Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB98CEY)

• DOT Name: Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B)
• Synonyms: hWALp4
• Gene Name: BAZ2B
• Related Disease: Complex neurodevelopmental disorder
• UniProt ID: BAZ2B_HUMAN
• PDB ID: 2E7O ; 3G0L ; 3Q2F ; 4CUP ; 4CUQ ; 4CUR ; 4CUS ; 4CUT ; 4CUU ; 4IR3 ; 4IR4 ; 4IR5 ; 4IR6 ; 4NR9 ; 4NRA ; 4NRB ; 4NRC ; 4QC1 ; 4QC3 ; 4QF3 ; 4RVR ; 4XUA ; 4XUB ; 5CQ3 ; 5CQ4 ; 5CQ5 ; 5CQ6 ; 5CQ7 ; 5CQ8 ; 5CQA ; 5CU8 ; 5CUA ; 5CUB ; 5CUC ; 5CUD ; 5CUE ; 5CUG ; 5DYU ; 5DYX ; 5E73 ; 5E74 ; 5E9I ; 5E9K ; 5E9L ; 5E9M ; 5E9Y ; 5L8T ; 5L8U ; 5L96 ; 5L97 ; 5L98 ; 5L99 ; 5MGE ; 5MGF ; 5MGG ; 5OR9 ; 5ORB ; 5PB7 ; 5PB8 ; 5PB9 ; 5PBA ; 5PBB ; 5PBC ; 5PBD ; 5PBE ; 5PBF ; 5PBG ; 5PBH ; 5PBI ; 5PBJ ; 5PBK ; 5PBL ; 5PBM ; 5PBN ; 5PBO ; 5PBP ; 5PBQ ; 5PBR ; 5PBS ; 5PBT ; 5PBU ; 5PBV ; 5PBW ; 5PBX ; 5PBY ; 5PBZ ; 5PC0 ; 5PC1 ; 5PC2 ; 5PC3 ; 5PC4 ; 5PC5 ; 5PC6 ; 5PC7 ; 5PC8 ; 5PC9 ; 5PCA ; 5PCB ; 5PCC ; 5PCD ; 5PCE ; 5PCF ; 5PCG ; 5PCH ; 5PCI ; 5PCJ ; 5PCK ; 5PCL ; 5PCM ; 5PCN ; 5PCO ; 5PCP ; 5PCQ ; 5PCR ; 5PCS ; 5PCT ; 5PCU ; 5PCV ; 5PCW ; 5PCX ; 5PCZ ; 5PD0 ; 5PD1 ; 5PD2 ; 5PD3 ; 5PD4 ; 5PD5 ; 5PD6 ; 5PD7 ; 5PD8 ; 5PD9 ; 5PDA ; 5PDB ; 5PDC ; 5PDD ; 5PDE ; 5PDF ; 5PDG ; 5PDH ; 5PDI ; 5PDJ ; 5PDK ; 5PDL ; 5PDM ; 5PDN ; 5PDO ; 5PDP ; 5PDQ ; 5PDR ; 5PDS ; 5PDT ; 5PDU ; 5PDV ; 5PDW ; 5PDX ; 5PDY ; 5PDZ ; 5PE0 ; 5PE1 ; 5PE2 ; 5PE3 ; 5PE4 ; 5PE5 ; 5PE6 ; 5PE7 ; 5PE8 ; 5PE9 ; 5PEA ; 5PEB ; 5PEC ; 5PED ; 5PEE ; 5PEF ; 5PEG ; 5PEH ; 5PEI ; 5PEJ ; 5PEK ; 5PEL ; 5PEM ; 5PEN ; 5PEO ; 5PEQ ; 5PER ; 5PES ; 5PET ; 5PEU ; 5PEV ; 5PEW ; 5PEX ; 5PEY ; 5PEZ ; 5PF0 ; 5PF1 ; 5PF2 ; 5PF3 ; 5PF4 ; 5PF5 ; 5PF6 ; 5PF7 ; 5PF8 ; 5PF9 ; 5PFA ; 5PFB ; 5PFC ; 5PFD ; 5PFE ; 5PFF ; 5PFG ; 5PFH ; 5PFI ; 5PFJ ; 5PFL ; 5PFM ; 5PFN ; 5PFO ; 5PFP ; 5PFQ ; 5PFR ; 5PFS ; 5PFT ; 5PFU ; 5PFV ; 5PFW ; 5PFX ; 5PFY ; 5PFZ ; 5PG0 ; 5PG1 ; 5PG2 ; 5PG3 ; 5PG4 ; 5PG5 ; 5PG6 ; 5PG7 ; 5PG8 ; 5PG9 ; 5PGA ; 5PGB ; 5PGC ; 5PGD ; 5PGE ; 5PGF ; 5PGG ; 5PGH ; 5PGI ; 5PGJ ; 5PGK ; 5PGL ; 5PGN ; 5PGO ; 5PGP ; 5PGQ ; 5PGR ; 5PGS ; 5PGT ; 6FGT ; 6FGU ; 6FH6 ; 6FH7 ; 6FHQ ; 6FI1 ; 7Q42 ; 7WIN
• Pfam ID: PF00439 ; PF02791 ; PF01429 ; PF00628 ; PF15613
• Sequence:
  MESGERLPSSAASSTTPTSSSTPSVASVVSKGGLSTGVASLSSTINPCGHLFRTAGDQPF
  NLSTVSSAFPMVSHPVFGLHSASSGHSEFGGLGTLGTPTALAAHPQLASFPGAEWWRTTD
  AHTRTGATFFPPLLGIPPLFAPPAQNHDSSSFHSRTSGKSNRNGPEKGVNGSINGSNTSS
  VIGINTSVLSTTASSSMGQTKSTSSGGGNRKCNQEQSKNQPLDARVDKIKDKKPRKKAME
  SSSNSDSDSGTSSDTSSEGISSSDSDDLEEDEEEEDQSIEESEDDDSDSESEAQHKSNNQ
  VLLHGISDPKADGQKATEKAQEKRIHQPLPLASESQTHSFQSQQKQPQVLSQQLPFIFQS
  SQAKEESVNKHTSVIQSTGLVSNVKPLSLVNQAKKETYMKLIVPSPDVLKAGNKNTSEES
  SLLTSELRSKREQYKQAFPSQLKKQESSKSLKKVIAALSNPKATSSSPAHPKQTLENNHP
  NPFLTNALLGNHQPNGVIQSVIQEAPLALTTKTKMQSKINENIAAASSTPFSSPVNLSTS
  GRRTPGNQTPVMPSASPILHSQGKEKAVSNNVNPVKTQHHSHPAKSLVEQFRGTDSDIPS
  SKDSEDSNEDEEEDDEEEDEEDDEDDESDDSQSESDSNSESDTEGSEEEDDDDKDQDESD
  SDTEGEKTSMKLNKTTSSVKSPSMSLTGHSTPRNLHIAKAPGSAPAALCSESQSPAFLGT
  SSSTLTSSPHSGTSKRRRVTDERELRIPLEYGWQRETRIRNFGGRLQGEVAYYAPCGKKL
  RQYPEVIKYLSRNGIMDISRDNFSFSAKIRVGDFYEARDGPQGMQWCLLKEEDVIPRIRA
