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PDBsum entry 1l6o
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protein ligands Protein-protein interface(s) links
Gene regulation PDB id
1l6o

 

 

 

 

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Contents
Protein chains
95 a.a. *
Ligands
SER-LEU-LYS-LEU-
MET-THR-THR-VAL ×3
Waters ×25
* Residue conservation analysis
PDB id:
1l6o
Name: Gene regulation
Title: Xenopus dishevelled pdz domain
Structure: Segment polarity protein dishevelled homolog dvl-2. Chain: a, b, c. Synonym: dishevelled-2, dsh homolog 2, xdsh. Engineered: yes. Dapper 1. Chain: d, e, f. Synonym: dishevelled interacting antagonist, dpr1. Engineered: yes
Source: Xenopus laevis. African clawed frog. Organism_taxid: 8355. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: the peptide was chemically synthesized. The sequence is naturally found in xenopus laevis (african clawed frog).
Biol. unit: Hexamer (from PQS)
Resolution:
2.20Å     R-factor:   0.279     R-free:   0.323
Authors: B.N.R.Cheyette,J.S.Waxman,J.R.Miller,K.-I.Takemaru,L.C.Sheldahl, N.Khlebtsova,E.P.Fox,T.Earnest,R.T.Moon
Key ref:
B.N.Cheyette et al. (2002). Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation. Dev Cell, 2, 449-461. PubMed id: 11970895 DOI: 10.1016/S1534-5807(02)00140-5
Date:
11-Mar-02     Release date:   03-Jun-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P51142  (DVL2_XENLA) -  Segment polarity protein dishevelled homolog DVL-2 from Xenopus laevis
Seq:
Struc: 		 
Seq:
Struc: 		736 a.a.
95 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 

 
DOI no: 10.1016/S1534-5807(02)00140-5 Dev Cell 2:449-461 (2002)
PubMed id: 11970895  
 
 
Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation.
B.N.Cheyette, J.S.Waxman, J.R.Miller, K.Takemaru, L.C.Sheldahl, N.Khlebtsova, E.P.Fox, T.Earnest, R.T.Moon.
 
  ABSTRACT  
 
Dapper was isolated in a screen for proteins interacting with Dishevelled, a key factor in Wnt signaling. Dapper and Dishevelled colocalize intracellularly and form a complex with Axin, GSK-3, CKI, and beta-catenin. Overexpression of Dapper increases Axin and GSK-3 in this complex, resulting in decreased soluble beta-catenin and decreased activation of beta-catenin-responsive genes. Dapper also inhibits activation by Dishevelled of c-Jun N-terminal kinase (JNK), a component of beta-catenin-independent Frizzled signaling. Inhibition of Dapper activates both beta-catenin-responsive genes and an AP1-responsive promoter, demonstrating that Dapper is a general Dishevelled antagonist. Depletion of maternal Dapper RNA from Xenopus embryos results in loss of notochord and head structures, demonstrating that Dapper is required for normal vertebrate development.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Sequence(A) Schemata of Xenopus Dsh (XDsh) and Dpr (XDpr) showing conserved domains DIX, PDZ, and DEP, and leucine zipper (LZ) and PDZ binding (PDZ-B) domains, respectively. Gray in XDsh indicates yeast two-hybrid bait. Vertical arrows indicate the positions of XDsh mutations discussed in the text. The horizontal arrow indicates the 5′ extent of XDpr clone obtained from the screen.(B) Alignment of XDpr (X) with orthologs from mouse (M) and human (H). Black residues are identical; gray residues are conserved; horizontal arrow as in (A). 		Figure 7.
Figure 7. Dpr Expression(A–G) mRNA whole-mount in situ hybridizations.(A) Sense controls: gastrula (bottom) and tailbud (top).(B) Early gastrula (stage 10 vegetal view; top, dorsal; dl, dorsal lip).(C) Early neurula (stage 14 dorsal view; top, anterior; ant ne, anterior neurectoderm).(D) Early tailbud (stage 19 dorsal view; top, anterior).(E and F) Tailbud (stage 21; [E], anterior view; [F], lateral view; arrows, neural folds; ey, eye fields; tb, tailbud).(G) Tadpole (stage 41 lateral view; left, anterior).(H) Northern analysis adult MDpr1 expression: br, brain; hrt, heart; kd, kidney; lvr, liver; lng, lung; ml, muscle; skn, skin; si, small intestine; spn, spleen; stm, stomach; ts, testis; thy, thymus.
 
