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Q60838 (DVL2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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
Gene names
Name:Dvl2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

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

General annotation (Comments)

Function

Participates in 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. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Ref.8 Ref.9 Ref.11

Subunit structure

Interacts through its PDZ domain with the C-terminal regions of VANGL1 and VANGL2. Interacts with Rac. Interacts with ARRB1; the interaction is enhanced by phosphorylation of DVL1 By similarity. Can form large oligomers (via DIX domain). Interacts (via DIX domain) with DIXDC1 (via DIX domain). Interacts (via DEP domain) with AP2M1 and the AP-2 complex. Interacts with FAM105B/otulin. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Subcellular location

Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmcytosol. Cytoplasmic vesicle. Note: Localizes at the cell membrane upon interaction with frizzled family members and promotes their internalization. Localizes to cytoplasmic puncta. Ref.8 Ref.9 Ref.11

Tissue specificity

Ubiquitous.

Domain

The DIX domain mediates homooligomerization. Ref.9

Post-translational modification

Phosphorylated by CSNK1D By similarity.

Sequence similarities

Belongs to the DSH family.

Contains 1 DEP domain.

Contains 1 DIX domain.

Contains 1 PDZ (DHR) domain.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCell membrane
Cytoplasm
Cytoplasmic vesicle
Membrane
   Molecular functionDevelopmental protein
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Non-traceable author statement PubMed 8856345. Source: BHF-UCL

Wnt signaling pathway, planar cell polarity pathway

Inferred from genetic interaction PubMed 16116426. Source: MGI

canonical Wnt signaling pathway

Inferred from direct assay PubMed 18606138. Source: MGI

canonical Wnt signaling pathway involved in regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

cell migration in hindbrain

Inferred from Biological aspect of Ancestor. Source: RefGenome

cellular protein localization

Inferred from direct assay PubMed 17606995. Source: MGI

cochlea morphogenesis

Inferred from genetic interaction PubMed 16116426PubMed 19008950. Source: MGI

convergent extension involved in neural plate elongation

Inferred from mutant phenotype PubMed 16571627. Source: MGI

convergent extension involved in organogenesis

Inferred from genetic interaction PubMed 16116426. Source: MGI

heart development

Inferred from mutant phenotype PubMed 12421720PubMed 12464179. Source: MGI

heart morphogenesis

Inferred from genetic interaction PubMed 19008950. Source: MGI

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

neural tube closure

Inferred from mutant phenotype PubMed 12421720. Source: MGI

outflow tract morphogenesis

Inferred from mutant phenotype PubMed 12464179. Source: BHF-UCL

planar cell polarity pathway involved in neural tube closure

Inferred from mutant phenotype PubMed 16571627. Source: MGI

positive regulation of JUN kinase activity

Inferred from direct assay PubMed 10829020. Source: BHF-UCL

positive regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype Ref.9. Source: UniProtKB

positive regulation of protein tyrosine kinase activity

Inferred from genetic interaction PubMed 19920076. Source: MGI

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of JNK cascade

Inferred from Biological aspect of Ancestor. Source: RefGenome

segment specification

Inferred from mutant phenotype PubMed 12421720. Source: MGI

segmentation

Inferred from genetic interaction Ref.1. Source: BHF-UCL

transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentapical part of cell

Inferred from direct assay PubMed 19300477. Source: MGI

cell cortex

Inferred from sequence orthology PubMed 10330403. Source: MGI

clathrin-coated vesicle

Inferred from direct assay PubMed 17005174. Source: MGI

cytoplasm

Inferred from direct assay PubMed 19465938. Source: UniProtKB

cytoplasmic vesicle

Inferred from sequence orthology PubMed 23209302. Source: MGI

cytoskeleton

Non-traceable author statement PubMed 8856345. Source: BHF-UCL

cytosol

Inferred from direct assay Ref.9. Source: UniProtKB

nucleus

Inferred from mutant phenotype PubMed 19465938. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 20534871. Source: UniProtKB

   Molecular_functionfrizzled binding

Inferred from physical interaction PubMed 20802536. Source: UniProtKB

identical protein binding

Inferred from physical interaction Ref.9. Source: IntAct

protein domain specific binding

Inferred from physical interaction PubMed 15579909. Source: MGI

protein self-association

Inferred from direct assay Ref.9. Source: UniProtKB

signal transducer activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-641940,EBI-641940
CSNK1DP487302EBI-641940,EBI-751621From a different organism.
CSNK1EP496743EBI-641940,EBI-749343From a different organism.
Dact1Q8R4A33EBI-641940,EBI-3870250
DIXDC1Q155Q34EBI-641940,EBI-1104700From a different organism.
Dvl3Q610623EBI-641940,EBI-1538450
PLK1P5335012EBI-641940,EBI-476768From a different organism.
Vangl1Q80Z964EBI-641940,EBI-1750708
Vangl2Q91ZD44EBI-641940,EBI-1750744

