Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYO1C46)

• DOT Name: Protein mono-ADP-ribosyltransferase PARP15 (PARP15)
• Synonyms: EC 2.4.2.-; ADP-ribosyltransferase diphtheria toxin-like 7; ARTD7; B-aggressive lymphoma protein 3; Poly polymerase 15; PARP-15
• Gene Name: PARP15
• Related Disease:
  Advanced cancer
  Major depressive disorder
  Acute myelogenous leukaemia
• UniProt ID: PAR15_HUMAN
• PDB ID: 3BLJ ; 3GEY ; 3V2B ; 4F0E ; 6EK3 ; 6RY4 ; 7F41 ; 7F42 ; 7F43 ; 7OQQ ; 7OSP ; 7OSS ; 7OSX ; 7OTF ; 7OTH ; 7OUW ; 7OUX ; 7PW3 ; 7PWA ; 7PWC ; 7PWK ; 7PWL ; 7PWM ; 7PWP ; 7PWQ ; 7PWR ; 7PWS ; 7PWU ; 7PWW ; 7PX6 ; 7PX7 ; 7R3O ; 7R4A ; 7R5D ; 7Z1V ; 7Z1W ; 7Z1Y ; 7Z2O ; 7Z2Q ; 7Z41
• EC Number: 2.4.2.-
• Pfam ID: PF01661 ; PF00644
• Sequence:
  MAAPGPLPAAALSPGAPTPRELMHGVAGVTSRAGRDREAGSVLPAGNRGARKASRRSSSR
  SMSRDNKFSKKDCLSIRNVVASIQTKEGLNLKLISGDVLYIWADVIVNSVPMNLQLGGGP
  LSRAFLQKAGPMLQKELDDRRRETEEKVGNIFMTSGCNLDCKAVLHAVAPYWNNGAETSW
  QIMANIIKKCLTTVEVLSFSSITFPMIGTGSLQFPKAVFAKLILSEVFEYSSSTRPITSP
  LQEVHFLVYTNDDEGCQAFLDEFTNWSRINPNKARIPMAGDTQGVVGTVSKPCFTAYEMK
  IGAITFQVATGDIATEQVDVIVNSTARTFNRKSGVSRAILEGAGQAVESECAVLAAQPHR
  DFIITPGGCLKCKIIIHVPGGKDVRKTVTSVLEECEQRKYTSVSLPAIGTGNAGKNPITV
  ADNIIDAIVDFSSQHSTPSLKTVKVVIFQPELLNIFYDSMKKRDLSASLNFQSTFSMTTC
  NLPEHWTDMNHQLFCMVQLEPGQSEYNTIKDKFTRTCSSYAIEKIERIQNAFLWQSYQVK
  KRQMDIKNDHKNNERLLFHGTDADSVPYVNQHGFNRSCAGKNAVSYGKGTYFAVDASYSA
  KDTYSKPDSNGRKHMYVVRVLTGVFTKGRAGLVTPPPKNPHNPTDLFDSVTNNTRSPKLF
  VVFFDNQAYPEYLITFTA
• Function: Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins. Acts as a negative regulator of transcription.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[1]

2 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 increases the methylation of Protein mono-ADP-ribosyltransferase PARP15 (PARP15).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Protein mono-ADP-ribosyltransferase PARP15 (PARP15).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein mono-ADP-ribosyltransferase PARP15 (PARP15).	[4]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PJ34	DMXO6YH	Preclinical	PJ34 affects the binding of Protein mono-ADP-ribosyltransferase PARP15 (PARP15).	[5]

References

• [1] Genetic Association of PARP15 Polymorphisms with Clinical Outcome of Acute Myeloid Leukemia in a Korean Population.Genet Test Mol Biomarkers. 2016 Nov;20(11):696-701. doi: 10.1089/gtmb.2016.0007. Epub 2016 Sep 9.
• [2] A novel relationship for schizophrenia, bipolar and major depressive disorder Part 7: A hint from chromosome 7 high density association screen.Behav Brain Res. 2015 Oct 15;293:241-51. doi: 10.1016/j.bbr.2015.06.043. Epub 2015 Jul 17.
• [3] 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.
• [4] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [5] Identification of pim kinases as novel targets for PJ34 with confounding effects in PARP biology. ACS Chem Biol. 2012 Dec 21;7(12):1962-7. doi: 10.1021/cb300317y. Epub 2012 Oct 8.
• [6] 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.