Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3RBPFL)

DOT Name Puratrophin-1 (PLEKHG4)
Synonyms Pleckstrin homology domain-containing family G member 4; PH domain-containing family G member 4; Purkinje cell atrophy-associated protein 1
Gene Name PLEKHG4
Related Disease
Cardiac arrest ( )
Cerebellar ataxia ( )
Cerebellar disorder ( )
Dentatorubral-pallidoluysian atrophy ( )
Hereditary ataxia ( )
Spinocerebellar ataxia ( )
Spinocerebellar ataxia type 31 ( )
Spinocerebellar ataxia type 3 ( )
UniProt ID
PKHG4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00621
Sequence
MERPLENGDESPDSQGHATDWRFAVCSFRDAWEEEEPASQMHVKDPGPPRPPAGATQDEE
LQGSPLSRKFQLPPAADESGDAQRGTVESSSVLSEGPGPSGVESLLCPMSSHLSLAQGES
DTPGVGLVGDPGPSRAMPSGLSPGALDSDPVGLGDPLSEISKLLEAAPSGSGLPKPADCL
LAQDLCWELLASGMATLPGTRDVQGRAVLLLCAHSPAWLQSECSSQELIRLLLYLRSIPR
PEVQALGLTVLVDARICAPSSSLFSGLSQLQEAAPGAVYQVLLVGSTLLKEVPSGLQLEQ
LPSQSLLTHIPTAGLPTSLGGGLPYCHQAWLDFRRRLEALLQNCQAACALLQGAIESVKA
VPQPMEPGEVGQLLQQTEVLMQQVLDSPWLAWLQCQGGRELTWLKQEVPEVTLSPDYRTA
MDKADELYDRVDGLLHQLTLQSNQRIQALELVQTLEARESGLHQIEVWLQQVGWPALEEA
GEPSLDMLLQAQGSFQELYQVAQEQVRQGEKFLQPLTGWEAAELDPPGARFLALRAQLTE
FSRALAQRCQRLADAERLFQLFREALTWAEEGQRVLAELEQERPGVVLQQLQLHWTRHPD
LPPAHFRKMWALATGLGSEAIRQECRWAWARCQDTWLALDQKLEASLKLPPVGSTASLCV
SQVPAAPAHPPLRKAYSFDRNLGQSLSEPACHCHHAATIAACRRPEAGGGALPQASPTVP
PPGSSDPRSLNRLQLVLAEMVATEREYVRALEYTMENYFPELDRPDVPQGLRGQRAHLFG
NLEKLRDFHCHFFLRELEACTRHPPRVAYAFLRHRVQFGMYALYSKNKPRSDALMSSYGH
TFFKDKQQALGDHLDLASYLLKPIQRMGKYALLLQELARACGGPTQELSALREAQSLVHF
QLRHGNDLLAMDAIQGCDVNLKEQGQLVRQDEFVVRTGRHKSVRRIFLFEELLLFSKPRH
GPTGVDTFAYKRSFKMADLGLTECCGNSNLRFEIWFRRRKARDTFVLQASSLAIKQAWTA
DISHLLWRQAVHNKEVRMAEMVSMGVGNKAFRDIAPSEEAINDRTVNYVLKCREVRSRAS
IAVAPFDHDSLYLGASNSLPGDPASCSVLGSLNLHLYRDPALLGLRCPLYPSFPEEAALE
AEAELGGQPSLTAEDSEISSQCPSASGSSGSDSSCVSGQALGRGLEDLPCV
Function Possible role in intracellular signaling and cytoskeleton dynamics at the Golgi.
Tissue Specificity
Expressed in kidney, Leydig cells in the testis, epithelial cells in the prostate gland and Langerhans islet in the pancreas. Isoform 1 and isoform 3 are strongly expressed in Purkinje cells and to a lower extent in other neurons (at protein level). Widely expressed at low levels. More strongly expressed in testis and pancreas.
Reactome Pathway
CDC42 GTPase cycle (R-HSA-9013148 )
RAC1 GTPase cycle (R-HSA-9013149 )
RHOA GTPase cycle (R-HSA-8980692 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Cardiac arrest DIS9DIA4 Strong Genetic Variation [1]
Cerebellar ataxia DIS9IRAV Strong Genetic Variation [2]
Cerebellar disorder DIS2O7WM Strong Genetic Variation [3]
Dentatorubral-pallidoluysian atrophy DISHWE0K Strong Biomarker [4]
Hereditary ataxia DIS6JNI3 Strong Genetic Variation [5]
Spinocerebellar ataxia DISYMHUK Strong Genetic Variation [6]
Spinocerebellar ataxia type 31 DISUPR8L Disputed Biomarker [7]
Spinocerebellar ataxia type 3 DISQBQID Limited Genetic Variation [8]
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⏷ Show the Full List of 8 Disease(s)
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 Puratrophin-1 (PLEKHG4). [9]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Puratrophin-1 (PLEKHG4). [19]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Puratrophin-1 (PLEKHG4). [21]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Puratrophin-1 (PLEKHG4). [22]
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11 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Puratrophin-1 (PLEKHG4). [10]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Puratrophin-1 (PLEKHG4). [11]
Quercetin DM3NC4M Approved Quercetin increases the expression of Puratrophin-1 (PLEKHG4). [12]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Puratrophin-1 (PLEKHG4). [13]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Puratrophin-1 (PLEKHG4). [14]
Niclosamide DMJAGXQ Approved Niclosamide increases the expression of Puratrophin-1 (PLEKHG4). [15]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Puratrophin-1 (PLEKHG4). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Puratrophin-1 (PLEKHG4). [17]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of Puratrophin-1 (PLEKHG4). [18]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Puratrophin-1 (PLEKHG4). [20]
GALLICACID DM6Y3A0 Investigative GALLICACID increases the expression of Puratrophin-1 (PLEKHG4). [23]
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⏷ Show the Full List of 11 Drug(s)

