Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF6I8RV)

DOT Name Pleckstrin homology domain-containing family G member 3 (PLEKHG3)
Synonyms PH domain-containing family G member 3
Gene Name PLEKHG3
Related Disease
Autism ( )
UniProt ID
PKHG3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00169 ; PF00621
Sequence
MPVSTSLHQDGSQERPVSLTSTTSSSGSSCDSRSAMEEPSSSEAPAKNGAGSLRSRHLPN
SNNNSSSWLNVKGPLSPFNSRAAAGPAHHKLSYLGRVVREIVETERMYVQDLRSIVEDYL
LKIIDTPGLLKPEQVSALFGNIENIYALNSQLLRDLDSCNSDPVAVASCFVERSQEFDIY
TQYCNNYPNSVAALTECMRDKQQAKFFRDRQELLQHSLPLGSYLLKPVQRILKYHLLLQE
IAKHFDEEEDGFEVVEDAIDTMTCVAWYINDMKRRHEHAVRLQEIQSLLINWKGPDLTTY
GELVLEGTFRVHRVRNERTFFLFDKTLLITKKRGDHFVYKGNIPCSSLMLIESTRDSLCF
TVTHYKHSKQQYSIQAKTVEEKRNWTHHIKRLILENHHATIPQKAKEAILEMDSYYPNRY
RCSPERLKKAWSSQDEVSTNVRQGRRQSEPTKHLLRQLNEKARAAGMKGKGRRESESSRS
SRRPSGRSPTSTEKRMSFESISSLPEVEPDPEAGSEQEVFSAVEGPSAEETPSDTESPEV
LETQLDAHQGLLGMDPPGDMVDFVAAESTEDLKALSSEEEEEMGGAAQEPESLLPPSVLD
QASVIAERFVSSFSRRSSVAQEDSKSSGFGSPRLVSRSSSVLSLEGSEKGLARHGSATDS
LSCQLSPEVDISVGVATEDSPSVNGMEPPSPGCPVEPDRSSCKKKESALSTRDRLLLDKI
KSYYENAEHHDAGFSVRRRESLSYIPKGLVRNSISRFNSLPRPDPEPVPPVGSKRQVGSR
PTSWALFELPGPSQAVKGDPPPISDAEFRPSSEIVKIWEGMESSGGSPGKGPGQGQANGF
DLHEPLFILEEHELGAITEESATASPESSSPTEGRSPAHLARELKELVKELSSSTQGELV
APLHPRIVQLSHVMDSHVSERVKNKVYQLARQYSLRIKSNKPVMARPPLQWEKVAPERDG
KSPTVPCLQEEAGEPLGGKGKRKPVLSLFDYEQLMAQEHSPPKPSSAGEMSPQRFFFNPS
AVSQRTTSPGGRPSARSPLSPTETFSWPDVRELCSKYASRDEARRAGGGRPRGPPVNRSH
SVPENMVEPPLSGRVGRCRSLSTKRGRGGGEAAQSPGPLPQSKPDGGETLYVTADLTLED
NRRVIVMEKGPLPSPTAGLEESSGQGPSSPVALLGQVQDFQQSAECQPKEEGSRDPADPS
QQGRVRNLREKFQALNSVG
Function Plays a role in controlling cell polarity and cell motility by selectively binding newly polymerized actin and activating RAC1 and CDC42 to enhance local actin polymerization.
Reactome Pathway
CDC42 GTPase cycle (R-HSA-9013148 )
RAC1 GTPase cycle (R-HSA-9013149 )
RHOQ GTPase cycle (R-HSA-9013406 )
RHOG GTPase cycle (R-HSA-9013408 )
RHOA GTPase cycle (R-HSA-8980692 )

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autism DISV4V1Z Strong Biomarker [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Arsenic trioxide DM61TA4 Approved Pleckstrin homology domain-containing family G member 3 (PLEKHG3) decreases the response to substance of Arsenic trioxide. [20]
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15 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate affects the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [2]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [3]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [5]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [7]
Triclosan DMZUR4N Approved Triclosan increases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [8]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [9]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [10]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [11]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [12]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [13]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [14]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [15]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [16]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [19]
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⏷ Show the Full List of 15 Drug(s)
4 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 Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [6]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [17]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [18]
Coumarin DM0N8ZM Investigative Coumarin affects the phosphorylation of Pleckstrin homology domain-containing family G member 3 (PLEKHG3). [17]
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References

1 A de novo 1.5Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis.Autism Res. 2011 Jun;4(3):221-7. doi: 10.1002/aur.186. Epub 2011 Feb 28.
2 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.
3 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.
4 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.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 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.
7 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.
8 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
9 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
10 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
11 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
14 New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
15 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.
16 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
17 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.
18 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
19 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
20 The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel. BMC Med Genomics. 2010 Aug 13;3:37. doi: 10.1186/1755-8794-3-37.