Details of Drug Off-Target (DOT)

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

• DOT Name: Protein mono-ADP-ribosyltransferase PARP12 (PARP12)
• Synonyms: EC 2.4.2.-; ADP-ribosyltransferase diphtheria toxin-like 12; ARTD12; Poly polymerase 12; PARP-12; Zinc finger CCCH domain-containing protein 1
• Gene Name: PARP12
• Related Disease:
  Influenza
  Vitiligo
  Zika virus infection
  Coronary heart disease
  Age-related macular degeneration
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: PAR12_HUMAN
• PDB ID: 2PQF; 6V3W
• EC Number: 2.4.2.-
• Pfam ID: PF00644 ; PF02825 ; PF00642
• Sequence:
  MAQAGVVGEVTQVLCAAGGALELPELRRRLRMGLSADALERLLRQRGRFVVAVRAGGAAA
  APERVVLAASPLRLCRAHQGSKPGCVGLCAQLHLCRFMVYGACKFLRAGKNCRNSHSLTT
  EHNLSVLRTHGVDHLSYNELCQLLFQNDPWLLPEICQHYNKGDGPHGSCAFQKQCIKLHI
  CQYFLQGECKFGTSCKRSHDFSNSENLEKLEKLGMSSDLVSRLPTIYRNAHDIKNKSSAP
  SRVPPLFVPQGTSERKDSSGSVSPNTLSQEEGDQICLYHIRKSCSFQDKCHRVHFHLPYR
  WQFLDRGKWEDLDNMELIEEAYCNPKIERILCSESASTFHSHCLNFNAMTYGATQARRLS
  TASSVTKPPHFILTTDWIWYWSDEFGSWQEYGRQGTVHPVTTVSSSDVEKAYLAYCTPGS
  DGQAATLKFQAGKHNYELDFKAFVQKNLVYGTTKKVCRRPKYVSPQDVTTMQTCNTKFPG
  PKSIPDYWDSSALPDPGFQKITLSSSSEEYQKVWNLFNRTLPFYFVQKIERVQNLALWEV
  YQWQKGQMQKQNGGKAVDERQLFHGTSAIFVDAICQQNFDWRVCGVHGTSYGKGSYFARD
  AAYSHHYSKSDTQTHTMFLARVLVGEFVRGNASFVRPPAKEGWSNAFYDSCVNSVSDPSI
  FVIFEKHQVYPEYVIQYTTSSKPSVTPSILLALGSLFSSRQ
• Function: Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Influenza	DIS3PNU3	Strong	Biomarker	[1]
Vitiligo	DISR05SL	Strong	Genetic Variation	[2]
Zika virus infection	DISQUCTY	Strong	Altered Expression	[3]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[4]
Age-related macular degeneration	DIS0XS2C	Limited	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[6]
Neoplasm	DISZKGEW	Limited	Biomarker	[6]

14 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 PARP12 (PARP12).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[13]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[15]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[16]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[20]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[22]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein mono-ADP-ribosyltransferase PARP12 (PARP12).	[21]

References

• [1] A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.PLoS One. 2013;8(1):e52198. doi: 10.1371/journal.pone.0052198. Epub 2013 Jan 9.
• [2] Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.
• [3] PARP12 suppresses Zika virus infection through PARP-dependent degradation of NS1 and NS3 viral proteins.Sci Signal. 2018 Jun 19;11(535):eaas9332. doi: 10.1126/scisignal.aas9332.
• [4] Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
• [5] Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration.Nat Genet. 2019 Apr;51(4):606-610. doi: 10.1038/s41588-019-0351-9. Epub 2019 Feb 11.
• [6] PARP12 (ARTD12) suppresses hepatocellular carcinoma metastasis through interacting with FHL2 and regulating its stability.Cell Death Dis. 2018 Aug 28;9(9):856. doi: 10.1038/s41419-018-0906-1.
• [7] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [8] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [9] 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.
• [10] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [11] 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.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Persistent and non-persistent changes in gene expression result from long-term estrogen exposure of MCF-7 breast cancer cells. J Steroid Biochem Mol Biol. 2011 Feb;123(3-5):140-50.
• [14] 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.
• [15] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [16] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [17] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [18] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [19] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [20] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [21] 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.
• [22] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.