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DVL1 (dishevelled, dsh homolog 1 (Drosophila))

Written2011-06Ho-Jin Lee, Jie J Zheng
St Jude Children's Research Hospital, Department of Structural Biology, 262 Danny Thomas Place, Memphis, TN 38105, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesdishevelled 1 (homologous to Drosophila dsh)
dishevelled, dsh homolog 1 (Drosophila)
Other aliasDVL
DVL1L1
MGC54245
HGNC (Hugo) DVL1
LocusID (NCBI) 1855
Atlas_Id 463
Location 1p36.33  [Link to chromosome band 1p36]
Location_base_pair Starts at 1335278 and ends at 1349112 bp from pter ( according to hg19-Feb_2009)  [Mapping DVL1.png]
Fusion genes
(updated 2016)
MELTF (3q29) / DVL1 (1p36.33)

DNA/RNA

Note A human DVL1 cDNA was first isolated from a human adult caudate cDNA library by screening with a 200 bp RT-PCR fragment obtained from human fetal brain total RNA that was probed with oligonucleotides corresponding to the mouse Dishevelled homolog (Pizzuti et al., 1996). The cDNA recovered encoded a 670 amino acid protein that was termed DVL-1L. Around the same time, Semënov and Snyder (1997) cloned and characterized 3 human homologs of the Drosophila Dishevelled gene, one of which encoded DVL1, a 695-amino acid protein (GenBank: AF006011.1).
Description The DVL1 gene comprises 15 verified exons.

Protein

 
  Schematic diagram of DVL1 protein. Homology model respective structure of DIX, PDZ, or DEP domain in DVL1 protein was generated by using X-ray and NMR structures (for DIX domain, PDB code: 3PZ8; for PDZ domain, PDB codes: 1L06 and 1MC7; for DEP domain, PDB code: 1FSH).
Description Human DVL1 encodes DVL1 protein, which contains 695 amino acid residues (size 75.2 kDa) (Semënov and Snyder, 1997). DVL1 comprises three domains, DIX (aa 1-82, DIshevelled-aXin), PDZ (aa 249-342, Post Synaptic Density-95, Discs large and Zonula-occludens 1), and DEP (aa 404-502, Dishevelled-EGL-10-Pleckstrin) (Wharton, 2003; Malbon and Wang, 2006; Wallingford and Habas, 2005). In the mouse, the DIX domain of Dvls can associate with the DIX domain of Axin and Dvls (Schwarz-Romond et al., 2007a; Schwarz-Romond et al., 2007b). The PDZ domain of Dvls is the protein-protein interaction module (Wong et al., 2003; Lee and Zheng, 2010) and at least 20 Dvl-binding partners were reported (Wallingford and Habas, 2005). The DEP domain of Dvl proteins has a polybasic stretch region that is responsible for its membrane-targeting activity (Wong et al., 2000; Simons et al., 2009). Furthermore, Dvl proteins have conserved regions harboring positively charged (basic) amino acid residues, proline-rich putative Src-homology 3 (SH3) binding domains (Penton et al., 2002), and highly conserved C-terminal regions (Wallingford and Habas, 2005), but their roles are unknown.

Structure. The overall structure of the intact DVL1 protein remains unknown; however, each individual domain in DVL1 has been investigated. The 3D structure of the DIX domain of Dvl-1 has not been reported. The homology model of the DVL1 DIX domain was generated from the 3D structure of the Axin DIX domain (PDB code: 1WSP) and that of a mutant DIX(Y17D) was solved by using X-ray crystallography (PDB code: 3PZ8), which consists of 4 beta-sheets and 1 helix structures (Schwarz-Romond et al., 2007a; Liu et al., 2011). The structure of DVL1's PDZ domain comprises 6 beta-sheets (betaA~betaF) and 2 alpha-helices (alphaA and alphaB) (Wong et al., 2003). The DEP domain of DVL1 consists of a helix bundle with three a-helices (H1-H3), a beta-hairpin "arm" composed of two beta-strands (B1 and B2) between H1 and H2, and two short beta-strands (B3 and B4) (Wong et al., 2000).

