Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJGDLB6)

• DOT Name: Adenosine 5'-monophosphoramidase HINT3 (HINT3)
• Synonyms: EC 3.9.1.-; Histidine triad nucleotide-binding protein 3; HINT-3
• Gene Name: HINT3
• Related Disease: Narcolepsy
• UniProt ID: HINT3_HUMAN
• EC Number: 3.9.1.-
• Pfam ID: PF11969
• Sequence:
  MAEEQVNRSAGLAPDCEASATAETTVSSVGTCEAAGKSPEPKDYDSTCVFCRIAGRQDPG
  TELLHCENEDLICFKDIKPAATHHYLVVPKKHIGNCRTLRKDQVELVENMVTVGKTILER
  NNFTDFTNVRMGFHMPPFCSISHLHLHVLAPVDQLGFLSKLVYRVNSYWFITADHLIEKL
  RT
• Function: Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2. Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase. Hydrolyzes 3-indolepropionic acyl-adenylate and fluorogenic purine nucleoside tryptamine phosphoramidates in vitro.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[9]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[14]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[15]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Adenosine 5'-monophosphoramidase HINT3 (HINT3).	[16]

References

• [1] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [2] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [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] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [11] 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.
• [12] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.
• [16] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.