Details of Drug Off-Target (DOT)

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

DOT Name Neuralized-like protein 4 (NEURL4)
Gene Name NEURL4
Related Disease
Autoimmune disease ( )
Autoimmune disease, susceptibility to, 6 ( )
STAT3-related early-onset multisystem autoimmune disease ( )
UniProt ID
NEUL4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2.00E+63
Pfam ID
PF07177
Sequence
MAAGSGGSGGSGGGPGPGPGGGGGPSGSGSGPGSNGGLGSGGELHPRTGRLVSLSACGRT
ARRQQPGQEFNHGLVLSREPLRDGRVFTVRIDRKVNSWSGSIEIGVTALDPSVLDFPSSA
TGLKGGSWVVSGCSVLRDGRSVLEEYGQDLDQLGEGDRVGVERTVAGELRLWVNGRDCGV
AATGLPPRVWAVVDLYGKCTQITVLPPEPGFSPPTPIPTPPLEPLAPTEDSALAEQGTSA
DEAFMVSPAQARPETFPNSLESHNDFANMELSEVVSNTILSAYNGGLLNVNLSSPPAGEG
LGSSGAATSPILTSNDALLFHEKCGTLIKLSNNNKTAERRRPLDEFNNGVVMTNRPLRDN
EMFEIRIDKLVDKWSGSIEIGVTTHNPNSLEYPATMTNLQSGTIMMSGCGILTNGKGTRR
EYCEFSLDELQEGDHIGLTRKSNSALHFFINGIDQGVATPLTPPVVYGVVDLYGMAVKVT
IVHNNNHSDRLRRNNAILRALSPEGALRRAAPAAQAEPERLLFHPNCGQKAAITHEGRTA
LRPHATDDFNHGVVLSSRALRDGEVFQVRIDKMVDKWAGSIEIGVTTHNPAYLQLPSTMT
NLRSGTWMMTGNGVMHNGTTILDEYGHNLDRLKAGDTVGVVRREDGTLHFFVNGMTQGPA
AWNVPPGVYAVVDLYGQAAQATIVDDVEVAPVPEPLPEGNNQVSPSSPSSGAGGSDLRFH
QLHGSNAVITNGGRTALRHNCRSEFNDAIVISNRALRDGELFEIVIQKMVDRWSGSIEAG
VTAIRPEDLEFPNTMTDIDYDTWMLSGTAIMQDGNTMRNNYGCDLDALGTGARIGMMRTA
KGDLHYFINGQDQGAACSGLPPGKEVYAVVDLYGQCVQVSITNATGPMDNSLATSNTATE
KSFPLHSPVAGVAHRFHSTCGKNVTLEEDGTRAVRAAGYAHGLVFSTKELRAEEVFEVKV
EELDEKWAGSLRLGLTTLAPGEMGPGAGGGGPGLPPSLPELRTKTTWMVSSCEVRRDGQL
QRMNYGRNLERLGVGSRVGVRRGADDTMHILVDGEDMGPAATGIAKNVWAVLDLYGPVRG
VSIVSSTRLEESEGTQPPSPSSDTGSEGEEDDEGEEHGLGGQNEVGIIPTTLEFLENHGK
NILLSNGNRTATRVASYNQGIVVINQPLVPQLLVQVRIDFLNRQWTSSLVLGVITCAPER
LNFPASACALKRAAWLLRGRGVFHNGLKICEKFGPNLDTCPEGTILGLRLDSSGGLHLHV
NGVDQGVAVPDVPQPCHALVDLYGQCEQVTIVNPEPGAASGKSAGTQGDMEKADMVDGIK
ESVCWGPPPAASPLKSCEYHALCSRFQELLLLPEDYFMPPPKRSLCYCESCRKLRGDEAH
RRRGEPPREYALPFGWCRFNLRVNPRLEAGTLTKKWHMAYHGSNVAAVRRVLDRGELGAG
TASILSCRPLKGEPGVGFEEPGENCAPPREEQPPPVLLSPSLQYAGAETLASKVQFRDPK
SQRTHQAQVAFQVCVRPGSYTPGPPSAALGEPPDPHFSPAELEWVTKEKGATLLCALLVR
VE
Function
Promotes CCP110 ubiquitination and proteasome-dependent degradation. By counteracting accumulation of CP110, maintains normal centriolar homeostasis and preventing formation of ectopic microtubular organizing centers.
Tissue Specificity Widely expressed at high levels (including brain).

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autoimmune disease DISORMTM Strong Genetic Variation [1]
Autoimmune disease, susceptibility to, 6 DISHNUXI Strong Genetic Variation [1]
STAT3-related early-onset multisystem autoimmune disease DISAXTN7 Strong Genetic Variation [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Neuralized-like protein 4 (NEURL4). [2]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Neuralized-like protein 4 (NEURL4). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Neuralized-like protein 4 (NEURL4). [5]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Neuralized-like protein 4 (NEURL4). [8]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Neuralized-like protein 4 (NEURL4). [3]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Neuralized-like protein 4 (NEURL4). [6]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Neuralized-like protein 4 (NEURL4). [7]
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References

1 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
4 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.
5 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.
6 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
7 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
8 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.