Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ1GUD9)

• DOT Name: SERTA domain-containing protein 4 (SERTAD4)
• Gene Name: SERTAD4
• UniProt ID: SRTD4_HUMAN
• Pfam ID: PF06031
• Sequence:
  MTLVLSMNRFCEPIVSEGAAEIAGYQTLWEADSYGGPSPPGPAQAPLQGDRGAGPPLAGS
  HYRGISNPITTSKITYFKRKYVEEEDFHPPLSSCSHKTISIFEERAHILYMSLEKLKFID
  DPEVYLRRSVLINNLMKRIHGEIIMQNNWCFPACSFNGTSAQEWFMAQDCPYRKRPRMAK
  EECEKFHACCFYQECGGHYLNLPLSVNANVGSASTAASSPSASSSSSSSSSSPPLPLPSC
  SRQVDFDVGSASIYKSDGQIPANEIFVTNVRSLGVQEKAKLNDEKANDDTNRDGGPLSHE
  PVGNDLAFECKGQFYDYFETGYNERNNVNESWKKSLRKKEASPPSNKLCCSKGSKI

Molecular Interaction Atlas (MIA) of This DOT

3 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 SERTA domain-containing protein 4 (SERTAD4).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of SERTA domain-containing protein 4 (SERTAD4).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of SERTA domain-containing protein 4 (SERTAD4).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SERTA domain-containing protein 4 (SERTAD4).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of SERTA domain-containing protein 4 (SERTAD4).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of SERTA domain-containing protein 4 (SERTAD4).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of SERTA domain-containing protein 4 (SERTAD4).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of SERTA domain-containing protein 4 (SERTAD4).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of SERTA domain-containing protein 4 (SERTAD4).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of SERTA domain-containing protein 4 (SERTAD4).	[9]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of SERTA domain-containing protein 4 (SERTAD4).	[10]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of SERTA domain-containing protein 4 (SERTAD4).	[11]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of SERTA domain-containing protein 4 (SERTAD4).	[12]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of SERTA domain-containing protein 4 (SERTAD4).	[13]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of SERTA domain-containing protein 4 (SERTAD4).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SERTA domain-containing protein 4 (SERTAD4).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of SERTA domain-containing protein 4 (SERTAD4).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of SERTA domain-containing protein 4 (SERTAD4).	[18]

References

• [1] 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.
• [2] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] 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.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [10] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [11] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [12] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [13] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [14] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [15] 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.
• [16] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [17] 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.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.