  MEGRRGRPPNPDRQRAREESRMRRRKGRPPNVGNAEFLDNADAKLLRKLQAQEIARQAAQ
  IKLLRKLQKQEQARVAKEAKKQQAIMAAEEKRKQKEQIKIMKQQEKIKRIQQIRMEKELR
  AQQILEAKKKKKEEAANAKLLEAEKRIKEKEMRRQQAVLLKHQERERRRQHMMLMKAMEA
  RKKAEEKERLKQEKRDEKRLNKERKLEQRRLELEMAKELKKPNEDMCLADQKPLPELPRI
  PGLVLSGSTFSDCLMVVQFLRNFGKVLGFDVNIDVPNLSVLQEGLLNIGDSMGEVQDLLV
  RLLSAAVCDPGLITGYKAKTALGEHLLNVGVNRDNVSEILQIFMEAHCGQTELTESLKTK
  AFQAHTPAQKASVLAFLINELACSKSVVSEIDKNIDYMSNLRRDKWVVEGKLRKLRIIHA
  KKTGKRDTSGGIDLGEEQHPLGTPTPGRKRRRKGGDSDYDDDDDDDSDDQGDEDDEDEED
  KEDKKGKKTDICEDEDEGDQAASVEELEKQIEKLSKQQSQYRRKLFDASHSLRSVMFGQD
  RYRRRYWILPQCGGIFVEGMESGEGLEEIAKEREKLKKAESVQIKEEMFETSGDSLNCSN
  TDHCEQKEDLKEKDNTNLFLQKPGSFSKLSKLLEVAKMPPESEVMTPKPNAGANGCTLSY
  QNSGKHSLGSVQSTATQSNVEKADSNNLFNTGSSGPGKFYSPLPNDQLLKTLTEKNRQWF
  SLLPRTPCDDTSLTHADMSTASLVTPQSQPPSKSPSPTPAPLGSSAQNPVGLNPFALSPL
  QVKGGVSMMGLQFCGWPTGVVTSNIPFTSSVPSLGSGLGLSEGNGNSFLTSNVASSKSES
  PVPQNEKATSAQPAAVEVAKPVDFPSPKPIPEEMQFGWWRIIDPEDLKALLKVLHLRGIR
  EKALQKQIQKHLDYITQACLKNKDVAIIELNENEENQVTRDIVENWSVEEQAMEMDLSVL
  QQVEDLERRVASASLQVKGWMCPEPASEREDLVYFEHKSFTKLCKEHDGEFTGEDESSAH
  ALERKSDNPLDIAVTRLADLERNIERRIEEDIAPGLRVWRRALSEARSAAQVALCIQQLQ
  KSIAWEKSIMKVYCQICRKGDNEELLLLCDGCDKGCHTYCHRPKITTIPDGDWFCPACIA
  KASGQTLKIKKLHVKGKKTNESKKGKKVTLTGDTEDEDSASTSSSLKRGNKDLKKRKMEE
  NTSINLSKQESFTSVKKPKRDDSKDLALCSMILTEMETHEDAWPFLLPVNLKLVPGYKKV
  IKKPMDFSTIREKLSSGQYPNLETFALDVRLVFDNCETFNEDDSDIGRAGHNMRKYFEKK
  WTDTFKVS
• Function: Regulatory subunit of the ATP-dependent BRF-1 and BRF-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. The BRF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the BRF-5 ISWI chromatin remodeling complex. Chromatin reader protein, which may play a role in transcriptional regulation via interaction with ISWI. Involved in positively modulating the rate of age-related behavioral deterioration. Represses the expression of mitochondrial function-related genes, perhaps by occupying their promoter regions, working in concert with histone methyltransferase EHMT1.
• Tissue Specificity: Expressed at varying levels in several tissues, whereas a smaller transcript was expressed specifically in testis.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal dominant	[1]

11 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 Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[7]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[8]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[14]
geraniol	DMS3CBD	Investigative	geraniol increases the expression of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Bromodomain adjacent to zinc finger domain protein 2B (BAZ2B).	[13]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] 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.
• [8] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [9] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] 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.
• [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] 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.
• [14] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
• [15] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.