Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB5X6EG)

• DOT Name: Tetratricopeptide repeat protein 1 (TTC1)
• Synonyms: TPR repeat protein 1
• Gene Name: TTC1
• Related Disease: Anxiety disorder
• UniProt ID: TTC1_HUMAN
• Pfam ID: PF00515 ; PF13181
• Sequence:
  MGEKSENCGVPEDLLNGLKVTDTQEAECAGPPVPDPKNQHSQSKLLRDDEAHLQEDQGEE
  ECFHDCSASFEEEPGADKVENKSNEDVNSSELDEEYLIELEKNMSDEEKQKRREESTRLK
  EEGNEQFKKGDYIEAESSYSRALEMCPSCFQKERSILFSNRAAARMKQDKKEMAINDCSK
  AIQLNPSYIRAILRRAELYEKTDKLDEALEDYKSILEKDPSIHQAREACMRLPKQIEERN
  ERLKEEMLGKLKDLGNLVLRPFGLSTENFQIKQDSSTGSYSINFVQNPNNNR

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anxiety disorder	DISBI2BT	Limited	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tetratricopeptide repeat protein 1 (TTC1).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tetratricopeptide repeat protein 1 (TTC1).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tetratricopeptide repeat protein 1 (TTC1).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Tetratricopeptide repeat protein 1 (TTC1).	[8]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Tetratricopeptide repeat protein 1 (TTC1).	[5]

3 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 decreases the methylation of Tetratricopeptide repeat protein 1 (TTC1).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Tetratricopeptide repeat protein 1 (TTC1).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Tetratricopeptide repeat protein 1 (TTC1).	[7]

References

• [1] CRY2 genetic variants associate with dysthymia.PLoS One. 2013 Aug 8;8(8):e71450. doi: 10.1371/journal.pone.0071450. eCollection 2013.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [6] 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.
• [7] 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.
• [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.