References

1 Molecular genetic analysis of a new form of spinocerebellar ataxia in a Chinese Han family.Neurosci Lett. 2010 Aug 2;479(3):321-6. doi: 10.1016/j.neulet.2010.05.089.
2 Clinical and genetic characterization of 16q-linked autosomal dominant spinocerebellar ataxia in South Kyushu, Japan.J Hum Genet. 2009 Jul;54(7):377-81. doi: 10.1038/jhg.2009.44. Epub 2009 May 15.
3 A gene on SCA4 locus causes dominantly inherited pure cerebellar ataxia.Neurology. 2000 May 23;54(10):1971-5. doi: 10.1212/wnl.54.10.1971.
4 Frequency of spinocerebellar ataxia type 1, dentatorubropallidoluysian atrophy, and Machado-Joseph disease mutations in a large group of spinocerebellar ataxia patients.Neurology. 1996 Jan;46(1):214-8. doi: 10.1212/wnl.46.1.214.
5 Mutations of the puratrophin-1 (PLEKHG4) gene on chromosome 16q22.1 are not a common genetic cause of cerebellar ataxia in a European population.J Hum Genet. 2006;51(4):363-367. doi: 10.1007/s10038-006-0372-y. Epub 2006 Feb 21.
6 Spectrum and prevalence of autosomal dominant spinocerebellar ataxia in Hokkaido, the northern island of Japan: a study of 113 Japanese families.J Hum Genet. 2007;52(10):848-855. doi: 10.1007/s10038-007-0182-x. Epub 2007 Sep 5.
7 Analysis of an insertion mutation in a cohort of 94 patients with spinocerebellar ataxia type 31 from Nagano, Japan.Neurogenetics. 2010 Oct;11(4):409-15. doi: 10.1007/s10048-010-0245-6. Epub 2010 Apr 28.
8 Localization of autosomal dominant cerebellar ataxia associated with retinal degeneration and anticipation to chromosome 3p12-p21.1.Hum Mol Genet. 1995 Aug;4(8):1441-5. doi: 10.1093/hmg/4.8.1441.
9 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.
10 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
11 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
12 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.
13 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.
14 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
15 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
16 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
17 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.
18 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
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 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
21 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
22 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.
23 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.