  The above figures are reprinted by permission from Cell Press: Dev Cell (2002, 2, 449-461) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19435464 E.N.McMurray, E.D.Rogers, and J.V.Schmidt (2010).
Imprinting analysis in the Acrodysplasia region of mouse chromosome 12.
  Biosci Rep, 30, 119-124.  
20509869 H.J.Lee, and J.J.Zheng (2010).
PDZ domains and their binding partners: structure, specificity, and modification.
  Cell Commun Signal, 8, 8.  
  21092292 L.Ma, Y.Wang, C.C.Malbon, and H.Y.Wang (2010).
Dishevelled-3 C-terminal His single amino acid repeats are obligate for Wnt5a activation of non-canonical signaling.
  J Mol Signal, 5, 19.  
20457807 M.Nishita, S.Itsukushima, A.Nomachi, M.Endo, Z.Wang, D.Inaba, S.Qiao, S.Takada, A.Kikuchi, and Y.Minami (2010).
Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating dishevelled polymerization.
  Mol Cell Biol, 30, 3610-3619.  
19073771 C.Lagathu, C.Christodoulides, S.Virtue, W.P.Cawthorn, C.Franzin, W.A.Kimber, E.D.Nora, M.Campbell, G.Medina-Gomez, B.N.Cheyette, A.J.Vidal-Puig, and J.K.Sethi (2009).
Dact1, a nutritionally regulated preadipocyte gene, controls adipogenesis by coordinating the Wnt/beta-catenin signaling network.
  Diabetes, 58, 609-619.  
19383605 D.Grandy, J.Shan, X.Zhang, S.Rao, S.Akunuru, H.Li, Y.Zhang, I.Alpatov, X.A.Zhang, R.A.Lang, D.L.Shi, and J.J.Zheng (2009).
Discovery and characterization of a small molecule inhibitor of the PDZ domain of dishevelled.
  J Biol Chem, 284, 16256-16263.  
19440376 E.Teran, A.D.Branscomb, and J.M.Seeling (2009).
Dpr Acts as a molecular switch, inhibiting Wnt signaling when unphosphorylated, but promoting Wnt signaling when phosphorylated by casein kinase Idelta/epsilon.
  PLoS ONE, 4, e5522.  
  19637179 H.J.Lee, N.X.Wang, D.L.Shi, and J.J.Zheng (2009).
Sulindac inhibits canonical Wnt signaling by blocking the PDZ domain of the protein Dishevelled.
  Angew Chem Int Ed Engl, 48, 6448-6452.
PDB code: 2kaw
19157887 H.J.Lee, N.X.Wang, Y.Shao, and J.J.Zheng (2009).
Identification of tripeptides recognized by the PDZ domain of Dishevelled.
  Bioorg Med Chem, 17, 1701-1708.  
18780146 J.Shan, and J.J.Zheng (2009).
Optimizing Dvl PDZ domain inhibitor by exploring chemical space.
  J Comput Aided Mol Des, 23, 37-47.  
19701191 R.Suriben, S.Kivimäe, D.A.Fisher, R.T.Moon, and B.N.Cheyette (2009).
Posterior malformations in Dact1 mutant mice arise through misregulated Vangl2 at the primitive streak.
  Nat Genet, 41, 977-985.  
19433865 S.Rashid, I.Pilecka, A.Torun, M.Olchowik, B.Bielinska, and M.Miaczynska (2009).
Endosomal Adaptor Proteins APPL1 and APPL2 Are Novel Activators of {beta}-Catenin/TCF-mediated Transcription.
  J Biol Chem, 284, 18115-18128.  
18953581 X.Chen, and Y.Deng (2009).
Simulations of a specific inhibitor of the dishevelled PDZ domain.
  J Mol Model, 15, 91-96.  
19050695 Y.G.Chen (2009).
Endocytic regulation of TGF-beta signaling.
  Cell Res, 19, 58-70.  
18031219 J.Miao, T.Ishikawa, Q.Shen, and T.Earnest (2008).
