Details of Drug Off-Target (DOT)

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

• DOT Name: Protein mono-ADP-ribosyltransferase PARP11 (PARP11)
• Synonyms: EC 2.4.2.-; ADP-ribosyltransferase diphtheria toxin-like 11; ARTD11; Poly polymerase 11; PARP-11
• Gene Name: PARP11
• Related Disease: Isolated congenital microcephaly
• UniProt ID: PAR11_HUMAN
• PDB ID: 2DK6
• EC Number: 2.4.2.-
• Pfam ID: PF00644 ; PF02825
• Sequence:
  MWEANPEMFHKAEELFSKTTNNEVDDMDTSDTQWGWFYLAECGKWHMFQPDTNSQCSVSS
  EDIEKSFKTNPCGSISFTTSKFSYKIDFAEMKQMNLTTGKQRLIKRAPFSISAFSYICEN
  EAIPMPPHWENVNTQVPYQLIPLHNQTHEYNEVANLFGKTMDRNRIKRIQRIQNLDLWEF
  FCRKKAQLKKKRGVPQINEQMLFHGTSSEFVEAICIHNFDWRINGIHGAVFGKGTYFARD
  AAYSSRFCKDDIKHGNTFQIHGVSLQQRHLFRTYKSMFLARVLIGDYINGDSKYMRPPSK
  DGSYVNLYDSCVDDTWNPKIFVVFDANQIYPEYLIDFH
• Function: Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins. Plays a role in nuclear envelope stability and nuclear remodeling during spermiogenesis.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Isolated congenital microcephaly	DISUXHZ6	moderate	Biomarker	[1]

3 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 Protein mono-ADP-ribosyltransferase PARP11 (PARP11).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein mono-ADP-ribosyltransferase PARP11 (PARP11).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Protein mono-ADP-ribosyltransferase PARP11 (PARP11).	[6]

3 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 Protein mono-ADP-ribosyltransferase PARP11 (PARP11).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein mono-ADP-ribosyltransferase PARP11 (PARP11).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein mono-ADP-ribosyltransferase PARP11 (PARP11).	[7]

References

• [1] Genotype-phenotype relationship in a child with 2.3 Mb de novo interstitial 12p13.33-p13.32 deletion.Eur J Med Genet. 2014 Jul;57(7):334-8. doi: 10.1016/j.ejmg.2014.04.009. Epub 2014 Apr 26.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [6] 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.
• [7] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.