Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW394V5)

• DOT Name: Guanine deaminase (GDA)
• Synonyms: Guanase; Guanine aminase; EC 3.5.4.3; Guanine aminohydrolase; GAH; p51-nedasin
• Gene Name: GDA
• UniProt ID: GUAD_HUMAN
• PDB ID: 2UZ9; 3E0L; 4AQL
• EC Number: 3.5.4.3
• Pfam ID: PF01979
• Sequence:
  MCAAQMPPLAHIFRGTFVHSTWTCPMEVLRDHLLGVSDSGKIVFLEEASQQEKLAKEWCF
  KPCEIRELSHHEFFMPGLVDTHIHASQYSFAGSSIDLPLLEWLTKYTFPAEHRFQNIDFA
  EEVYTRVVRRTLKNGTTTACYFATIHTDSSLLLADITDKFGQRAFVGKVCMDLNDTFPEY
  KETTEESIKETERFVSEMLQKNYSRVKPIVTPRFSLSCSETLMGELGNIAKTRDLHIQSH
  ISENRDEVEAVKNLYPSYKNYTSVYDKNNLLTNKTVMAHGCYLSAEELNVFHERGASIAH
  CPNSNLSLSSGFLNVLEVLKHEVKIGLGTDVAGGYSYSMLDAIRRAVMVSNILLINKVNE
  KSLTLKEVFRLATLGGSQALGLDGEIGNFEVGKEFDAILINPKASDSPIDLFYGDFFGDI
  SEAVIQKFLYLGDDRNIEEVYVGGKQVVPFSSSV
• Function: Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway: Purine catabolism (R-HSA-74259)
• BioCyc Pathway: MetaCyc:HS04276-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

12 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 Guanine deaminase (GDA).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Guanine deaminase (GDA).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Guanine deaminase (GDA).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Guanine deaminase (GDA).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Guanine deaminase (GDA).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Guanine deaminase (GDA).	[6]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Guanine deaminase (GDA).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Guanine deaminase (GDA).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Guanine deaminase (GDA).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Guanine deaminase (GDA).	[12]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Guanine deaminase (GDA).	[13]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Guanine deaminase (GDA).	[14]

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 Guanine deaminase (GDA).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Guanine deaminase (GDA).	[11]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Aberrantly expressed genes in HaCaT keratinocytes chronically exposed to arsenic trioxide. Biomark Insights. 2011 Feb 8;6:7-16.
• [7] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] 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.
• [10] 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.
• [11] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] 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.
• [14] The Ah receptor regulates growth factor expression in head and neck squamous cell carcinoma cell lines. Mol Carcinog. 2014 Oct;53(10):765-76.