Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH6MITE)

• DOT Name: Mitochondrial import receptor subunit TOM34 (TOMM34)
• Synonyms: hTom34; Translocase of outer membrane 34 kDa subunit
• Gene Name: TOMM34
• Related Disease:
  Advanced cancer
  Breast carcinoma
  Carcinoma
  Colonic neoplasm
  Colorectal carcinoma
  Colorectal neoplasm
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Mucinous adenocarcinoma
  Neoplasm
  Ovarian cancer
  Invasive breast carcinoma
  Transitional cell carcinoma
  Urothelial carcinoma
• UniProt ID: TOM34_HUMAN
• Pfam ID: PF00515
• Sequence:
  MAPKFPDSVEELRAAGNESFRNGQYAEASALYGRALRVLQAQGSSDPEEESVLYSNRAAC
  HLKDGNCRDCIKDCTSALALVPFSIKPLLRRASAYEALEKYPMAYVDYKTVLQIDDNVTS
  AVEGINRMTRALMDSLGPEWRLKLPSIPLVPVSAQKRWNSLPSENHKEMAKSKSKETTAT
  KNRVPSAGDVEKARVLKEEGNELVKKGNHKKAIEKYSESLLCSNLESATYSNRALCYLVL
  KQYTEAVKDCTEALKLDGKNVKAFYRRAQAHKALKDYKSSFADISNLLQIEPRNGPAQKL
  RQEVKQNLH
• Function: Plays a role in the import of cytosolically synthesized preproteins into mitochondria. Binds the mature portion of precursor proteins. Interacts with cellular components, and possesses weak ATPase activity. May be a chaperone-like protein that helps to keep newly synthesized precursors in an unfolded import compatible state.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Carcinoma	DISH9F1N	Strong	Altered Expression	[1]
Colonic neoplasm	DISSZ04P	Strong	Biomarker	[3]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[4]
Colorectal neoplasm	DISR1UCN	Strong	Altered Expression	[5]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Lung cancer	DISCM4YA	Strong	Altered Expression	[7]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[7]
Mucinous adenocarcinoma	DISKNFE8	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[1]
Invasive breast carcinoma	DISANYTW	Disputed	Altered Expression	[8]
Transitional cell carcinoma	DISWVVDR	Limited	Altered Expression	[2]
Urothelial carcinoma	DISRTNTN	Limited	Altered Expression	[2]

13 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 import receptor subunit TOM34 (TOMM34).	[9]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[11]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[14]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[15]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[18]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[19]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[20]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Mitochondrial import receptor subunit TOM34 (TOMM34).	[21]

1 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 decreases the methylation of Mitochondrial import receptor subunit TOM34 (TOMM34).	[16]

References

• [1] Tomm34 is commonly expressed in epithelial ovarian cancer and associates with tumour type and high FIGO stage.J Ovarian Res. 2019 Mar 27;12(1):30. doi: 10.1186/s13048-019-0498-0.
• [2] Expression of TOMM34 and Its Clinicopathological Correlations in Urothelial Carcinoma of the Bladder.Pathol Oncol Res. 2020 Jan;26(1):411-418. doi: 10.1007/s12253-018-0524-3. Epub 2018 Oct 31.
• [3] Identification of TOMM34, which shows elevated expression in the majority of human colon cancers, as a novel drug target.Int J Oncol. 2006 Aug;29(2):381-6.
• [4] Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.Cancer Sci. 2018 May;109(5):1545-1551. doi: 10.1111/cas.13547. Epub 2018 Mar 31.
• [5] RT-qPCR analysis of the tumor antigens TOMM34 and RNF43 in samples extracted from paraffin-embedded specimens of colorectal cancer.Oncol Lett. 2017 Aug;14(2):2281-2287. doi: 10.3892/ol.2017.6412. Epub 2017 Jun 19.
• [6] Overexpression of heat shock protein HSP90AA1 and translocase of the outer mitochondrial membrane TOM34 in HCV-induced hepatocellular carcinoma: A pilot study.Clin Biochem. 2019 Jan;63:10-17. doi: 10.1016/j.clinbiochem.2018.12.001. Epub 2018 Dec 3.
• [7] Differential Expression of TOM34, AL1A1, PADI2 and KLRBA in NNK Induced Lung Cancer in Wistar Rats and their Implications.Curr Cancer Drug Targets. 2019;19(11):919-929. doi: 10.2174/1871525717666190717162646.
• [8] TOMM34 expression in early invasive breast cancer: a biomarker associated with poor outcome.Breast Cancer Res Treat. 2012 Nov;136(2):419-27. doi: 10.1007/s10549-012-2249-4. Epub 2012 Oct 4.
• [9] 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.
• [10] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [11] 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.
• [12] 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.
• [13] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [14] 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.
• [15] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [16] 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.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [19] 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.
• [20] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [21] 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.