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P51142 (DVL2_XENLA) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Segment polarity protein dishevelled homolog DVL-2

Short name=Dishevelled-2
Alternative name(s):
DSH homolog 2
Xdsh
Gene names
Name:dvl2
Synonyms:dsh
OrganismXenopus laevis (African clawed frog)
Taxonomic identifier8355 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiAmphibiaBatrachiaAnuraPipoideaPipidaeXenopodinaeXenopusXenopus

Protein attributes

Sequence length736 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in at least 2 independent signaling cascades, controlling cell fate via canonical Wnt signaling and cell polarity via a planar cell polarity (PCP) cascade. Acts synergistically with dal/dapple-like to activate Wnt signaling, stabilizing ctnnb1/beta-catenin and leading to dorsal axis formation. Also prevents degradation of ctnnb1/beta-catenin by displacing gsk3 from a complex with ARP/Axin-related protein. Has an additional role in anterior-posterior (A/P) axis formation, specifying different neuroectodermal cell fates along the A/P axis in a dose-dependent manner by activating several early patterning genes. In the PCP pathway, required at the cell membrane for PCP-mediated neural and mesodermal convergent extension during gastrulation and subsequent neural tube closure, acting to activate jnk. Also involved in blastopore closure and archenteron elongation during early, but not late, gastrulation. Associates with ephrin receptors and ligands and acts as part of a downstream PCP pathway to mediate ephrin-mediated cell repulsion via activation of rhoa. Required for efnb1/ephrin-B1-driven movement of non-retinal progenitor cells into the retina during eye field formation. Patterns the hindbrain. Required for ciliogenesis. Controls the docking of basal bodies to the apical plasma membrane; mediates the activation, but not localization of rhoa at the apical surface of ciliated cells during basal body docking. Furthermore, required for the association of basal bodies with membrane-bound vesicles and the vesicle-trafficking protein exoc4/sec8, and this association is in turn required for basal body docking. Once basal bodies are docked, required for the planar polarization of basal bodies that underlies ciliary beating and the directional fluid flow across ciliated epithelia. Ref.1 Ref.3 Ref.4 Ref.5 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.22 Ref.23

Subunit structure

Can form homomultimers. Interacts with prickle1. Interacts (via PDZ domain) with ccdc88c/dal and dact1-B/dpr. Interacts (via DIX domain) with ARP/Axin-related protein and dact1-A/frodo. Interacts with sdc4, possibly via fz7. Interacts directly (via DEP domain) with efnb1/ephrin-B1 and indirectly with the phosphorylated ephrin receptors ephb1 and ephb2, via association with SH domain-containing adapters. May interact with lrrc6. Ref.7 Ref.8 Ref.12 Ref.13 Ref.14 Ref.17 Ref.19 Ref.20 Ref.21 Ref.23

Subcellular location

Cytoplasm. Cytoplasmic vesicle. Cell projectioncilium. Nucleus. Cell membrane; Peripheral membrane protein. Note: Phosphorylated and recruited from the cytoplasm to the cell membrane by frizzled proteins. Also relocated to the cell membrane by sdc4 and ephb1/ephrin-B1. Concentrated at cell membrane in both ciliated and non-ciliated cells. Enriched at the apical surface of ciliated cells. Localized to the cilium rootlet. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.16 Ref.19 Ref.20 Ref.22 Ref.23

Tissue specificity

Expressed equally in both animal-vegetal and dorsal-ventral directions of the early blastula. Becomes enriched on the dorsal side of the embryo after cortical rotation. Expressed along the anterior margin of eye field of neurulae (stage 16 embryos) and in the anterolateral crescent that borders the eye field. Continues to be expressed in the optic cup at stage 26. Expressed in the central nervous system throughout the early tailbud stage including the entire hindbrain. Ref.1 Ref.5 Ref.14 Ref.19

Developmental stage

Expressed maternally. Most abundant in eggs and expressed at a low level in blastulae, gastrulae, neurulae and tailbud embryonic stages. Ref.1

Domain

The C-terminal region containing the DEP domain is required for membrane accumulation and phosphorylation. Wnt signaling and axis induction requires the DIX domain. The C-terminus contributes to the localization at the cilia base. Ref.7 Ref.8 Ref.22

Post-translational modification

Phosphorylated. Phosphorylation is controlled by frizzled proteins, correlates with the onset of embryo dorsalizing events and is higher in the dorsal half of early cleavage embryos. Phosphorylated on tyrosine residues in response to association with efnb1/ephrin-B1. Ref.7 Ref.14

Sequence similarities

Belongs to the DSH family.

Contains 1 DEP domain.

Contains 1 DIX domain.

Contains 1 PDZ (DHR) domain.

