Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXC5APO)

• DOT Name: 60S ribosomal export protein NMD3 (NMD3)
• Synonyms: hNMD3
• Gene Name: NMD3
• Related Disease:
  T-cell acute lymphoblastic leukaemia
  Amyotrophic lateral sclerosis
• UniProt ID: NMD3_HUMAN
• PDB ID: 6LQM; 6LSR; 6LU8
• Pfam ID: PF04981 ; PF21192 ; PF21193
• Sequence:
  MEYMAESTDRSPGHILCCECGVPISPNPANICVACLRSKVDISQGIPKQVSISFCKQCQR
  YFQPPGTWIQCALESRELLALCLKKIKAPLSKVRLVDAGFVWTEPHSKRLKVKLTIQKEV
  MNGAILQQVFVVDYVVQSQMCGDCHRVEAKDFWKAVIQVRQKTLHKKTFYYLEQLILKYG
  MHQNTLRIKEIHDGLDFYYSSKQHAQKMVEFLQCTVPCRYKASQRLISQDIHSNTYNYKS
  TFSVEIVPICKDNVVCLSPKLAQSLGNMNQICVCIRVTSAIHLIDPNTLQVADIDGSTFW
  SHPFNSLCHPKQLEEFIVMECSIVQDIKRAAGAGMISKKHTLGEVWVQKTSEMNTDKQYF
  CRTHLGHLLNPGDLVLGFDLANCNLNDEHVNKMNSDRVPDVVLIKKSYDRTKRQRRRNWK
  LKELARERENMDTDDERQYQDFLEDLEEDEAIRKNVNIYRDSAIPVESDTDDEGAPRISL
  AEMLEDLHISQDATGEEGASMLT
• Function: Acts as an adapter for the XPO1/CRM1-mediated export of the 60S ribosomal subunit.
• KEGG Pathway:
  Ribosome biogenesis in eukaryotes (hsa03008)
  Nucleocytoplasmic transport (hsa03013)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Genetic Variation	[1]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Genetic Variation	[2]

11 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 60S ribosomal export protein NMD3 (NMD3).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of 60S ribosomal export protein NMD3 (NMD3).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of 60S ribosomal export protein NMD3 (NMD3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of 60S ribosomal export protein NMD3 (NMD3).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of 60S ribosomal export protein NMD3 (NMD3).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of 60S ribosomal export protein NMD3 (NMD3).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of 60S ribosomal export protein NMD3 (NMD3).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of 60S ribosomal export protein NMD3 (NMD3).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of 60S ribosomal export protein NMD3 (NMD3).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of 60S ribosomal export protein NMD3 (NMD3).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of 60S ribosomal export protein NMD3 (NMD3).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of 60S ribosomal export protein NMD3 (NMD3).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of 60S ribosomal export protein NMD3 (NMD3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of 60S ribosomal export protein NMD3 (NMD3).	[15]

References

• [1] The T-cell leukemia related rpl10-R98S mutant traps the 60S export adapter Nmd3 in the ribosomal P site in yeast.PLoS Genet. 2017 Jul 17;13(7):e1006894. doi: 10.1371/journal.pgen.1006894. eCollection 2017 Jul.
• [2] Determining the Effect of the HNMT, STK39, and NMD3 Polymorphisms on the Incidence of Parkinson's Disease, Amyotrophic Lateral Sclerosis, and Multiple System Atrophy in Chinese Populations.J Mol Neurosci. 2018 Apr;64(4):574-580. doi: 10.1007/s12031-018-1048-8. Epub 2018 Mar 21.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [8] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [9] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [10] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [14] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.