Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT25O8ME)

• DOT Name: Tubulin polyglutamylase complex subunit 2 (TPGS2)
• Synonyms: PGs2
• Gene Name: TPGS2
• Related Disease:
  Colonic neoplasm
  Neoplasm
  Type-1 diabetes
  Type-1/2 diabetes
• UniProt ID: TPGS2_HUMAN
• Sequence:
  MEEEASSPGLGCSKPHLEKLTLGITRILESSPGVTEVTIIEKPPAERHMISSWEQKNNCV
  MPEDVKNFYLMTNGFHMTWSVKLDEHIIPLGSMAINSISKLTQLTQSSMYSLPNAPTLAD
  LEDDTHEASDDQPEKPHFDSRSVIFELDSCNGSGKVCLVYKSGKPALAEDTEIWFLDRAL
  YWHFLTDTFTAYYRLLITHLGLPQWQYAFTSYGISPQAKQWFSMYKPITYNTNLLTEETD
  SFVNKLDPSKVFKSKNKIVIPKKKGPVQPAGGQKGPSGPSGPSTSSTSKSSSGSGNPTRK
• Function: Subunit of the tubulin polyglutamylase complex (TPGC). The complex mediates cilia and flagella polyglutamylation which is essential for their biogenesis and motility.
• Reactome Pathway: Carboxyterminal post-translational modifications of tubulin (R-HSA-8955332)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Type-1 diabetes	DIS7HLUB	Strong	Altered Expression	[2]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tubulin polyglutamylase complex subunit 2 (TPGS2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tubulin polyglutamylase complex subunit 2 (TPGS2).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tubulin polyglutamylase complex subunit 2 (TPGS2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Tubulin polyglutamylase complex subunit 2 (TPGS2).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Tubulin polyglutamylase complex subunit 2 (TPGS2).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tubulin polyglutamylase complex subunit 2 (TPGS2).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tubulin polyglutamylase complex subunit 2 (TPGS2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Tubulin polyglutamylase complex subunit 2 (TPGS2).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Tubulin polyglutamylase complex subunit 2 (TPGS2).	[12]

References

• [1] Metabolic alterations of zinc and prostaglandins in both human and animal colonic tumor cells.J Am Coll Nutr. 1995 Oct;14(5):473-9. doi: 10.1080/07315724.1995.10718538.
• [2] IL10 resistant PGS2 expression in at-risk/Type 1 diabetic human monocytes.J Autoimmun. 2004 May;22(3):227-33. doi: 10.1016/j.jaut.2003.12.006.
• [3] Aberrant prostaglandin synthase 2 expression defines an antigen-presenting cell defect for insulin-dependent diabetes mellitus.J Clin Invest. 1999 Aug;104(4):515-23. doi: 10.1172/JCI4852.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell. 2004 Mar;15(3):1262-72. doi: 10.1091/mbc.e03-06-0360. Epub 2003 Dec 29.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.