Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEJP0GH)

• DOT Name: DNA (DNMT3A)
• Synonyms: cytosine-5)-methyltransferase 3A (Dnmt3a; EC 2.1.1.37; Cysteine methyltransferase DNMT3A; EC 2.1.1.-; DNA methyltransferase HsaIIIA; DNA MTase HsaIIIA; M.HsaIIIA
• Gene Name: DNMT3A
• Related Disease:
  Tatton-Brown-Rahman overgrowth syndrome
  Heyn-Sproul-Jackson syndrome
• UniProt ID: DNM3A_HUMAN
• PDB ID: 2QRV; 3A1A; 3A1B; 3LLR; 3SVM; 4QBQ; 4QBR; 4QBS; 4U7P; 4U7T; 5YX2; 6BRR; 6F57; 6PA7; 6W89; 6W8B; 6W8D; 6W8J; 8BA5
• EC Number: 2.1.1.-; 2.1.1.37
• Pfam ID: PF17980 ; PF21255 ; PF00145 ; PF00855
• Sequence:
  MPAMPSSGPGDTSSSAAEREEDRKDGEEQEEPRGKEERQEPSTTARKVGRPGRKRKHPPV
  ESGDTPKDPAVISKSPSMAQDSGASELLPNGDLEKRSEPQPEEGSPAGGQKGGAPAEGEG
  AAETLPEASRAVENGCCTPKEGRGAPAEAGKEQKETNIESMKMEGSRGRLRGGLGWESSL
  RQRPMPRLTFQAGDPYYISKRKRDEWLARWKREAEKKAKVIAGMNAVEENQGPGESQKVE
  EASPPAVQQPTDPASPTVATTPEPVGSDAGDKNATKAGDDEPEYEDGRGFGIGELVWGKL
  RGFSWWPGRIVSWWMTGRSRAAEGTRWVMWFGDGKFSVVCVEKLMPLSSFCSAFHQATYN
  KQPMYRKAIYEVLQVASSRAGKLFPVCHDSDESDTAKAVEVQNKPMIEWALGGFQPSGPK
  GLEPPEEEKNPYKEVYTDMWVEPEAAAYAPPPPAKKPRKSTAEKPKVKEIIDERTRERLV
  YEVRQKCRNIEDICISCGSLNVTLEHPLFVGGMCQNCKNCFLECAYQYDDDGYQSYCTIC
  CGGREVLMCGNNNCCRCFCVECVDLLVGPGAAQAAIKEDPWNCYMCGHKGTYGLLRRRED
  WPSRLQMFFANNHDQEFDPPKVYPPVPAEKRKPIRVLSLFDGIATGLLVLKDLGIQVDRY
  IASEVCEDSITVGMVRHQGKIMYVGDVRSVTQKHIQEWGPFDLVIGGSPCNDLSIVNPAR
  KGLYEGTGRLFFEFYRLLHDARPKEGDDRPFFWLFENVVAMGVSDKRDISRFLESNPVMI
  DAKEVSAAHRARYFWGNLPGMNRPLASTVNDKLELQECLEHGRIAKFSKVRTITTRSNSI
  KQGKDQHFPVFMNEKEDILWCTEMERVFGFPVHYTDVSNMSRLARQRLLGRSWSVPVIRH
  LFAPLKEYFACV
• 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. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. Can actively repress transcription through the recruitment of HDAC activity. Also has weak auto-methylation activity on Cys-710 in absence of DNA.
• Tissue Specificity: Highly expressed in fetal tissues, skeletal muscle, heart, peripheral blood mononuclear cells, kidney, and at lower levels in placenta, brain, liver, colon, spleen, small intestine and lung.
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Metabolic pathways (hsa01100)
  Efferocytosis (hsa04148)
  MicroR.s in cancer (hsa05206)
• Reactome Pathway:
  RMTs methylate histone arginines (R-HSA-3214858)
  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
Tatton-Brown-Rahman overgrowth syndrome	DISECISP	Definitive	Autosomal dominant	[1]
Heyn-Sproul-Jackson syndrome	DIS26Q3S	Strong	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of DNA (DNMT3A).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of DNA (DNMT3A).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of DNA (DNMT3A).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of DNA (DNMT3A).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA (DNMT3A).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of DNA (DNMT3A).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of DNA (DNMT3A).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of DNA (DNMT3A).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of DNA (DNMT3A).	[12]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of DNA (DNMT3A).	[13]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of DNA (DNMT3A).	[14]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of DNA (DNMT3A).	[15]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of DNA (DNMT3A).	[16]
Ethanol	DMDRQZU	Approved	Ethanol affects the expression of DNA (DNMT3A).	[17]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of DNA (DNMT3A).	[18]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of DNA (DNMT3A).	[19]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of DNA (DNMT3A).	[20]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of DNA (DNMT3A).	[21]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of DNA (DNMT3A).	[20]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of DNA (DNMT3A).	[20]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of DNA (DNMT3A).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of DNA (DNMT3A).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of DNA (DNMT3A).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of DNA (DNMT3A).	[28]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of DNA (DNMT3A).	[29]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of DNA (DNMT3A).	[30]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of DNA (DNMT3A).	[31]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR increases the expression of DNA (DNMT3A).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of DNA (DNMT3A).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of DNA (DNMT3A).	[23]
TAK-243	DM4GKV2	Phase 1	TAK-243 affects the sumoylation of DNA (DNMT3A).	[25]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of DNA (DNMT3A).	[26]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of DNA (DNMT3A).	[26]

References

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