P51142 (DVL2_XENLA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Xenopus laevis (African clawed frog)

Taxonomic identifier

8355 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Amphibia › Batrachia › Anura › Mesobatrachia › Pipoidea › Pipidae › Xenopodinae › Xenopus › Xenopus

Protein attributes

Sequence length	736 AA.
Sequence status	Complete.
Protein existence	Evidence 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 projection › cilium. 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 process	Cilium biogenesis/degradation Gastrulation Wnt signaling pathway
Cellular component	Cell membrane Cell projection Cilium Cytoplasm Cytoplasmic vesicle Membrane Nucleus
Molecular function	Developmental protein
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	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 receptor signaling pathway Inferred from genetic interaction Ref.6. Source: BHF-UCL cilium assembly Inferred from mutant phenotype Ref.22. 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 microtubule basal body organization Inferred from mutant phenotype Ref.22. Source: UniProtKB 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 component	cell cortex Inferred from direct assay. Source: MGI cell surface Inferred from direct assay Ref.22. Source: UniProtKB ciliary rootlet Inferred from direct assay Ref.22. Source: UniProtKB cytoplasmic membrane-bounded vesicle Inferred from direct assay Ref.5. 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 function	ephrin receptor binding Inferred from direct assay Ref.14. Source: UniProtKB signal transducer activity Inferred from electronic annotation. Source: InterPro syndecan binding Inferred from physical interaction Ref.20. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 736

736

Segment polarity protein dishevelled homolog DVL-2

PRO_0000145748

Regions

Domain

1 – 82

82

DIX

Domain

254 – 326

73

PDZ

Domain

428 – 502

75

DEP

Compositional bias

99 – 113

15

Poly-Pro

Compositional bias

222 – 227

6

Poly-Arg

Compositional bias

680 – 687

8

Poly-Pro

Experimental info

Mutagenesis

272 – 275

4

QSNE → AANA: No effect on interaction with dact1-B/dpr. Ref.23

Mutagenesis

317

1

N → T: Abolishes interaction with dact1-B/dpr. Ref.23

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

736

Helix Strand Turn

Details...

Beta strand

252 – 257

6

Turn

259 – 261

3

Beta strand

267 – 272

6

Beta strand

280 – 286

7

Helix

291 – 295

5

Beta strand

303 – 307

5

Helix

317 – 328

12

Beta strand

330 – 332

3

Beta strand

334 – 339

6

Sequences

	Sequence		Length	Mass (Da)
	P51142 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: AF6C9A1662DD7CEB	FASTA	736	79,787
	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

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: 7600981] [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: 7588081] [Abstract]
[3]	"Analysis of Dishevelled signalling pathways during Xenopus development." Sokol S.Y. Curr. Biol. 6:1456-1467(1996) [PubMed: 8939601] [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: 9076682] [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: 10427095] [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: 10906785] [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: 10698942] [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: 10688669] [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: 10811222] [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: 11493574] [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: 12421719] [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: 11941372] [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: 12699625] [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: 12574121] [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: 15548584] [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: 15936275] [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: 16026968] [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: 15677333] [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: 16362052] [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: 16604063] [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: 18539122] [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: 18552847] [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: 11970895] [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.

PIR

I51691.

RefSeq

NP_001084096.1. NM_001090627.1.

UniGene

Xl.7670.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1L6O	X-ray	2.20	A/B/C	252-340	[»]
2F0A	X-ray	1.80	A/B/C/D	252-340	[»]
3FY5	X-ray	2.40	A/B	254-343	[»]

ProteinModelPortal

P51142.

SMR

P51142. Positions 252-340, 412-502.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-100832.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

399301.

KEGG

xla:399301.

Organism-specific databases

CTD

1856.

Xenbase

XB-GENE-1017467. dvl2.

Phylogenomic databases

HOVERGEN

HBG005542.

Family and domain databases

InterPro

IPR000591. DEP_dom.
IPR008339. Dishevelled.
IPR008341. Dishevelled_2.
IPR024580. Dishevelled_C-dom.
IPR003351. Dishevelled_protein_dom.
IPR001158. DIX.
IPR015506. Dsh.
IPR001478. PDZ/DHR/GLGF.
IPR011991. WHTH_trsnscrt_rep_DNA-bd.
[Graphical view]

Gene3D

G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.

KO

K02353.

PANTHER

PTHR10878. Dsh. 1 hit.

Pfam

PF00610. DEP. 1 hit.
PF02377. Dishevelled. 1 hit.
PF00778. DIX. 1 hit.
PF12316. Dsh_C. 1 hit.
PF00595. PDZ. 1 hit.
[Graphical view]

PRINTS

PR01760. DISHEVELLED.
PR01762. DISHEVELLED2.

SMART

SM00021. DAX. 1 hit.
SM00049. DEP. 1 hit.
SM00228. PDZ. 1 hit.
[Graphical view]

SUPFAM

SSF50156. PDZ. 1 hit.

PROSITE

PS50186. DEP. 1 hit.
PS50841. DIX. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

DVL2_XENLA

Accession

Primary (citable) accession number: P51142

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program