Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS7WBCP)

• DOT Name: Damage-control phosphatase ARMT1 (ARMT1)
• Synonyms: EC 3.1.3.-; Acidic residue methyltransferase 1; Protein-glutamate O-methyltransferase; EC 2.1.1.-; Sugar phosphate phosphatase ARMT1
• Gene Name: ARMT1
• Related Disease: Advanced cancer
• UniProt ID: ARMT1_HUMAN
• PDB ID: 6UMQ; 6UMR
• EC Number: 2.1.1.-; 3.1.3.-
• Pfam ID: PF01937
• Sequence:
  MAVVPASLSGQDVGSFAYLTIKDRIPQILTKVIDTLHRHKSEFFEKHGEEGVEAEKKAIS
  LLSKLRNELQTDKPFIPLVEKFVDTDIWNQYLEYQQSLLNESDGKSRWFYSPWLLVECYM
  YRRIHEAIIQSPPIDYFDVFKESKEQNFYGSQESIIALCTHLQQLIRTIEDLDENQLKDE
  FFKLLQISLWGNKCDLSLSGGESSSQNTNVLNSLEDLKPFILLNDMEHLWSLLSNCKKTR
  EKASATRVYIVLDNSGFELVTDLILADFLLSSELATEVHFYGKTIPWFVSDTTIHDFNWL
  IEQVKHSNHKWMSKCGADWEEYIKMGKWVYHNHIFWTLPHEYCAMPQVAPDLYAELQKAH
  LILFKGDLNYRKLTGDRKWEFSVPFHQALNGFHPAPLCTIRTLKAEIQVGLQPGQGEQLL
  ASEPSWWTTGKYGIFQYDGPL
• Function: Metal-dependent phosphatase that shows phosphatase activity against several substrates, including fructose-1-phosphate and fructose-6-phosphate. Its preference for fructose-1-phosphate, a strong glycating agent that causes DNA damage rather than a canonical yeast metabolite, suggests a damage-control function in hexose phosphate metabolism. Has also been shown to have O-methyltransferase activity that methylates glutamate residues of target proteins to form gamma-glutamyl methyl ester residues. Possibly methylates PCNA, suggesting it is involved in the DNA damage response.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Damage-control phosphatase ARMT1 (ARMT1).	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Damage-control phosphatase ARMT1 (ARMT1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Damage-control phosphatase ARMT1 (ARMT1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Damage-control phosphatase ARMT1 (ARMT1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Damage-control phosphatase ARMT1 (ARMT1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Damage-control phosphatase ARMT1 (ARMT1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Damage-control phosphatase ARMT1 (ARMT1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Damage-control phosphatase ARMT1 (ARMT1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Damage-control phosphatase ARMT1 (ARMT1).	[10]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Damage-control phosphatase ARMT1 (ARMT1).	[11]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Damage-control phosphatase ARMT1 (ARMT1).	[11]

References

• [1] Identification of a neoantigen epitope in a melanoma patient with good response to anti-PD-1 antibody therapy.Immunol Lett. 2019 Apr;208:52-59. doi: 10.1016/j.imlet.2019.02.004. Epub 2019 Mar 14.
• [2] 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.
• [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] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.