Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJL2TOC)

DOT Name Neurabin-1 (PPP1R9A)
Synonyms Neurabin-I; Neural tissue-specific F-actin-binding protein I; Protein phosphatase 1 regulatory subunit 9A
Gene Name PPP1R9A
Related Disease
Bipolar disorder ( )
Central nervous system lymphoma ( )
Hepatocellular carcinoma ( )
Hepatosplenic T-cell lymphoma ( )
Liver cancer ( )
Schizophrenia ( )
Neurodevelopmental disorder ( )
UniProt ID
NEB1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1WF8
Pfam ID
PF00595 ; PF17817 ; PF07647
Sequence
MLKTESSGERTTLRSASPHRNAYRTEFQALKSTFDKPKSDGEQKTKEGEGSQQSRGRKYG
SNVNRIKNLFMQMGMEPNENAAVIAKTRGKGGHSSPQRRMKPKEFLEKTDGSVVKLESSV
SERISRFDTMYDGPSYSKFTETRKMFERSVHESGQNNRYSPKKEKAGGSEPQDEWGGSKS
NRGSTDSLDSLSSRTEAVSPTVSQLSAVFENTDSPSAIISEKAENNEYSVTGHYPLNLPS
VTVTNLDTFGHLKDSNSWPPSNKRGVDTEDAHKSNATPVPEVASKSTSLASIPGEEIQQS
KEPEDSTSNQQTPDSIDKDGPEEPCAESKAMPKSEIPSPQSQLLEDAEANLVGREAAKQQ
RKELAGGDFTSPDASASSCGKEVPEDSNNFDGSHVYMHSDYNVYRVRSRYNSDWGETGTE
QDEEEDSDENSYYQPDMEYSEIVGLPEEEEIPANRKIKFSSAPIKVFNTYSNEDYDRRND
EVDPVAASAEYELEKRVEKLELFPVELEKDEDGLGISIIGMGVGADAGLEKLGIFVKTVT
EGGAAQRDGRIQVNDQIVEVDGISLVGVTQNFAATVLRNTKGNVRFVIGREKPGQVSEVA
QLISQTLEQERRQRELLEQHYAQYDADDDETGEYATDEEEDEVGPVLPGSDMAIEVFELP
ENEDMFSPSELDTSKLSHKFKELQIKHAVTEAEIQKLKTKLQAAENEKVRWELEKTQLQQ
NIEENKERMLKLESYWIEAQTLCHTVNEHLKETQSQYQALEKKYNKAKKLIKDFQQKELD
FIKRQEAERKKIEDLEKAHLVEVQGLQVRIRDLEAEVFRLLKQNGTQVNNNNNIFERRTS
LGEVSKGDTMENLDGKQTSCQDGLSQDLNEAVPETERLDSKALKTRAQLSVKNRRQRPSR
TRLYDSVSSTDGEDSLERKNFTFNDDFSPSSTSSADLSGLGAEPKTPGLSQSLALSSDES
LDMIDDEILDDGQSPKHSQCQNRAVQEWSVQQVSHWLMSLNLEQYVSEFSAQNITGEQLL
QLDGNKLKALGMTASQDRAVVKKKLKEMKMSLEKARKAQEKMEKQREKLRRKEQEQMQRK
SKKTEKMTSTTAEGAGEQ
Function Binds to actin filaments (F-actin) and shows cross-linking activity. Binds along the sides of the F-actin. May be involved in neurite formation. Inhibits protein phosphatase 1-alpha activity.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Bipolar disorder DISAM7J2 Strong Biomarker [1]
Central nervous system lymphoma DISBYQTA Strong Biomarker [2]
Hepatocellular carcinoma DIS0J828 Strong ModifyingMutation [3]
Hepatosplenic T-cell lymphoma DIS7KMY9 Strong Biomarker [4]
Liver cancer DISDE4BI Strong ModifyingMutation [3]
Schizophrenia DISSRV2N Strong Biomarker [1]
Neurodevelopmental disorder DIS372XH moderate Biomarker [5]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Biotransformations of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
RTR-003632 DM45NHF Phase 2 Neurabin-1 (PPP1R9A) affects the hydrolysis of RTR-003632. [22]
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4 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 Neurabin-1 (PPP1R9A). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Neurabin-1 (PPP1R9A). [19]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Neurabin-1 (PPP1R9A). [20]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Neurabin-1 (PPP1R9A). [20]
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15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Neurabin-1 (PPP1R9A). [7]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Neurabin-1 (PPP1R9A). [8]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Neurabin-1 (PPP1R9A). [9]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Neurabin-1 (PPP1R9A). [10]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Neurabin-1 (PPP1R9A). [11]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Neurabin-1 (PPP1R9A). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Neurabin-1 (PPP1R9A). [13]
Selenium DM25CGV Approved Selenium decreases the expression of Neurabin-1 (PPP1R9A). [14]
Menadione DMSJDTY Approved Menadione affects the expression of Neurabin-1 (PPP1R9A). [15]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of Neurabin-1 (PPP1R9A). [16]
Testosterone enanthate DMB6871 Approved Testosterone enanthate affects the expression of Neurabin-1 (PPP1R9A). [17]
Paclitaxel DMLB81S Approved Paclitaxel decreases the expression of Neurabin-1 (PPP1R9A). [18]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Neurabin-1 (PPP1R9A). [16]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Neurabin-1 (PPP1R9A). [14]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Neurabin-1 (PPP1R9A). [21]
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⏷ Show the Full List of 15 Drug(s)

References

1 Altered prefrontal cortical MARCKS and PPP1R9A mRNA expression in schizophrenia and bipolar disorder.Schizophr Res. 2015 May;164(1-3):100-8. doi: 10.1016/j.schres.2015.02.005. Epub 2015 Mar 7.
2 Hyper-N-glycosylated SAMD14 and neurabin-I as driver autoantigens of primary central nervous system lymphoma.Blood. 2018 Dec 27;132(26):2744-2753. doi: 10.1182/blood-2018-03-836932. Epub 2018 Sep 24.
3 Mitochondrial prohibitins and septin 9 are implicated in the onset of rat hepatocarcinogenesis.Toxicol Sci. 2011 Jan;119(1):61-72. doi: 10.1093/toxsci/kfq307. Epub 2010 Oct 8.
4 Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma.PLoS One. 2014 Jul 24;9(7):e102977. doi: 10.1371/journal.pone.0102977. eCollection 2014.
5 Indexing Effects of Copy Number Variation on Genes Involved in Developmental Delay.Sci Rep. 2016 Jul 1;6:28663. doi: 10.1038/srep28663.
6 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.
7 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
8 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.
9 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
10 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.
11 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.
12 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.
13 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
14 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
15 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.
16 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.
17 Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
18 Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells. Acta Pharmacol Sin. 2004 Mar;25(3):378-84.
19 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.
20 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.
21 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
22 Effects of PON polymorphisms and haplotypes on molecular phenotype in Mexican-American mothers and children. Environ Mol Mutagen. 2011 Mar;52(2):105-16. doi: 10.1002/em.20567.