Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNUMAZ0)

DOT Name Pleckstrin homology domain-containing family A member 7 (PLEKHA7)
Synonyms PH domain-containing family A member 7
Gene Name PLEKHA7
Related Disease
Primary angle-closure glaucoma ( )
Angle-closure glaucoma ( )
Breast lobular carcinoma ( )
Epithelial ovarian cancer ( )
Glomerulonephritis ( )
Glomerulosclerosis ( )
High blood pressure ( )
Neoplasm ( )
Open-angle glaucoma ( )
Coronary heart disease ( )
Isolated cleft lip ( )
Glaucoma/ocular hypertension ( )
Pneumonia ( )
UniProt ID
PKHA7_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7KJO; 7KJZ; 7KK7
Pfam ID
PF00169
Sequence
MAAATVGRDTLPEHWSYGVCRDGRVFFINDQLRCTTWLHPRTGEPVNSGHMIRSDLPRGW
EEGFTEEGASYFIDHNQQTTAFRHPVTGQFSPENSEFILQEEPNPHMSKQDRNQRPSSMV
SETSTAGTASTLEAKPGPKIIKSSSKVHSFGKRDQAIRRNPNVPVVVRGWLHKQDSSGMR
LWKRRWFVLADYCLFYYKDSREEAVLGSIPLPSYVISPVAPEDRISRKYSFKAVHTGMRA
LIYNSSTAGSQAEQSGMRTYYFSADTQEDMNAWVRAMNQAAQVLSRSSLKRDMEKVERQA
VPQANHTESCHECGRVGPGHTRDCPHRGHDDIVNFERQEQEGEQYRSQRDPLEGKRDRSK
ARSPYSPAEEDALFMDLPTGPRGQQAQPQRAEKNGMLPASYGPGEQNGTGGYQRAFPPRT
NPEKHSQRKSNLAQVEHWARAQKGDSRSLPLDQTLPRQGPGQSLSFPENYQTLPKSTRHP
SGGSSPPPRNLPSDYKYAQDRASHLKMSSEERRAHRDGTVWQLYEWQQRQQFRHGSPTAP
ICLGSPEFTDQGRSRSMLEVPRSISVPPSPSDIPPPGPPRVFPPRRPHTPAERVTVKPPD
QRRSVDISLGDSPRRARGHAVKNSSHVDRRSMPSMGYMTHTVSAPSLHGKSADDTYLQLK
KDLEYLDLKMTGRDLLKDRSLKPVKIAESDTDVKLSIFCEQDRVLQDLEDKIRALKENKD
QLESVLEVLHRQMEQYRDQPQHLEKIAYQQKLLQEDLVHIRAELSRESTEMENAWNEYLK
LENDVEQLKQTLQEQHRRAFFFQEKSQIQKDLWRIEDVTAGLSANKENFRILVESVKNPE
RKTVPLFPHPPVPSLSTSESKPPPQPSPPTSPVRTPLEVRLFPQLQTYVPYRPHPPQLRK
VTSPLQSPTKAKPKVEDEAPPRPPLPELYSPEDQPPAVPPLPREATIIRHTSVRGLKRQS
DERKRDRELGQCVNGDSRVELRSYVSEPELATLSGDMAQPSLGLVGPESRYQTLPGRGLS
GSTSRLQQSSTIAPYVTLRRGLNAESSKATFPRPKSALERLYSGDHQRGKMSAEEQLERM
KRHQKALVRERKRTLGQGERTGLPSSRYLSRPLPGDLGSVC
Function
Required for zonula adherens biogenesis and maintenance. Acts via its interaction with CAMSAP3, which anchors microtubules at their minus-ends to zonula adherens, leading to the recruitment of KIFC3 kinesin to the junctional site. Mediates docking of ADAM10 to zonula adherens through a PDZD11-dependent interaction with the ADAM10-binding protein TSPAN33.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Primary angle-closure glaucoma DISX8UKZ Definitive Genetic Variation [1]
Angle-closure glaucoma DISZ95KY Strong Genetic Variation [1]
Breast lobular carcinoma DISBY98Q Strong Altered Expression [2]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [3]
Glomerulonephritis DISPZIQ3 Strong Biomarker [4]
Glomerulosclerosis DISJF20Z Strong Biomarker [4]
High blood pressure DISY2OHH Strong Genetic Variation [5]
Neoplasm DISZKGEW Strong Altered Expression [3]
Open-angle glaucoma DISSZEE8 Strong Genetic Variation [6]
Coronary heart disease DIS5OIP1 moderate Genetic Variation [7]
Isolated cleft lip DIS2O2JV moderate Biomarker [8]
Glaucoma/ocular hypertension DISLBXBY Limited Biomarker [9]
Pneumonia DIS8EF3M Limited Biomarker [10]
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⏷ Show the Full List of 13 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
5 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 Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [11]
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [21]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [24]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [26]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [21]
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12 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 Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [12]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [13]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [14]
Doxorubicin DMVP5YE Approved Doxorubicin affects the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [15]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [16]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [17]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [18]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [19]
Progesterone DMUY35B Approved Progesterone increases the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [20]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [22]
PEITC DMOMN31 Phase 2 PEITC decreases the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [23]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Pleckstrin homology domain-containing family A member 7 (PLEKHA7). [25]
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⏷ Show the Full List of 12 Drug(s)

