Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCE1K4J)

• DOT Name: Vascular endothelial zinc finger 1
• Synonyms: Putative transcription factor DB1; Zinc finger protein 161
• Gene Name: VEZF1
• Related Disease:
  Autism spectrum disorder
  Cardiomyopathy, dilated, 100
• UniProt ID: VEZF1_HUMAN
• Pfam ID: PF00096 ; PF13894
• Sequence:
  MEANWTAFLFQAHEASHHQQQAAQNSLLPLLSSAVEPPDQKPLLPIPITQKPQGAPETLK
  DAIGIKKEKPKTSFVCTYCSKAFRDSYHLRRHESCHTGIKLVSRPKKTPTTVVPLISTIA
  GDSSRTSLVSTIAGILSTVTTSSSGTNPSSSASTTAMPVTQSVKKPSKPVKKNHACEMCG
  KAFRDVYHLNRHKLSHSDEKPFECPICNQRFKRKDRMTYHVRSHEGGITKPYTCSVCGKG
  FSRPDHLSCHVKHVHSTERPFKCQTCTAAFATKDRLRTHMVRHEGKVSCNICGKLLSAAY
  ITSHLKTHGQSQSINCNTCKQGISKTCMSEETSNQKQQQQQQQQQQQQQQQQQQHVTSWP
  GKQVETLRLWEEAVKARKKEAANLCQTSTAATTPVTLTTPFSITSSVSSGTMSNPVTVAA
  AMSMRSPVNVSSAVNITSPMNIGHPVTITSPLSMTSPLTLTTPVNLPTPVTAPVNIAHPV
  TITSPMNLPTPMTLAAPLNIAMRPVESMPFLPQALPTSPPW
• Function: Possible transcription factor. Specifically binds to the CT/GC-rich region of the interleukin-3 promoter and mediates tax transactivation of IL-3.
• Tissue Specificity: Ubiquitously expressed. Highest levels in skeletal muscle and kidney.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Limited	Autosomal dominant	[1]
Cardiomyopathy, dilated, 100	DISAMUP4	Limited	Autosomal dominant	[1]

12 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 Vascular endothelial zinc finger 1.	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Vascular endothelial zinc finger 1.	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Vascular endothelial zinc finger 1.	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Vascular endothelial zinc finger 1.	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Vascular endothelial zinc finger 1.	[6]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Vascular endothelial zinc finger 1.	[7]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Vascular endothelial zinc finger 1.	[9]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Vascular endothelial zinc finger 1.	[10]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Vascular endothelial zinc finger 1.	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Vascular endothelial zinc finger 1.	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Vascular endothelial zinc finger 1.	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Vascular endothelial zinc finger 1.	[15]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Vascular endothelial zinc finger 1.	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Vascular endothelial zinc finger 1.	[13]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [10] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] 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.
• [14] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.