Ontologies

Keywords
   Biological processCilium biogenesis/degradation
Gastrulation
Wnt signaling pathway
   Cellular componentCell membrane
Cell projection
Cilium
Cytoplasm
Cytoplasmic vesicle
Membrane
Nucleus
   Molecular functionDevelopmental protein
   PTMPhosphoprotein
   Technical term3D-structure
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from genetic interaction Ref.3. Source: UniProtKB

activation of Rho GTPase activity

Inferred from mutant phenotype Ref.22. Source: UniProtKB

anterior/posterior axis specification

Inferred from mutant phenotype Ref.4. Source: UniProtKB

canonical Wnt signaling pathway

Inferred from genetic interaction Ref.6. Source: BHF-UCL

ciliary basal body organization

Inferred from mutant phenotype Ref.22. Source: UniProtKB

cilium assembly

Inferred from mutant phenotype Ref.22. Source: UniProtKB

convergent extension

Inferred from mutant phenotype Ref.10Ref.11Ref.3. Source: UniProtKB

convergent extension involved in gastrulation

Inferred from mutant phenotype Ref.9. Source: UniProtKB

dorsal/ventral axis specification

Inferred from mutant phenotype Ref.1. Source: UniProtKB

ephrin receptor signaling pathway

Inferred from direct assay Ref.14Ref.19. Source: UniProtKB

establishment of planar polarity

Inferred from mutant phenotype Ref.22. Source: UniProtKB

establishment or maintenance of cell polarity

Inferred from mutant phenotype Ref.9. Source: UniProtKB

gastrulation with mouth forming second

Inferred from mutant phenotype Ref.15. Source: UniProtKB

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

neural tube closure

Inferred from mutant phenotype Ref.11. Source: UniProtKB

neurogenesis

Inferred from mutant phenotype Ref.1. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from genetic interaction Ref.6. Source: BHF-UCL

protein homooligomerization

Inferred from physical interaction Ref.7. Source: UniProtKB

protein stabilization

Inferred from mutant phenotype Ref.5. Source: UniProtKB

   Cellular_componentcell cortex

Inferred from direct assay PubMed 10330403. Source: MGI

cell surface

Inferred from direct assay Ref.22. Source: UniProtKB

ciliary rootlet

Inferred from direct assay Ref.22. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.9Ref.23Ref.19Ref.20. Source: UniProtKB

cytoplasmic membrane-bounded vesicle

Inferred from direct assay Ref.5. Source: UniProtKB

cytoplasmic vesicle

Inferred from direct assay Ref.5Ref.8Ref.7. Source: UniProtKB

nucleus

Inferred from direct assay Ref.23. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.7Ref.9Ref.23Ref.19Ref.20Ref.22. Source: UniProtKB

   Molecular_functionephrin receptor binding

Inferred from direct assay Ref.14. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.8PubMed 11780127Ref.23Ref.13. Source: UniProtKB

signal transducer activity

Inferred from electronic annotation. Source: InterPro

syndecan binding

Inferred from physical interaction Ref.20. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 736736Segment polarity protein dishevelled homolog DVL-2
PRO_0000145748

Regions

Domain1 – 8282DIX
Domain254 – 32673PDZ
Domain428 – 50275DEP
Compositional bias99 – 11315Poly-Pro
Compositional bias222 – 2276Poly-Arg
Compositional bias680 – 6878Poly-Pro

Experimental info

Mutagenesis272 – 2754QSNE → AANA: No effect on interaction with dact1-B/dpr. Ref.23
Mutagenesis3171N → T: Abolishes interaction with dact1-B/dpr. Ref.23

Secondary structure

.................. 736
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P51142 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: AF6C9A1662DD7CEB

FASTA73679,787
        10         20         30         40         50         60 
MAETKVIYHL DEEETPYLVK VPVPATDIRL RDFKAALGRG HAKYFFKAMD QDFGVVKEEI 

        70         80         90        100        110        120 
SDDNAKLPCF NDRVVSWLAS SEGSQPDSAP PAPATEVRPE PPPPVPPPIP PPPAERTSGI 

       130        140        150        160        170        180 
GDSRPPSFHP NVSGSTEQLD QDNESVISMR RDRVRRRESS EQAGVGRGVN GRTERHLSGY 

       190        200        210        220        230        240 
ESSSTLLTSE IETSICDSEE DDTMSRFSSS TEQSSASRLL KRHRRRRKQR PPRLERTSSF 

       250        260        270        280        290        300 
SSVTDSTMSL NIITVTLNME KYNFLGISIV GQSNERGDGG IYIGSIMKGG AVAADGRIEP 

