Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT687RIX)

• DOT Name: Torsin-1A-interacting protein 2 (TOR1AIP2)
• Synonyms: Lumenal domain-like LAP1
• Gene Name: TOR1AIP2
• Related Disease: Dystonia
• UniProt ID: TOIP2_HUMAN
• PDB ID: 5J1S; 5J1T
• Pfam ID: PF05609 ; PF20443
• Sequence:
  MADSGLREPQEDSQKDLENDPSVNSQAQETTIIASNAEEAEILHSACGLSKDHQEVETEG
  PESADTGDKSESPDEANVGKHPKDKTEDENKQSFLDGGKGHHLPSENLGKEPLDPDPSHS
  PSDKVGRADAHLGSSSVALPKEASDGTGASQEPPTTDSQEAQSPGHSSAGQEGEDTLRRR
  LLAPEAGSHPQQTQKLEEIKENAQDTMRQINKKGFWSYGPVILVVLVVAVVASSVNSYYS
  SPAQQVPKNPALEAFLAQFSQLEDKFPGQSSFLWQRGRKFLQKHLNASNPTEPATIIFTA
  AREGRETLKCLSHHVADAYTSSQKVSPIQIDGAGRTWQDSDTVKLLVDLELSYGFENGQK
  AAVVHHFESFPAGSTLIFYKYCDHENAAFKDVALVLTVLLEEETLEASVGPRETEEKVRD
  LLWAKFTNSDTPTSFNHMDSDKLSGLWSRISHLVLPVQPVSSIEEQGCLF
• Function: Required for endoplasmic reticulum integrity. Regulates the distribution of TOR1A between the endoplasmic reticulum and the nuclear envelope as well as induces TOR1A, TOR1B and TOR3A ATPase activity.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dystonia	DISJLFGW	moderate	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Torsin-1A-interacting protein 2 (TOR1AIP2).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Torsin-1A-interacting protein 2 (TOR1AIP2).	[9]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Torsin-1A-interacting protein 2 (TOR1AIP2).	[9]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Torsin-1A-interacting protein 2 (TOR1AIP2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Torsin-1A-interacting protein 2 (TOR1AIP2).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Torsin-1A-interacting protein 2 (TOR1AIP2).	[4]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Torsin-1A-interacting protein 2 (TOR1AIP2).	[5]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Torsin-1A-interacting protein 2 (TOR1AIP2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Torsin-1A-interacting protein 2 (TOR1AIP2).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Torsin-1A-interacting protein 2 (TOR1AIP2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Torsin-1A-interacting protein 2 (TOR1AIP2).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Torsin-1A-interacting protein 2 (TOR1AIP2).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Torsin-1A-interacting protein 2 (TOR1AIP2).	[11]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of Torsin-1A-interacting protein 2 (TOR1AIP2).	[13]

References

• [1] LULL1 retargets TorsinA to the nuclear envelope revealing an activity that is impaired by the DYT1 dystonia mutation.Mol Biol Cell. 2009 Jun;20(11):2661-72. doi: 10.1091/mbc.e09-01-0094. Epub 2009 Apr 1.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [5] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [6] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [9] 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.
• [10] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [11] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [12] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.
• [13] Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines. Toxicol Appl Pharmacol. 2010 Nov 15;249(1):91-100.