Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0D7GC4)

• DOT Name: Acyl-coenzyme A diphosphatase NUDT19 (NUDT19)
• Synonyms: EC 3.6.1.-; Nucleoside diphosphate-linked moiety X motif 19; Nudix motif 19
• Gene Name: NUDT19
• Related Disease: Cranio-osteoarthropathy
• UniProt ID: NUD19_HUMAN
• EC Number: 3.6.1.-
• Sequence:
  MSSSLRPGPSRWRRAASIVLAAGWSRPETATPPSRPPPAEGFRLLLLQRSPHQGFMPGAH
  VFSGGVLDAADRSADWLGLFAPHHGPPRFGLGPAPFSRTAFPSLPDTDDHKTDNTGTLPE
  DVAFRICAVREAFEEAGVLLLRPRTSPPGPAPGPGLALEPPPGLASWRDRVRQDPRHFLR
  LCAHLDCTPDIWALHNWSAWLTPFLRGTTRRFDTAFFLCCLREPPPVYPDLAEVVGYQWS
  SPSEATESFLSKEIWLPPPQFYEVRRLANFASLSDLHKFCLGRALEGLERWLPIILLTAD
  GMVHLLPGDELYLEDSDFLENLMSTEKKTEEIMKEGKQFHRIVTYHRHLYDIHVTVQPKY
  KHVYPKNSVVRKSHL
• Function: Fatty acyl-coenzyme A (CoA) diphosphatase that hydrolyzes fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-bisphosphate. Mediates the hydrolysis of a wide range of CoA esters, including choloyl-CoA and branched-chain fatty-acyl-CoA esters and at low substrate concentrations medium and long-chain fatty-acyl-CoA esters are the primary substrates. Highest activity seen with medium-chain acyl-CoA esters and higher rates of activity seen with the unsaturated acyl-CoA esters compared with the saturated esters. Exhibits decapping activity towards dpCoA-capped RNAs in vitro.
• KEGG Pathway: Peroxisome (hsa04146)
• Reactome Pathway:
  Peroxisomal protein import (R-HSA-9033241)
  Peroxisomal lipid metabolism (R-HSA-390918)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cranio-osteoarthropathy	DISJ5ZZB	Strong	Biomarker	[1]

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 Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Acyl-coenzyme A diphosphatase NUDT19 (NUDT19).	[15]

References

• [1] Nudt19 is a renal CoA diphosphohydrolase with biochemical and regulatory properties that are distinct from the hepatic Nudt7 isoform.J Biol Chem. 2018 Mar 16;293(11):4134-4148. doi: 10.1074/jbc.RA117.001358. Epub 2018 Jan 29.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [13] 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.
• [14] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [15] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.