Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDJXF99)

• DOT Name: Translation machinery-associated protein 16 (TMA16)
• Gene Name: TMA16
• Related Disease: Small-cell lung cancer
• UniProt ID: TMA16_HUMAN
• PDB ID: 6LSS; 6LU8; 8FLA; 8FLB; 8FLC; 8IDT; 8IDY; 8INE; 8INF
• Pfam ID: PF11176
• Sequence:
  MPKAPKGKSAGREKKVIHPYSRKAAQITREAHKQEKKEKLKNEKALRLNLVGEKLQWFQN
  HLDPQKKRYSKKDACELIERYLNRFSSELEQIELHNSIRDRQGRRHCSRETVIKQTMERE
  RQQFEGYGLEIPDILNASNLKTFREWDFDLKKLPNIKMRKICANDAIPKTCKRKTIITVD
  QDLGELELNDESSDSDEEMTAVA
• Function: Involved in the biogenesis of the 60S ribosomal subunit in the nucleus.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Small-cell lung cancer	DISK3LZD	Limited	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Translation machinery-associated protein 16 (TMA16).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Translation machinery-associated protein 16 (TMA16).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Translation machinery-associated protein 16 (TMA16).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Translation machinery-associated protein 16 (TMA16).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Translation machinery-associated protein 16 (TMA16).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Translation machinery-associated protein 16 (TMA16).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Translation machinery-associated protein 16 (TMA16).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Translation machinery-associated protein 16 (TMA16).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Translation machinery-associated protein 16 (TMA16).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Translation machinery-associated protein 16 (TMA16).	[11]

References

• [1] Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.Nat Genet. 2017 Jul;49(7):1126-1132. doi: 10.1038/ng.3892. Epub 2017 Jun 12.
• [2] 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.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] 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.
• [11] 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.