Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRXGZ1X)

• DOT Name: Tigger transposable element-derived protein 2 (TIGD2)
• Gene Name: TIGD2
• Related Disease: Tourette syndrome
• UniProt ID: TIGD2_HUMAN
• Pfam ID: PF04218 ; PF03184 ; PF03221
• Sequence:
  MLGKRKRVVLTIKDKLDIIKKLEEGISFKKLSVVYGIGESTVRDIKKNKERIINYANSSD
  PTSGVSKRKSMKSSTYEELDRVMIEWFNQQKTDGIPVSGTICAKQAKFFFDALGMEGDFN
  ASSGWLTRFKQRHGIPKAAGKGTKLKGDETAAREFCGSFQEFVEKENLQPEQIYGADQTG
  LFWKCLPSRTLTLETDQSTSGCRSSRERIIIMCCANATGLHKLNLCVVGKAKKPRAFKGT
  DLSNLPVTYYSQKGAWIEQSVFRQWFEKYFVPQVQKHLKSKGLLEKAVLLLDFPPARPNE
  EMLSSDDGRIIVKYLPPNVTSLIQPMSQGVLATVKRYYRAGLLQKYMDEGNDPKIFWKNL
  TVLDAIYEVSRAWNMVKSSTITKAWKKLFPGNEENSGMNIDEGAILAANLATVLQNTEEC
  EHVDIENIDQWFDSRSSDSSCQVLTDSESAEDQTKAAEQKPSSKSRKTELNPEKHISHKA
  ALEWTENLLDYLEQQDDMLLSDKLVLRRLRTIIRKKQKIQNNKNH

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tourette syndrome	DISX9D54	No Known	Unknown	[1]

13 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 Tigger transposable element-derived protein 2 (TIGD2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[7]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Tigger transposable element-derived protein 2 (TIGD2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Tigger transposable element-derived protein 2 (TIGD2).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Tigger transposable element-derived protein 2 (TIGD2).	[16]

References

• [1] De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron. 2017 May 3;94(3):486-499.e9. doi: 10.1016/j.neuron.2017.04.024.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [8] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [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] 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.