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 736736Segment polarity protein dishevelled homolog DVL-2
PRO_0000145747

Regions

Domain11 – 9383DIX
Domain267 – 33973PDZ
Domain433 – 50775DEP
Compositional bias7 – 126Poly-Gly
Compositional bias112 – 12211Poly-Pro
Compositional bias235 – 2406Poly-Arg
Compositional bias686 – 6916Poly-Pro

Amino acid modifications

Modified residue2111Phosphoserine By similarity

Experimental info

Mutagenesis151K → A: Reduces oligomerization. Reduces activation of Wnt signaling. Ref.9
Mutagenesis171I → A: Reduces oligomerization. Abolishes interaction with DIXDC1. Reduces activation of Wnt signaling. Ref.9
Mutagenesis271Y → D: Loss of oligomerization. Abolishes interaction with DIXDC1. Abolishes activation of Wnt signaling. Ref.9
Mutagenesis561F → H: Reduces oligomerization. Strongly reduced activation of Wnt signaling. Ref.9
Mutagenesis611D → A: Reduces oligomerization. Reduces activation of Wnt signaling. Ref.9
Mutagenesis631D → A: Reduces oligomerization. Reduces activation of Wnt signaling. Ref.9
Mutagenesis641F → A: Reduces oligomerization. Reduces activation of Wnt signaling.
Mutagenesis651G → D: Loss of oligomerization. Abolishes activation of Wnt signaling. Ref.9
Mutagenesis661V → D: Reduces oligomerization. Reduces activation of Wnt signaling. Ref.9
Mutagenesis681K → A: Loss of oligomerization. Strongly reduced activation of Wnt signaling. Ref.9
Mutagenesis841R → A: Strongly reduced interaction with DIXDC1.
Sequence conflict3561D → G in AAC52827. Ref.1

Secondary structure

............... 736
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q60838 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 928A527143BBBBB0

FASTA73678,861
        10         20         30         40         50         60 
MAGSSAGGGG VGETKVIYHL DEEETPYLVK IPVPAERITL GDFKSVLQRP AGAKYFFKSM 

        70         80         90        100        110        120 
DQDFGVVKEE ISDDNARLPC FNGRVVSWLV SSDTPQPEVA PPAHESRTEL VPPPPPLPPL 

       130        140        150        160        170        180 
PPERTSGIGD SRPPSFHPNV SSSHENLEPE TETESVVSLR RDRPRRRDSS EHGAGGHRPG 

       190        200        210        220        230        240 
GPSRLERHLA GYESSSTLMT SELESTSLGD SDEDDTMSRF SSSTEQSSAS RLLKRHRRRR 

       250        260        270        280        290        300 
KQRPPRMERT SSFSSVTDST MSLNIITVTL NMEKYNFLGI SIVGQSNERG DGGIYIGSIM 

       310        320        330        340        350        360 
KGGAVAADGR IEPGDMLLQV NDMNFENMSN DDAVRVLRDI VHKPGPIVLT VAKCWDPSPQ 

       370        380        390        400        410        420 
AYFTLPRNEP IQPIDPAAWV SHSAALTGAF PAYPGSSSMS TITSGSSLPD GCEGRGLSVH 

       430        440        450        460        470        480 
MDMASVTKAM AAPESGLEVR DRMWLKITIP NAFLGSDVVD WLYHHVEGFP ERREARKYAS 

       490        500        510        520        530        540 
GLLKAGLIRH TVNKITFSEQ CYYVFGDLSG GCESYLVNLS LNDNDGSSGA SDQDTLAPLP 

       550        560        570        580        590        600 
GATPWPLLPT FSYQYPAPHP YSPQPPPYHE LSSYTYGGGS ASSQHSEGSR SSGSTRSDGG 

       610        620        630        640        650        660 
AGRTGRPEER APESKSGSGS ESELSSRGGS LRRGGEPGGT GDGGPPPSRG STGAPPNLRA 

       670        680        690        700        710        720 
LPGLHPYGAP SGMALPYNPM MVVMMPPPPP PVSTAVQPPG APPVRDLGSV PPELTASRQS 