Extending X-ray crystallography to allow the imaging of noncrystalline materials, cells, and single protein complexes.
  Annu Rev Phys Chem, 59, 387-410.  
18256687 K.Tanegashima, H.Zhao, and I.B.Dawid (2008).
WGEF activates Rho in the Wnt-PCP pathway and controls convergent extension in Xenopus gastrulation.
  EMBO J, 27, 606-617.  
18028338 T.O.Hansen, R.Borup, T.Marstrand, J.F.Rehfeld, and F.C.Nielsen (2008).
Cholecystokinin-2 receptor mediated gene expression in neuronal PC12 cells.
  J Neurochem, 104, 1450-1465.  
18936100 X.Gao, J.Wen, L.Zhang, X.Li, Y.Ning, A.Meng, and Y.G.Chen (2008).
Dapper1 is a nucleocytoplasmic shuttling protein that negatively modulates wnt signaling in the nucleus.
  J Biol Chem, 283, 35679-35688.  
18538736 X.Jiang, J.Tan, J.Li, S.Kivimäe, X.Yang, L.Zhuang, P.L.Lee, M.T.Chan, L.W.Stanton, E.T.Liu, B.N.Cheyette, and Q.Yu (2008).
DACT3 is an epigenetic regulator of Wnt/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications.
  Cancer Cell, 13, 529-541.  
18691226 Y.Funato, T.Michiue, T.Terabayashi, A.Yukita, H.Danno, M.Asashima, and H.Miki (2008).
Nucleoredoxin regulates the Wnt/planar cell polarity pathway in Xenopus.
  Genes Cells, 13, 965-975.  
18981481 Y.Li, S.A.Rankin, D.Sinner, A.P.Kenny, P.A.Krieg, and A.M.Zorn (2008).
Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling.
  Genes Dev, 22, 3050-3063.  
17433285 J.D.Leonard, and C.A.Ettensohn (2007).
Analysis of dishevelled localization and function in the early sea urchin embryo.
  Dev Biol, 306, 50-65.  
17684012 L.Ma, and H.Y.Wang (2007).
Mitogen-activated protein kinase p38 regulates the Wnt/cyclic GMP/Ca2+ non-canonical pathway.
  J Biol Chem, 282, 28980-28990.  
17627283 R.H.Lee, H.Iioka, M.Ohashi, S.Iemura, T.Natsume, and N.Kinoshita (2007).
XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathway.
  EMBO J, 26, 3592-3606.  
16881060 D.A.Fisher, S.Kivimäe, J.Hoshino, R.Suriben, P.M.Martin, N.Baxter, and B.N.Cheyette (2006).
Three Dact gene family members are expressed during embryonic development and in the adult brains of mice.
  Dev Dyn, 235, 2620-2630.  
16446366 L.Zhang, X.Gao, J.Wen, Y.Ning, and Y.G.Chen (2006).
Dapper 1 antagonizes Wnt signaling by promoting dishevelled degradation.
  J Biol Chem, 281, 8607-8612.  
17002371 N.Basdevant, H.Weinstein, and M.Ceruso (2006).
Thermodynamic basis for promiscuity and selectivity in protein-protein interactions: PDZ domains, a case study.
  J Am Chem Soc, 128, 12766-12777.  
16278878 N.L.Hunter, H.Hikasa, S.M.Dymecki, and S.Y.Sokol (2006).
Vertebrate homologues of Frodo are dynamically expressed during embryonic development in tissues undergoing extensive morphogenetic movements.
  Dev Dyn, 235, 279-284.  
17013874 R.Suriben, D.A.Fisher, and B.N.Cheyette (2006).
Dact1 presomitic mesoderm expression oscillates in phase with Axin2 in the somitogenesis clock of mice.
  Dev Dyn, 235, 3177-3183.  
16219036 B.K.Brott, and S.Y.Sokol (2005).
Frodo proteins: modulators of Wnt signaling in vertebrate development.
  Differentiation, 73, 323-329.  
15720722 J.B.Weitzman (2005).
Dishevelled nuclear shuttling.
