Details of Drug Off-Target (DOT)

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

DOT Name	Segment polarity protein dishevelled homolog DVL-2 (DVL2)
Synonyms	Dishevelled-2; DSH homolog 2
Gene Name	DVL2
Related Disease	Arthritis ( ) Rheumatoid arthritis ( ) Adenoma ( ) Advanced cancer ( ) Carcinoma ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Colorectal adenoma ( ) Esophageal squamous cell carcinoma ( ) Familial adenomatous polyposis ( ) Gaucher disease type I ( ) Glioblastoma multiforme ( ) Glioma ( ) Mantle cell lymphoma ( ) Medulloblastoma ( ) Neoplasm ( ) Neural tube defect ( ) Renal cell carcinoma ( ) Transposition of the great arteries ( ) Hirschsprung disease ( ) Leukemia ( ) Osteoarthritis ( ) Pancreatic cancer ( ) Prostate cancer ( ) Prostate carcinoma ( ) Prostate neoplasm ( ) Small lymphocytic lymphoma ( ) Tetralogy of fallot ( ) Mycoses ( ) Ankylosing spondylitis ( ) Colorectal carcinoma ( ) Hepatocellular carcinoma ( ) Hyperlipidemia ( ) Lung neoplasm ( )
UniProt ID	DVL2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2REY; 3CBX; 3CBY; 3CBZ; 3CC0; 4WIP; 5LNP; 5SUY; 5SUZ; 6IW3; 6JCK
Pfam ID	PF00610 ; PF02377 ; PF00778 ; PF12316 ; PF00595
Sequence	MAGSSTGGGGVGETKVIYHLDEEETPYLVKIPVPAERITLGDFKSVLQRPAGAKYFFKSM DQDFGVVKEEISDDNARLPCFNGRVVSWLVSSDNPQPEMAPPVHEPRAELAPPAPPLPPL PPERTSGIGDSRPPSFHPNVSSSHENLEPETETESVVSLRRERPRRRDSSEHGAGGHRTG GPSRLERHLAGYESSSTLMTSELESTSLGDSDEEDTMSRFSSSTEQSSASRLLKRHRRRR KQRPPRLERTSSFSSVTDSTMSLNIITVTLNMEKYNFLGISIVGQSNERGDGGIYIGSIM KGGAVAADGRIEPGDMLLQVNDMNFENMSNDDAVRVLRDIVHKPGPIVLTVAKCWDPSPQ AYFTLPRNEPIQPIDPAAWVSHSAALTGTFPAYPGSSSMSTITSGSSLPDGCEGRGLSVH TDMASVTKAMAAPESGLEVRDRMWLKITIPNAFLGSDVVDWLYHHVEGFPERREARKYAS GLLKAGLIRHTVNKITFSEQCYYVFGDLSGGCESYLVNLSLNDNDGSSGASDQDTLAPLP GATPWPLLPTFSYQYPAPHPYSPQPPPYHELSSYTYGGGSASSQHSEGSRSSGSTRSDGG AGRTGRPEERAPESKSGSGSESEPSSRGGSLRRGGEASGTSDGGPPPSRGSTGGAPNLRA HPGLHPYGPPPGMALPYNPMMVVMMPPPPPPVPPAVQPPGAPPVRDLGSVPPELTASRQS FHMAMGNPSEFFVDVM
Function	Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling.
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 ) Signaling by Hippo (R-HSA-2028269 ) PCP/CE pathway (R-HSA-4086400 ) Asymmetric localization of PCP proteins (R-HSA-4608870 ) Degradation of DVL (R-HSA-4641258 ) Disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262 ) WNT5A-dependent internalization of FZD4 (R-HSA-5099900 ) Negative regulation of TCF-dependent signaling by DVL-interacting proteins (R-HSA-5368598 ) RHO GTPases Activate Formins (R-HSA-5663220 ) Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825 ) Clathrin-mediated endocytosis (R-HSA-8856828 ) 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
Arthritis	DIST1YEL	Definitive	Altered Expression	[1]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Genetic Variation	[4]
Colon cancer	DISVC52G	Strong	Altered Expression	[5]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[5]
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[2]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[6]
Familial adenomatous polyposis	DISW53RE	Strong	Genetic Variation	[7]
Gaucher disease type I	DIS87KKY	Strong	Altered Expression	[8]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[9]
Glioma	DIS5RPEH	Strong	Biomarker	[10]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[11]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[13]
Neural tube defect	DIS5J95E	Strong	Biomarker	[14]
Renal cell carcinoma	DISQZ2X8	Strong	Genetic Variation	[4]
Transposition of the great arteries	DISPXJ8X	Strong	Biomarker	[15]
Hirschsprung disease	DISUUSM1	moderate	Altered Expression	[16]
Leukemia	DISNAKFL	moderate	Biomarker	[17]
Osteoarthritis	DIS05URM	moderate	Biomarker	[18]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[19]
Prostate cancer	DISF190Y	moderate	Biomarker	[20]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[20]
Prostate neoplasm	DISHDKGQ	moderate	Biomarker	[20]
Small lymphocytic lymphoma	DIS30POX	moderate	Altered Expression	[17]
Tetralogy of fallot	DISMHFNW	moderate	Biomarker	[21]
Mycoses	DIS9K7PB	Disputed	Genetic Variation	[22]
Ankylosing spondylitis	DISRC6IR	Limited	Altered Expression	[23]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[7]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[24]
Hyperlipidemia	DIS61J3S	Limited	Altered Expression	[25]
Lung neoplasm	DISVARNB	Limited	Altered Expression	[26]
------------------------------------------------------------------------------------


