Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT9RKL6)

• DOT Name: Transmembrane 7 superfamily member 3 (TM7SF3)
• Synonyms: Seven span transmembrane protein
• Gene Name: TM7SF3
• UniProt ID: TM7S3_HUMAN
• Pfam ID: PF13886
• Sequence:
  MGFLQLLVVAVLASEHRVAGAAEVFGNSSEGLIEFSVGKFRYFELNRPFPEEAILHDISS
  NVTFLIFQIHSQYQNTTVSFSPTLLSNSSETGTASGLVFILRPEQSTCTWYLGTSGIQPV
  QNMAILLSYSERDPVPGGCNLEFDLDIDPNIYLEYNFFETTIKFAPANLGYARGVDPPPC
  DAGTDQDSRWRLQYDVYQYFLPENDLTEEMLLKHLQRMVSVPQVKASALKVVTLTANDKT
  SVSFSSLPGQGVIYNVIVWDPFLNTSAAYIPAHTYACSFEAGEGSCASLGRVSSKVFFTL
  FALLGFFICFFGHRFWKTELFFIGFIIMGFFFYILITRLTPIKYDVNLILTAVTGSVGGM
  FLVAVWWRFGILSICMLCVGLVLGFLISSVTFFTPLGNLKIFHDDGVFWVTFSCIAILIP
  VVFMGCLRILNILTCGVIGSYSVVLAIDSYWSTSLSYITLNVLKRALNKDFHRAFTNVPF
  QTNDFIILAVWGMLAVSGITLQIRRERGRPFFPPHPYKLWKQERERRVTNILDPSYHIPP
  LRERLYGRLTQIKGLFQKEQPAGERTPLLL
• Function: Involved in the inhibition of cytokine-induced death of pancreatic beta cells. Involved in the promotion of insulin secretion from pancreatic beta cells. Is a downstream transcriptional target of p53/TP53, and acts as a pro-survival homeostatic factor that attenuates the development of cellular stress. Maintains protein homeostasis and promotes cell survival through attenuation of endoplasmic reticulum (ER) stress and the subsequent induction of unfolded protein response (UPR).
• Tissue Specificity: Widely expressed. Highly expressed in kidney and pancreas.

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 decreases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[8]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[9]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[12]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Transmembrane 7 superfamily member 3 (TM7SF3).	[13]

References

• [1] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Identification of novel biomarkers for doxorubicin-induced toxicity in human cardiomyocytes derived from pluripotent stem cells. Toxicology. 2015 Feb 3;328:102-11. doi: 10.1016/j.tox.2014.12.018. Epub 2014 Dec 18.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [10] Growth-suppressive effect of non-steroidal anti-inflammatory drugs on 11 colon-cancer cell lines and fluorescence differential display of genes whose expression is influenced by sulindac. Int J Cancer. 2000 Dec 15;88(6):873-80. doi: 10.1002/1097-0215(20001215)88:6<873::aid-ijc6>3.0.co;2-b.
• [11] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [13] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.