General Information of Drug Off-Target (DOT) (ID: OTL4E94L)

DOT Name Negative elongation factor E (NELFE)
Synonyms NELF-E; RNA-binding protein RD
Gene Name NELFE
Related Disease
Neoplasm ( )
Age-related macular degeneration ( )
Dystonia ( )
Glioma ( )
Graves disease ( )
Hepatitis ( )
Hepatitis A virus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Multiple sclerosis ( )
Pancreatic adenocarcinoma ( )
Parkinson disease ( )
Proliferative diabetic retinopathy ( )
X-linked reticulate pigmentary disorder ( )
Pancreatic cancer ( )
Systemic lupus erythematosus ( )
Glycogen storage disease type II ( )
Migraine, familial hemiplegic, 2 ( )
Parkinsonian disorder ( )
UniProt ID
NELFE_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1X5P; 2BZ2; 2JX2; 5OOB; 6GML; 7YCX
Pfam ID
PF00076
Sequence
MLVIPPGLSEEEEALQKKFNKLKKKKKALLALKKQSSSSTTSQGGVKRSLSEQPVMDTAT
ATEQAKQLVKSGAISAIKAETKNSGFKRSRTLEGKLKDPEKGPVPTFQPFQRSISADDDL
QESSRRPQRKSLYESFVSSSDRLRELGPDGEEAEGPGAGDGPPRSFDWGYEERSGAHSSA
SPPRSRSRDRSHERNRDRDRDRERDRDRDRDRDRERDRDRDRDRDRDRERDRDRERDRDR
DREGPFRRSDSFPERRAPRKGNTLYVYGEDMTPTLLRGAFSPFGNIIDLSMDPPRNCAFV
TYEKMESADQAVAELNGTQVESVQLKVNIARKQPMLDAATGKSVWGSLAVQNSPKGCHRD
KRTQIVYSDDVYKENLVDGF
Function
Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II. The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex. Provides the strongest RNA binding activity of the NELF complex and may initially recruit the NELF complex to RNA ; (Microbial infection) The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II.
Tissue Specificity Widely expressed. Expressed in heart, brain, lung, placenta, liver, skeletal muscle, kidney and pancreas.
KEGG Pathway
Viral life cycle - HIV-1 (hsa03250 )
Reactome Pathway
Formation of the Early Elongation Complex (R-HSA-113418 )
Formation of HIV elongation complex in the absence of HIV Tat (R-HSA-167152 )
Formation of the HIV-1 Early Elongation Complex (R-HSA-167158 )
Formation of HIV-1 elongation complex containing HIV-1 Tat (R-HSA-167200 )
Pausing and recovery of Tat-mediated HIV elongation (R-HSA-167238 )
Abortive elongation of HIV-1 transcript in the absence of Tat (R-HSA-167242 )
Tat-mediated HIV elongation arrest and recovery (R-HSA-167243 )
Tat-mediated elongation of the HIV-1 transcript (R-HSA-167246 )
HIV elongation arrest and recovery (R-HSA-167287 )
Pausing and recovery of HIV elongation (R-HSA-167290 )
RNA Polymerase II Pre-transcription Events (R-HSA-674695 )
TP53 Regulates Transcription of DNA Repair Genes (R-HSA-6796648 )
RNA Polymerase II Transcription Elongation (R-HSA-75955 )
Formation of RNA Pol II elongation complex (R-HSA-112382 )

