Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEHKN1M)

• DOT Name: Myc-associated zinc finger protein (MAZ)
• Synonyms: MAZI; Pur-1; Purine-binding transcription factor; Serum amyloid A-activating factor-1; SAF-1; Transcription factor Zif87; ZF87; Zinc finger protein 801
• Gene Name: MAZ
• UniProt ID: MAZ_HUMAN
• Pfam ID: PF00096 ; PF13894
• Sequence:
  MFPVFPCTLLAPPFPVLGLDSRGVGGLMNSFPPPQGHAQNPLQVGAELQSRFFASQGCAQ
  SPFQAAPAPPPTPQAPAAEPLQVDLLPVLAAAQESAAAAAAAAAAAAAVAAAPPAPAAAS
  TVDTAALKQPPAPPPPPPPVSAPAAEAAPPASAATIAAAAATAVVAPTSTVAVAPVASAL
  EKKTKSKGPYICALCAKEFKNGYNLRRHEAIHTGAKAGRVPSGAMKMPTMVPLSLLSVPQ
  LSGAGGGGGEAGAGGGAAAVAAGGVVTTTASGKRIRKNHACEMCGKAFRDVYHLNRHKLS
  HSDEKPYQCPVCQQRFKRKDRMSYHVRSHDGAVHKPYNCSHCGKSFSRPDHLNSHVRQVH
  STERPFKCEKCEAAFATKDRLRAHTVRHEEKVPCHVCGKMLSSAYISDHMKVHSQGPHHV
  CELCNKGTGEVCPMAAAAAAAAAAAAAAVAAPPTAVGSLSGAEGVPVSSQPLPSQPW
• Function: Transcriptional regulator, potentially with dual roles in transcription initiation and termination; [Isoform 1]: Binds DNA and functions as a transcriptional activator. Binds to two G/A-rich sites, ME1a1 and ME1a2, within the MYC promoter having greater affinity for the former. Also binds to multiple G/C-rich sites within the promoter of the Sp1 family of transcription factors ; [Isoform 2]: Binds DNA and functions as a transcriptional activator. Inhibits MAZ isoform 1-mediated transcription ; [Isoform 3]: Binds DNA and functions as a transcriptional activator.
• Tissue Specificity: Present in kidney, liver and brain. In the brain, highest levels are found in motor cortex and midfrontal cortex (at protein level).; [Isoform 1]: Expressed in the heart, brain, placenta, lung, liver, skeletal muscle and weakly expressed in the kidney . Expressed in the joint synovium .

Molecular Interaction Atlas (MIA) of This DOT

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 Myc-associated zinc finger protein (MAZ).	[1]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Myc-associated zinc finger protein (MAZ).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Myc-associated zinc finger protein (MAZ).	[10]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Myc-associated zinc finger protein (MAZ).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Myc-associated zinc finger protein (MAZ).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Myc-associated zinc finger protein (MAZ).	[3]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Myc-associated zinc finger protein (MAZ).	[4]
Selenium	DM25CGV	Approved	Selenium increases the expression of Myc-associated zinc finger protein (MAZ).	[6]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Myc-associated zinc finger protein (MAZ).	[7]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Myc-associated zinc finger protein (MAZ).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Myc-associated zinc finger protein (MAZ).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Myc-associated zinc finger protein (MAZ).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Myc-associated zinc finger protein (MAZ).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Myc-associated zinc finger protein (MAZ).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Myc-associated zinc finger protein (MAZ).	[15]

References

• [1] 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.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res. 2011 Jun;27(2):99-107. doi: 10.5625/lar.2011.27.2.99. Epub 2011 Jun 22.
• [5] 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.
• [6] 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.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] 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.
• [9] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [12] 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.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [15] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.