Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWPK14C)

• DOT Name: Small integral membrane protein 3 (SMIM3)
• Synonyms: NGF-induced differentiation clone 67 protein; Small membrane protein NID67
• Gene Name: SMIM3
• UniProt ID: SMIM3_HUMAN
• Pfam ID: PF17307
• Sequence: MDAVSQVPMEVVLPKHILDIWVIVLIILATIVIMTSLLLCPATAVIIYRMRTHPILSGAV

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Small integral membrane protein 3 (SMIM3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Small integral membrane protein 3 (SMIM3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Small integral membrane protein 3 (SMIM3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small integral membrane protein 3 (SMIM3).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Small integral membrane protein 3 (SMIM3).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Small integral membrane protein 3 (SMIM3).	[2]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Small integral membrane protein 3 (SMIM3).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Small integral membrane protein 3 (SMIM3).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Small integral membrane protein 3 (SMIM3).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Small integral membrane protein 3 (SMIM3).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Small integral membrane protein 3 (SMIM3).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Small integral membrane protein 3 (SMIM3).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Small integral membrane protein 3 (SMIM3).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Small integral membrane protein 3 (SMIM3).	[15]

2 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 increases the methylation of Small integral membrane protein 3 (SMIM3).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Small integral membrane protein 3 (SMIM3).	[14]

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] 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.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 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.
• [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] 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.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [11] Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
• [12] 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.
• [13] 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.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.