Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5QVYBZ)

• DOT Name: BET1-like protein (BET1L)
• Synonyms: Golgi SNARE with a size of 15 kDa; GOS-15; GS15; Vesicle transport protein GOS15
• Gene Name: BET1L
• Related Disease:
  Leiomyoma
  Uterine fibroids
  Benign prostatic hyperplasia
• UniProt ID: BET1L_HUMAN
• Sequence:
  MADWARAQSPGAVEEILDRENKRMADSLASKVTRLKSLALDIDRDAEDQNRYLDGMDSDF
  TSMTSLLTGSVKRFSTMARSGQDNRKLLCGMAVGLIVAFFILSYFLSRART
• Function: Vesicle SNARE required for targeting and fusion of retrograde transport vesicles with the Golgi complex. Required for the integrity of the Golgi complex.
• KEGG Pathway: S.RE interactions in vesicular transport (hsa04130)
• Reactome Pathway:
  Intra-Golgi traffic (R-HSA-6811438)
  COPI-mediated anterograde transport (R-HSA-6807878)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leiomyoma	DISLDDFN	Strong	Genetic Variation	[1]
Uterine fibroids	DISBZRMJ	Strong	Genetic Variation	[2]
Benign prostatic hyperplasia	DISI3CW2	moderate	Genetic Variation	[3]

4 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 BET1-like protein (BET1L).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of BET1-like protein (BET1L).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of BET1-like protein (BET1L).	[10]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of BET1-like protein (BET1L).	[12]

6 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 BET1-like protein (BET1L).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of BET1-like protein (BET1L).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of BET1-like protein (BET1L).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of BET1-like protein (BET1L).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of BET1-like protein (BET1L).	[9]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of BET1-like protein (BET1L).	[11]

References

• [1] Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans.Hum Genet. 2013 Dec;132(12):1361-9. doi: 10.1007/s00439-013-1340-1. Epub 2013 Jul 28.
• [2] A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids.Front Genet. 2019 Jun 12;10:511. doi: 10.3389/fgene.2019.00511. eCollection 2019.
• [3] Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA.Nat Commun. 2018 Nov 8;9(1):4568. doi: 10.1038/s41467-018-06920-9.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [10] 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.
• [11] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [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.