Expression DVL1 gene is found in fetal and adult tissues, including brain, lung, kidney, skeletal muscle, and heart; according to Northern blot analysis, the highest mRNA levels are found in adult skeletal muscle, pancreas, and heart muscle (Pizzuti et al., 1996).
Localisation Normally present in cytoplasm. After activation of Wnt signaling, the translocation of DVLs is occurred from the cytoplasm to the plasma membrane (Park et al., 2005; Simons et al., 2009) and to the nucleus (Torres and Nelson, 2000; Itoh et al., 2005; Gan et al., 2008).
Function Dvl family proteins mediate Wnt signaling pathways: Wnt/beta-catenin, Wnt/JNK (planar cell polarity or convergent extension), and Wnt/Ca2+ signaling (Klingensmith et al., 1994; Li et al., 1999; Boutros and Mlodzik, 1999; Wallingford et al., 2000; Gao and Chen, 2010). The DIX and PDZ domains are used for canonical Wnt signaling; the PDZ and DEP domains are used for non-canonical Wnt signaling. After Wnt activates signaling, CK1epsilon, CKII, PKCalpha, or Par-1 kinases hyperphosphorylate Dvl proteins on serine/threonine residues (Yanagawa et al., 1995; Peters et al., 1999; Sakanaka et al., 1999; Kishida et al., 2001; Schulte et al., 2005; Kibardin et al., 2006; Klimowski et al., 2006; Bilic et al., 2007; Zhang et al., 2007; Zeng et al., 2008). DVL1 can interact with a variety of other binding partners including protein phosphatases and kinases (Boutros and Mlodzik, 1999; Williams et al., 2005).