References

1 COL11A1 Polymorphisms Are Associated with Primary Angle-Closure Glaucoma Severity.J Ophthalmol. 2019 Jan 27;2019:2604386. doi: 10.1155/2019/2604386. eCollection 2019.
2 Genetic up-regulation and overexpression of PLEKHA7 differentiates invasive lobular carcinomas from invasive ductal carcinomas.Hum Pathol. 2012 Nov;43(11):1902-9. doi: 10.1016/j.humpath.2012.01.017. Epub 2012 Apr 25.
3 Simultaneous E-cadherin and PLEKHA7 expression negatively affects E-cadherin/EGFR mediated ovarian cancer cell growth.J Exp Clin Cancer Res. 2018 Jul 11;37(1):146. doi: 10.1186/s13046-018-0796-1.
4 Mutation of Plekha7 attenuates salt-sensitive hypertension in the rat.Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):12817-22. doi: 10.1073/pnas.1410745111. Epub 2014 Aug 18.
5 Genetic variations in CYP17A1, CACNB2 and PLEKHA7 are associated with blood pressure and/or hypertension in She ethnic minority of China.Atherosclerosis. 2011 Dec;219(2):709-14. doi: 10.1016/j.atherosclerosis.2011.09.006. Epub 2011 Sep 16.
6 Genome-wide association analyses identify three new susceptibility loci for primary angle closure glaucoma.Nat Genet. 2012 Oct;44(10):1142-1146. doi: 10.1038/ng.2390. Epub 2012 Aug 26.
7 Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.Circ Res. 2018 Feb 2;122(3):433-443. doi: 10.1161/CIRCRESAHA.117.312086. Epub 2017 Dec 6.
8 Mutations in the Epithelial Cadherin-p120-Catenin Complex Cause Mendelian Non-Syndromic Cleft Lip with or without Cleft Palate.Am J Hum Genet. 2018 Jun 7;102(6):1143-1157. doi: 10.1016/j.ajhg.2018.04.009. Epub 2018 May 24.
9 Extended association study of PLEKHA7 and COL11A1 with primary angle closure glaucoma in a Han Chinese population.Invest Ophthalmol Vis Sci. 2014 May 22;55(6):3797-802. doi: 10.1167/iovs.14-14370.
10 The adherens junctions control susceptibility to Staphylococcus aureus -toxin.Proc Natl Acad Sci U S A. 2015 Nov 17;112(46):14337-42. doi: 10.1073/pnas.1510265112. Epub 2015 Oct 21.
11 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.
12 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.
13 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
14 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
15 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.
16 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
17 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.
18 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
19 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.
20 Effects of progesterone treatment on expression of genes involved in uterine quiescence. Reprod Sci. 2011 Aug;18(8):781-97.
21 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.
22 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
23 Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
24 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.
25 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.
26 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.