Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOD1QC3)

• DOT Name: Protein mago nashi homolog 2 (MAGOHB)
• Gene Name: MAGOHB
• Related Disease: Advanced cancer
• UniProt ID: MGN2_HUMAN
• PDB ID: 5XJC; 5YZG; 6ICZ; 6QDV
• Pfam ID: PF02792
• Sequence:
  MAVASDFYLRYYVGHKGKFGHEFLEFEFRPDGKLRYANNSNYKNDVMIRKEAYVHKSVME
  ELKRIIDDSEITKEDDALWPPPDRVGRQELEIVIGDEHISFTTSKIGSLIDVNQSKDPEG
  LRVFYYLVQDLKCLVFSLIGLHFKIKPI
• Function: Required for pre-mRNA splicing as component of the spliceosome. Plays a redundant role with MAGOH in the exon junction complex and in the nonsense-mediated decay (NMD) pathway.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway:
  Nucleocytoplasmic transport (hsa03013)
  mR. surveillance pathway (hsa03015)
  Spliceosome (hsa03040)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  mRNA 3'-end processing (R-HSA-72187)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  Regulation of expression of SLITs and ROBOs (R-HSA-9010553)
  Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) (R-HSA-975957)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)

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	Biomarker	[1]

9 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 Protein mago nashi homolog 2 (MAGOHB).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein mago nashi homolog 2 (MAGOHB).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein mago nashi homolog 2 (MAGOHB).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein mago nashi homolog 2 (MAGOHB).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein mago nashi homolog 2 (MAGOHB).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein mago nashi homolog 2 (MAGOHB).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein mago nashi homolog 2 (MAGOHB).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein mago nashi homolog 2 (MAGOHB).	[10]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Protein mago nashi homolog 2 (MAGOHB).	[11]

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 decreases the methylation of Protein mago nashi homolog 2 (MAGOHB).	[7]

References

• [1] Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.Nat Genet. 2018 Jul;50(7):937-943. doi: 10.1038/s41588-018-0155-3. Epub 2018 Jun 28.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] 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.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [9] 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.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [11] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.