Binding partners
- AXIN interacts with the DIX domain of DVLs, which leads to the activation of beta-catenin-mediated signaling (Li et al., 1999; Smalley et al., 1999; Cliffe et al., 2003; Kishida et al., 1999; Schwarz-Romond et al., 2007a; Schwarz-Romond et al., 2007b; Fiedler et al., 2011).
- BP75 (bromodomain-containing M(r) 75000 protein) binds to the DIX domain of mouse Dvl1 in mammalian cells and enhances Wnt signaling by inactivating GSK3beta (Kim et al., 2003).
- CK1epsilon (casein kinase Iepsilon) binds to the Dvl proteins and increases the phosphorylation of DVLs in a variety of tissue culture and in vitro assays (Peters et al., 1999; Sakanaka et al., 1999; Kishida et al., 2001). CK1epsilon phosphorylates two highly conserved residues, S139 and S142, of mouse Dvl1 protein, as confirmed by mass spectroscopy. Phosphoserines -139 and -142 are positive regulators of Dvl1-dependent Wnt signal transduction (Klimowski et al., 2006). In Drosophila, CK1epsilon phosphorylates the Ser236 residue in Dsh protein as confirmed by mutagenesis analysis (Klein et al., 2006). In Xenopus, CK1epsilon activates the Wnt/beta-catenin signaling pathway positively. The interaction between the kinase domain of CK1epsilon and the PDZ domain of Xenopus Dishevelled (Xdsh) was identified by a yeast two-hybrid assay (Peters et al., 1999). However, another study suggested that the entire DEP domain, but not the PDZ domain, is necessary for the binding of DVL1 to CK1epsilon in mammalian intact cell assays (Kishida et al., 2001). In Drosophila, studies suggested that CK1epsilon facilitates both Wnt/beta-catenin and Wnt/PCP signaling pathways (Strutt et al., 2006; Klein et al., 2006). Consistent with this finding, CK1epsilon activates Dvl proteins via non-canonical Wnt ligands in SN4741 cells, suggesting that CK1epsilon-mediated phosphorylation of Dvl proteins may be a common step in both canonical and non-canonical pathways (Bryja et al., 2007).
- CKII (casein kinase II) is a serine/threonine kinase that can phosphorylate and associate with the PDZ domain of Drosophila Dsh (or DVLs) (Willert et al., 1997; Lee et al., 1999).
- Diversin regulates heart formation and gastrulation movements during development. Diversin's ankyrin repeats are necessary for interaction with the DVL DEP domain, for activation of the non-canonical Wnt signaling pathway, and for other biological responses (Moeller et al., 2006).
- Dapper (Dpr) binds to the PDZ domain of DVL1, which inhibits the Wnt/beta-catenin signaling (Wong et al., 2003). However,another study showed that human DPR1 can bind the DEP domain of DVL1 and inhibit Wnt signaling by promoting DVL1 degradation (Zhang et al., 2006).
- Daam1, a Formin-Homology (FH) protein, binds to both DVL and Rho proteins and mediates Wnt-induced Dvl1-Rho complex formation. Xenopus Daam1 regulates gastrulation (Habas et al., 2001).
- EphrinB1 interacts with the PDZ domain of Dishevelled. In Xenopus embryos, EphrinB1 plays a role in retinal progenitor cell movement into the eye field through an interaction with DVL (Tanaka et al., 2003; Lee et al., 2006; Lee HS et al., 2009). Phosphorylation of tyrosines 324 and 325 disrupts the EphrinB1/Dsh interaction, thus modulating retinal progenitor movement that is dependent on the planar cell polarity pathway (Lee HS et al., 2009).
- Frat protein was originally isolated on the basis of its tumor-promoting activity in human lymphocytes (Jonkers et al., 1997). It also binds to the basic region (aa 220-230) of DVL1 (Li et al., 1999; Hino et al., 2003), an interaction that is enhanced by CK1epsilon, which activates Wnt/beta-catenin signaling (Hino et al., 2003).
- Frizzled (Fz) protein, a key component of Wnt signaling, interacts with Dvl proteins (Wong et al., 2003; Shafer et al., 2011). NMR studies showed that a peptide derived from a conserved motif (KTxxxW) located two amino acids C-terminal to the seventh transmembrance domain of Fz directly binds to the PDZ domain of Dvl-1, implying that its interaction is necessary for activating the Wnt/beta-catenin signaling (Wong et al., 2003). Interestinly, Dvl-1 can inhibit PCP signaling by increasing hyperphosphorylation of Fz3 and preventing its internalization (Shafer et al., 2011).
- Idax (Inhibition of the Dvl and AXin complex) bound to the PDZ domain of DVL was identified in a rat brain cDNA library that was screened by the yeast two-hybrid method (Hino et al., 2001). Idax interacts with DVL in intact cells also. NMR spectroscopy identified the minimum region in rat Idax protein required for binding to mouse Dvl1 PDZ domain as the internal sequence of the KTxxxI motif (London et al., 2004). Idax suppresses the Wnt3a-dependent accumulation of beta-catenin and activation of Tcf in L cells (Hino et al., 2001). The levels of CXXC4 mRNA, which encodes the protein Idax, in renal cell carcinoma were significantly lower in patients with metastases than in patients without metastases (P=0.0016) (Kojima et al., 2009).
- Naked cuticle (Nkd) regulates early Wnt activity by acting as an inducible antagonist. The Nkd EFX domain interacts with the basic/PDZ domain of Drosophila Dsh or DVLs in the yeast two-hybrid assay (Wharton et al., 2001).
- MuSK kinase domain interacts with Dvl1 DEP domain in a mouse muscle cell line and in HEK293 cells transfected with the mouse constructs, which plays an important role in the agrin- and neuro-induced AChR (acethylcholine receptor) clustering (Luo et al., 2002). In Dvl1 mutant mice AchR clusters had a more disperse distribution at the endplate (Henriquez et al., 2008).
- PAR-1 is a serine/threonine kinase. In Drosophila, Par-1 binds to and phosphorylates Dsh/Dvl protein and promotes Wnt/beta-catenin signaling at the expense of JNK signaling (Sun et al., 2001). Par-1 target sites in Dsh are essential for proper Dsh translocation from the cytoplasmic vesicles to the cell cortex but not for Dsh activity in the canonical Wnt/beta-catenin pathway. Different PAR-1 isoforms mediate two distinct and essential roles in Xenopus axial development. PAR-1BY plays an essential role in the PCP branch and mediates Dsh membrane localization while PAR-1A and PAR-BX are essential for canonical Wnt signaling, possibly via targets other than Dishevelled (Ossipova et al., 2005). Mammalian Par-1b promotes cell-cell adhesion and inhibits Dvl-mediated transformation of Madin-Darby canine kidney cells.
- PIP5K1 (phosphatidylinositol-4-phosphate 5-kinase type I) and DVL co-immunoprecipitate when they are overexpressed in HEK293 cells. The N-terminal half of the PIP5K1beta kinase domain interacts with Dvl1 fragment that contains the DIX and PDZ domains; Wnt3a may regulate this interaction (Pan et al., 2008).
- Ror2 is a receptor tyrosin kinase (RTK) binds the Dvl C-terminus (Witte et al., 2010).
- Syndecan-4 (Syn4) interacts with Dvl protein and also functionally and biochemically with the Wnt receptor Fz7 in Xenopus embryos (Muñoz et al., 2006).
- Transmembrane 88 (TMEM88), a two-transmembrane-type protein, interacts with the PDZ domain of Dvl. Using NMR spectroscopy, the interaction between the C-terminal tail of TMEM88 and the PDZ domain of Dvl-1 was confirmed (Lee et al., 2010). In HEK293 cells, TMEM88 attenuated the Wnt/beta-catenin signaling induced by Wnt-1 ligand in a dose-dependent manner, and TMEM88 knockdown by RNAi increased Wnt activity. In Xenopus, TMEM88 protein is sublocalized at the cell membrane and inhibits Wnt signaling induced by Xdsh, but not beta-catenin (Lee et al., 2010).

Homology Three DVL genes (DVL1, DVL2, and DVL3) have been isolated in mammals and Xenopus. Dvl homologs are conserved in Drosophila (dishevelled, dsh).

