Details of Drug Off-Target (DOT)

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

DOT Name	Segment polarity protein dishevelled homolog DVL-3 (DVL3)
Synonyms	Dishevelled-3; DSH homolog 3
Gene Name	DVL3
Related Disease	Autosomal dominant Robinow syndrome 2 ( ) Neural tube defect ( ) Pneumocystis pneumonia ( ) Advanced cancer ( ) Anencephaly ( ) Astrocytoma ( ) Autosomal dominant Robinow syndrome 1 ( ) Autosomal dominant Robinow syndrome 3 ( ) B-cell lymphoma ( ) Breast cancer ( ) Breast carcinoma ( ) Carcinoma ( ) Esophageal squamous cell carcinoma ( ) Hepatocellular carcinoma ( ) Major depressive disorder ( ) Meningioma ( ) Mesothelioma ( ) Neoplasm ( ) Non-small-cell lung cancer ( ) Prostate adenocarcinoma ( ) Prostate cancer ( ) Prostate carcinoma ( ) Robinow syndrome ( ) Squamous cell carcinoma ( ) Ventricular septal defect ( ) Chronic obstructive pulmonary disease ( ) Hirschsprung disease ( ) Lung cancer ( ) Lung carcinoma ( ) Autosomal dominant Robinow syndrome ( ) Adult glioblastoma ( ) Glioblastoma multiforme ( ) Lung neoplasm ( ) Metastatic malignant neoplasm ( ) Neuroblastoma ( )
UniProt ID	DVL3_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	6V7O; 6ZBQ; 6ZBZ; 6ZC3; 6ZC4; 6ZC6; 6ZC7; 6ZC8
Pfam ID	PF00610 ; PF02377 ; PF00778 ; PF12316 ; PF00595
Sequence	MGETKIIYHLDGQETPYLVKLPLPAERVTLADFKGVLQRPSYKFFFKSMDDDFGVVKEEI SDDNAKLPCFNGRVVSWLVSAEGSHPDPAPFCADNPSELPPPMERTGGIGDSRPPSFHPH AGGGSQENLDNDTETDSLVSAQRERPRRRDGPEHATRLNGTAKGERRREPGGYDSSSTLM SSELETTSFFDSDEDDSTSRFSSSTEQSSASRLMRRHKRRRRKQKVSRIERSSSFSSITD STMSLNIITVTLNMEKYNFLGISIVGQSNERGDGGIYIGSIMKGGAVAADGRIEPGDMLL QVNEINFENMSNDDAVRVLREIVHKPGPITLTVAKCWDPSPRGCFTLPRSEPIRPIDPAA WVSHTAAMTGTFPAYGMSPSLSTITSTSSSITSSIPDTERLDDFHLSIHSDMAAIVKAMA SPESGLEVRDRMWLKITIPNAFIGSDVVDWLYHNVEGFTDRREARKYASNLLKAGFIRHT VNKITFSEQCYYIFGDLCGNMANLSLHDHDGSSGASDQDTLAPLPHPGAAPWPMAFPYQY PPPPHPYNPHPGFPELGYSYGGGSASSQHSEGSRSSGSNRSGSDRRKEKDPKAGDSKSGG SGSESDHTTRSSLRGPRERAPSERSGPAASEHSHRSHHSLASSLRSHHTHPSYGPPGVPP LYGPPMLMMPPPPAAMGPPGAPPGRDLASVPPELTASRQSFRMAMGNPSEFFVDVM
Function	Involved in the signal transduction pathway mediated by multiple Wnt genes.
KEGG Pathway	mTOR sig.ling pathway (hsa04150 ) Wnt sig.ling pathway (hsa04310 ) Notch sig.ling pathway (hsa04330 ) Hippo sig.ling pathway (hsa04390 ) Sig.ling pathways regulating pluripotency of stem cells (hsa04550 ) Melanogenesis (hsa04916 ) Cushing syndrome (hsa04934 ) Alzheimer disease (hsa05010 ) Pathways of neurodegeneration - multiple diseases (hsa05022 ) Human papillomavirus infection (hsa05165 ) Pathways in cancer (hsa05200 ) Basal cell carcinoma (hsa05217 ) Breast cancer (hsa05224 ) Hepatocellular carcinoma (hsa05225 ) Gastric cancer (hsa05226 )
Reactome Pathway	WNT mediated activation of DVL (R-HSA-201688 ) PCP/CE pathway (R-HSA-4086400 ) Degradation of DVL (R-HSA-4641258 ) Disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262 ) Negative regulation of TCF-dependent signaling by DVL-interacting proteins (R-HSA-5368598 ) RHO GTPases Activate Formins (R-HSA-5663220 ) WNT5 (R-HSA-9673324 ) TCF dependent signaling in response to WNT (R-HSA-201681 )

