Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT29167O)

• DOT Name: Tetraspanin-14 (TSPAN14)
• Synonyms: Tspan-14; DC-TM4F2; Transmembrane 4 superfamily member 14
• Gene Name: TSPAN14
• Related Disease:
  Non-small-cell lung cancer
  Chronic obstructive pulmonary disease
  Coronary heart disease
  Ankylosing spondylitis
  Crohn disease
  Inflammatory bowel disease
  Psoriasis
  Sclerosing cholangitis
  Ulcerative colitis
• UniProt ID: TSN14_HUMAN
• Pfam ID: PF00335
• Sequence:
  MHYYRYSNAKVSCWYKYLLFSYNIIFWLAGVVFLGVGLWAWSEKGVLSDLTKVTRMHGID
  PVVLVLMVGVVMFTLGFAGCVGALRENICLLNFFCGTIVLIFFLELAVAVLAFLFQDWVR
  DRFREFFESNIKSYRDDIDLQNLIDSLQKANQCCGAYGPEDWDLNVYFNCSGASYSREKC
  GVPFSCCVPDPAQKVVNTQCGYDVRIQLKSKWDESIFTKGCIQALESWLPRNIYIVAGVF
  IAISLLQIFGIFLARTLISDIEAVKAGHHF
• 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. Negatively regulates ADAM10-mediated cleavage of GP6. Promotes ADAM10-mediated cleavage of CDH5.
• Reactome Pathway:
  Amyloid fiber formation (R-HSA-977225)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Genetic Variation	[1]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[3]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[4]
Crohn disease	DIS2C5Q8	Limited	Genetic Variation	[5]
Inflammatory bowel disease	DISGN23E	Limited	Genetic Variation	[5]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[4]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[4]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[4]

4 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-14 (TSPAN14).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Tetraspanin-14 (TSPAN14).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tetraspanin-14 (TSPAN14).	[16]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Tetraspanin-14 (TSPAN14).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tetraspanin-14 (TSPAN14).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Tetraspanin-14 (TSPAN14).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tetraspanin-14 (TSPAN14).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tetraspanin-14 (TSPAN14).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tetraspanin-14 (TSPAN14).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Tetraspanin-14 (TSPAN14).	[13]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tetraspanin-14 (TSPAN14).	[14]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Tetraspanin-14 (TSPAN14).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Tetraspanin-14 (TSPAN14).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Tetraspanin-14 (TSPAN14).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Tetraspanin-14 (TSPAN14).	[19]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Tetraspanin-14 (TSPAN14).	[20]

References

• [1] Identification of genes associated with non-small-cell lung cancer promotion and progression.Lung Cancer. 2010 Feb;67(2):151-9. doi: 10.1016/j.lungcan.2009.04.010. Epub 2009 May 26.
• [2] Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations.Nat Genet. 2019 Mar;51(3):494-505. doi: 10.1038/s41588-018-0342-2. Epub 2019 Feb 25.
• [3] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [4] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [5] Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.Nat Genet. 2017 Feb;49(2):256-261. doi: 10.1038/ng.3760. Epub 2017 Jan 9.
• [6] 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.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [9] 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.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
• [13] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [14] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [15] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [16] 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.
• [17] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [18] 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.
• [19] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [20] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.