Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5ZUKVF)

• DOT Name: Adenine phosphoribosyltransferase (APRT)
• Synonyms: APRT; EC 2.4.2.7
• Gene Name: APRT
• Related Disease: Adenine phosphoribosyltransferase deficiency
• UniProt ID: APT_HUMAN
• PDB ID: 1ORE; 1ZN7; 1ZN8; 1ZN9; 4X44; 4X45; 6FCH; 6FCI; 6FCL; 6FD4; 6FD5; 6FD6; 6HGP; 6HGQ; 6HGR; 6HGS
• EC Number: 2.4.2.7
• Pfam ID: PF00156
• Sequence:
  MADSELQLVEQRIRSFPDFPTPGVVFRDISPVLKDPASFRAAIGLLARHLKATHGGRIDY
  IAGLDSRGFLFGPSLAQELGLGCVLIRKRGKLPGPTLWASYSLEYGKAELEIQKDALEPG
  QRVVVVDDLLATGGTMNAACELLGRLQAEVLECVSLVELTSLKGREKLAPVPFFSLLQYE
• Function: Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Metabolic pathways (hsa01100)
  Nucleotide metabolism (hsa01232)
• Reactome Pathway:
  Purine salvage (R-HSA-74217)
  Defective APRT disrupts adenine salvage (R-HSA-9734195)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenine phosphoribosyltransferase deficiency	DISL7NZ6	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Adenine phosphoribosyltransferase (APRT).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Adenine phosphoribosyltransferase (APRT).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Adenine phosphoribosyltransferase (APRT).	[4]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Adenine phosphoribosyltransferase (APRT).	[5]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Adenine phosphoribosyltransferase (APRT).	[6]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the mutagenesis of Adenine phosphoribosyltransferase (APRT).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Adenine phosphoribosyltransferase (APRT).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Adenine phosphoribosyltransferase (APRT).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adenine phosphoribosyltransferase (APRT).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Adenine phosphoribosyltransferase (APRT).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Adenine phosphoribosyltransferase (APRT).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Adenine phosphoribosyltransferase (APRT).	[14]
Lead acetate	DML0GZ2	Investigative	Lead acetate decreases the activity of Adenine phosphoribosyltransferase (APRT).	[15]

1 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 Adenine phosphoribosyltransferase (APRT).	[10]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [6] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [7] Mutagenicity and loss of heterozygosity at the APRT locus in human lymphoblastoid cells exposed to 3'-azido-3'-deoxythymidine. Mutagenesis. 2000 Sep;15(5):405-10. doi: 10.1093/mutage/15.5.405.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [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] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] 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.
• [13] 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.
• [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] Inhibition of erythrocyte phosphoribosyltransferases (APRT and HPRT) by Pb2+: a potential mechanism of lead toxicity. Toxicology. 2009 May 2;259(1-2):77-83.