Details of Drug Off-Target (DOT)

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

• DOT Name: Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A)
• Synonyms: ATP-dependent chromatin-remodeling protein; ATP-utilizing chromatin assembly and remodeling factor 1; hACF1; CHRAC subunit ACF1; Williams syndrome transcription factor-related chromatin-remodeling factor 180; WCRF180; hWALp1
• Gene Name: BAZ1A
• Related Disease:
  Advanced cancer
  Clear cell renal carcinoma
  Cocaine addiction
  Crohn disease
  Lung adenocarcinoma
  Major depressive disorder
  Mood disorder
  Non-small-cell lung cancer
  Renal cell carcinoma
  Intellectual disability
  Multiple congenital anomalies/dysmorphic syndrome
• UniProt ID: BAZ1A_HUMAN
• PDB ID: 5UIY
• Pfam ID: PF00439 ; PF02791 ; PF00628 ; PF10537 ; PF15612 ; PF15613
• Sequence:
  MPLLHRKPFVRQKPPADLRPDEEVFYCKVTNEIFRHYDDFFERTILCNSLVWSCAVTGRP
  GLTYQEALESEKKARQNLQSFPEPLIIPVLYLTSLTHRSRLHEICDDIFAYVKDRYFVEE
  TVEVIRNNGARLQCRILEVLPPSHQNGFANGHVNSVDGETIIISDSDDSETQSCSFQNGK
  KKDAIDPLLFKYKVQPTKKELHESAIVKATQISRRKHLFSRDKLKLFLKQHCEPQDGVIK
  IKASSLSTYKIAEQDFSYFFPDDPPTFIFSPANRRRGRPPKRIHISQEDNVANKQTLASY
  RSKATKERDKLLKQEEMKSLAFEKAKLKREKADALEAKKKEKEDKEKKREELKKIVEEER
  LKKKEEKERLKVEREKEREKLREEKRKYVEYLKQWSKPREDMECDDLKELPEPTPVKTRL
  PPEIFGDALMVLEFLNAFGELFDLQDEFPDGVTLEVLEEALVGNDSEGPLCELLFFFLTA
  IFQAIAEEEEEVAKEQLTDADTKDLTEALDEDADPTKSALSAVASLAAAWPQLHQGCSLK
  SLDLDSCTLSEILRLHILASGADVTSANAKYRYQKRGGFDATDDACMELRLSNPSLVKKL
  SSTSVYDLTPGEKMKILHALCGKLLTLVSTRDFIEDYVDILRQAKQEFRELKAEQHRKER
  EEAAARIRKRKEEKLKEQEQKMKEKQEKLKEDEQRNSTADISIGEEEREDFDTSIESKDT
  EQKELDQDMVTEDEDDPGSHKRGRRGKRGQNGFKEFTRQEQINCVTREPLTADEEEALKQ
  EHQRKEKELLEKIQSAIACTNIFPLGRDRMYRRYWIFPSIPGLFIEEDYSGLTEDMLLPR
  PSSFQNNVQSQDPQVSTKTGEPLMSESTSNIDQGPRDHSVQLPKPVHKPNRWCFYSSCEQ
  LDQLIEALNSRGHRESALKETLLQEKSRICAQLARFSEEKFHFSDKPQPDSKPTYSRGRS
  SNAYDPSQMCAEKQLELRLRDFLLDIEDRIYQGTLGAIKVTDRHIWRSALESGRYELLSE
  ENKENGIIKTVNEDVEEMEIDEQTKVIVKDRLLGIKTETPSTVSTNASTPQSVSSVVHYL
  AMALFQIEQGIERRFLKAPLDASDSGRSYKTVLDRWRESLLSSASLSQVFLHLSTLDRSV
  IWSKSILNARCKICRKKGDAENMVLCDGCDRGHHTYCVRPKLKTVPEGDWFCPECRPKQR
  SRRLSSRQRPSLESDEDVEDSMGGEDDEVDGDEEEGQSEEEEYEVEQDEDDSQEEEEVSL
  PKRGRPQVRLPVKTRGKLSSSFSSRGQQQEPGRYPSRSQQSTPKTTVSSKTGRSLRKINS
  APPTETKSLRIASRSTRHSHGPLQADVFVELLSPRRKRRGRKSANNTPENSPNFPNFRVI
  ATKSSEQSRSVNIASKLSLQESESKRRCRKRQSPEPSPVTLGRRSSGRQGGVHELSAFEQ
  LVVELVRHDDSWPFLKLVSKIQVPDYYDIIKKPIALNIIREKVNKCEYKLASEFIDDIEL
  MFSNCFEYNPRNTSEAKAGTRLQAFFHIQAQKLGLHVTPSNVDQVSTPPAAKKSRI
• Function: Regulatory subunit of the ATP-dependent ACF-1 and ACF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and slide edge- and center-positioned histone octamers away from their original location on the DNA template to 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 in an ATP-dependent manner. The ACF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the ACF-5 ISWI chromatin remodeling complex. Has a role in sensing the length of DNA which flank nucleosomes, which modulates the nucleosome spacing activity of the ACF-5 ISWI chromatin remodeling complex. Involved in DNA replication and together with SMARCA5/SNF2H is required for replication of pericentric heterochromatin in S-phase. May have a role in nuclear receptor-mediated transcription repression.
• Tissue Specificity: Highly expressed in testis and at low or undetectable levels in other tissues analyzed.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[2]
Cocaine addiction	DISHTRXG	Strong	Biomarker	[3]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[4]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[5]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[6]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[5]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[2]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[7]
Multiple congenital anomalies/dysmorphic syndrome	DIS0LF2K	Limited	Autosomal dominant	[8]

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 Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[9]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[19]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[26]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[12]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[13]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[14]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[16]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[17]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[18]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[16]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[20]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[21]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[22]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[23]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[24]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[28]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Bromodomain adjacent to zinc finger domain protein 1A (BAZ1A).	[29]

References

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• [21] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
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• [26] 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.
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