Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR9YPA4)

• DOT Name: Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2)
• Synonyms: Multisynthase complex auxiliary component p38; Protein JTV-1
• Gene Name: AIMP2
• Related Disease: Leukodystrophy, hypomyelinating, 17
• UniProt ID: AIMP2_HUMAN
• PDB ID: 4DPG; 4YCU; 4YCW; 5A1N; 5A34; 5A5H; 5Y6L; 6ILD; 6IY6; 6JPV; 6K39
• Pfam ID: PF16780 ; PF00043 ; PF18569
• Sequence:
  MPMYQVKPYHGGGAPLRVELPTCMYRLPNVHGRSYGPAPGAGHVQEESNLSLQALESRQD
  DILKRLYELKAAVDGLSKMIQTPDADLDVTNIIQADEPTTLTTNALDLNSVLGKDYGALK
  DIVINANPASPPLSLLVLHRLLCEHFRVLSTVHTHSSVKSVPENLLKCFGEQNKKQPRQD
  YQLGFTLIWKNVPKTQMKFSIQTMCPIEGEGNIARFLFSLFGQKHNAVNATLIDSWVDIA
  IFQLKEGSSKEKAAVFRSMNSALGKSPWLAGNELTVADVVLWSVLQQIGGCSVTVPANVQ
  RWMRSCENLAPFNTALKLLK
• Function: Required for assembly and stability of the aminoacyl-tRNA synthase complex. Mediates ubiquitination and degradation of FUBP1, a transcriptional activator of MYC, leading to MYC down-regulation which is required for aveolar type II cell differentiation. Blocks MDM2-mediated ubiquitination and degradation of p53/TP53. Functions as a proapoptotic factor.
• Reactome Pathway:
  Cytosolic tRNA aminoacylation (R-HSA-379716)
  Selenoamino acid metabolism (R-HSA-2408522)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leukodystrophy, hypomyelinating, 17	DISFRMBA	Definitive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2) affects the response to substance of Acetaminophen.	[14]

12 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 Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[12]
Z-Pro-Prolinal	DM43O2U	Investigative	Z-Pro-Prolinal increases the expression of Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2).	[13]

References

• [1] Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis. J Hum Genet. 2018 Jan;63(1):19-25. doi: 10.1038/s10038-017-0363-1. Epub 2017 Nov 16.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] 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.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [11] BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 2012 Oct 4;120(14):2843-52.
• [12] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [13] Prolyl endopeptidase is involved in cellular signalling in human neuroblastoma SH-SY5Y cells. Neurosignals. 2011;19(2):97-109. doi: 10.1159/000326342. Epub 2011 Apr 10.
• [14] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.