Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ0JCNP)

• DOT Name: DNA (DNMT3B)
• Synonyms: cytosine-5)-methyltransferase 3B (Dnmt3b; EC 2.1.1.37; DNA methyltransferase HsaIIIB; DNA MTase HsaIIIB; M.HsaIIIB
• Gene Name: DNMT3B
• Related Disease:
  Immunodeficiency-centromeric instability-facial anomalies syndrome 1
  Immunodeficiency-centromeric instability-facial anomalies syndrome
• UniProt ID: DNM3B_HUMAN
• PDB ID: 3FLG; 3QKJ; 5CIU; 5NR3; 5NRR; 5NRS; 5NRV; 5NV0; 5NV2; 5NV7; 5NVO; 6KDA; 6KDB; 6KDL; 6KDP; 6KDT; 6PA7; 6R3E; 6U8P; 6U8V; 6U8W; 6U8X; 6U90; 6U91; 7O45; 7V0E; 7X9D; 8EIH; 8EII; 8EIJ; 8EIK
• EC Number: 2.1.1.37
• Pfam ID: PF17980 ; PF21255 ; PF00145 ; PF00855
• Sequence:
  MKGDTRHLNGEEDAGGREDSILVNGACSDQSSDSPPILEAIRTPEIRGRRSSSRLSKREV
  SSLLSYTQDLTGDGDGEDGDGSDTPVMPKLFRETRTRSESPAVRTRNNNSVSSRERHRPS
  PRSTRGRQGRNHVDESPVEFPATRSLRRRATASAGTPWPSPPSSYLTIDLTDDTEDTHGT
  PQSSSTPYARLAQDSQQGGMESPQVEADSGDGDSSEYQDGKEFGIGDLVWGKIKGFSWWP
  AMVVSWKATSKRQAMSGMRWVQWFGDGKFSEVSADKLVALGLFSQHFNLATFNKLVSYRK
  AMYHALEKARVRAGKTFPSSPGDSLEDQLKPMLEWAHGGFKPTGIEGLKPNNTQPVVNKS
  KVRRAGSRKLESRKYENKTRRRTADDSATSDYCPAPKRLKTNCYNNGKDRGDEDQSREQM
  ASDVANNKSSLEDGCLSCGRKNPVSFHPLFEGGLCQTCRDRFLELFYMYDDDGYQSYCTV
  CCEGRELLLCSNTSCCRCFCVECLEVLVGTGTAAEAKLQEPWSCYMCLPQRCHGVLRRRK
  DWNVRLQAFFTSDTGLEYEAPKLYPAIPAARRRPIRVLSLFDGIATGYLVLKELGIKVGK
  YVASEVCEESIAVGTVKHEGNIKYVNDVRNITKKNIEEWGPFDLVIGGSPCNDLSNVNPA
  RKGLYEGTGRLFFEFYHLLNYSRPKEGDDRPFFWMFENVVAMKVGDKRDISRFLECNPVM
  IDAIKVSAAHRARYFWGNLPGMNRPVIASKNDKLELQDCLEYNRIAKLKKVQTITTKSNS
  IKQGKNQLFPVVMNGKEDVLWCTELERIFGFPVHYTDVSNMGRGARQKLLGRSWSVPVIR
  HLFAPLKDYFACE
• Function: Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing. In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Functions as a transcriptional corepressor by associating with ZHX1. Required for DUX4 silencing in somatic cells.
• Tissue Specificity: Ubiquitous; highly expressed in fetal liver, heart, kidney, placenta, and at lower levels in spleen, colon, brain, liver, small intestine, lung, peripheral blood mononuclear cells, and skeletal muscle. Isoform 1 is expressed in all tissues except brain, skeletal muscle and PBMC, 3 is ubiquitous, 4 is expressed in all tissues except brain, skeletal muscle, lung and prostate and 5 is detectable only in testis and at very low level in brain and prostate.
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Metabolic pathways (hsa01100)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  NoRC negatively regulates rRNA expression (R-HSA-427413)
  SUMOylation of DNA methylation proteins (R-HSA-4655427)
  DNA methylation (R-HSA-5334118)
  Defective pyroptosis (R-HSA-9710421)
  PRC2 methylates histones and DNA (R-HSA-212300)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immunodeficiency-centromeric instability-facial anomalies syndrome 1	DISQAV62	Definitive	Autosomal recessive	[1]
Immunodeficiency-centromeric instability-facial anomalies syndrome	DISQ0KIE	Supportive	Autosomal recessive	[2]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	DNA (DNMT3B) decreases the response to substance of Cisplatin.	[32]
Hydrogen peroxide	DM1NG5W	Approved	DNA (DNMT3B) decreases the response to substance of Hydrogen peroxide.	[32]
Decitabine	DMQL8XJ	Approved	DNA (DNMT3B) decreases the response to substance of Decitabine.	[34]
Etoposide	DMNH3PG	Approved	DNA (DNMT3B) decreases the response to substance of Etoposide.	[32]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	DNA (DNMT3B) affects the metabolism of Arsenic.	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of DNA (DNMT3B).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of DNA (DNMT3B).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA (DNMT3B).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of DNA (DNMT3B).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of DNA (DNMT3B).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of DNA (DNMT3B).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of DNA (DNMT3B).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of DNA (DNMT3B).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of DNA (DNMT3B).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of DNA (DNMT3B).	[11]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of DNA (DNMT3B).	[12]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of DNA (DNMT3B).	[13]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of DNA (DNMT3B).	[14]
Ethanol	DMDRQZU	Approved	Ethanol affects the expression of DNA (DNMT3B).	[15]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of DNA (DNMT3B).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of DNA (DNMT3B).	[17]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of DNA (DNMT3B).	[18]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of DNA (DNMT3B).	[19]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of DNA (DNMT3B).	[18]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of DNA (DNMT3B).	[20]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of DNA (DNMT3B).	[22]
T83193	DMHO29Y	Patented	T83193 decreases the expression of DNA (DNMT3B).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of DNA (DNMT3B).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DNA (DNMT3B).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DNA (DNMT3B).	[28]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of DNA (DNMT3B).	[29]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of DNA (DNMT3B).	[30]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde decreases the expression of DNA (DNMT3B).	[25]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the expression of DNA (DNMT3B).	[31]

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 decreases the methylation of DNA (DNMT3B).	[21]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of DNA (DNMT3B).	[23]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of DNA (DNMT3B).	[24]

References

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