Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTDPQF1)

• DOT Name: Tetraspanin-2 (TSPAN2)
• Synonyms: Tspan-2; Tetraspan NET-3
• Gene Name: TSPAN2
• Related Disease:
  Migraine with aura
  Stroke
  Lung cancer
  Lung carcinoma
  Meningioma
  Metastatic malignant neoplasm
  Advanced cancer
• UniProt ID: TSN2_HUMAN
• Pfam ID: PF00335
• Sequence:
  MGRFRGGLRCIKYLLLGFNLLFWLAGSAVIAFGLWFRFGGAIKELSSEDKSPEYFYVGLY
  VLVGAGALMMAVGFFGCCGAMRESQCVLGSFFTCLLVIFAAEVTTGVFAFIGKGVAIRHV
  QTMYEEAYNDYLKDRGKGNGTLITFHSTFQCCGKESSEQVQPTCPKELLGHKNCIDEIET
  IISVKLQLIGIVGIGIAGLTIFGMIFSMVLCCAIRNSRDVI
• Function: May play a role in signalling in oligodendrocytes in the early stages of their terminal differentiation into myelin-forming glia and may also function in stabilizing the mature sheath.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Migraine with aura	DISDM7I8	Strong	Genetic Variation	[1]
Stroke	DISX6UHX	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	moderate	Biomarker	[3]
Lung carcinoma	DISTR26C	moderate	Biomarker	[3]
Meningioma	DISPT4TG	moderate	Genetic Variation	[4]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[5]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[5]

13 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 Tetraspanin-2 (TSPAN2).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tetraspanin-2 (TSPAN2).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tetraspanin-2 (TSPAN2).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tetraspanin-2 (TSPAN2).	[9]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Tetraspanin-2 (TSPAN2).	[10]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Tetraspanin-2 (TSPAN2).	[11]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tetraspanin-2 (TSPAN2).	[12]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Tetraspanin-2 (TSPAN2).	[13]
Rofecoxib	DM3P5DA	Approved	Rofecoxib decreases the expression of Tetraspanin-2 (TSPAN2).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tetraspanin-2 (TSPAN2).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tetraspanin-2 (TSPAN2).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tetraspanin-2 (TSPAN2).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Tetraspanin-2 (TSPAN2).	[19]

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-2 (TSPAN2).	[15]

References

• [1] Replication study of previous migraine genome-wide association study findings in a Spanish sample of migraine with aura.Cephalalgia. 2015 Aug;35(9):776-82. doi: 10.1177/0333102414557841. Epub 2014 Nov 11.
• [2] Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.Nat Genet. 2018 Apr;50(4):524-537. doi: 10.1038/s41588-018-0058-3. Epub 2018 Mar 12.
• [3] TSPAN2 is involved in cell invasion and motility during lung cancer progression.Cell Rep. 2014 Apr 24;7(2):527-538. doi: 10.1016/j.celrep.2014.03.027. Epub 2014 Apr 13.
• [4] A comparison of the prevalence and risk factors of complications in intracranial tumor embolization between the Japanese Registry of NeuroEndovascular Therapy 2 (JR-NET2) and JR-NET3.Acta Neurochir (Wien). 2019 Aug;161(8):1675-1682. doi: 10.1007/s00701-019-03970-w. Epub 2019 Jun 7.
• [5] Tspan2: a tetraspanin protein involved in oligodendrogenesis and cancer metastasis.Biochem Soc Trans. 2017 Apr 15;45(2):465-475. doi: 10.1042/BST20160022.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [8] 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.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [11] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [12] 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.
• [13] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [14] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [17] 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.
• [18] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [19] 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.