Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWLY0UE)

• DOT Name: DAZ-associated protein 1 (DAZAP1)
• Synonyms: Deleted in azoospermia-associated protein 1
• Gene Name: DAZAP1
• Related Disease:
  Advanced cancer
  Bipolar disorder
  Schizophrenia
  Acute lymphocytic leukaemia
• UniProt ID: DAZP1_HUMAN
• PDB ID: 2DGS; 2DH8
• Pfam ID: PF00076
• Sequence:
  MNNSGADEIGKLFVGGLDWSTTQETLRSYFSQYGEVVDCVIMKDKTTNQSRGFGFVKFKD
  PNCVGTVLASRPHTLDGRNIDPKPCTPRGMQPERTRPKEGWQKGPRSDNSKSNKIFVGGI
  PHNCGETELREYFKKFGVVTEVVMIYDAEKQRPRGFGFITFEDEQSVDQAVNMHFHDIMG
  KKVEVKRAEPRDSKSQAPGQPGASQWGSRVVPNAANGWAGQPPPTWQQGYGPQGMWVPAG
  QAIGGYGPPPAGRGAPPPPPPFTSYIVSTPPGGFPPPQGFPQGYGAPPQFSFGYGPPPPP
  PDQFAPPGVPPPPATPGAAPLAFPPPPSQAAPDMSKPPTAQPDFPYGQYAGYGQDLSGFG
  QGFSDPSQQPPSYGGPSVPGSGGPPAGGSGFGRGQNHNVQGFHPYRR
• Function: RNA-binding protein, which may be required during spermatogenesis.
• Tissue Specificity: Mainly expressed in testis. Expressed to a lower level in thymus. Weakly or not expressed in heart, liver, brain, placenta, lung, skeletal muscle, kidney and pancreas.
• KEGG Pathway: mR. surveillance pathway (hsa03015)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Bipolar disorder	DISAM7J2	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[2]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Biomarker	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Josamycin	DMKJ8LB	Approved	DAZ-associated protein 1 (DAZAP1) affects the response to substance of Josamycin.	[15]

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 DAZ-associated protein 1 (DAZAP1).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of DAZ-associated protein 1 (DAZAP1).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of DAZ-associated protein 1 (DAZAP1).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of DAZ-associated protein 1 (DAZAP1).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DAZ-associated protein 1 (DAZAP1).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of DAZ-associated protein 1 (DAZAP1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of DAZ-associated protein 1 (DAZAP1).	[8]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of DAZ-associated protein 1 (DAZAP1).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DAZ-associated protein 1 (DAZAP1).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DAZ-associated protein 1 (DAZAP1).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DAZ-associated protein 1 (DAZAP1).	[14]

References

• [1] Cloning and functional characterization of MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins created by a variant t(1;19)(q23;p13.3) in acute lymphoblastic leukemia.Leukemia. 2005 May;19(5):806-13. doi: 10.1038/sj.leu.2403684.
• [2] Maternal stress induces epigenetic signatures of psychiatric and neurological diseases in the offspring.PLoS One. 2013;8(2):e56967. doi: 10.1371/journal.pone.0056967. Epub 2013 Feb 22.
• [3] Cooperative transformation by MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins generated by the variant t(1;19) in acute lymphoblastic leukemia.Leukemia. 2007 Dec;21(12):2470-5. doi: 10.1038/sj.leu.2404962. Epub 2007 Sep 27.
• [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] 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] 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.
• [7] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [8] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [9] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [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] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [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.
• [13] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [14] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.