       310        320        330        340        350        360 
GDMLLQVNDI NFENMSNDDA VRVLRDIVHK PGPIVLTVAK CWDPSPQGYF TLPRNEPIHP 

       370        380        390        400        410        420 
IDPAAWVSHS AALSGSFPVY PGSASMSSMT SSTSVTETEL SHALPPVSLF SLSVHTDLAS 

       430        440        450        460        470        480 
VVKVMASPES GLEVRDRMWL KITIPNAFLG SDVVDWLYHH VEGFQDRREA RKFASNLLKA 

       490        500        510        520        530        540 
GFIRHTVNKI TFSEQCYYIF GDLTGCENYM TNLSLNDNDG SSGASDQDTL APLPLPGASP 

       550        560        570        580        590        600 
WPLLPTFSYQ YQAPHPYSTQ PPAYHELSSY SYGMGSAGSQ HSEGSRSSGS NRSDGGRGMQ 

       610        620        630        640        650        660 
KDDRSGVAGV GGGDSKSGSG SESEYSTRSS IRRVGGGEAG PPSERSTSSR LPPHHPPSVH 

       670        680        690        700        710        720 
SYAAPGVPLS YNPMMLMMMP PPPLPPPGVC PPNSSVPPGA PPLVRDLASV PPELTATRQS 

       730 
FHMAMGNPSE FFVDVM 

« Hide

References

[1]"Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled."
Sokol S.Y., Klingensmith J., Perrimon N., Itoh K.
Development 121:1637-1647(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Tissue: Oocyte.
[2]Erratum
Sokol S.Y., Klingensmith J., Perrimon N., Itoh K.
Development 121:3487-3487(1995) [PubMed] [Europe PMC] [Abstract]
[3]"Analysis of Dishevelled signalling pathways during Xenopus development."
Sokol S.Y.
Curr. Biol. 6:1456-1467(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"Graded amounts of Xenopus dishevelled specify discrete anteroposterior cell fates in prospective ectoderm."
Itoh K., Sokol S.Y.
Mech. Dev. 61:113-125(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Establishment of the dorsal-ventral axis in Xenopus embryos coincides with the dorsal enrichment of dishevelled that is dependent on cortical rotation."
Miller J.R., Rowning B.A., Larabell C.A., Yang-Snyder J.A., Bates R.L., Moon R.T.
J. Cell Biol. 146:427-437(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]"Interaction of Frizzled 7 and Dishevelled in Xenopus."
Medina A., Steinbeisser H.
Dev. Dyn. 218:671-680(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis."
Rothbaecher U., Laurent M.N., Deardorff M.A., Klein P.S., Cho K.W.Y., Fraser S.E.
EMBO J. 19:1010-1022(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION, DOMAIN.
[8]"Interaction of dishevelled and Xenopus axin-related protein is required for wnt signal transduction."
Itoh K., Antipova A., Ratcliffe M.J., Sokol S.Y.
Mol. Cell. Biol. 20:2228-2238(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ARP, SUBCELLULAR LOCATION, DOMAIN.
[9]"Dishevelled controls cell polarity during Xenopus gastrulation."
Wallingford J.B., Rowning B.A., Vogeli K.M., Rothbaecher U., Fraser S.E., Harland R.M.
Nature 405:81-85(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]"Xenopus Dishevelled signaling regulates both neural and mesodermal convergent extension: parallel forces elongating the body axis."
Wallingford J.B., Harland R.M.
Development 128:2581-2592(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Neural tube closure requires Dishevelled-dependent convergent extension of the midline."
Wallingford J.B., Harland R.M.
Development 129:5815-5825(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Frodo interacts with Dishevelled to transduce Wnt signals."
Gloy J., Hikasa H., Sokol S.Y.
Nat. Cell Biol. 4:351-357(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DACT1-A.
[13]"The prickle-related gene in vertebrates is essential for gastrulation cell movements."
Takeuchi M., Nakabayashi J., Sakaguchi T., Yamamoto T.S., Takahashi H., Takeda H., Ueno N.
Curr. Biol. 13:674-679(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRICKLE1.
[14]"Association of Dishevelled with Eph tyrosine kinase receptor and ephrin mediates cell repulsion."
Tanaka M., Kamo T., Ota S., Sugimura H.
EMBO J. 22:847-858(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EFNB1; EPHB1 AND EPHB2, TISSUE SPECIFICITY, TYROSINE PHOSPHORYLATION.
[15]"Regional requirements for Dishevelled signaling during Xenopus gastrulation: separable effects on blastopore closure, mesendoderm internalization and archenteron formation."
Ewald A.J., Peyrot S.M., Tyszka J.M., Fraser S.E., Wallingford J.B.
Development 131:6195-6209(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Subcellular localization and signaling properties of dishevelled in developing vertebrate embryos."
Park T.J., Gray R.S., Sato A., Habas R., Wallingford J.B.
Curr. Biol. 15:1039-1044(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[17]"Novel Daple-like protein positively regulates both the Wnt/beta-catenin pathway and the Wnt/JNK pathway in Xenopus."
Kobayashi H., Michiue T., Yukita A., Danno H., Sakurai K., Fukui A., Kikuchi A., Asashima M.
Mech. Dev. 122:1138-1153(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CCDC88C.
[18]"Identification of the Wnt signaling activator leucine-rich repeat in Flightless interaction protein 2 by a genome-wide functional analysis."
Liu J., Bang A.G., Kintner C., Orth A.P., Chanda S.K., Ding S., Schultz P.G.
Proc. Natl. Acad. Sci. U.S.A. 102:1927-1932(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"Dishevelled mediates ephrinB1 signalling in the eye field through the planar cell polarity pathway."
Lee H.-S., Bong Y.-S., Moore K.B., Soria K., Moody S.A., Daar I.O.
Nat. Cell Biol. 8:55-63(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH EFNB1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[20]"Syndecan-4 regulates non-canonical Wnt signalling and is essential for convergent and extension movements in Xenopus embryos."
Munoz R., Moreno M., Oliva C., Orbenes C., Larrain J.
Nat. Cell Biol. 8:492-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SDC4, SUBCELLULAR LOCATION.
[21]"Cystic kidney gene seahorse regulates cilia-mediated processes and Wnt pathways."
Kishimoto N., Cao Y., Park A., Sun Z.
Dev. Cell 14:954-961(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LRRC6.
[22]"Dishevelled controls apical docking and planar polarization of basal bodies in ciliated epithelial cells."
Park T.J., Mitchell B.J., Abitua P.B., Kintner C., Wallingford J.B.
Nat. Genet. 40:871-879(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DOMAIN.
[23]"Dapper, a Dishevelled-associated antagonist of beta-catenin and JNK signaling, is required for notochord formation."
Cheyette B.N.R., Waxman J.S., Miller J.R., Takemaru K., Sheldahl L.C., Khlebtsova N., Fox E.P., Earnest T.N., Moon R.T.
Dev. Cell 2:449-461(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 252-340 IN COMPLEX WITH DACT1-B, FUNCTION, INTERACTION WITH DACT1-B, SUBCELLULAR LOCATION, MUTAGENESIS OF 272-GLN--GLU-275 AND ASN-317.
[24]"Conformational flexibility in the PDZ domain of Dishevelled induced by target binding."
Friedland N., Hung L.-W., Cheyette B.N.R., Miller J.R., Moon R.T., Earnest T.N.
Submitted (NOV-2005) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 252-340.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U31552 mRNA. Translation: AAB00688.1.
PIRI51691.
RefSeqNP_001084096.1. NM_001090627.1.
UniGeneXl.7670.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1L6OX-ray2.20A/B/C252-340[»]
2F0AX-ray1.80A/B/C/D252-340[»]
3FY5X-ray2.40A/B254-343[»]
ProteinModelPortalP51142.
SMRP51142. Positions 252-340, 412-502.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid100626. 2 interactions.
IntActP51142. 5 interactions.
MINTMINT-100832.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID399301.
KEGGxla:399301.