⏷ Show the Full List of 35 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Segment polarity protein dishevelled homolog DVL-2 (DVL2).	[27]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Segment polarity protein dishevelled homolog DVL-2 (DVL2).	[28]
Calphostin C	DM9X2D0	Terminated	Calphostin C increases the expression of Segment polarity protein dishevelled homolog DVL-2 (DVL2).	[31]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Segment polarity protein dishevelled homolog DVL-2 (DVL2).	[32]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Segment polarity protein dishevelled homolog DVL-2 (DVL2).	[33]
------------------------------------------------------------------------------------

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Segment polarity protein dishevelled homolog DVL-2 (DVL2).	[29]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Segment polarity protein dishevelled homolog DVL-2 (DVL2).	[30]
------------------------------------------------------------------------------------

References

1	Dishevelled2 promotes apoptosis and inhibits inflammatory cytokine secretion in rheumatoid arthritis fibroblast-like synoviocytes through crosstalk with the NF-B pathway.Oncotarget. 2017 Feb 21;8(8):12649-12663. doi: 10.18632/oncotarget.15172.
2	Dvl2 promotes intestinal length and neoplasia in the ApcMin mouse model for colorectal cancer.Cancer Res. 2010 Aug 15;70(16):6629-38. doi: 10.1158/0008-5472.CAN-10-1616. Epub 2010 Jul 27.
3	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.
4	TFE3-Fusion Variant Analysis Defines Specific Clinicopathologic Associations Among Xp11 Translocation Cancers.Am J Surg Pathol. 2016 Jun;40(6):723-37. doi: 10.1097/PAS.0000000000000631.
5	Epsin is required for Dishevelled stability and Wnt signalling activation in colon cancer development.Nat Commun. 2015 Mar 16;6:6380. doi: 10.1038/ncomms7380.
6	RAP1B, a DVL2 binding protein, activates Wnt/beta-catenin signaling in esophageal squamous cell carcinoma.Gene. 2017 May 5;611:15-20. doi: 10.1016/j.gene.2017.01.021. Epub 2017 Jan 21.
7	Genetic Polymorphisms in APC, DVL2, and AXIN1 Are Associated with Susceptibility, Advanced TNM Stage or Tumor Location in Colorectal Cancer.Tohoku J Exp Med. 2019 Nov;249(3):173-183. doi: 10.1620/tjem.249.173.
8	A transcriptional and post-transcriptional dysregulation of Dishevelled 1 and 2 underlies the Wnt signaling impairment in type I Gaucher disease experimental models.Hum Mol Genet. 2020 Jan 15;29(2):274-285. doi: 10.1093/hmg/ddz293.
9	Dishevelled 2 signaling promotes self-renewal and tumorigenicity in human gliomas.Cancer Res. 2011 Dec 1;71(23):7280-90. doi: 10.1158/0008-5472.CAN-11-1531. Epub 2011 Oct 11.
10	ATDC contributes to sustaining the growth and invasion of glioma cells through regulating Wnt/-catenin signaling.Chem Biol Interact. 2019 May 25;305:148-155. doi: 10.1016/j.cbi.2019.03.033. Epub 2019 Mar 29.
11	Constitutive activation of the Wnt canonical pathway in mantle cell lymphoma.Blood. 2008 Dec 15;112(13):5171-9. doi: 10.1182/blood-2008-02-139212. Epub 2008 Sep 11.
