Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5P591E)

• DOT Name: Nuclear prelamin A recognition factor (NARF)
• Synonyms: Iron-only hydrogenase-like protein 2; IOP2
• Gene Name: NARF
• UniProt ID: NARF_HUMAN
• Pfam ID: PF02906 ; PF02256
• Sequence:
  MKCEHCTRKECSKKTKTDDQENVSADAPSPAQENGEKGEFHKLADAKIFLSDCLACDSCM
  TAEEGVQLSQQNAKDFFRVLNLNKKCDTSKHKVLVVSVCPQSLPYFAAKFNLSVTDASRR
  LCGFLKSLGVHYVFDTTIAADFSILESQKEFVRRYRQHSEEERTLPMLTSACPGWVRYAE
  RVLGRPITAHLCTAKSPQQVMGSLVKDYFARQQNLSPEKIFHVIVAPCYDKKLEALQESL
  PPALHGSRGADCVLTSGEIAQIMEQGDLSVRDAAVDTLFGDLKEDKVTRHDGASSDGHLA
  HIFRHAAKELFNEDVEEVTYRALRNKDFQEVTLEKNGEVVLRFAAAYGFRNIQNMILKLK
  KGKFPFHFVEVLACAGGCLNGRGQAQTPDGHADKALLRQMEGIYADIPVRRPESSAHVQE
  LYQEWLEGINSPKAREVLHTTYQSQERGTHSLDIKW
• Tissue Specificity: Ubiquitous. Predominantly expressed in skeletal muscle, heart and brain.

Molecular Interaction Atlas (MIA) of This DOT

16 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 prelamin A recognition factor (NARF).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Nuclear prelamin A recognition factor (NARF).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Nuclear prelamin A recognition factor (NARF).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Nuclear prelamin A recognition factor (NARF).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear prelamin A recognition factor (NARF).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nuclear prelamin A recognition factor (NARF).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nuclear prelamin A recognition factor (NARF).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Nuclear prelamin A recognition factor (NARF).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Nuclear prelamin A recognition factor (NARF).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Nuclear prelamin A recognition factor (NARF).	[10]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Nuclear prelamin A recognition factor (NARF).	[11]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Nuclear prelamin A recognition factor (NARF).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Nuclear prelamin A recognition factor (NARF).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Nuclear prelamin A recognition factor (NARF).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Nuclear prelamin A recognition factor (NARF).	[15]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Nuclear prelamin A recognition factor (NARF).	[16]

2 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 increases the methylation of Nuclear prelamin A recognition factor (NARF).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Nuclear prelamin A recognition factor (NARF).	[14]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] 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.
• [13] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [14] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [15] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [16] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.