Implicated in

Note
  
Entity Breast cancers
Note The DVL1 gene is amplified and DVL1 protein is over-expressed in 13 of 14 primary breast cancers examined. DVL1 protein is prominent in the cytoplasm of cancer cells, but not in normal epithelial cells of the mammary duct or in myoepithelial cells (Nagahata et al., 2003; Schlange et al., 2007). In invasive ductal carcinoma of the breast, immunohistochemical analysis of 96 tumor samples showed that 30% of tumors displayed both nuclear and cytoplasmic staining of DVL protein, while 52% showed nuclear loclalization. There is a correlation between nuclear localization of DVL and beta-catenin (p<0.01, OR=15.8) (Prasad et al., 2007).
  
  
Entity Cervical squamous cell carcinoma
Note Up-regulation and overproduction of DVL1 mRNA were found in these malignant cells (Okino et al., 2003). DVL1 protein was prominent in the cytoplasm of cancer cells whereas it was unreactive in the surrounding normal cervical squamous cells (Okino et al., 2003).
  
  
Entity Prostate cancer
Note Semi-quantitative PCR in 20 primary prostate cancers and assessed the protein expression revealed that DVL1 is significantly overexpressed in prostate cancer (65%). A correlation between DVL1 expression and beta-catenin expression was confirmed (Mizutani et al., 2005).
  
  
Entity Lung cancer
Note RT-PCR of 13 matched normal and invasive squamous cell carcinoma samples revealed that the tumors significantly overexpressed Notch and Wnt pathway family members, including DVL1 (P=0.003), LRP8 (P=0.008) and NOTCH2 (P=0.029) (Garnis et al., 2005). All DVL family members are expressed in non-small cell lung cancer (Wei et al., 2008). The expression levels of DVL1 and DVL3 are significantly higher in nodal metastases than in primary growths, and DVL1 expression is correlated with beta-catenin expression in the metastases (Wei et al., 2008).
  
  
Entity Irritable bowel disease (IBD)-related colon cancer
Note You et al. (2007) found that DVL1 was uniformly expressed in the affected tissues of IBD patients and sporadic colon cancer patients, even though no DVL1 expression was seen in the normal tissues of the same patients. Remarkably, DVL2 and DVL3 were expressed in all normal mucosa samples tested, and were expressed in sporadic colon cancer but were not expressed in colon cancers arising in patients with IBD (You et al., 2007).
  

To be noted

Animal model. Mice lacking Dvl1 are viable, fertile, and structurally normal; however, they exhibit abnormal social behavior and sensorimotor gating (Lijam et al., 1997). Mutant mice lacking both DVL-1 and DVL-2 have revealed that DVL proteins are required during neural fold closure and cardiac development, but not during early axial patterning (Hamblet et al., 2002; Lijam et al., 1997). Phenotypes of double DVL-1 and DVL-2 mutants display the skeletal defects, organ of corti defects, conotruncal defects, and craniorachishisis; and phenotypes of double DVL-1 and DVL-3 mutants display lethality between E13.5 and E15.5 (Etheridge et al., 2008).
Pharmaceutical target. In Wnt/beta-catenin signaling, Wnt ligands bind to the co-receptors of both LRP5/LRP6 and Frizzled (Fz), a 7-membrane domain protein, and activate the phosphoprotein DVL (Wallingford and Habas, 2005). The activated DVL protein relays the Wnt signals to the downstream components. Although the role of DVLs in Wnt signaling is not completely understood, the protein-protein interaction between the membrane-bound Fz receptor and the DVL PDZ domain in the cytoplasm plays a role in transducing the Wnt signals downstream (Umbhauer et al., 2000; Wong et al., 2003; Bilic et al., 2007). In Xenopus, peptides bound to the DVL PDZ domain attenuate Wnt-induced signaling at the DVL level (Wong et al., 2003). In addition, in several cancer models, peptides and small molecules bound to the DVL PDZ domain inhibit the Wnt signaling induced by Wnt ligands (Wang et al., 2008; Shan et al., 2005; Zhang et al., 2009; Shan and Zheng, 2009; Grandy et al. 2009; Lee et al., 2009a; Lee et al., 2009b). Interestingly, sulindac, a non-steroidal anti-inflammatory drug with chemoprotective effects for several cancer types, interacts with DVL in this fashion (Lee et al., 2009b). Thus, developing inhibitors of the DVL PDZ domain is very attractive because these inhibitors could be used as tools to dissect molecular mechanisms and as potential pharmaceutical agents (Wang et al., 2008).

