Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL4LIHB)

• DOT Name: Tetraspanin-10 (TSPAN10)
• Synonyms: Tspan-10; Oculospanin
• Gene Name: TSPAN10
• Related Disease:
  Myocardial infarction
  Stroke
  Myopia
• UniProt ID: TSN10_HUMAN
• Pfam ID: PF00335
• Sequence:
  MEEGERSPLLSQETAGQKPLSVHRPPTSGCLGPVPREDQAEAWGCSCCPPETKHQALSGT
  PKKGPAPSLSPGSSCVKYLIFLSNFPFSLLGLLALAIGLWGLAVKGSLGSDLGGPLPTDP
  MLGLALGGLVVSAASLAGCLGALCENTCLLRGFSGGILAFLVLEAVAGALVVALWGPLQD
  SLEHTLRVAIAHYQDDPDLRFLLDQVQLGLRCCGAASYQDWQQNLYFNCSSPGVQACSLP
  ASCCIDPREDGASVNDQCGFGVLRLDADAAQRVVYLEGCGPPLRRWLRANLAASGGYAIA
  VVLLQGAELLLAARLLGALAARSGAAYGPGAHGEDRAGPQSPSPGAPPAAKPARG
• 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.
• Tissue Specificity: Expressed in the eye, including iris, ciliary body, retinal pigment epithelium, but not lens (protein level).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Definitive	Biomarker	[1]
Stroke	DISX6UHX	Definitive	Biomarker	[1]
Myopia	DISK5S60	Limited	Genetic Variation	[2]

2 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-10 (TSPAN10).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Tetraspanin-10 (TSPAN10).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tetraspanin-10 (TSPAN10).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tetraspanin-10 (TSPAN10).	[5]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Tetraspanin-10 (TSPAN10).	[6]
AM251	DMTAWHL	Investigative	AM251 increases the expression of Tetraspanin-10 (TSPAN10).	[8]

References

• [1] Heritability of ischemic stroke in relation to age, vascular risk factors, and subtypes of incident stroke in population-based studies.Stroke. 2004 Apr;35(4):819-24. doi: 10.1161/01.STR.0000121646.23955.0f. Epub 2004 Mar 4.
• [2] Detection and interpretation of shared genetic influences on 42 human traits.Nat Genet. 2016 Jul;48(7):709-17. doi: 10.1038/ng.3570. Epub 2016 May 16.
• [3] 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.
• [4] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [5] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [6] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [7] 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.
• [8] Cannabinoid derivatives induce cell death in pancreatic MIA PaCa-2 cells via a receptor-independent mechanism. FEBS Lett. 2006 Mar 20;580(7):1733-9.