Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGZO1MT)

• DOT Name: Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B)
• Synonyms: DDP-like protein; Deafness dystonia protein 2
• Gene Name: TIMM8B
• Related Disease: Deafness dystonia syndrome
• UniProt ID: TIM8B_HUMAN
• Pfam ID: PF02953
• Sequence:
  MAELGEADEAELQRLVAAEQQKAQFTAQVHHFMELCWDKCVEKPGNRLDSRTENCLSSCV
  DRFIDTTLAITSRFAQIVQKGGQ
• Function: Probable mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space.
• Tissue Specificity: Ubiquitous, with highest expression in heart, kidney, liver and skeletal muscle.
• Reactome Pathway: Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Deafness dystonia syndrome	DIS0480U	Limited	Biomarker	[1]

12 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 inner membrane translocase subunit Tim8 B (TIMM8B).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[7]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[9]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[12]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mitochondrial import inner membrane translocase subunit Tim8 B (TIMM8B).	[6]

References

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• [2] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [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] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [10] 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.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.