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PMID 12883684
 
Distinct PAR-1 proteins function in different branches of Wnt signaling during vertebrate development.
Ossipova O, Dhawan S, Sokol S, Green JB.
Dev Cell. 2005 Jun;8(6):829-41.
PMID 15935773
 
Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation.
Pan W, Choi SC, Wang H, Qin Y, Volpicelli-Daley L, Swan L, Lucast L, Khoo C, Zhang X, Li L, Abrams CS, Sokol SY, Wu D.
Science. 2008 Sep 5;321(5894):1350-3.
PMID 18772438
 
Subcellular localization and signaling properties of dishevelled in developing vertebrate embryos.
Park TJ, Gray RS, Sato A, Habas R, Wallingford JB.
Curr Biol. 2005 Jun 7;15(11):1039-44.
PMID 15936275
 
A mutational analysis of dishevelled in Drosophila defines novel domains in the dishevelled protein as well as novel suppressing alleles of axin.
Penton A, Wodarz A, Nusse R.
Genetics. 2002 Jun;161(2):747-62.
PMID 12072470
 
Casein kinase I transduces Wnt signals.
Peters JM, McKay RM, McKay JP, Graff JM.
Nature. 1999 Sep 23;401(6751):345-50.
PMID 10517632
 
cDNA characterization and chromosomal mapping of two human homologues of the Drosophila dishevelled polarity gene.
Pizzuti A, Amati F, Calabrese G, Mari A, Colosimo A, Silani V, Giardino L, Ratti A, Penso D, Calza L, Palka G, Scarlato G, Novelli G, Dallapiccola B.
Hum Mol Genet. 1996 Jul;5(7):953-8.
PMID 8817329
 
Wnt signaling pathway in invasive ductal carcinoma of the breast: relationship between beta-catenin, dishevelled and cyclin D1 expression.
Prasad CP, Gupta SD, Rath G, Ralhan R.
Oncology. 2007;73(1-2):112-7. Epub 2008 Mar 13.
PMID 18337623
 
Casein kinase iepsilon in the wnt pathway: regulation of beta-catenin function.
Sakanaka C, Leong P, Xu L, Harrison SD, Williams LT.
Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12548-52.
PMID 10535959
 
Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation.
Schlange T, Matsuda Y, Lienhard S, Huber A, Hynes NE.
Breast Cancer Res. 2007;9(5):R63.
PMID 17897439
 
Purified Wnt-5a increases differentiation of midbrain dopaminergic cells and dishevelled phosphorylation.
Schulte G, Bryja V, Rawal N, Castelo-Branco G, Sousa KM, Arenas E.
J Neurochem. 2005 Mar;92(6):1550-3.
PMID 15748172
 
Dynamic recruitment of axin by Dishevelled protein assemblies.
Schwarz-Romond T, Metcalfe C, Bienz M.
J Cell Sci. 2007b Jul 15;120(Pt 14):2402-12.
PMID 17606995
 
Human dishevelled genes constitute a DHR-containing multigene family.
Semenov MV, Snyder M.
Genomics. 1997 Jun 1;42(2):302-10.
PMID 9192851
 
Vangl2 promotes Wnt/planar cell polarity-like signaling by antagonizing Dvl1-mediated feedback inhibition in growth cone guidance.
Shafer B, Onishi K, Lo C, Colakoglu G, Zou Y.
Dev Cell. 2011 Feb 15;20(2):177-91.
PMID 21316586
 
Identification of a specific inhibitor of the dishevelled PDZ domain.
Shan J, Shi DL, Wang J, Zheng J.
Biochemistry. 2005 Nov 29;44(47):15495-503.
PMID 16300398
 
Optimizing Dvl PDZ domain inhibitor by exploring chemical space.
Shan J, Zheng JJ.
J Comput Aided Mol Des. 2009 Jan;23(1):37-47. Epub 2008 Sep 9.
PMID 18780146
 
Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization.
Simons M, Gault WJ, Gotthardt D, Rohatgi R, Klein TJ, Shao Y, Lee HJ, Wu AL, Fang Y, Satlin LM, Dow JT, Chen J, Zheng J, Boutros M, Mlodzik M.
Nat Cell Biol. 2009 Mar;11(3):286-94. Epub 2009 Feb 22.
PMID 19234454
 
Interaction of axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription.
Smalley MJ, Sara E, Paterson H, Naylor S, Cook D, Jayatilake H, Fryer LG, Hutchinson L, Fry MJ, Dale TC.
EMBO J. 1999 May 17;18(10):2823-35.
PMID 10329628
 
Planar polarity is positively regulated by casein kinase Iepsilon in Drosophila.
Strutt H, Price MA, Strutt D.
Curr Biol. 2006 Jul 11;16(13):1329-36.
PMID 16824921
 
PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling.
Sun TQ, Lu B, Feng JJ, Reinhard C, Jan YN, Fantl WJ, Williams LT.
Nat Cell Biol. 2001 Jul;3(7):628-36.
PMID 11433294
 
Association of Dishevelled with Eph tyrosine kinase receptor and ephrin mediates cell repulsion.
Tanaka M, Kamo T, Ota S, Sugimura H.
EMBO J. 2003 Feb 17;22(4):847-58.
PMID 12574121
 
