Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK5FDF6)

DOT Name Inactive phospholipase C-like protein 2 (PLCL2)
Synonyms PLC-L(2); PLC-L2; Phospholipase C-L2; Phospholipase C-epsilon-2; PLC-epsilon-2
Gene Name PLCL2
Related Disease
Alcohol dependence ( )
Major depressive disorder ( )
Mood disorder ( )
Myocardial infarction ( )
Primary biliary cholangitis ( )
Psoriatic arthritis ( )
Rheumatoid arthritis ( )
Schizophrenia ( )
Systemic sclerosis ( )
Psoriasis ( )
UniProt ID
PLCL2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00168 ; PF09279 ; PF16457 ; PF00388 ; PF00387
Sequence
MAECGRGGAAGGALPTSPGPALGAKGALKAGVGEGGGGGGRLGHGRARYDSGGVSNGDCS
LGVSGDEARASPTRGPRGVALAPTPSAVVCTLPRESKPGGLPRRSSIIKDGTKQKRERKK
TVSFSSMPTEKKISSASDCINSMVEGSELKKVRSNSRIYHRYFLLDADMQSLRWEPSKKD
SEKAKIDIKSIKEVRTGKNTDIFRSNGISDQISEDCAFSVIYGENYESLDLVANSADVAN
IWVTGLRYLISYGKHTLDMLESSQDNMRTSWVSQMFSEIDVDNLGHITLCNAVQCIRNLN
PGLKTSKIELKFKELHKSKDKAGTEVTKEEFIEVFHELCTRPEIYFLLVQFSSNKEFLDT
KDLMMFLEAEQGVAHINEEISLEIIHKYEPSKEGQEKGWLSIDGFTNYLMSPDCYIFDPE
HKKVCQDMKQPLSHYFINSSHNTYLIEDQFRGPSDITGYIRALKMGCRSVELDVWDGPDN
EPVIYTGHTMTSQIVFRSVIDIINKYAFFASEYPLILCLENHCSIKQQKVMVQHMKKLLG
DKLYTTSPNVEESYLPSPDVLKGKILIKAKKLSSNCSGVEGDVTDEDEGAEMSQRMGKEN
MEQPNNVPVKRFQLCKELSELVSICKSVQFKEFQVSFQVQKYWEVCSFNEVLASKYANEN
PGDFVNYNKRFLARVFPSPMRIDSSNMNPQDFWKCGCQIVAMNFQTPGLMMDLNIGWFRQ
NGNCGYVLRPAIMREEVSFFSANTKDSVPGVSPQLLHIKIISGQNFPKPKGSGAKGDVVD
PYVYVEIHGIPADCAEQRTKTVHQNGDAPIFDESFEFQINLPELAMVRFVVLDDDYIGDE
FIGQYTIPFECLQTGYRHVPLQSLTGEVLAHASLFVHVAITNRRGGGKPHKRGLSVRKGK
KSREYASLRTLWIKTVDEVFKNAQPPIRDATDLRENMQNAVVSFKELCGLSSVANLMQCM
LAVSPRFLGPDNTPLVVLNLSEQYPTMELQGIVPEVLKKIVTTYDMMIQSLKALIENADA
VYEKIVHCQKAAMEFHEHLHSIGTKEGLKERKLQKAVESFTWNITILKGQADLLKYAKNE
TLENLKQIHFAAVSCGLNKPGTENADVQKPRRSLEVIPEKANDETGE
Function May play an role in the regulation of Ins(1,4,5)P3 around the endoplasmic reticulum.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alcohol dependence DIS4ZSCO Strong Genetic Variation [1]
Major depressive disorder DIS4CL3X Strong Genetic Variation [2]
Mood disorder DISLVMWO Strong Genetic Variation [2]
Myocardial infarction DIS655KI Strong Genetic Variation [3]
Primary biliary cholangitis DIS43E0O Strong Genetic Variation [4]
Psoriatic arthritis DISLWTG2 Strong Genetic Variation [5]
Rheumatoid arthritis DISTSB4J Strong Genetic Variation [6]
Schizophrenia DISSRV2N Strong Genetic Variation [7]
Systemic sclerosis DISF44L6 Strong Biomarker [8]
Psoriasis DIS59VMN Limited Genetic Variation [9]
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⏷ Show the Full List of 10 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 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 Inactive phospholipase C-like protein 2 (PLCL2). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Inactive phospholipase C-like protein 2 (PLCL2). [19]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Inactive phospholipase C-like protein 2 (PLCL2). [23]
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11 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 Inactive phospholipase C-like protein 2 (PLCL2). [11]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Inactive phospholipase C-like protein 2 (PLCL2). [12]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Inactive phospholipase C-like protein 2 (PLCL2). [13]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Inactive phospholipase C-like protein 2 (PLCL2). [14]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Inactive phospholipase C-like protein 2 (PLCL2). [15]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of Inactive phospholipase C-like protein 2 (PLCL2). [16]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Inactive phospholipase C-like protein 2 (PLCL2). [17]
Melphalan DMOLNHF Approved Melphalan decreases the expression of Inactive phospholipase C-like protein 2 (PLCL2). [18]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Inactive phospholipase C-like protein 2 (PLCL2). [20]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Inactive phospholipase C-like protein 2 (PLCL2). [21]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Inactive phospholipase C-like protein 2 (PLCL2). [22]
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⏷ Show the Full List of 11 Drug(s)

References

1 Genome-wide association study of alcohol dependence implicates KIAA0040 on chromosome 1q.Neuropsychopharmacology. 2012 Jan;37(2):557-66. doi: 10.1038/npp.2011.229. Epub 2011 Sep 28.
2 Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
3 A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese.Eur J Hum Genet. 2015 Mar;23(3):374-80. doi: 10.1038/ejhg.2014.110. Epub 2014 Jun 11.
4 International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.Nat Commun. 2015 Sep 22;6:8019. doi: 10.1038/ncomms9019.
5 Comprehensive assessment of rheumatoid arthritis susceptibility loci in a large psoriatic arthritis cohort.Ann Rheum Dis. 2012 Aug;71(8):1350-4. doi: 10.1136/annrheumdis-2011-200802. Epub 2012 Feb 10.
6 Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Hum Mol Genet. 2019 Mar 1;28(5):858-874. doi: 10.1093/hmg/ddy395.
7 Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
8 Identification of NF-B and PLCL2 as new susceptibility genes and highlights on a potential role of IRF8 through interferon signature modulation in systemic sclerosis.Arthritis Res Ther. 2015 Mar 21;17(1):71. doi: 10.1186/s13075-015-0572-y.
9 Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci.Nat Commun. 2015 May 5;6:7001. doi: 10.1038/ncomms8001.
10 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.
11 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.
12 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
13 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
14 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
15 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
16 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
17 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
18 Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
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 Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
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 In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.
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.