12	The SFRP family of WNT inhibitors function as novel tumor suppressor genes epigenetically silenced in medulloblastoma.Oncogene. 2010 May 20;29(20):3017-24. doi: 10.1038/onc.2010.32. Epub 2010 Mar 8.
13	Overexpression of Dishevelled-2 contributes to proliferation and migration of human esophageal squamous cell carcinoma.J Mol Histol. 2016 Jun;47(3):287-95. doi: 10.1007/s10735-016-9674-3. Epub 2016 Apr 15.
14	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.
15	Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure.Development. 2002 Dec;129(24):5827-38. doi: 10.1242/dev.00164.
16	Expression patterns of dishevelled-2 in different colon tissue segments in Hirschsprung's disease.Mol Med Rep. 2015 Mar;11(3):2092-6. doi: 10.3892/mmr.2014.2932. Epub 2014 Nov 12.
17	Dishevelled proteins are significantly upregulated in chronic lymphocytic leukaemia.Tumour Biol. 2016 Sep;37(9):11947-11957. doi: 10.1007/s13277-016-5039-5. Epub 2016 Apr 16.
18	Dishevelled? modulates osteogenic differentiation of human synovial fibroblasts in osteoarthritis.Mol Med Rep. 2018 Jul;18(1):292-298. doi: 10.3892/mmr.2018.8975. Epub 2018 May 4.
19	MicroRNA-137 reduces stemness features of pancreatic cancer cells by targeting KLF12.J Exp Clin Cancer Res. 2019 Mar 12;38(1):126. doi: 10.1186/s13046-019-1105-3.
20	Dishevelled-2 silencing reduces androgen-dependent prostate tumor cell proliferation and migration and expression of Wnt-3a and matrix metalloproteinases.Mol Biol Rep. 2013 Jul;40(7):4241-50. doi: 10.1007/s11033-013-2506-6. Epub 2013 May 8.
21	A Rare Rs139365823 Polymorphism in Pre-miR-138 Is Associated with Risk of Congenital Heart Disease in a Chinese Population.DNA Cell Biol. 2018 Feb;37(2):109-116. doi: 10.1089/dna.2017.4013. Epub 2018 Jan 3.
22	The Fungal Metabolite Brefeldin A Inhibits Dvl2-Plk1-Dependent Primary Cilium Disassembly.Mol Cells. 2017 Jun 30;40(6):401-409. doi: 10.14348/molcells.2017.0032. Epub 2017 Jun 14.
23	MiR-495 targeting dvl-2 represses the inflammatory response of ankylosing spondylitis.Am J Transl Res. 2019 May 15;11(5):2742-2753. eCollection 2019.
24	Dynamic expression of ZNF382 and its tumor-suppressor role in hepatitis B virus-related hepatocellular carcinogenesis.Oncogene. 2019 Jun;38(24):4804-4819. doi: 10.1038/s41388-019-0759-9. Epub 2019 Feb 25.
25	Study of microRNAs targeted Dvl2 on the osteoblasts differentiation of rat BMSCs in hyperlipidemia environment.J Cell Physiol. 2018 Sep;233(9):6758-6766. doi: 10.1002/jcp.26392. Epub 2018 Apr 6.
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	The anti-helminthic niclosamide inhibits Wnt/Frizzled1 signaling. Biochemistry. 2009 Nov 3;48(43):10267-74. doi: 10.1021/bi9009677.
28	Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
29	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.
30	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.
31	Targeting the beta-catenin/TCF transcriptional complex in the treatment of multiple myeloma. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7516-21. doi: 10.1073/pnas.0610299104. Epub 2007 Apr 23.
32	Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
33	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.