Details of Drug Off-Target (DOT)

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

• DOT Name: NGFI-A-binding protein 1 (NAB1)
• Synonyms: EGR-1-binding protein 1; Transcriptional regulatory protein p54
• Gene Name: NAB1
• Related Disease:
  Gastric cancer
  Myocardial infarction
  Primary biliary cholangitis
  Stomach cancer
  Systemic sclerosis
  Neuropathy, congenital hypomelinating
• UniProt ID: NAB1_HUMAN
• PDB ID: 2YUF
• Pfam ID: PF04902 ; PF04904 ; PF04905
• Sequence:
  MAAALPRTLGELQLYRILQKANLLSYFDAFIQQGGDDVQQLCEAGEEEFLEIMALVGMAS
  KPLHVRRLQKALRDWVTNPGLFNQPLTSLPVSSIPIYKLPEGSPTWLGISCSSYERSSNA
  REPHLKIPKCAATTCVQSLGQGKSDVVGSLALQSVGESRLWQGHHATESEHSLSPADLGS
  PASPKESSEALDAAAALSVAECVERMAPTLPKSDLNEVKELLKTNKKLAKMIGHIFEMND
  DDPHKEEEIRKYSAIYGRFDSKRKDGKHLTLHELTVNEAAAQLCVKDNALLTRRDELFAL
  ARQISREVTYKYTYRTTKSKCGERDELSPKRIKVEDGFPDFQDSVQTLFQQARAKSEELA
  ALSSQQPEKVMAKQMEFLCNQAGYERLQHAERRLSAGLYRQSSEEHSPNGLTSDNSDGQG
  ERPLNLRMPNLQNRQPHHFVVDGELSRLYPSEAKSHSSESLGILKDYPHSAFTLEKKVIK
  TEPEDSR
• Function: Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2.
• Tissue Specificity: Isoform Short is found in myeloid leukemia cell line KG-1.
• Reactome Pathway:
  EGR2 and SOX10-mediated initiation of Schwann cell myelination (R-HSA-9619665)
  NGF-stimulated transcription (R-HSA-9031628)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Strong	Altered Expression	[1]
Myocardial infarction	DIS655KI	Strong	Biomarker	[2]
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[3]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[1]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[4]
Neuropathy, congenital hypomelinating	DISZUW4L	Limited	Biomarker	[5]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	NGFI-A-binding protein 1 (NAB1) affects the response to substance of Cisplatin.	[21]
Topotecan	DMP6G8T	Approved	NGFI-A-binding protein 1 (NAB1) affects the response to substance of Topotecan.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of NGFI-A-binding protein 1 (NAB1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of NGFI-A-binding protein 1 (NAB1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of NGFI-A-binding protein 1 (NAB1).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of NGFI-A-binding protein 1 (NAB1).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of NGFI-A-binding protein 1 (NAB1).	[10]
Marinol	DM70IK5	Approved	Marinol decreases the expression of NGFI-A-binding protein 1 (NAB1).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of NGFI-A-binding protein 1 (NAB1).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of NGFI-A-binding protein 1 (NAB1).	[10]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of NGFI-A-binding protein 1 (NAB1).	[13]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of NGFI-A-binding protein 1 (NAB1).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of NGFI-A-binding protein 1 (NAB1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of NGFI-A-binding protein 1 (NAB1).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of NGFI-A-binding protein 1 (NAB1).	[20]

4 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 NGFI-A-binding protein 1 (NAB1).	[16]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of NGFI-A-binding protein 1 (NAB1).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of NGFI-A-binding protein 1 (NAB1).	[19]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of NGFI-A-binding protein 1 (NAB1).	[19]

References

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• [2] Regulation of macrophage migration in ischemic mouse hearts via an AKT2/NBA1/SPK1 pathway.Oncotarget. 2017 Dec 15;8(70):115345-115359. doi: 10.18632/oncotarget.23263. eCollection 2017 Dec 29.
• [3] International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.Nat Commun. 2015 Sep 22;6:8019. doi: 10.1038/ncomms9019.
• [4] GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways.Nat Commun. 2019 Oct 31;10(1):4955. doi: 10.1038/s41467-019-12760-y.
• [5] Nab proteins are essential for peripheral nervous system myelination.Nat Neurosci. 2005 Jul;8(7):932-40. doi: 10.1038/nn1490.
• [6] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] 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.
• [10] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [11] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [12] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [21] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.