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Autosomal dominant Robinow syndrome 2	DIS9MS2G	Definitive	Autosomal dominant	[1]
Neural tube defect	DIS5J95E	Definitive	Biomarker	[2]
Pneumocystis pneumonia	DISFSOM3	Definitive	Genetic Variation	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
Anencephaly	DISIYW6T	Strong	Genetic Variation	[5]
Astrocytoma	DISL3V18	Strong	Biomarker	[4]
Autosomal dominant Robinow syndrome 1	DISLYVHM	Strong	CausalMutation	[1]
Autosomal dominant Robinow syndrome 3	DISRJPAS	Strong	Autosomal dominant	[6]
B-cell lymphoma	DISIH1YQ	Strong	Genetic Variation	[7]
Breast cancer	DIS7DPX1	Strong	Biomarker	[8]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[9]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[12]
Meningioma	DISPT4TG	Strong	Genetic Variation	[13]
Mesothelioma	DISKWK9M	Strong	Altered Expression	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[16]
Prostate adenocarcinoma	DISBZYU8	Strong	Biomarker	[17]
Prostate cancer	DISF190Y	Strong	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Robinow syndrome	DISK1CNU	Strong	Genetic Variation	[19]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[20]
Ventricular septal defect	DISICO41	Strong	Biomarker	[21]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Altered Expression	[22]
Hirschsprung disease	DISUUSM1	moderate	Biomarker	[23]
Lung cancer	DISCM4YA	moderate	Biomarker	[24]
Lung carcinoma	DISTR26C	moderate	Biomarker	[24]
Autosomal dominant Robinow syndrome	DIS94N80	Supportive	Autosomal dominant	[1]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[25]
Glioblastoma multiforme	DISK8246	Limited	Biomarker	[25]
Lung neoplasm	DISVARNB	Limited	Altered Expression	[26]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[26]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[27]
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Molecular Interaction Atlas (MIA)

MIA Detail

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 decreases the methylation of Segment polarity protein dishevelled homolog DVL-3 (DVL3).	[28]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Segment polarity protein dishevelled homolog DVL-3 (DVL3).	[30]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Segment polarity protein dishevelled homolog DVL-3 (DVL3).	[32]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Segment polarity protein dishevelled homolog DVL-3 (DVL3).	[33]
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3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Segment polarity protein dishevelled homolog DVL-3 (DVL3).	[29]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Segment polarity protein dishevelled homolog DVL-3 (DVL3).	[31]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Segment polarity protein dishevelled homolog DVL-3 (DVL3).	[34]
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References