       730 
FHMAMGNPSE FFVDVM 

« Hide

References

« Hide 'large scale' references
[1]"Conservation of dishevelled structure and function between flies and mice: isolation and characterization of Dvl2."
Klingensmith J., Yang Y., Axelrod J.D., Beier D.R., Perrimon N., Sussman D.J.
Mech. Dev. 58:15-26(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
Tissue: Brain.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Amnion and Kidney.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
[6]"The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms."
Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C.
J. Biol. Chem. 279:39366-39373(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DIXDC1 AND RAC.
[7]"Independent mutations in mouse Vangl2 that cause neural tube defects in looptail mice impair interaction with members of the Dishevelled family."
Torban E., Wang H.-J., Groulx N., Gros P.
J. Biol. Chem. 279:52703-52713(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH VANGL1 AND VANGL2.
[8]"Association of Dishevelled with the clathrin AP-2 adaptor is required for Frizzled endocytosis and planar cell polarity signaling."
Yu A., Rual J.F., Tamai K., Harada Y., Vidal M., He X., Kirchhausen T.
Dev. Cell 12:129-141(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH THE AP-2 COMPLEX.
[9]"Molecular basis of Wnt activation via the DIX-domain protein Ccd1."
Liu Y.T., Dan Q.J., Wang J., Feng Y., Chen L., Liang J., Li Q., Lin S.C., Wang Z.X., Wu J.W.
J. Biol. Chem. 286:8597-8608(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DIXDC1, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-15; ILE-17; TYR-27; PHE-56; ASP-61; ASP-63; GLY-65; VAL-66 AND LYS-68, DOMAIN.
[10]"The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis."
Rivkin E., Almeida S.M., Ceccarelli D.F., Juang Y.C., Maclean T.A., Srikumar T., Huang H., Dunham W.H., Fukumura R., Xie G., Gondo Y., Raught B., Gingras A.C., Sicheri F., Cordes S.P.
Nature 498:318-324(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FAM105B.
[11]"Structural analysis of the interaction between Dishevelled2 and clathrin AP-2 adaptor, a critical step in noncanonical Wnt signaling."
Yu A., Xing Y., Harrison S.C., Kirchhausen T.
Structure 18:1311-1320(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 417-510 IN COMPLEX WITH AP2M1, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U24160 mRNA. Translation: AAC52827.1.
AK146822 mRNA. Translation: BAE27460.1.
AK159895 mRNA. Translation: BAE35461.1.
AK168376 mRNA. Translation: BAE40307.1.
AL596185 Genomic DNA. Translation: CAI35165.1.
CH466596 Genomic DNA. Translation: EDL12520.1.
BC053050 mRNA. Translation: AAH53050.1.
RefSeqNP_031914.3. NM_007888.3.
UniGeneMm.5114.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3ML6X-ray3.50A/B/C/D/E/F417-510[»]
ProteinModelPortalQ60838.
SMRQ60838. Positions 13-90, 263-353, 421-582.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid199343. 18 interactions.
DIPDIP-29399N.
IntActQ60838. 23 interactions.
MINTMINT-1591968.

PTM databases

PhosphoSiteQ60838.

Proteomic databases

PaxDbQ60838.
PRIDEQ60838.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000019362; ENSMUSP00000019362; ENSMUSG00000020888.
ENSMUST00000102575; ENSMUSP00000099635; ENSMUSG00000020888.
GeneID13543.
KEGGmmu:13543.
UCSCuc007jtm.1. mouse.

Organism-specific databases

CTD1856.
MGIMGI:106613. Dvl2.

Phylogenomic databases

eggNOGNOG322275.
GeneTreeENSGT00390000013552.
HOGENOMHOG000017084.
HOVERGENHBG005542.
InParanoidQ7TN14.
KOK02353.
OMAPNVSSSR.
OrthoDBEOG7BP82N.
TreeFamTF318198.

Gene expression databases

ArrayExpressQ60838.
BgeeQ60838.
CleanExMM_DVL2.
GenevestigatorQ60838.

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.
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.
PROSITEPS50186. DEP. 1 hit.
PS50841. DIX. 1 hit.
PS50106. PDZ. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDVL2. mouse.
NextBio284146.
PROQ60838.
SOURCESearch...

Entry information

Entry nameDVL2_MOUSE
AccessionPrimary (citable) accession number: Q60838
Secondary accession number(s): Q7TN14
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 124 of the entry and version 2 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot