Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9AV8B1)

DOT Name Nuclear factor related to kappa-B-binding protein (NFRKB)
Synonyms DNA-binding protein R kappa-B; INO80 complex subunit G
Gene Name NFRKB
Related Disease
Narcolepsy ( )
UniProt ID
NFRKB_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3U21; 4UF5; 4UF6; 4WLP
Pfam ID
PF14465
Sequence
MDSLDHMLTDPLELGPCGDGHGTRIMEDCLLGGTRVSLPEDLLEDPEIFFDVVSLSTWQE
VLSDSQREHLQQFLPQFPEDSAEQQNELILALFSGENFRFGNPLHIAQKLFRDGHFNPEV
VKYRQLCFKSQYKRYLNSQQQYFHRLLKQILASRSDLLEMARRSGPALPFRQKRPSPSRT
PEEREWRTQQRYLKVLREVKEECGDTALSSDEEDLSSWLPSSPARSPSPAVPLRVVPTLS
TTDMKTADKVELGDSDLKIMLKKHHEKRKHQPDHPDLLTGDLTLNDIMTRVNAGRKGSLA
ALYDLAVLKKKVKEKEEKKKKKIKTIKSEAEDLAEPLSSTEGVAPLSQAPSPLAIPAIKE
EPLEDLKPCLGINEISSSFFSLLLEILLLESQASLPMLEERVLDWQSSPASSLNSWFSAA
PNWAELVLPALQYLAGESRAVPSSFSPFVEFKEKTQQWKLLGQSQDNEKELAALFQLWLE
TKDQAFCKQENEDSSDATTPVPRVRTDYVVRPSTGEEKRVFQEQERYRYSQPHKAFTFRM
HGFESVVGPVKGVFDKETSLNKAREHSLLRSDRPAYVTILSLVRDAAARLPNGEGTRAEI
CELLKDSQFLAPDVTSTQVNTVVSGALDRLHYEKDPCVKYDIGRKLWIYLHRDRSEEEFE
RIHQAQAAAAKARKALQQKPKPPSKVKSSSKESSIKVLSSGPSEQSQMSLSDSSMPPTPV
TPVTPTTPALPAIPISPPPVSAVNKSGPSTVSEPAKSSSGVLLVSSPTMPHLGTMLSPAS
SQTAPSSQAAARVVSHSGSAGLSQVRVVAQPSLPAVPQQSGGPAQTLPQMPAGPQIRVPA
TATQTKVVPQTVMATVPVKAQTTAATVQRPGPGQTGLTVTSLPATASPVSKPATSSPGTS
APSASTAAVIQNVTGQNIIKQVAITGQLGVKPQTGNSIPLTATNFRIQGKDVLRLPPSSI
TTDAKGQTVLRITPDMMATLAKSQVTTVKLTQDLFGTGGNTTGKGISATLHVTSNPVHAA
DSPAKASSASAPSSTPTGTTVVKVTPDLKPTEASSSAFRLMPALGVSVADQKGKSTVASS
EAKPAATIRIVQGLGVMPPKAGQTITVATHAKQGASVASGSGTVHTSAVSLPSMNAAVSK
TVAVASGAASTPISISTGAPTVRQVPVSTTVVSTSQAGKLPTRITVPLSVISQPMKGKSV
VTAPIIKGNLGANLSGLGRNIILTTMPAGTKLIAGNKPVSFLTAQQLQQLQQQGQATQVR
IQTVPASHLQQGTASGSSKAVSTVVVTTAPSPKQAPEQQ
Function
Binds to the DNA consensus sequence 5'-GGGGAATCTCC-3'; Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Modulates the deubiquitinase activity of UCHL5 in the INO80 complex.
Tissue Specificity Expressed in thymus, brain, testes, spleen and liver.
KEGG Pathway
ATP-dependent chromatin remodeling (hsa03082 )
Reactome Pathway
DNA Damage Recognition in GG-NER (R-HSA-5696394 )
UCH proteinases (R-HSA-5689603 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Narcolepsy DISLCNLI Definitive Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Nuclear factor related to kappa-B-binding protein (NFRKB). [2]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Nuclear factor related to kappa-B-binding protein (NFRKB). [3]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Nuclear factor related to kappa-B-binding protein (NFRKB). [6]
TAK-243 DM4GKV2 Phase 1 TAK-243 decreases the sumoylation of Nuclear factor related to kappa-B-binding protein (NFRKB). [7]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Nuclear factor related to kappa-B-binding protein (NFRKB). [9]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Nuclear factor related to kappa-B-binding protein (NFRKB). [9]
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⏷ Show the Full List of 6 Drug(s)
5 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Nuclear factor related to kappa-B-binding protein (NFRKB). [4]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Nuclear factor related to kappa-B-binding protein (NFRKB). [5]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Nuclear factor related to kappa-B-binding protein (NFRKB). [8]
4-hydroxy-2-nonenal DM2LJFZ Investigative 4-hydroxy-2-nonenal decreases the expression of Nuclear factor related to kappa-B-binding protein (NFRKB). [4]
QUERCITRIN DM1DH96 Investigative QUERCITRIN increases the expression of Nuclear factor related to kappa-B-binding protein (NFRKB). [10]
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References

1 Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
2 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
3 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.
4 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
5 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.
6 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
7 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.
8 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.
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 Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.