Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVN2VGH)

• DOT Name: Tetratricopeptide repeat protein 33 (TTC33)
• Synonyms: TPR repeat protein 33; Osmosis-responsive factor
• Gene Name: TTC33
• Related Disease:
  Schizophrenia
  Stomach cancer
• UniProt ID: TTC33_HUMAN
• Sequence:
  MASFGWKRKIGEKVSKVTSQQFEAEAADEKDVVDNDEGNWLHAIKRRKEILLEGCAEKSK
  QLKDEGASLAENKRYREAIQKWDEALQLTPNDATLYEMKSQVLMSLHEMFPAVHAAEMAV
  QQNPHSWESWQTLGRAQLGLGEIILAIRSFQVALHIYPMNPEIWKEDLSWARTLQEQQKV
  AQRIKKSEAPAEVTHFSPKSIPDYDFESDEIVAVCAAIAEKEKTVSANKTMVIVSASGAI
  ETVTEKEDGATPPDGSVFIKAR

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[2]

6 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 Tetratricopeptide repeat protein 33 (TTC33).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tetratricopeptide repeat protein 33 (TTC33).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tetratricopeptide repeat protein 33 (TTC33).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Tetratricopeptide repeat protein 33 (TTC33).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Tetratricopeptide repeat protein 33 (TTC33).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Tetratricopeptide repeat protein 33 (TTC33).	[8]

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 increases the methylation of Tetratricopeptide repeat protein 33 (TTC33).	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Tetratricopeptide repeat protein 33 (TTC33).	[10]

References

• [1] Common variants on 8p12 and 1q24.2 confer risk of schizophrenia.Nat Genet. 2011 Oct 30;43(12):1224-7. doi: 10.1038/ng.980.
• [2] Meta-analysis of genome-wide association studies and functional assays decipher susceptibility genes for gastric cancer in Chinese populations.Gut. 2020 Apr;69(4):641-651. doi: 10.1136/gutjnl-2019-318760. Epub 2019 Aug 5.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] 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.
• [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] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.