Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT01JWJB)

• DOT Name: Trifunctional purine biosynthetic protein adenosine-3 (GART)
• Gene Name: GART
• UniProt ID: PUR2_HUMAN
• PDB ID: 1MEJ ; 1MEN ; 1MEO ; 1NJS ; 1RBM ; 1RBQ ; 1RBY ; 1RBZ ; 1RC0 ; 1RC1 ; 1ZLX ; 1ZLY ; 2QK4 ; 2V9Y ; 4EW1 ; 4EW2 ; 4EW3 ; 4ZYT ; 4ZYU ; 4ZYV ; 4ZYW ; 4ZYX ; 4ZYY ; 4ZYZ ; 4ZZ0 ; 4ZZ1 ; 4ZZ2 ; 4ZZ3 ; 5J9F ; 7JG0 ; 7JG3 ; 7JG4 ; 8FDX ; 8FDY ; 8FDZ ; 8FE0 ; 8FJV ; 8FJW ; 8FJX ; 8FJY
• EC Number: 2.1.2.2; 6.3.3.1; 6.3.4.13
• Pfam ID: PF00586 ; PF02769 ; PF00551 ; PF01071 ; PF02843 ; PF02844
• Sequence:
  MAARVLIIGSGGREHTLAWKLAQSHHVKQVLVAPGNAGTACSEKISNTAISISDHTALAQ
  FCKEKKIEFVVVGPEAPLAAGIVGNLRSAGVQCFGPTAEAAQLESSKRFAKEFMDRHGIP
  TAQWKAFTKPEEACSFILSADFPALVVKASGLAAGKGVIVAKSKEEACKAVQEIMQEKAF
  GAAGETIVIEELLDGEEVSCLCFTDGKTVAPMPPAQDHKRLLEGDGGPNTGGMGAYCPAP
  QVSNDLLLKIKDTVLQRTVDGMQQEGTPYTGILYAGIMLTKNGPKVLEFNCRFGDPECQV
  ILPLLKSDLYEVIQSTLDGLLCTSLPVWLENHTALTVVMASKGYPGDYTKGVEITGFPEA
  QALGLEVFHAGTALKNGKVVTHGGRVLAVTAIRENLISALEEAKKGLAAIKFEGAIYRKD
  VGFRAIAFLQQPRSLTYKESGVDIAAGNMLVKKIQPLAKATSRSGCKVDLGGFAGLFDLK
  AAGFKDPLLASGTDGVGTKLKIAQLCNKHDTIGQDLVAMCVNDILAQGAEPLFFLDYFSC
  GKLDLSVTEAVVAGIAKACGKAGCALLGGETAEMPDMYPPGEYDLAGFAVGAMERDQKLP
  HLERITEGDVVVGIASSGLHSNGFSLVRKIVAKSSLQYSSPAPDGCGDQTLGDLLLTPTR
  IYSHSLLPVLRSGHVKAFAHITGGGLLENIPRVLPEKLGVDLDAQTWRIPRVFSWLQQEG
  HLSEEEMARTFNCGVGAVLVVSKEQTEQILRDIQQHKEEAWVIGSVVARAEGSPRVKVKN
  LIESMQINGSVLKNGSLTNHFSFEKKKARVAVLISGTGSNLQALIDSTREPNSSAQIDIV
  ISNKAAVAGLDKAERAGIPTRVINHKLYKNRVEFDSAIDLVLEEFSIDIVCLAGFMRILS
  GPFVQKWNGKMLNIHPSLLPSFKGSNAHEQALETGVTVTGCTVHFVAEDVDAGQIILQEA
  VPVKRGDTVATLSERVKLAEHKIFPAALQLVASGTVQLGENGKICWVKEE
• Function: Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
• KEGG Pathway:
  Purine metabolism (hsa00230)
  One carbon pool by folate (hsa00670)
  Metabolic pathways (hsa01100)
  Antifolate resistance (hsa01523)
• Reactome Pathway: Purine ribonucleoside monophosphate biosynthesis (R-HSA-73817)
• BioCyc Pathway: MetaCyc:HS08358-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Floxuridine	DM04LR2	Approved	Trifunctional purine biosynthetic protein adenosine-3 (GART) affects the response to substance of Floxuridine.	[22]

22 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 Trifunctional purine biosynthetic protein adenosine-3 (GART).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[11]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[13]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[11]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[16]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[19]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[20]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Trifunctional purine biosynthetic protein adenosine-3 (GART).	[15]

References

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• [13] Expression profiling of nucleotide metabolism-related genes in human breast cancer cells after treatment with 5-fluorouracil. Cancer Invest. 2009 Jun;27(5):561-7.
• [14] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
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• [20] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [21] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [22] Folic Acid-Metabolizing Enzymes Regulate the Antitumor Effect of 5-Fluoro-2'-Deoxyuridine in Colorectal Cancer Cell Lines. PLoS One. 2016 Sep 29;11(9):e0163961. doi: 10.1371/journal.pone.0163961. eCollection 2016.