Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX4FKPQ)

• DOT Name: Intraflagellar transport protein 70A (IFT70A)
• Synonyms: Tetratricopeptide repeat protein 30A; TPR repeat protein 30A
• Gene Name: IFT70A
• UniProt ID: IT70A_HUMAN
• Pfam ID: PF13432
• Sequence:
  MAGLSGAQIPDGEFTALVYRLIRDARYAEAVQLLGRELQRSPRSRAGLSLLGYCYYRLQE
  FALAAECYEQLGQLHPELEQYRLYQAQALYKACLYPEATRVAFLLLDNPAYHSRVLRLQA
  AIKYSEGDLPGSRSLVEQLLSGEGGEESGGDNETDGQVNLGCLLYKEGQYEAACSKFSAT
  LQASGYQPDLSYNLALAYYSSRQYASALKHIAEIIERGIRQHPELGVGMTTEGFDVRSVG
  NTLVLHQTALVEAFNLKAAIEYQLRNYEVAQETLTDMPPRAEEELDPVTLHNQALMNMDA
  RPTEGFEKLQFLLQQNPFPPETFGNLLLLYCKYEYFDLAADVLAENAHLTYKFLTPYLYD
  FLDALITCQTAPEEAFIKLDGLAGMLTEQLRRLTKQVQEARHNRDDEAIKKAVNEYDETM
  EKYIPVLMAQAKIYWNLENYPMVEKVFRKSVEFCNDHDVWKLNVAHVLFMQENKYKEAIG
  FYEPIVKKHYDNILNVSAIVLANLCVSYIMTSQNEEAEELMRKIEKEEEQLSYDDPNRKM
  YHLCIVNLVIGTLYCAKGNYEFGISRVIKSLEPYNKKLGTDTWYYAKRCFLSLLENMSKH
  MIVIHDSVIQECVQFLGHCELYGTNIPAVIEQPLEEERMHVGKNTVTDESRQLKALIYEI
  IGWNK
• Function: Required for polyglutamylation of axonemal tubulin. Plays a role in anterograde intraflagellar transport (IFT), the process by which cilia precursors are transported from the base of the cilium to the site of their incorporation at the tip.
• Reactome Pathway: Intraflagellar transport (R-HSA-5620924)

Molecular Interaction Atlas (MIA) of This DOT

2 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 Intraflagellar transport protein 70A (IFT70A).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Intraflagellar transport protein 70A (IFT70A).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Intraflagellar transport protein 70A (IFT70A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Intraflagellar transport protein 70A (IFT70A).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Intraflagellar transport protein 70A (IFT70A).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Intraflagellar transport protein 70A (IFT70A).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Intraflagellar transport protein 70A (IFT70A).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Intraflagellar transport protein 70A (IFT70A).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Intraflagellar transport protein 70A (IFT70A).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Intraflagellar transport protein 70A (IFT70A).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Intraflagellar transport protein 70A (IFT70A).	[11]

References

• [1] 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.
• [2] 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.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [7] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.