Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7WS6ZI)

• DOT Name: Tetraspanin-3 (TSPAN3)
• Synonyms: Tspan-3; Tetraspanin TM4-A; Transmembrane 4 superfamily member 8
• Gene Name: TSPAN3
• Related Disease:
  Acute myelogenous leukaemia
  Acute undifferentiated leukemia
  Alzheimer disease
  Alzheimer disease 3
  Leukemia
  Neuroblastoma
  Non-insulin dependent diabetes
• UniProt ID: TSN3_HUMAN
• Pfam ID: PF00335
• Sequence:
  MGQCGITSSKTVLVFLNLIFWGAAGILCYVGAYVFITYDDYDHFFEDVYTLIPAVVIIAV
  GALLFIIGLIGCCATIRESRCGLATFVIILLLVFVTEVVVVVLGYVYRAKVENEVDRSIQ
  KVYKTYNGTNPDAASRAIDYVQRQLHCCGIHNYSDWENTDWFKETKNQSVPLSCCRETAS
  NCNGSLAHPSDLYAEGCEALVVKKLQEIMMHVIWAALAFAAIQLLGMLCACIVLCRRSRD
  PAYELLITGGTYA
• Function: Regulates the proliferation and migration of oligodendrocytes, a process essential for normal myelination and repair.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[1]
Acute undifferentiated leukemia	DISJ4SSG	Strong	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Alzheimer disease 3	DISVT69G	Strong	Altered Expression	[3]
Leukemia	DISNAKFL	Strong	Biomarker	[2]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Tetraspanin-3 (TSPAN3).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tetraspanin-3 (TSPAN3).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Tetraspanin-3 (TSPAN3).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tetraspanin-3 (TSPAN3).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tetraspanin-3 (TSPAN3).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tetraspanin-3 (TSPAN3).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tetraspanin-3 (TSPAN3).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tetraspanin-3 (TSPAN3).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Tetraspanin-3 (TSPAN3).	[13]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Tetraspanin-3 (TSPAN3).	[14]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Tetraspanin-3 (TSPAN3).	[15]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Tetraspanin-3 (TSPAN3).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tetraspanin-3 (TSPAN3).	[18]

1 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 Tetraspanin-3 (TSPAN3).	[17]

References

• [1] LncRNA KCNQ1OT1 contributes to the progression and chemoresistance in acute myeloid leukemia by modulating Tspan3 through suppressing miR-193a-3p.Life Sci. 2020 Jan 15;241:117161. doi: 10.1016/j.lfs.2019.117161. Epub 2019 Dec 11.
• [2] Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia.Cell Stem Cell. 2015 Aug 6;17(2):152-164. doi: 10.1016/j.stem.2015.06.006. Epub 2015 Jul 23.
• [3] Tetraspanin 3: A central endocytic membrane component regulating the expression of ADAM10, presenilin and the amyloid precursor protein.Biochim Biophys Acta Mol Cell Res. 2017 Jan;1864(1):217-230. doi: 10.1016/j.bbamcr.2016.11.003. Epub 2016 Nov 3.
• [4] Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population.Nat Genet. 2019 Mar;51(3):379-386. doi: 10.1038/s41588-018-0332-4. Epub 2019 Feb 4.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [11] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [12] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [13] 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.
• [14] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [15] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [16] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [17] 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.
• [18] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.