Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXK12ZB)

• DOT Name: Amidophosphoribosyltransferase (PPAT)
• Synonyms: ATase; EC 2.4.2.14; Glutamine phosphoribosylpyrophosphate amidotransferase; GPAT
• Gene Name: PPAT
• UniProt ID: PUR1_HUMAN
• EC Number: 2.4.2.14
• Pfam ID: PF13522 ; PF00156
• Sequence:
  MELEELGIREECGVFGCIASGEWPTQLDVPHVITLGLVGLQHRGQESAGIVTSDGSSVPT
  FKSHKGMGLVNHVFTEDNLKKLYVSNLGIGHTRYATTGKCELENCQPFVVETLHGKIAVA
  HNGELVNAARLRKKLLRHGIGLSTSSDSEMITQLLAYTPPQEQDDTPDWVARIKNLMKEA
  PTAYSLLIMHRDVIYAVRDPYGNRPLCIGRLIPVSDINDKEKKTSETEGWVVSSESCSFL
  SIGARYYREVLPGEIVEISRHNVQTLDIISRSEGNPVAFCIFEYVYFARPDSMFEDQMVY
  TVRYRCGQQLAIEAPVDADLVSTVPESATPAALAYAGKCGLPYVEVLCKNRYVGRTFIQP
  NMRLRQLGVAKKFGVLSDNFKGKRIVLVDDSIVRGNTISPIIKLLKESGAKEVHIRVASP
  PIKYPCFMGINIPTKEELIANKPEFDHLAEYLGANSVVYLSVEGLVSSVQEGIKFKKQKE
  KKHDIMIQENGNGLECFEKSGHCTACLTGKYPVELEW
• Function: Catalyzes the formation of phosphoribosylamine from phosphoribosylpyrophosphate (PRPP) and glutamine.
• Tissue Specificity: Ubiquitously expressed.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  Alanine, aspartate and glutamate metabolism (hsa00250)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)
• BioCyc Pathway: MetaCyc:HS05157-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 Amidophosphoribosyltransferase (PPAT).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Amidophosphoribosyltransferase (PPAT).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Amidophosphoribosyltransferase (PPAT).	[3]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Amidophosphoribosyltransferase (PPAT).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Amidophosphoribosyltransferase (PPAT).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Amidophosphoribosyltransferase (PPAT).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Amidophosphoribosyltransferase (PPAT).	[8]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Amidophosphoribosyltransferase (PPAT).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Amidophosphoribosyltransferase (PPAT).	[10]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Amidophosphoribosyltransferase (PPAT).	[2]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Amidophosphoribosyltransferase (PPAT).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Amidophosphoribosyltransferase (PPAT).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Amidophosphoribosyltransferase (PPAT).	[6]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Amidophosphoribosyltransferase (PPAT).	[12]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dasatinib	DMJV2EK	Approved	Dasatinib affects the binding of Amidophosphoribosyltransferase (PPAT).	[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] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [3] 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.
• [4] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [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] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [7] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [8] 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.
• [9] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Gene expression profile of human lymphoid CEM cells sensitive and resistant to glucocorticoid-evoked apoptosis. Genomics. 2003 Jun;81(6):543-55.
• [11] The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107.
• [12] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [13] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.