Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8VA2ZF)

• DOT Name: Nuclear transport factor 2 (NUTF2)
• Synonyms: NTF-2; Placental protein 15; PP15
• Gene Name: NUTF2
• Related Disease:
  Non-insulin dependent diabetes
  Type-1/2 diabetes
  Chikungunya virus infection
  Diabetic retinopathy
  HIV infectious disease
• UniProt ID: NTF2_HUMAN
• PDB ID: 1GY5
• Pfam ID: PF02136
• Sequence:
  MGDKPIWEQIGSSFIQHYYQLFDNDRTQLGAIYIDASCLTWEGQQFQGKAAIVEKLSSLP
  FQKIQHSITAQDHQPTPDSCIISMVVGQLKADEDPIMGFHQMFLLKNINDAWVCTNDMFR
  LALHNFG
• Function: Mediates the import of GDP-bound RAN from the cytoplasm into the nucleus which is essential for the function of RAN in cargo receptor-mediated nucleocytoplasmic transport. Thereby, plays indirectly a more general role in cargo receptor-mediated nucleocytoplasmic transport. Interacts with GDP-bound RAN in the cytosol, recruits it to the nuclear pore complex via its interaction with nucleoporins and promotes its nuclear import.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Altered Expression	[1]
Type-1/2 diabetes	DISIUHAP	Definitive	Altered Expression	[1]
Chikungunya virus infection	DISDXEHY	Strong	Biomarker	[2]
Diabetic retinopathy	DISHGUJM	Strong	Therapeutic	[1]
HIV infectious disease	DISO97HC	Strong	Biomarker	[3]

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 Nuclear transport factor 2 (NUTF2).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nuclear transport factor 2 (NUTF2).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear transport factor 2 (NUTF2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Nuclear transport factor 2 (NUTF2).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Nuclear transport factor 2 (NUTF2).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Nuclear transport factor 2 (NUTF2).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Nuclear transport factor 2 (NUTF2).	[11]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Nuclear transport factor 2 (NUTF2).	[5]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Nuclear transport factor 2 (NUTF2).	[11]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Nuclear transport factor 2 (NUTF2).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Nuclear transport factor 2 (NUTF2).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Nuclear transport factor 2 (NUTF2).	[9]

References

• [1] Overexpression of nuclear transport factor 2 may protect against diabetic retinopathy.Mol Vis. 2009;15:861-9. Epub 2009 Apr 27.
• [2] Separate domains of G3BP promote efficient clustering of alphavirus replication complexes and recruitment of the translation initiation machinery.PLoS Pathog. 2019 Jun 14;15(6):e1007842. doi: 10.1371/journal.ppat.1007842. eCollection 2019 Jun.
• [3] Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.J Virol. 2004 Sep;78(17):9458-73. doi: 10.1128/JVI.78.17.9458-9473.2004.
• [4] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [5] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [6] 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.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] Global expression profiling of theophylline response genes in macrophages: evidence of airway anti-inflammatory regulation. Respir Res. 2005 Aug 8;6(1):89. doi: 10.1186/1465-9921-6-89.
• [13] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.