Colocalization and redistribution of dishevelled and actin during Wnt-induced mesenchymal morphogenesis.
Torres MA, Nelson WJ.
J Cell Biol. 2000 Jun 26;149(7):1433-42.
PMID 10871283
 
The C-terminal cytoplasmic Lys-thr-X-X-X-Trp motif in frizzled receptors mediates Wnt/beta-catenin signalling.
Umbhauer M, Djiane A, Goisset C, Penzo-Mendez A, Riou JF, Boucaut JC, Shi DL.
EMBO J. 2000 Sep 15;19(18):4944-54.
PMID 10990458
 
The developmental biology of Dishevelled: an enigmatic protein governing cell fate and cell polarity.
Wallingford JB, Habas R.
Development. 2005 Oct;132(20):4421-36. (REVIEW)
PMID 16192308
 
Therapeutic use of PDZ protein-protein interaction antagonism.
Wang NX, Lee HJ, Zheng JJ.
Drug News Perspect. 2008 Apr;21(3):137-41. (REVIEW)
PMID 18560611
 
Dishevelled family proteins are expressed in non-small cell lung cancer and function differentially on tumor progression.
Wei Q, Zhao Y, Yang ZQ, Dong QZ, Dong XJ, Han Y, Zhao C, Wang EH.
Lung Cancer. 2008 Nov;62(2):181-92. Epub 2008 Aug 9.
PMID 18692936
 
Runnin' with the Dvl: proteins that associate with Dsh/Dvl and their significance to Wnt signal transduction.
Wharton KA Jr.
Dev Biol. 2003 Jan 1;253(1):1-17. (REVIEW)
PMID 12490194
 
Casein kinase 2 associates with and phosphorylates dishevelled.
Willert K, Brink M, Wodarz A, Varmus H, Nusse R.
EMBO J. 1997 Jun 2;16(11):3089-96.
PMID 9214626
 
Negative regulation of Wnt signaling mediated by CK1-phosphorylated Dishevelled via Ror2.
Witte F, Bernatik O, Kirchner K, Masek J, Mahl A, Krejci P, Mundlos S, Schambony A, Bryja V, Stricker S.
FASEB J. 2010 Jul;24(7):2417-26. Epub 2010 Mar 9.
PMID 20215527
 
Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled.
Wong HC, Bourdelas A, Krauss A, Lee HJ, Shao Y, Wu D, Mlodzik M, Shi DL, Zheng J.
Mol Cell. 2003 Nov;12(5):1251-60.
PMID 14636582
 
Structural basis of the recognition of the dishevelled DEP domain in the Wnt signaling pathway.
Wong HC, Mao J, Nguyen JT, Srinivas S, Zhang W, Liu B, Li L, Wu D, Zheng J.
Nat Struct Biol. 2000 Dec;7(12):1178-84.
PMID 11101902
 
The dishevelled protein is modified by wingless signaling in Drosophila.
Yanagawa S, van Leeuwen F, Wodarz A, Klingensmith J, Nusse R.
Genes Dev. 1995 May 1;9(9):1087-97.
PMID 7744250
 
Expression of Wnt pathway components frizzled and disheveled in colon cancer arising in patients with inflammatory bowel disease.
You XJ, Bryant PJ, Jurnak F, Holcombe RF.
Oncol Rep. 2007 Sep;18(3):691-4.
PMID 17671721
 
Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions.
Zeng X, Huang H, Tamai K, Zhang X, Harada Y, Yokota C, Almeida K, Wang J, Doble B, Woodgett J, Wynshaw-Boris A, Hsieh JC, He X.
Development. 2008 Jan;135(2):367-75. Epub 2007 Dec 12.
PMID 18077588
 
Dapper 1 antagonizes Wnt signaling by promoting dishevelled degradation.
Zhang L, Gao X, Wen J, Ning Y, Chen YG.
J Biol Chem. 2006 Mar 31;281(13):8607-12. Epub 2006 Jan 30.
PMID 16446366
 
Dishevelled promotes axon differentiation by regulating atypical protein kinase C.
Zhang X, Zhu J, Yang GY, Wang QJ, Qian L, Chen YM, Chen F, Tao Y, Hu HS, Wang T, Luo ZG.
Nat Cell Biol. 2007 Jul;9(7):743-54. Epub 2007 Jun 10.
PMID 17558396
 
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Citation

This paper should be referenced as such :
Lee, HJ ; Zheng, JJ
DVL1 (dishevelled, dsh homolog 1 (Drosophila))
Atlas Genet Cytogenet Oncol Haematol. 2011;15(12):998-1004.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/DVL1ID463ch1p36.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ]
  t(1;9)(p13;p12) PAX5/HIPK1
t(1;17)(p36;q21) WNT3 or NSF/PRDM16


