Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1ZMQTU)

• DOT Name: DNA methyltransferase 1-associated protein 1 (DMAP1)
• Synonyms: DNMAP1; DNMT1-associated protein 1
• Gene Name: DMAP1
• Related Disease:
  Neoplasm
  Advanced cancer
  Gastric cancer
  Non-insulin dependent diabetes
  Pancreatic cancer
  Polycystic ovarian syndrome
  Stomach cancer
• UniProt ID: DMAP1_HUMAN
• PDB ID: 3HM5; 4IEJ
• Pfam ID: PF05499 ; PF16282
• Sequence:
  MATGADVRDILELGGPEGDAASGTISKKDIINPDKKKSKKSSETLTFKRPEGMHREVYAL
  LYSDKKDAPPLLPSDTGQGYRTVKAKLGSKKVRPWKWMPFTNPARKDGAMFFHWRRAAEE
  GKDYPFARFNKTVQVPVYSEQEYQLYLHDDAWTKAETDHLFDLSRRFDLRFVVIHDRYDH
  QQFKKRSVEDLKERYYHICAKLANVRAVPGTDLKIPVFDAGHERRRKEQLERLYNRTPEQ
  VAEEEYLLQELRKIEARKKEREKRSQDLQKLITAADTTAEQRRTERKAPKKKLPQKKEAE
  KPAVPETAGIKFPDFKSAGVTLRSQRMKLPSSVGQKKIKALEQMLLELGVELSPTPTEEL
  VHMFNELRSDLVLLYELKQACANCEYELQMLRHRHEALARAGVLGGPATPASGPGPASAE
  PAVTEPGLGPDPKDTIIDVVGAPLTPNSRKRRESASSSSSVKKAKKP
• Function: Involved in transcription repression and activation. Its interaction with HDAC2 may provide a mechanism for histone deacetylation in heterochromatin following replication of DNA at late firing origins. Can also repress transcription independently of histone deacetylase activity. May specifically potentiate DAXX-mediated repression of glucocorticoid receptor-dependent transcription. Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Participates in the nuclear localization of URI1 and increases its transcriptional corepressor activity.
• KEGG Pathway: ATP-dependent chromatin remodeling (hsa03082)
• Reactome Pathway: HATs acetylate histones (R-HSA-3214847)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Disputed	Biomarker	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[2]
Gastric cancer	DISXGOUK	Limited	Biomarker	[3]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Posttranslational Modification	[4]
Pancreatic cancer	DISJC981	Limited	Biomarker	[5]
Polycystic ovarian syndrome	DISZ2BNG	Limited	Posttranslational Modification	[4]
Stomach cancer	DISKIJSX	Limited	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of DNA methyltransferase 1-associated protein 1 (DMAP1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA methyltransferase 1-associated protein 1 (DMAP1).	[7]

5 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 affects the methylation of DNA methyltransferase 1-associated protein 1 (DMAP1).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of DNA methyltransferase 1-associated protein 1 (DMAP1).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of DNA methyltransferase 1-associated protein 1 (DMAP1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of DNA methyltransferase 1-associated protein 1 (DMAP1).	[11]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of DNA methyltransferase 1-associated protein 1 (DMAP1).	[10]

References

• [1] C-Src confers resistance to mitotic stress through inhibition DMAP1/Bub3 complex formation in pancreatic cancer.Mol Cancer. 2018 Dec 15;17(1):174. doi: 10.1186/s12943-018-0919-5.
• [2] Epigenetic regulation of active Chinese herbal components for cancer prevention and treatment: A follow-up review.Pharmacol Res. 2016 Dec;114:1-12. doi: 10.1016/j.phrs.2016.09.023. Epub 2016 Sep 30.
• [3] MDGA2 is a novel tumour suppressor cooperating with DMAP1 in gastric cancer and is associated with disease outcome.Gut. 2016 Oct;65(10):1619-31. doi: 10.1136/gutjnl-2015-309276. Epub 2015 Jul 23.
• [4] Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome.Sci Rep. 2016 Mar 15;6:22883. doi: 10.1038/srep22883.
• [5] Correction to: c-Src confers resistance to mitotic stress through inhibition of DMAP1/Bub3 complex formation in pancreatic cancer.Mol Cancer. 2019 Nov 29;18(1):172. doi: 10.1186/s12943-019-1067-2.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] 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.
• [8] 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.
• [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] 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.
• [11] 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.