Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQHOF8L)

DOT Name Plakophilin-4 (PKP4)
Synonyms p0071
Gene Name PKP4
Related Disease
Alzheimer disease ( )
Bipolar disorder ( )
Fragile X syndrome ( )
Neoplasm ( )
Neuromuscular disease ( )
Non-small-cell lung cancer ( )
Schizophrenia ( )
UniProt ID
PKP4_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00514
Sequence
MPAPEQASLVEEGQPQTRQEAASTGPGMEPETTATTILASVKEQELQFQRLTRELEVERQ
IVASQLERCRLGAESPSIASTSSTEKSFPWRSTDVPNTGVSKPRVSDAVQPNNYLIRTEP
EQGTLYSPEQTSLHESEGSLGNSRSSTQMNSYSDSGYQEAGSFHNSQNVSKADNRQQHSF
IGSTNNHVVRNSRAEGQTLVQPSVANRAMRRVSSVPSRAQSPSYVISTGVSPSRGSLRTS
LGSGFGSPSVTDPRPLNPSAYSSTTLPAARAASPYSQRPASPTAIRRIGSVTSRQTSNPN
GPTPQYQTTARVGSPLTLTDAQTRVASPSQGQVGSSSPKRSGMTAVPQHLGPSLQRTVHD
MEQFGQQQYDIYERMVPPRPDSLTGLRSSYASQHSQLGQDLRSAVSPDLHITPIYEGRTY
YSPVYRSPNHGTVELQGSQTALYRTGSVGIGNLQRTSSQRSTLTYQRNNYALNTTATYAE
PYRPIQYRVQECNYNRLQHAVPADDGTTRSPSIDSIQKDPREFAWRDPELPEVIHMLQHQ
FPSVQANAAAYLQHLCFGDNKVKMEVCRLGGIKHLVDLLDHRVLEVQKNACGALRNLVFG
KSTDENKIAMKNVGGIPALLRLLRKSIDAEVRELVTGVLWNLSSCDAVKMTIIRDALSTL
TNTVIVPHSGWNNSSFDDDHKIKFQTSLVLRNTTGCLRNLSSAGEEARKQMRSCEGLVDS
LLYVIHTCVNTSDYDSKTVENCVCTLRNLSYRLELEVPQARLLGLNELDDLLGKESPSKD
SEPSCWGKKKKKKKRTPQEDQWDGVGPIPGLSKSPKGVEMLWHPSVVKPYLTLLAESSNP
ATLEGSAGSLQNLSAGNWKFAAYIRAAVRKEKGLPILVELLRMDNDRVVSSVATALRNMA
LDVRNKELIGKYAMRDLVNRLPGGNGPSVLSDETMAAICCALHEVTSKNMENAKALADSG
GIEKLVNITKGRGDRSSLKVVKAAAQVLNTLWQYRDLRSIYKKDGWNQNHFITPVSTLER
DRFKSHPSLSTTNQQMSPIIQSVGSTSSSPALLGIRDPRSEYDRTQPPMQYYNSQGDATH
KGLYPGSSKPSPIYISSYSSPAREQNRRLQHQQLYYSQDDSNRKNFDAYRLYLQSPHSYE
DPYFDDRVHFPASTDYSTQYGLKSTTNYVDFYSTKRPSYRAEQYPGSPDSWV
Function Plays a role as a regulator of Rho activity during cytokinesis. May play a role in junctional plaques.
Tissue Specificity Expressed in salivary glands (at protein level) . Expressed in arrector pili muscle (at protein level) .
Reactome Pathway
Formation of the cornified envelope (R-HSA-6809371 )
RND3 GTPase cycle (R-HSA-9696264 )
RND2 GTPase cycle (R-HSA-9696270 )
RND1 GTPase cycle (R-HSA-9696273 )
Keratinization (R-HSA-6805567 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Biomarker [1]
Bipolar disorder DISAM7J2 Strong Biomarker [2]
Fragile X syndrome DISE8W3A Strong Biomarker [3]
Neoplasm DISZKGEW Strong Altered Expression [4]
Neuromuscular disease DISQTIJZ Strong Altered Expression [5]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [4]
Schizophrenia DISSRV2N Limited Biomarker [2]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
16 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 Plakophilin-4 (PKP4). [6]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Plakophilin-4 (PKP4). [7]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Plakophilin-4 (PKP4). [8]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Plakophilin-4 (PKP4). [9]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Plakophilin-4 (PKP4). [10]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Plakophilin-4 (PKP4). [11]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Plakophilin-4 (PKP4). [12]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Plakophilin-4 (PKP4). [12]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Plakophilin-4 (PKP4). [13]
Indomethacin DMSC4A7 Approved Indomethacin decreases the expression of Plakophilin-4 (PKP4). [14]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Plakophilin-4 (PKP4). [15]
Tamibarotene DM3G74J Phase 3 Tamibarotene decreases the expression of Plakophilin-4 (PKP4). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Plakophilin-4 (PKP4). [16]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Plakophilin-4 (PKP4). [17]
SB-431542 DM0YOXQ Preclinical SB-431542 increases the expression of Plakophilin-4 (PKP4). [19]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Plakophilin-4 (PKP4). [20]
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⏷ Show the Full List of 16 Drug(s)
2 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 Plakophilin-4 (PKP4). [18]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Plakophilin-4 (PKP4). [18]
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References

1 Direct interaction of Alzheimer's disease-related presenilin 1 with armadillo protein p0071.J Biol Chem. 1999 Apr 2;274(14):9141-8. doi: 10.1074/jbc.274.14.9141.
2 Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.Transl Psychiatry. 2017 Jun 20;7(6):e1155. doi: 10.1038/tp.2017.115.
3 FMRP regulates actin filament organization via the armadillo protein p0071.RNA. 2013 Nov;19(11):1483-96. doi: 10.1261/rna.037945.112. Epub 2013 Sep 23.
4 p0071 interacts with E-cadherin in the cytoplasm so as to promote the invasion and metastasis of non-small cell lung cancer.Mol Carcinog. 2018 Jan;57(1):89-96. doi: 10.1002/mc.22734. Epub 2017 Sep 25.
5 p0071, a member of the armadillo multigene family, is a constituent of sarcomeric I-bands in human skeletal muscle.J Muscle Res Cell Motil. 2000;21(6):577-86. doi: 10.1023/a:1026587530656.
6 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
7 Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
8 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.
9 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.
10 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
11 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.
12 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
13 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
14 Mechanisms of indomethacin-induced alterations in the choline phospholipid metabolism of breast cancer cells. Neoplasia. 2006 Sep;8(9):758-71.
15 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.
16 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.
17 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.
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 Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
20 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.