Organism-specific databases

CTD1856.
XenbaseXB-GENE-1017467. dvl2.

Phylogenomic databases

HOVERGENHBG005542.
KOK02353.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
2.30.42.10. 1 hit.
InterProIPR000591. DEP_dom.
IPR008341. Dishevelled_2.
IPR024580. Dishevelled_C-dom.
IPR008339. Dishevelled_fam.
IPR003351. Dishevelled_protein_dom.
IPR001158. DIX.
IPR015506. Dsh/Dvl-rel.
IPR001478. PDZ.
IPR029071. Ubiquitin-rel_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PANTHERPTHR10878. PTHR10878. 1 hit.
PTHR10878:SF8. PTHR10878:SF8. 1 hit.
PfamPF00610. DEP. 1 hit.
PF02377. Dishevelled. 1 hit.
PF00778. DIX. 1 hit.
PF12316. Dsh_C. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]
PRINTSPR01760. DISHEVELLED.
PR01762. DISHEVELLED2.
SMARTSM00021. DAX. 1 hit.
SM00049. DEP. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]
SUPFAMSSF50156. SSF50156. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEPS50186. DEP. 1 hit.
PS50841. DIX. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP51142.

Entry information

Entry nameDVL2_XENLA
AccessionPrimary (citable) accession number: P51142
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: June 11, 2014
This is version 112 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references