Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTULV5TA)

• DOT Name: Transketolase-like protein 2 (TKTL2)
• Synonyms: EC 2.2.1.1
• Gene Name: TKTL2
• Related Disease:
  Advanced cancer
  Colon cancer
  Colon carcinoma
  Hepatocellular carcinoma
  Type-1/2 diabetes
• UniProt ID: TKTL2_HUMAN
• EC Number: 2.2.1.1
• Pfam ID: PF02779 ; PF02780 ; PF00456
• Sequence:
  MMANDAKPDVKTVQVLRDTANRLRIHSIRATCASGSGQLTSCCSAAEVVSVLFFHTMKYK
  QTDPEHPDNDRFILSRGHAAPILYAAWVEVGDISESDLLNLRKLHSDLERHPTPRLPFVD
  VATGSLGQGLGTACGMAYTGKYLDKASYRVFCLMGDGESSEGSVWEAFAFASHYNLDNLV
  AVFDVNRLGQSGPAPLEHGADIYQNCCEAFGWNTYLVDGHDVEALCQAFWQASQVKNKPT
  AIVAKTFKGRGIPNIEDAENWHGKPVPKERADAIVKLIESQIQTNENLIPKSPVEDSPQI
  SITDIKMTSPPAYKVGDKIATQKTYGLALAKLGRANERVIVLSGDTMNSTFSEIFRKEHP
  ERFIECIIAEQNMVSVALGCATRGRTIAFAGAFAAFFTRAFDQLRMGAISQANINLIGSH
  CGVSTGEDGVSQMALEDLAMFRSIPNCTVFYPSDAISTEHAIYLAANTKGMCFIRTSQPE
  TAVIYTPQENFEIGQAKVVRHGVNDKVTVIGAGVTLHEALEAADHLSQQGISVRVIDPFT
  IKPLDAATIISSAKATGGRVITVEDHYREGGIGEAVCAAVSREPDILVHQLAVSGVPQRG
  KTSELLDMFGISTRHIIAAVTLTLMK
• Function: Plays an essential role in total transketolase activity and cell proliferation in cancer cells; after transfection with anti-TKTL1 siRNA, total transketolase activity dramatically decreases and proliferation was significantly inhibited in cancer cells. Plays a pivotal role in carcinogenesis.
• Tissue Specificity: Overexpressed in hepatoma cancer cells.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[2]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[1]

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 Transketolase-like protein 2 (TKTL2).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transketolase-like protein 2 (TKTL2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transketolase-like protein 2 (TKTL2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Transketolase-like protein 2 (TKTL2).	[7]

References

• [1] The human transketolase-like proteins TKTL1 and TKTL2 are bona fide transketolases.BMC Struct Biol. 2019 Jan 15;19(1):2. doi: 10.1186/s12900-018-0099-y.
• [2] The TKTL1 gene influences total transketolase activity and cell proliferation in human colon cancer LoVo cells.Anticancer Drugs. 2007 Apr;18(4):427-33. doi: 10.1097/CAD.0b013e328013d99e.
• [3] Gene silencing of TKTL1 by RNAi inhibits cell proliferation in human hepatoma cells.Cancer Lett. 2007 Aug 8;253(1):108-14. doi: 10.1016/j.canlet.2007.01.010. Epub 2007 Feb 23.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.