Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNTU9CB)

• DOT Name: Testis-expressed protein 10 (TEX10)
• Gene Name: TEX10
• Related Disease:
  Esophageal squamous cell carcinoma
  Neoplasm
  Pneumonitis
  Advanced cancer
  Hepatocellular carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Liver cancer
• UniProt ID: TEX10_HUMAN
• PDB ID: 8FL2; 8FL3; 8FL4
• Pfam ID: PF12333
• Sequence:
  MTKKRKRQHDFQKVKLKVGKKKPKLQNATPTNFKTKTIHLPEQLKEDGTLPTNNRKLNIK
  DLLSQMHHYNAGVKQSALLGLKDLLSQYPFIIDAHLSNILSEVTAVFTDKDANVRLAAVQ
  LLQFLAPKIRAEQISPFFPLVSAHLSSAMTHITEGIQEDSLKVLDILLEQYPALITGRSS
  ILLKNFVELISHQQLSKGLINRDRSQSWILSVNPNRRLTSQQWRLKVLVRLSKFLQALAD
  GSSRLRESEGLQEQKENPHATSNSIFINWKEHANDQQHIQVYENGGSQPNVSSQFRLRYL
  VGGLSGVDEGLSSTENLKGFIEIIIPLLIECWVEAVPPQLATPVGNGIEREPLQVMQQVL
  NIISLLWKLSKQQDETHKLESWLRKNYLIDFKHHFMSRFPYVLKEITKHKRKEPNKSIKH
  CTVLSNNIDHLLLNLTLSDIMVSLANASTLQKDCSWIEMIRKFVTETLEDGSRLNSKQLN
  RLLGVSWRLMQIQPNREDTETLIKAVYTLYQQRGLILPVRTLLLKFFSKIYQTEELRSCR
  FRYRSKVLSRWLAGLPLQLAHLGSRNPELSTQLIDIIHTAAARANKELLKSLQATALRIY
  DPQEGAVVVLPADSQQRLVQLVYFLPSLPADLLSRLSRCCIMGRLSSSLAAMLIGILHMR
  SSFSGWKYSAKDWLMSDVDYFSFLFSTLTGFSKEELTWLQSLRGVPHVIQTQLSPVLLYL
  TDLDQFLHHWDVTEAVFHSLLVIPARSQNFDILQSAISKHLVGLTVIPDSTAGCVFGVIC
  KLLDHTCVVSETLLPFLASCCYSLLYFLLTIEKGEAEHLRKRDKLWGVCVSILALLPRVL
  RLMLQSLRVNRVGPEELPVVGQLLRLLLQHAPLRTHMLTNAILVQQIIKNITTLKSGSVQ
  EQWLTDLHYCFNVYITGHPQGPSALATVY
• Function: Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes. Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit.
• KEGG Pathway: Polycomb repressive complex (hsa03083)
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Pneumonitis	DIS88E0K	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[1]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[3]
Liver cancer	DISDE4BI	Limited	Altered Expression	[3]

10 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 Testis-expressed protein 10 (TEX10).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Testis-expressed protein 10 (TEX10).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Testis-expressed protein 10 (TEX10).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Testis-expressed protein 10 (TEX10).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Testis-expressed protein 10 (TEX10).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Testis-expressed protein 10 (TEX10).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Testis-expressed protein 10 (TEX10).	[10]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Testis-expressed protein 10 (TEX10).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Testis-expressed protein 10 (TEX10).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Testis-expressed protein 10 (TEX10).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Testis-expressed protein 10 (TEX10).	[13]

References

• [1] Tex10 promotes stemness and EMT phenotypes in esophageal squamous cell carcinoma via the Wnt/catenin pathway.Oncol Rep. 2019 Dec;42(6):2600-2610. doi: 10.3892/or.2019.7376. Epub 2019 Oct 16.
• [2] Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results.J Clin Oncol. 2019 Jul 1;37(19):1608-1616. doi: 10.1200/JCO.19.00538. Epub 2019 May 17.
• [3] Tex10 is upregulated and promotes cancer stem cell properties and chemoresistance in hepatocellular carcinoma.Cell Cycle. 2018;17(11):1310-1318. doi: 10.1080/15384101.2018.1480208. Epub 2018 Jul 25.
• [4] 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.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] 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.
• [14] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.