Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5FD167)

• DOT Name: Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A)
• Synonyms: Transcription termination factor I-interacting protein 5; TTF-I-interacting protein 5; Tip5; hWALp3
• Gene Name: BAZ2A
• UniProt ID: BAZ2A_HUMAN
• PDB ID: 4LZ2 ; 4Q6F ; 4QBM ; 4QF2 ; 5AGQ ; 5MGJ ; 5MGK ; 5MGL ; 5MGM ; 5OR8 ; 5T8R ; 6FAP ; 6FG6 ; 6FGF ; 6FGG ; 6FGH ; 6FGI ; 6FGL ; 6FGV ; 6FGW ; 6FHU ; 6FI0 ; 6FKP ; 7B7B ; 7B7G ; 7B7I ; 7B82 ; 7BC2 ; 7BL8 ; 7BL9 ; 7BLA ; 7BLB ; 7BLC ; 7BLD ; 7FHJ ; 7MWH ; 7MWI ; 7MWL ; 7QVT ; 7QVU ; 7QVV ; 7QWF ; 7QWU ; 7QWY ; 7QX2 ; 7QX9 ; 7QXL ; 7QYE ; 7QYO ; 7QYT ; 7QYU ; 7QYV ; 7QYW ; 7QZ0 ; 7QZ4 ; 7QZB ; 7QZC ; 7QZI ; 7QZT ; 7R01 ; 7R0B
• Pfam ID: PF00439 ; PF02791 ; PF01429 ; PF00628 ; PF15612 ; PF15613
• Sequence:
  MEMEANDHFNFTGLPPAPAASGLKPSPSSGEGLYTNGSPMNFPQQGKSLNGDVNVNGLST
  VSHTTTSGILNSAPHSSSTSHLHHPSVAYDCLWNYSQYPSANPGSNLKDPPLLSQFSGGQ
  YPLNGILGGSRQPSSPSHNTNLRAGSQEFWANGTQSPMGLNFDSQELYDSFPDQNFEVMP
  NGPPSFFTSPQTSPMLGSSIQTFAPSQEVGSGIHPDEAAEKEMTSVVAENGTGLVGSLEL
  EEEQPELKMCGYNGSVPSVESLHQEVSVLVPDPTVSCLDDPSHLPDQLEDTPILSEDSLE
  PFNSLAPEPVSGGLYGIDDTELMGAEDKLPLEDSPVISALDCPSLNNATAFSLLADDSQT
  STSIFASPTSPPVLGESVLQDNSFDLNNGSDAEQEEMETQSSDFPPSLTQPAPDQSSTIQ
  LHPATSPAVSPTTSPAVSLVVSPAASPEISPEVCPAASTVVSPAVFSVVSPASSAVLPAV
  SLEVPLTASVTSPKASPVTSPAAAFPTASPANKDVSSFLETTADVEEITGEGLTASGSGD
  VMRRRIATPEEVRLPLQHGWRREVRIKKGSHRWQGETWYYGPCGKRMKQFPEVIKYLSRN
  VVHSVRREHFSFSPRMPVGDFFEERDTPEGLQWVQLSAEEIPSRIQAITGKRGRPRNTEK
  AKTKEVPKVKRGRGRPPKVKITELLNKTDNRPLKKLEAQETLNEEDKAKIAKSKKKMRQK
  VQRGECQTTIQGQARNKRKQETKSLKQKEAKKKSKAEKEKGKTKQEKLKEKVKREKKEKV
  KMKEKEEVTKAKPACKADKTLATQRRLEERQRQQMILEEMKKPTEDMCLTDHQPLPDFSR
  VPGLTLPSGAFSDCLTIVEFLHSFGKVLGFDPAKDVPSLGVLQEGLLCQGDSLGEVQDLL
  VRLLKAALHDPGFPSYCQSLKILGEKVSEIPLTRDNVSEILRCFLMAYGVEPALCDRLRT
  QPFQAQPPQQKAAVLAFLVHELNGSTLIINEIDKTLESMSSYRKNKWIVEGRLRRLKTVL
  AKRTGRSEVEMEGPEECLGRRRSSRIMEETSGMEEEEEEESIAAVPGRRGRRDGEVDATA
  SSIPELERQIEKLSKRQLFFRKKLLHSSQMLRAVSLGQDRYRRRYWVLPYLAGIFVEGTE
  GNLVPEEVIKKETDSLKVAAHASLNPALFSMKMELAGSNTTASSPARARGRPRKTKPGSM
  QPRHLKSPVRGQDSEQPQAQLQPEAQLHAPAQPQPQLQLQLQSHKGFLEQEGSPLSLGQS
  QHDLSQSAFLSWLSQTQSHSSLLSSSVLTPDSSPGKLDPAPSQPPEEPEPDEAESSPDPQ
  ALWFNISAQMPCNAAPTPPPAVSEDQPTPSPQQLASSKPMNRPSAANPCSPVQFSSTPLA
  GLAPKRRAGDPGEMPQSPTGLGQPKRRGRPPSKFFKQMEQRYLTQLTAQPVPPEMCSGWW
  WIRDPEMLDAMLKALHPRGIREKALHKHLNKHRDFLQEVCLRPSADPIFEPRQLPAFQEG
  IMSWSPKEKTYETDLAVLQWVEELEQRVIMSDLQIRGWTCPSPDSTREDLAYCEHLSDSQ
  EDITWRGRGREGLAPQRKTTNPLDLAVMRLAALEQNVERRYLREPLWPTHEVVLEKALLS
  TPNGAPEGTTTEISYEITPRIRVWRQTLERCRSAAQVCLCLGQLERSIAWEKSVNKVTCL
  VCRKGDNDEFLLLCDGCDRGCHIYCHRPKMEAVPEGDWFCTVCLAQQVEGEFTQKPGFPK
  RGQKRKSGYSLNFSEGDGRRRRVLLRGRESPAAGPRYSEEGLSPSKRRRLSMRNHHSDLT
  FCEIILMEMESHDAAWPFLEPVNPRLVSGYRRIIKNPMDFSTMRERLLRGGYTSSEEFAA
  DALLVFDNCQTFNEDDSEVGKAGHIMRRFFESRWEEFYQGKQANL
• Function: Regulatory subunit of the ATP-dependent NoRC-1 and NoRC-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair. Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template. Directly stimulates the ATPase activity of SMARCA5 in the NoRC-5 ISWI chromatin remodeling complex. The NoRC-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the NoRC-5 ISWI chromatin remodeling complex. Within the NoRC-5 ISWI chromatin remodeling complex, mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription. Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac. Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing.
• Tissue Specificity: Expressed at moderate levels in most tissues analyzed, including heart, brain, placenta, lung, skeletal muscle, kidney and pancreas.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)
• Reactome Pathway: NoRC negatively regulates rRNA expression (R-HSA-427413)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[2]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[6]
Marinol	DM70IK5	Approved	Marinol increases the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Bromodomain adjacent to zinc finger domain protein 2A (BAZ2A).	[11]

References

• [1] 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.
• [2] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [3] Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells. Mol Carcinog. 2006 Oct;45(10):752-63.
• [4] 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.
• [5] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.