Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRE9DGT)

DOT Name Cingulin-like protein 1 (CGNL1)
Synonyms Junction-associated coiled-coil protein; Paracingulin
Gene Name CGNL1
Related Disease
Schizophrenia ( )
Bipolar disorder ( )
UniProt ID
CGNL1_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF01576
Sequence
MELYFGEYQHVQQEYGVHLRLASDDTQKSRSSQNSKAGSYGVSIRVQGIDGHPYIVLNNT
ERCLAGTSFSENGPPFPPPVINNLPLHSSNGSVPKENSEELQLPENPYAQPSPIRNLKQP
LLHEGKNGVLDRKDGSVKPSHLLNFQRHPELLQPYDPEKNELNLQNHQPSESNWLKTLTE
EGINNKKPWTCFPKPSNSQPTSPSLEDPAKSGVTAIRLCSSVVIEDPKKQTSVCVNVQSC
TKERVGEEALFTSGRPLTAHSPHAHPETKKTRPDVLPFRRQDSAGPVLDGARSRRSSSSS
TTPTSANSLYRFLLDDQECAIHADNVNRHENRRYIPFLPGTGRDIDTGSIPGVDQLIEKF
DQKPGLQRRGRSGKRNRINTDDRKRSRSVDSAFPFGLQGNSEYLIEFSRNLGKSSEHLLR
PSQVCPQRPLSQERRGKQSVGRTFAKLQGAAHGASCAHSRPPQPNIDGKVLETEGSQEST
VIRAPSLGAQSKKEEEVKTATATLMLQNRATATSPDSGAKKISVKTFPSASNTQATPDLL
KGQQELTQQTNEETAKQILYNYLKEGSTDNDDATKRKVNLVFEKIQTLKSRAAGSAQGNN
QACNSTSEVKDLLEQKSKLTIEVAELQRQLQLEVKNQQNIKEERERMRANLEELRSQHNE
KVEENSTLQQRLEESEGELRKNLEELFQVKMEREQHQTEIRDLQDQLSEMHDELDSAKRS
EDREKGALIEELLQAKQDLQDLLIAKEEQEDLLRKRERELTALKGALKEEVSSHDQEMDK
LKEQYDAELQALRESVEEATKNVEVLASRSNTSEQDQAGTEMRVKLLQEENEKLQGRSEE
LERRVAQLQRQIEDLKGDEAKAKETLKKYEGEIRQLEEALVHARKEEKEAVSARRALENE
LEAAQGNLSQTTQEQKQLSEKLKEESEQKEQLRRLKNEMENERWHLGKTIEKLQKEMADI
VEASRTSTLELQNQLDEYKEKNRRELAEMQRQLKEKTLEAEKSRLTAMKMQDEMRLMEEE
LRDYQRAQDEALTKRQLLEQTLKDLEYELEAKSHLKDDRSRLVKQMEDKVSQLEMELEEE
RNNSDLLSERISRSREQMEQLRNELLQERAARQDLECDKISLERQNKDLKSRIIHLEGSY
RSSKEGLVVQMEARIAELEDRLESEERDRANLQLSNRRLERKVKELVMQVDDEHLSLTDQ
KDQLSLRLKAMKRQVEEAEEEIDRLESSKKKLQRELEEQMDMNEHLQGQLNSMKKDLRLK
KLPSKVLDDMDDDDDLSTDGGSLYEAPVSYTFSKDSTVASQI
Function May be involved in anchoring the apical junctional complex, especially tight junctions, to actin-based cytoskeletons.
Tissue Specificity Smooth muscle, spleen, testis, fetal brain, amygdala, corpus callosum, cerebellum, thalamus and subthalamic nucleus of adult brain.
KEGG Pathway
Tight junction (hsa04530 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Schizophrenia DISSRV2N Strong Genetic Variation [1]
Bipolar disorder DISAM7J2 moderate Genetic Variation [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
20 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Cingulin-like protein 1 (CGNL1). [3]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Cingulin-like protein 1 (CGNL1). [4]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Cingulin-like protein 1 (CGNL1). [5]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Cingulin-like protein 1 (CGNL1). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Cingulin-like protein 1 (CGNL1). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Cingulin-like protein 1 (CGNL1). [8]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Cingulin-like protein 1 (CGNL1). [9]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Cingulin-like protein 1 (CGNL1). [10]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Cingulin-like protein 1 (CGNL1). [11]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Cingulin-like protein 1 (CGNL1). [12]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Cingulin-like protein 1 (CGNL1). [13]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Cingulin-like protein 1 (CGNL1). [14]
Menadione DMSJDTY Approved Menadione affects the expression of Cingulin-like protein 1 (CGNL1). [15]
Panobinostat DM58WKG Approved Panobinostat increases the expression of Cingulin-like protein 1 (CGNL1). [16]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Cingulin-like protein 1 (CGNL1). [17]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Cingulin-like protein 1 (CGNL1). [16]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Cingulin-like protein 1 (CGNL1). [4]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Cingulin-like protein 1 (CGNL1). [19]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Cingulin-like protein 1 (CGNL1). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Cingulin-like protein 1 (CGNL1). [21]
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⏷ Show the Full List of 20 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Cingulin-like protein 1 (CGNL1). [18]
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References

1 CNV analysis in a large schizophrenia sample implicates deletions at 16p12.1 and SLC1A1 and duplications at 1p36.33 and CGNL1.Hum Mol Genet. 2014 Mar 15;23(6):1669-76. doi: 10.1093/hmg/ddt540. Epub 2013 Oct 26.
2 Genome-wide association analysis of age at onset and psychotic symptoms in bipolar disorder.Am J Med Genet B Neuropsychiatr Genet. 2011 Apr;156B(3):370-8. doi: 10.1002/ajmg.b.31172. Epub 2011 Feb 8.
3 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.
4 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.
5 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
6 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
7 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.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 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.
10 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.
11 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.
12 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
13 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
14 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
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 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
18 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.
19 Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
20 Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.
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.