External links

Nomenclature
HGNC (Hugo)DVL1   3084
Cards
AtlasDVL1ID463ch1p36
Entrez_Gene (NCBI)DVL1  1855  dishevelled segment polarity protein 1
AliasesDRS2; DVL; DVL1L1; DVL1P1
GeneCards (Weizmann)DVL1
Ensembl hg19 (Hinxton)ENSG00000107404 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000107404 [Gene_View]  chr1:1335278-1349112 [Contig_View]  DVL1 [Vega]
ICGC DataPortalENSG00000107404
TCGA cBioPortalDVL1
AceView (NCBI)DVL1
Genatlas (Paris)DVL1
WikiGenes1855
SOURCE (Princeton)DVL1
Genetics Home Reference (NIH)DVL1
Genomic and cartography
GoldenPath hg38 (UCSC)DVL1  -     chr1:1335278-1349112 -  1p36.33   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)DVL1  -     1p36.33   [Description]    (hg19-Feb_2009)
EnsemblDVL1 - 1p36.33 [CytoView hg19]  DVL1 - 1p36.33 [CytoView hg38]
Mapping of homologs : NCBIDVL1 [Mapview hg19]  DVL1 [Mapview hg38]
OMIM180700   601365   616331   
Gene and transcription
Genbank (Entrez)AB209210 AF006011 AK093189 AK095867 AK293286
RefSeq transcript (Entrez)NM_001330311 NM_004421 NM_181870 NM_182779
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)DVL1
Cluster EST : UnigeneHs.731450 [ NCBI ]
CGAP (NCI)Hs.731450
Alternative Splicing GalleryENSG00000107404
Gene ExpressionDVL1 [ NCBI-GEO ]   DVL1 [ EBI - ARRAY_EXPRESS ]   DVL1 [ SEEK ]   DVL1 [ MEM ]
Gene Expression Viewer (FireBrowse)DVL1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1855
GTEX Portal (Tissue expression)DVL1
Protein : pattern, domain, 3D structure
UniProt/SwissProtO14640   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO14640  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO14640
Splice isoforms : SwissVarO14640
PhosPhoSitePlusO14640
Domaine pattern : Prosite (Expaxy)DEP (PS50186)    DIX (PS50841)    PDZ (PS50106)   
Domains : Interpro (EBI)DEP_dom    Dishevelled_C-dom    Dishevelled_fam    Dishevelled_protein_dom    DIX    Dsh/Dvl-rel    DVL-1    PDZ    Ubiquitin-rel_dom    WHTH_DNA-bd_dom   
Domain families : Pfam (Sanger)DEP (PF00610)    Dishevelled (PF02377)    DIX (PF00778)    Dsh_C (PF12316)    PDZ (PF00595)   
Domain families : Pfam (NCBI)pfam00610    pfam02377    pfam00778    pfam12316    pfam00595   
Domain families : Smart (EMBL)DAX (SM00021)  DEP (SM00049)  PDZ (SM00228)  
Conserved Domain (NCBI)DVL1
DMDM Disease mutations1855
Blocks (Seattle)DVL1
SuperfamilyO14640
Human Protein AtlasENSG00000107404
Peptide AtlasO14640
HPRD03220
IPIIPI00023100   IPI00643229   IPI00008404   IPI01015347   IPI00335110   IPI00556615   
Protein Interaction databases
DIP (DOE-UCLA)O14640
IntAct (EBI)O14640
FunCoupENSG00000107404
BioGRIDDVL1
STRING (EMBL)DVL1
ZODIACDVL1
Ontologies - Pathways
QuickGOO14640
Ontology : AmiGOregulation of neurotransmitter levels  positive regulation of protein phosphorylation  molecular_function  frizzled binding  frizzled binding  protein binding  cytosol  cytosol  microtubule  transcription from RNA polymerase II promoter  negative regulation of protein kinase activity  neurotransmitter secretion  axon guidance  heart development  neuromuscular junction development  beta-catenin binding  positive regulation of neuron projection development  postsynaptic density  lateral plasma membrane  enzyme binding  protein kinase binding  neural tube development  convergent extension involved in neural plate elongation  clathrin-coated vesicle  positive regulation of Wnt signaling pathway  axon  growth cone  cytoplasmic microtubule organization  cytoplasmic vesicle  cytoplasmic vesicle  negative regulation of protein binding  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  protein localization to nucleus  social behavior  protein localization to microtubule  intracellular signal transduction  identical protein binding  neuron projection  neuronal cell body  receptor clustering  dendritic spine  synapse  positive regulation of transcription, DNA-templated  Rac GTPase binding  collateral sprouting  axon extension  dendrite morphogenesis  synapse organization  protein stabilization  canonical Wnt signaling pathway  canonical Wnt signaling pathway  canonical Wnt signaling pathway  Wnt signaling pathway, planar cell polarity pathway  Wnt signaling pathway, planar cell polarity pathway  prepulse inhibition  dendritic spine morphogenesis  skeletal muscle acetylcholine-gated channel clustering  negative regulation of canonical Wnt signaling pathway  cochlea morphogenesis  planar cell polarity pathway involved in neural tube closure  positive regulation of canonical Wnt signaling pathway  presynapse  presynapse assembly  regulation of cellular protein localization  beta-catenin destruction complex disassembly  positive regulation of protein localization to presynapse  Wnt signalosome  positive regulation of excitatory postsynaptic potential  