  J Biol, 4, 1.  
15677333 J.Liu, A.G.Bang, C.Kintner, A.P.Orth, S.K.Chanda, S.Ding, and P.G.Schultz (2005).
Identification of the Wnt signaling activator leucine-rich repeat in Flightless interaction protein 2 by a genome-wide functional analysis.
  Proc Natl Acad Sci U S A, 102, 1927-1932.  
16225669 J.Roffers-Agarwal, J.B.Xanthos, and J.R.Miller (2005).
Regulation of actin cytoskeleton architecture by Eps8 and Abi1.
  BMC Cell Biol, 6, 36.  
15765513 J.S.Waxman (2005).
Regulation of the early expression patterns of the zebrafish Dishevelled-interacting proteins Dapper1 and Dapper2.
  Dev Dyn, 233, 194-200.  
15580267 M.Wanzel, D.Kleine-Kohlbrecher, S.Herold, A.Hock, K.Berns, J.Park, B.Hemmings, and M.Eilers (2005).
Akt and 14-3-3eta regulate Miz1 to control cell-cycle arrest after DNA damage.
  Nat Cell Biol, 7, 30-41.  
15008826 A.Miyakoshi, N.Ueno, and N.Kinoshita (2004).
Rho guanine nucleotide exchange factor xNET1 implicated in gastrulation movements during Xenopus development.
  Differentiation, 72, 48-55.  
14966280 F.Cong, L.Schweizer, and H.Varmus (2004).
Casein kinase Iepsilon modulates the signaling specificities of dishevelled.
  Mol Cell Biol, 24, 2000-2011.  
15459392 L.Zhang, H.Zhou, Y.Su, Z.Sun, H.Zhang, L.Zhang, Y.Zhang, Y.Ning, Y.G.Chen, and A.Meng (2004).
Zebrafish Dpr2 inhibits mesoderm induction by promoting degradation of nodal receptors.
  Science, 306, 114-117.  
15188426 M.Gillhouse, M.Wagner Nyholm, H.Hikasa, S.Y.Sokol, and Y.Grinblat (2004).
Two Frodo/Dapper homologs are expressed in the developing brain and mesoderm of zebrafish.
  Dev Dyn, 230, 403-409.  
15625010 Y.G.Chen, and A.M.Meng (2004).
Negative regulation of TGF-beta signaling in development.
  Cell Res, 14, 441-449.  
14750955 A.Oshita, S.Kishida, H.Kobayashi, T.Michiue, T.Asahara, M.Asashima, and A.Kikuchi (2003).
Identification and characterization of a novel Dvl-binding protein that suppresses Wnt signalling pathway.
  Genes Cells, 8, 1005-1017.  
14636582 H.C.Wong, A.Bourdelas, A.Krauss, H.J.Lee, Y.Shao, D.Wu, M.Mlodzik, D.L.Shi, and J.Zheng (2003).
Direct binding of the PDZ domain of Dishevelled to a conserved internal sequence in the C-terminal region of Frizzled.
  Mol Cell, 12, 1251-1260.
PDB code: 1mc7
12573432 J.H.van Es, N.Barker, and H.Clevers (2003).
You Wnt some, you lose some: oncogenes in the Wnt signaling pathway.
  Curr Opin Genet Dev, 13, 28-33.  
12709432 Z.Xu, K.O.Lai, H.M.Zhou, S.C.Lin, and N.Y.Ip (2003).
Ephrin-B1 reverse signaling activates JNK through a novel mechanism that is independent of tyrosine phosphorylation.
  J Biol Chem, 278, 24767-24775.  
12127767 K.M.Cadigan (2002).
Wnt signaling--20 years and counting.
  Trends Genet, 18, 340-342.  
12183362 T.Schwarz-Romond, C.Asbrand, J.Bakkers, M.Kühl, H.J.Schaeffer, J.Huelsken, J.Behrens, M.Hammerschmidt, and W.Birchmeier (2002).
The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling.
  Genes Dev, 16, 2073-2084.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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