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neoplasm DISZKGEW Definitive Altered Expression [1]
Age-related macular degeneration DIS0XS2C Strong Genetic Variation [2]
Dystonia DISJLFGW Strong Biomarker [3]
Glioma DIS5RPEH Strong Biomarker [4]
Graves disease DISU4KOQ Strong Genetic Variation [5]
Hepatitis DISXXX35 Strong Altered Expression [6]
Hepatitis A virus infection DISUMFQV Strong Altered Expression [6]
Hepatitis C virus infection DISQ0M8R Strong Altered Expression [6]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [7]
Multiple sclerosis DISB2WZI Strong Genetic Variation [8]
Pancreatic adenocarcinoma DISKHX7S Strong Biomarker [9]
Parkinson disease DISQVHKL Strong Biomarker [10]
Proliferative diabetic retinopathy DISQZ13G Strong Biomarker [11]
X-linked reticulate pigmentary disorder DIS0RB5A Strong Biomarker [11]
Pancreatic cancer DISJC981 moderate Altered Expression [1]
Systemic lupus erythematosus DISI1SZ7 moderate Genetic Variation [12]
Glycogen storage disease type II DISXZPBC Limited Genetic Variation [13]
Migraine, familial hemiplegic, 2 DISJPXBR Limited Biomarker [3]
Parkinsonian disorder DISHGY45 Limited Biomarker [3]
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⏷ Show the Full List of 19 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
8 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 Negative elongation factor E (NELFE). [14]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Negative elongation factor E (NELFE). [15]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Negative elongation factor E (NELFE). [16]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Negative elongation factor E (NELFE). [17]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Negative elongation factor E (NELFE). [18]
Quercetin DM3NC4M Approved Quercetin increases the expression of Negative elongation factor E (NELFE). [20]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Negative elongation factor E (NELFE). [21]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Negative elongation factor E (NELFE). [24]
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⏷ Show the Full List of 8 Drug(s)
5 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 Negative elongation factor E (NELFE). [19]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Negative elongation factor E (NELFE). [22]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Negative elongation factor E (NELFE). [23]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Negative elongation factor E (NELFE). [23]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid decreases the phosphorylation of Negative elongation factor E (NELFE). [25]
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References

1 NELFE promoted pancreatic cancer metastasis and the epithelialtomesenchymal transition by decreasing the stabilization of NDRG2 mRNA.Int J Oncol. 2019 Dec;55(6):1313-1323. doi: 10.3892/ijo.2019.4890. Epub 2019 Oct 2.
2 Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis.Ann Hum Genet. 2013 May;77(3):215-31. doi: 10.1111/ahg.12011.
3 Migraine- and dystonia-related disease-mutations of Na+/K+-ATPases: relevance of behavioral studies in mice to disease symptoms and neurological manifestations in humans.Neurosci Biobehav Rev. 2012 Feb;36(2):855-71. doi: 10.1016/j.neubiorev.2011.10.005. Epub 2011 Nov 2.
4 Targeted therapy of intracranial glioma model mice with curcumin nanoliposomes.Int J Nanomedicine. 2018 Mar 15;13:1601-1610. doi: 10.2147/IJN.S157019. eCollection 2018.
5 Identification of independent risk loci for Graves' disease within the MHC in the Japanese population.J Hum Genet. 2011 Nov;56(11):772-8. doi: 10.1038/jhg.2011.99. Epub 2011 Sep 8.
6 Overexpression of the RD RNA binding protein in hepatitis C virus-related hepatocellular carcinoma.Oncol Rep. 2012 Aug;28(2):728-34. doi: 10.3892/or.2012.1821. Epub 2012 May 18.
7 NELFE-Dependent MYC Signature Identifies a Unique Cancer Subtype in Hepatocellular Carcinoma.Sci Rep. 2019 Mar 4;9(1):3369. doi: 10.1038/s41598-019-39727-9.
8 Evidence for VAV2 and ZNF433 as susceptibility genes for multiple sclerosis.J Neuroimmunol. 2010 Oct 8;227(1-2):162-6. doi: 10.1016/j.jneuroim.2010.06.003. Epub 2010 Jul 2.
9 Comparison of robotic vs laparoscopic vs open distal pancreatectomy. A systematic review and network meta-analysis.HPB (Oxford). 2019 Oct;21(10):1268-1276. doi: 10.1016/j.hpb.2019.04.010. Epub 2019 May 9.
10 A novel peptide delivers plasmids across blood-brain barrier into neuronal cells as a single-component transfer vector.PLoS One. 2013;8(3):e59642. doi: 10.1371/journal.pone.0059642. Epub 2013 Mar 29.
11 Retinal Nonperfusion Characteristics on Ultra-Widefield Angiography in Eyes With Severe Nonproliferative Diabetic Retinopathy and Proliferative Diabetic Retinopathy.JAMA Ophthalmol. 2019 Jun 1;137(6):626-631. doi: 10.1001/jamaophthalmol.2019.0440.
12 GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
13 Associations of the C2-CFB-RDBP-SKIV2L locus with age-related macular degeneration and polypoidal choroidal vasculopathy.Ophthalmology. 2013 Apr;120(4):837-43. doi: 10.1016/j.ophtha.2012.10.003. Epub 2012 Dec 20.
14 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.
15 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
16 Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
17 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.
18 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.
19 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.
20 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
21 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.
22 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.
23 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.
24 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.
25 Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.