Details of Drug Off-Target (DOT)

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

• DOT Name: Tetraspanin-17 (TSPAN17)
• Synonyms: Tspan-17; F-box only protein 23; Tetraspan protein SB134; Transmembrane 4 superfamily member 17
• Gene Name: TSPAN17
• Related Disease: Neoplasm
• UniProt ID: TSN17_HUMAN
• Pfam ID: PF00335
• Sequence:
  MPGKHQHFQEPEVGCCGKYFLFGFNIVFWVLGALFLAIGLWAWGEKGVLSNISALTDLGG
  LDPVWLFVVVGGVMSVLGFAGCIGALRENTFLLKFFSVFLGLIFFLELATGILAFVFKDW
  IRDQLNLFINNNVKAYRDDIDLQNLIDFAQEYWSCCGARGPNDWNLNIYFNCTDLNPSRE
  RCGVPFSCCVRDPAEDVLNTQCGYDVRLKLELEQQGFIHTKGCVGQFEKWLQDNLIVVAG
  VFMGIALLQIFGICLAQNLVSDIKAVKANW
• Function: Part of TspanC8 subgroup, composed of 6 members that interact with the transmembrane metalloprotease ADAM10. This interaction is required for ADAM10 exit from the endoplasmic reticulum and for enzymatic maturation and trafficking to the cell surface as well as substrate specificity. Different TspanC8/ADAM10 complexes have distinct substrates. Seems to regulate VE-cadherin expression in endothelial cells probably through interaction with ADAM10, promoting leukocyte transmigration.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Tetraspanin-17 (TSPAN17).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tetraspanin-17 (TSPAN17).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tetraspanin-17 (TSPAN17).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tetraspanin-17 (TSPAN17).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tetraspanin-17 (TSPAN17).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tetraspanin-17 (TSPAN17).	[7]

References

• [1] miR?78a?p inhibits cellular proliferation and migration in glioblastoma multiforme by targeting tetraspanin 17.Oncol Rep. 2019 Nov;42(5):1957-1971. doi: 10.3892/or.2019.7283. Epub 2019 Aug 20.
• [2] 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.
• [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] 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.
• [5] 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.
• [6] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [7] 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.