Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2RIGR7)

• DOT Name: Tubulin epsilon and delta complex protein 1 (TEDC1)
• Gene Name: TEDC1
• UniProt ID: TEDC1_HUMAN
• Pfam ID: PF14970
• Sequence:
  MGRRRQRVDPAAGARAGALPEAIAALSRSLPSGPSPEIFRRAKFDRPEATSALWQLLFRV
  LSPLPAGNALASLALEVQARLVKSALCSQGYPRLALAQLPEDGSQGSRELLLALSWLLAR
  GPVPEQMLAQARVPLGDEMTVCQCEALASPGPPAPHMEAEGPVDVRHVQWLMGKLRFRWR
  QLVSSQQEQCALLSKIHLYTRGCHSDQSLSHLSVTEAEMLRDPEGGQQVSGAGAAQNLDL
  AYPKCLHSFCTPGMGPRTFWNDLWLVCEQPGLLPGDWAAPLDPGGASACSLLSPFRALLR
  TLERENQRLEAVLAWRRSELVFWRWMDTVLGTCAPEVPAAASQPTFLPWVPERGGGELDL
  VVRELQALEEELREAAERRRAAWEAKAGGCGRGPEWSAARRASREAVEKELGALQQCWER
  DGGPAQPHGPHRLVRREDGAAGDRDLRAAVVIRTLRSQEACLEAVLRRLQGQCRQELARL
  VGARPGLIWIPPPGR
• Function: Acts as a positive regulator of ciliary hedgehog signaling. Required for centriole stability. May play a role in counteracting perturbation of actin filaments, such as after treatment with the actin depolymerizing microbial metabolite Chivosazole F.

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 increases the methylation of Tubulin epsilon and delta complex protein 1 (TEDC1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Tubulin epsilon and delta complex protein 1 (TEDC1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tubulin epsilon and delta complex protein 1 (TEDC1).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tubulin epsilon and delta complex protein 1 (TEDC1).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Tubulin epsilon and delta complex protein 1 (TEDC1).	[5]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Tubulin epsilon and delta complex protein 1 (TEDC1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tubulin epsilon and delta complex protein 1 (TEDC1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tubulin epsilon and delta complex protein 1 (TEDC1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tubulin epsilon and delta complex protein 1 (TEDC1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tubulin epsilon and delta complex protein 1 (TEDC1).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Tubulin epsilon and delta complex protein 1 (TEDC1).	[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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [9] 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.
• [10] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [11] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.