Details of Drug Off-Target (DOT)

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

• DOT Name: Fasciculation and elongation protein zeta-2 (FEZ2)
• Synonyms: Zygin II; Zygin-2
• Gene Name: FEZ2
• Related Disease: Myocardial ischemia
• UniProt ID: FEZ2_HUMAN
• Pfam ID: PF07763
• Sequence:
  MAADGDWQDFYEFQEPARSLLDQENCNASPEPGAEAGAEAGGGADGFPAPACSLEEKLSL
  CFRPSDPGAEPPRTAVRPITERSLLQGDEIWNALTDNYGNVMPVDWKSSHTRTLHLLTLN
  LSEKGVSDSLLFDTSDDEELREQLDMHSIIVSCVNDEPLFTADQVIEEIEEMMQESPDPE
  DDETPTQSDRLSMLSQEIQTLKRSSTGSYEERVKRLSVSELNEILEEIETAIKEYSEELV
  QQLALRDELEFEKEVKNSFISVLIEVQNKQKEHKETAKKKKKLKNGSSQNGKNERSHMPG
  TYLTTVIPYEKKNGPPSVEDLQILTKILRAMKEDSEKVPSLLTDYILKVLCPT
• Function: Involved in axonal outgrowth and fasciculation.
• Tissue Specificity: Expressed in nonneural tissues, such as heart, lung, spleen, muscle, testis, placenta and melanocytes.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Fasciculation and elongation protein zeta-2 (FEZ2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Fasciculation and elongation protein zeta-2 (FEZ2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fasciculation and elongation protein zeta-2 (FEZ2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Fasciculation and elongation protein zeta-2 (FEZ2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Fasciculation and elongation protein zeta-2 (FEZ2).	[6]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Fasciculation and elongation protein zeta-2 (FEZ2).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fasciculation and elongation protein zeta-2 (FEZ2).	[2]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Fasciculation and elongation protein zeta-2 (FEZ2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Marinol	DM70IK5	Approved	Marinol increases the methylation of Fasciculation and elongation protein zeta-2 (FEZ2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Fasciculation and elongation protein zeta-2 (FEZ2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Fasciculation and elongation protein zeta-2 (FEZ2).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Fasciculation and elongation protein zeta-2 (FEZ2).	[12]

References

• [1] Cardioplegia prevents ischemia-induced transcriptional alterations of cytoprotective genes in rat hearts: a DNA microarray study.J Thorac Cardiovasc Surg. 2005 Oct;130(4):1151. doi: 10.1016/j.jtcvs.2005.06.027.
• [2] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [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] 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.
• [7] Evaluation of early biomarkers of muscle anabolic response to testosterone. J Cachexia Sarcopenia Muscle. 2011 Mar;2(1):45-56. doi: 10.1007/s13539-011-0021-y. Epub 2011 Feb 26.
• [8] Epigenetic activation of O-linked -N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia. EBioMedicine. 2020 Apr;54:102678. doi: 10.1016/j.ebiom.2020.102678. Epub 2020 Apr 6.
• [9] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [10] 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.
• [11] 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.
• [12] 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.