Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEEHL60)

• DOT Name: Protein Tob2 (TOB2)
• Synonyms: Protein Tob4; Transducer of erbB-2 2
• Gene Name: TOB2
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Vitiligo
  Periodontitis
• UniProt ID: TOB2_HUMAN
• Pfam ID: PF07742 ; PF07145
• Sequence:
  MQLEIKVALNFIISYLYNKLPRRRADLFGEELERLLKKKYEGHWYPEKPLKGSGFRCVHI
  GEMVDPVVELAAKRSGLAVEDVRANVPEELSVWIDPFEVSYQIGEKGAVKVLYLDDSEGC
  GAPELDKEIKSSFNPDAQVFVPIGSQDSSLSNSPSPSFGQSPSPTFIPRSAQPITFTTAS
  FAATKFGSTKMKKGGGAASGGGVASSGAGGQQPPQQPRMARSPTNSLLKHKSLSLSMHSL
  NFITANPAPQSQLSPNAKEFVYNGGGSPSLFFDAADGQGSGTPGPFGGSGAGTCNSSSFD
  MAQVFGGGANSLFLEKTPFVEGLSYNLNTMQYPSQQFQPVVLAN
• Function: Anti-proliferative protein inhibits cell cycle progression from the G0/G1 to S phases.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: R. degradation (hsa03018)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Vitiligo	DISR05SL	Strong	Biomarker	[2]
Periodontitis	DISI9JOI	Limited	Biomarker	[3]

14 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 Protein Tob2 (TOB2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein Tob2 (TOB2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein Tob2 (TOB2).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein Tob2 (TOB2).	[7]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Protein Tob2 (TOB2).	[8]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Protein Tob2 (TOB2).	[9]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Protein Tob2 (TOB2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein Tob2 (TOB2).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Protein Tob2 (TOB2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protein Tob2 (TOB2).	[5]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Protein Tob2 (TOB2).	[13]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Protein Tob2 (TOB2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Protein Tob2 (TOB2).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protein Tob2 (TOB2).	[16]

References

• [1] Upregulation of miR-362-3p Modulates Proliferation and Anchorage-Independent Growth by Directly Targeting Tob2 in Hepatocellular Carcinoma.J Cell Biochem. 2015 Aug;116(8):1563-73. doi: 10.1002/jcb.25110.
• [2] Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo.Nat Genet. 2012 May 6;44(6):676-80. doi: 10.1038/ng.2272.
• [3] MicroRNA-543 functions as an osteogenesis promoter in human periodontal ligament-derived stem cells by inhibiting transducer of ERBB2, 2.J Periodontal Res. 2018 Oct;53(5):832-841. doi: 10.1111/jre.12572. Epub 2018 May 31.
• [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] 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.
• [7] 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.
• [8] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [9] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [10] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.