 2017 Nov;157(5):798-807. doi: 10.1177/0194599817709224. Epub 2017 Jun 13.
• [12] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [13] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] 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.
• [19] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [20] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [21] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [22] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [23] 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.
• [24] An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.
• [25] Oleanolic acid induces HCT116 colon cancer cell death through the p38/FOXO3a/Sirt6 pathway. Chem Biol Interact. 2022 Aug 25;363:110010. doi: 10.1016/j.cbi.2022.110010. Epub 2022 Jun 9.