1	DVL3 Alleles Resulting in a -1 Frameshift of the Last Exon Mediate Autosomal-Dominant Robinow Syndrome. Am J Hum Genet. 2016 Mar 3;98(3):553-561. doi: 10.1016/j.ajhg.2016.01.005. Epub 2016 Feb 25.
2	Genetic analysis of disheveled 2 and disheveled 3 in human neural tube defects.J Mol Neurosci. 2013 Mar;49(3):582-8. doi: 10.1007/s12031-012-9871-9. Epub 2012 Aug 15.
3	Genetic analysis of Wnt/PCP genes in neural tube defects.BMC Med Genomics. 2018 Apr 4;11(1):38. doi: 10.1186/s12920-018-0355-9.
4	Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation.J Cell Mol Med. 2019 Jan;23(1):641-655. doi: 10.1111/jcmm.13969. Epub 2018 Nov 23.
5	Digenic variants of planar cell polarity genes in human neural tube defect patients.Mol Genet Metab. 2018 May;124(1):94-100. doi: 10.1016/j.ymgme.2018.03.005. Epub 2018 Mar 18.
6	Mercury in the dental profession: a neglected problem. J Conn State Dent Assoc. 1979 Summer;53(3):111-2.
7	Relapsed diffuse large B-cell lymphoma present different genomic profiles between early and late relapses.Oncotarget. 2016 Dec 20;7(51):83987-84002. doi: 10.18632/oncotarget.9793.
8	AMPK activators suppress breast cancer cell growth by inhibiting DVL3-facilitated Wnt/-catenin signaling pathway activity.Mol Med Rep. 2017 Feb;15(2):899-907. doi: 10.3892/mmr.2016.6094. Epub 2016 Dec 29.
9	cDNA cloning of a human dishevelled DVL-3 gene, mapping to 3q27, and expression in human breast and colon carcinomas.Biochem Biophys Res Commun. 1997 Oct 20;239(2):510-6. doi: 10.1006/bbrc.1997.7500.
10	Role and mechanism of Dvl3 in the esophageal squamous cell carcinoma.Eur Rev Med Pharmacol Sci. 2018 Nov;22(22):7716-7725. doi: 10.26355/eurrev_201811_16393.
11	Cripto-1 contributes to stemness in hepatocellular carcinoma by stabilizing Dishevelled-3 and activating Wnt/-catenin pathway.Cell Death Differ. 2018 Aug;25(8):1426-1441. doi: 10.1038/s41418-018-0059-x. Epub 2018 Feb 14.
12	Dvl3 polymorphism interacts with life events and pro-inflammatory cytokines to influence major depressive disorder susceptibility.Sci Rep. 2018 Sep 21;8(1):14181. doi: 10.1038/s41598-018-31530-2.
13	Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma.Tumour Biol. 2017 Jul;39(7):1010428317705791. doi: 10.1177/1010428317705791.
14	Synergistic effect of targeting dishevelled-3 and the epidermal growth factor receptor-tyrosine kinase inhibitor on mesothelioma cells in vitro.Oncol Lett. 2018 Jan;15(1):833-838. doi: 10.3892/ol.2017.7382. Epub 2017 Nov 9.
15	Identification of driver genes regulating immune cell infiltration in cervical cancer by multiple omics integration.Biomed Pharmacother. 2019 Dec;120:109546. doi: 10.1016/j.biopha.2019.109546. Epub 2019 Oct 30.
16	Dishevelled-3 activates p65 to upregulate p120-catenin transcription via a p38-dependent pathway in non-small cell lung cancer.Mol Carcinog. 2015 Jun;54 Suppl 1:E112-21. doi: 10.1002/mc.22196. Epub 2014 Aug 22.
17	Dishevelled segment polarity protein 3 (DVL3): a novel and easily applicable recurrence predictor in localised prostate adenocarcinoma.BJU Int. 2017 Sep;120(3):343-350. doi: 10.1111/bju.13783. Epub 2017 Feb 10.
18	Correction: ASPM promotes prostate cancer stemness and progression by augmenting Wnt-Dvl-3--catenin signaling.Oncogene. 2019 Feb;38(8):1354. doi: 10.1038/s41388-018-0561-0.
19	Autosomal dominant Robinow syndrome associated with a novel DVL3 splice mutation.Am J Med Genet A. 2018 Apr;176(4):992-996. doi: 10.1002/ajmg.a.38635.
20	Coamplification and cooperation: toward identifying biologically relevant oncogenes.Clin Cancer Res. 2013 Oct 15;19(20):5549-51. doi: 10.1158/1078-0432.CCR-13-2117. Epub 2013 Sep 4.
21	Frizzled 2 and frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes.Development. 2012 Dec 1;139(23):4383-94. doi: 10.1242/dev.083352. Epub 2012 Oct 24.
22	Activation of WNT/-catenin signaling in pulmonary fibroblasts by TGF-?is increased in chronic obstructive pulmonary disease.PLoS One. 2011;6(9):e25450. doi: 10.1371/journal.pone.0025450. Epub 2011 Sep 30.
23	Expression of dishevelled gene in Hirschsprung's disease.Int J Clin Exp Pathol. 2013 Aug 15;6(9):1791-8. eCollection 2013.
24	Integrating expression-related SNPs into genome-wide gene- and pathway-based analyses identified novel lung cancer susceptibility genes.Int J Cancer. 2018 Apr 15;142(8):1602-1610. doi: 10.1002/ijc.31182. Epub 2017 Dec 12.
25	Expression Levels and Localizations of DVL3 and sFRP3 in Glioblastoma.Dis Markers. 2017;2017:9253495. doi: 10.1155/2017/9253495. Epub 2017 Oct 19.
26	Dishevelled family proteins are expressed in non-small cell lung cancer and function differentially on tumor progression.Lung Cancer. 2008 Nov;62(2):181-92. doi: 10.1016/j.lungcan.2008.06.018. Epub 2008 Aug 9.
27	MSX1 induces the Wnt pathway antagonist genes DKK1, DKK2, DKK3, and SFRP1 in neuroblastoma cells, but does not block Wnt3 and Wnt5A signalling to DVL3.Cancer Lett. 2010 Mar 28;289(2):195-207. doi: 10.1016/j.canlet.2009.08.019. Epub 2009 Oct 7.
28	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.
29	Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
30	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.
31	Growth inhibition of ovarian tumor-initiating cells by niclosamide. Mol Cancer Ther. 2012 Aug;11(8):1703-12.
32	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.
33	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.
34	Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.