Ontology : EGO-EBIregulation of neurotransmitter levels  positive regulation of protein phosphorylation  molecular_function  frizzled binding  frizzled binding  protein binding  cytosol  cytosol  microtubule  transcription from RNA polymerase II promoter  negative regulation of protein kinase activity  neurotransmitter secretion  axon guidance  heart development  neuromuscular junction development  beta-catenin binding  positive regulation of neuron projection development  postsynaptic density  lateral plasma membrane  enzyme binding  protein kinase binding  neural tube development  convergent extension involved in neural plate elongation  clathrin-coated vesicle  positive regulation of Wnt signaling pathway  axon  growth cone  cytoplasmic microtubule organization  cytoplasmic vesicle  cytoplasmic vesicle  negative regulation of protein binding  positive regulation of proteasomal ubiquitin-dependent protein catabolic process  protein localization to nucleus  social behavior  protein localization to microtubule  intracellular signal transduction  identical protein binding  neuron projection  neuronal cell body  receptor clustering  dendritic spine  synapse  positive regulation of transcription, DNA-templated  Rac GTPase binding  collateral sprouting  axon extension  dendrite morphogenesis  synapse organization  protein stabilization  canonical Wnt signaling pathway  canonical Wnt signaling pathway  canonical Wnt signaling pathway  Wnt signaling pathway, planar cell polarity pathway  Wnt signaling pathway, planar cell polarity pathway  prepulse inhibition  dendritic spine morphogenesis  skeletal muscle acetylcholine-gated channel clustering  negative regulation of canonical Wnt signaling pathway  cochlea morphogenesis  planar cell polarity pathway involved in neural tube closure  positive regulation of canonical Wnt signaling pathway  presynapse  presynapse assembly  regulation of cellular protein localization  beta-catenin destruction complex disassembly  positive regulation of protein localization to presynapse  Wnt signalosome  positive regulation of excitatory postsynaptic potential  
Pathways : BIOCARTA [Genes]   
Pathways : KEGGWnt signaling pathway    Notch signaling pathway    Hippo signaling pathway    Melanogenesis    HTLV-I infection    Pathways in cancer    Basal cell carcinoma   
REACTOMEO14640 [protein]
REACTOME PathwaysR-HSA-5663220 [pathway]   
NDEx NetworkDVL1
Atlas of Cancer Signalling NetworkDVL1
Wikipedia pathwaysDVL1
Orthology - Evolution
OrthoDB1855
GeneTree (enSembl)ENSG00000107404
Phylogenetic Trees/Animal Genes : TreeFamDVL1
HOVERGENO14640
HOGENOMO14640
Homologs : HomoloGeneDVL1
Homology/Alignments : Family Browser (UCSC)DVL1
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerDVL1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)DVL1
dbVarDVL1
ClinVarDVL1
1000_GenomesDVL1 
Exome Variant ServerDVL1
ExAC (Exome Aggregation Consortium)DVL1 (select the gene name)
Genetic variants : HAPMAP1855
Genomic Variants (DGV)DVL1 [DGVbeta]
DECIPHERDVL1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisDVL1 
Mutations
ICGC Data PortalDVL1 
TCGA Data PortalDVL1 
Broad Tumor PortalDVL1
OASIS PortalDVL1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICDVL1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDDVL1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch DVL1
DgiDB (Drug Gene Interaction Database)DVL1
DoCM (Curated mutations)DVL1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)DVL1 (select a term)
intoGenDVL1
NCG5 (London)DVL1
Cancer3DDVL1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM180700    601365    616331   
Orphanet2781   
MedgenDVL1
Genetic Testing Registry DVL1
NextProtO14640 [Medical]
TSGene1855
GENETestsDVL1
Target ValidationDVL1
Huge Navigator DVL1 [HugePedia]
snp3D : Map Gene to Disease1855
BioCentury BCIQDVL1
ClinGenDVL1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1855
Chemical/Pharm GKB GenePA27540
Clinical trialDVL1
Miscellaneous
canSAR (ICR)DVL1 (select the gene name)
Probes
Litterature
PubMed104 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineDVL1
EVEXDVL1
GoPubMedDVL1
iHOPDVL1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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