Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQK9SOP)

• DOT Name: Protein mono-ADP-ribosyltransferase PARP16 (PARP16)
• Synonyms: EC 2.4.2.-; ADP-ribosyltransferase diphtheria toxin-like 15; Poly polymerase 16; PARP-16
• Gene Name: PARP16
• UniProt ID: PAR16_HUMAN
• PDB ID: 4F0D; 6HXR; 6HXS; 6W65
• EC Number: 2.4.2.-
• Pfam ID: PF18084 ; PF00644
• Sequence:
  MQPSGWAAAREAAGRDMLAADLRCSLFASALQSYKRDSVLRPFPASYARGDCKDFEALLA
  DASKLPNLKELLQSSGDNHKRAWDLVSWILSSKVLTIHSAGKAEFEKIQKLTGAPHTPVP
  APDFLFEIEYFDPANAKFYETKGERDLIYAFHGSRLENFHSIIHNGLHCHLNKTSLFGEG
  TYLTSDLSLALIYSPHGHGWQHSLLGPILSCVAVCEVIDHPDVKCQTKKKDSKEIDRRRA
  RIKHSEGGDIPPKYFVVTNNQLLRVKYLLVYSQKPPKRASSQLSWFSSHWFTVMISLYLL
  LLLIVSVINSSAFQHFWNRAKR
• Function: Intracellular mono-ADP-ribosyltransferase that plays a role in different processes, such as protein translation and unfolded protein response (UPR), through the mono-ADP-ribosylation of proteins involved in those processes. Acts as an inhibitor of protein translation by catalyzing mono-ADP-ribosylation of ribosomal subunits, such as RPL14 and RPS6, thereby inhibiting polysome assembly and mRNA loading. Mono-ADP-ribosylation of ribosomal subunits is promoted by NMNAT2. Involved in the unfolded protein response (UPR) by ADP-ribosylating and activating EIF2AK3 and ERN1, two important UPR effectors. May also mediate mono-ADP-ribosylation of karyopherin KPNB1 a nuclear import factor. May not modify proteins on arginine or cysteine residues compared to other mono-ADP-ribosyltransferases.
• Reactome Pathway:
  Maturation of nucleoprotein (R-HSA-9683610)
  Maturation of nucleoprotein (R-HSA-9694631)
  Nicotinamide salvaging (R-HSA-197264)

Molecular Interaction Atlas (MIA) of This DOT

6 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 Protein mono-ADP-ribosyltransferase PARP16 (PARP16).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein mono-ADP-ribosyltransferase PARP16 (PARP16).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein mono-ADP-ribosyltransferase PARP16 (PARP16).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein mono-ADP-ribosyltransferase PARP16 (PARP16).	[4]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Protein mono-ADP-ribosyltransferase PARP16 (PARP16).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Protein mono-ADP-ribosyltransferase PARP16 (PARP16).	[6]

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 PARP16 (PARP16).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Protein mono-ADP-ribosyltransferase PARP16 (PARP16).	[9]

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 PARP16 (PARP16).	[8]

References

• [1] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [5] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] 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.
• [8] 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.
• [9] 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.