Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK82YVT)

• DOT Name: NTF2-related export protein 2 (NXT2)
• Synonyms: Protein p15-2
• Gene Name: NXT2
• UniProt ID: NXT2_HUMAN
• Pfam ID: PF02136
• Sequence:
  MATSLDFKTYVDQACRAAEEFVNIYYETMDKRRRALTRLYLDKATLIWNGNAVSGLDALN
  NFFDTLPSSEFQVNMLDCQPVHEQATQSQTTVLVVTSGTVKFDGNKQHFFNQNFLLTAQS
  TPNNTVWKIASDCFRFQDWSSS
• Function: Regulator of protein export for NES-containing proteins. Also plays a role in mRNA nuclear export.
• KEGG Pathway:
  Ribosome biogenesis in eukaryotes (hsa03008)
  Nucleocytoplasmic transport (hsa03013)
  mR. surveillance pathway (hsa03015)
  Amyotrophic lateral sclerosis (hsa05014)
  Influenza A (hsa05164)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of NTF2-related export protein 2 (NXT2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of NTF2-related export protein 2 (NXT2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of NTF2-related export protein 2 (NXT2).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of NTF2-related export protein 2 (NXT2).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of NTF2-related export protein 2 (NXT2).	[5]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of NTF2-related export protein 2 (NXT2).	[6]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of NTF2-related export protein 2 (NXT2).	[7]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of NTF2-related export protein 2 (NXT2).	[8]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of NTF2-related export protein 2 (NXT2).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of NTF2-related export protein 2 (NXT2).	[10]

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 affects the methylation of NTF2-related export protein 2 (NXT2).	[9]

References

• [1] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [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] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [7] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [8] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [9] 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.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.