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O14641 (DVL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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 By similarity. Ref.13

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 By similarity. Interacts with DACT1 and FAM105B/otulin. Ref.5 Ref.6 Ref.11 Ref.12

Subcellular location

Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasmcytosol By similarity. Cytoplasmic vesicle By similarity. Note: Localizes at the cell membrane upon interaction with frizzled family members and promotes their internalization. Localizes to cytoplasmic puncta By similarity. Ref.1

Domain

The DIX domain mediates homooligomerization By similarity.

Post-translational modification

Phosphorylated by CSNK1D. Ref.1 Ref.9

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
   Coding sequence diversityPolymorphism
   Molecular functionDevelopmental protein
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from genetic interaction PubMed 16446366. Source: MGI

Wnt signaling pathway, planar cell polarity pathway

Inferred from direct assay PubMed 12805222. Source: BHF-UCL

canonical Wnt signaling pathway

Inferred from direct assay PubMed 17593335. Source: BHF-UCL

canonical Wnt signaling pathway involved in regulation of cell proliferation

Inferred from direct assay PubMed 18787224. Source: BHF-UCL

cell migration in hindbrain

Inferred from Biological aspect of Ancestor. Source: RefGenome

cellular protein localization

Inferred from electronic annotation. Source: Ensembl

cochlea morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

convergent extension

Inferred from Biological aspect of Ancestor. Source: RefGenome

convergent extension involved in neural plate elongation

Inferred from electronic annotation. Source: Ensembl

heart development

Inferred from sequence or structural similarity. Source: BHF-UCL

heart morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

hippo signaling

Traceable author statement. Source: Reactome

neural tube closure

Inferred from sequence or structural similarity. Source: BHF-UCL

non-canonical Wnt signaling pathway

Inferred from mutant phenotype PubMed 19137009. Source: BHF-UCL

outflow tract morphogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

planar cell polarity pathway involved in neural tube closure

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of JUN kinase activity

Inferred from direct assay PubMed 17593335. Source: BHF-UCL

positive regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from mutant phenotype PubMed 20137080. Source: BHF-UCL

positive regulation of protein tyrosine kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 17593335. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12805222PubMed 17593335. Source: BHF-UCL

segment specification

Inferred from sequence or structural similarity. Source: BHF-UCL

transcription from RNA polymerase II promoter

Inferred from direct assay Ref.5. Source: UniProtKB

   Cellular_componentapical part of cell

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell cortex

Inferred from Biological aspect of Ancestor. Source: RefGenome

clathrin-coated endocytic vesicle

Traceable author statement. Source: Reactome

clathrin-coated vesicle

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasm

Inferred from direct assay Ref.1. Source: BHF-UCL

cytoplasmic vesicle

Inferred from direct assay PubMed 23209302. Source: MGI

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionfrizzled binding

Inferred from physical interaction PubMed 19388021. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 16189514. Source: IntAct

protein binding

Inferred from physical interaction Ref.5PubMed 19465938Ref.11Ref.12. Source: UniProtKB

signal transducer activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 736736Segment polarity protein dishevelled homolog DVL-2
PRO_0000145746

Regions

Domain11 – 9383DIX
Domain267 – 33973PDZ
Domain433 – 50775DEP
Compositional bias7 – 126Poly-Gly
Compositional bias235 – 2406Poly-Arg
Compositional bias686 – 6949Poly-Pro

Amino acid modifications

Modified residue2111Phosphoserine Ref.7 Ref.8

Natural variations

Natural variant2821I → T Found in a renal cell carcinoma case; somatic mutation. Ref.15
VAR_064708

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
O14641 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 4BAD95B6C3FE531B

FASTA73678,948
        10         20         30         40         50         60 
MAGSSTGGGG VGETKVIYHL DEEETPYLVK IPVPAERITL GDFKSVLQRP AGAKYFFKSM 

        70         80         90        100        110        120 
DQDFGVVKEE ISDDNARLPC FNGRVVSWLV SSDNPQPEMA PPVHEPRAEL APPAPPLPPL 

       130        140        150        160        170        180 
PPERTSGIGD SRPPSFHPNV SSSHENLEPE TETESVVSLR RERPRRRDSS EHGAGGHRTG 

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

       250        260        270        280        290        300 
KQRPPRLERT 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 SHSAALTGTF PAYPGSSSMS TITSGSSLPD GCEGRGLSVH 

       430        440        450        460        470        480 
TDMASVTKAM 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 ESEPSSRGGS LRRGGEASGT SDGGPPPSRG STGGAPNLRA 

       670        680        690        700        710        720 
HPGLHPYGPP PGMALPYNPM MVVMMPPPPP PVPPAVQPPG APPVRDLGSV PPELTASRQS 

       730 
FHMAMGNPSE FFVDVM 

« Hide

References

« Hide 'large scale' references
[1]"Human dishevelled genes constitute a DHR-containing multigene family."
Semenov M.V., Snyder M.
Genomics 42:302-310(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, PHOSPHORYLATION.
[2]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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].
Tissue: Colon.
[5]"beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity through interaction with phosphorylated dishevelled proteins."
Chen W., Hu L.A., Semenov M.V., Yanagawa S., Kikuchi A., Lefkowitz R.J., Miller W.E.
Proc. Natl. Acad. Sci. U.S.A. 98:14889-14894(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB1.
[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]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth."
Greer Y.E., Rubin J.S.
J. Cell Biol. 192:993-1004(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY CSNK1D/CK1.
[10]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Identification of novel rare mutations of DACT1 in human neural tube defects."
Shi Y., Ding Y., Lei Y.P., Yang X.Y., Xie G.M., Wen J., Cai C.Q., Li H., Chen Y., Zhang T., Wu B.L., Jin L., Chen Y.G., Wang H.Y.
Hum. Mutat. 33:1450-1455(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DACT1.
[12]"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.
[13]"Inhibition of Wnt signaling by Dishevelled PDZ peptides."
Zhang Y., Appleton B.A., Wiesmann C., Lau T., Costa M., Hannoush R.N., Sidhu S.S.
Nat. Chem. Biol. 5:217-219(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF 264-353, FUNCTION.
[14]"Crystal structure of the PDZ domains of human dishevelled 2 (homologous to Drosophila dsh)."
Structural genomics consortium (SGC)
Submitted (FEB-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 261-354.
[15]"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. expand/collapse author list , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.
Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-282.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF006012 mRNA. Translation: AAB65243.1.
BT009822 mRNA. Translation: AAP88824.1.
CH471108 Genomic DNA. Translation: EAW90244.1.
CH471108 Genomic DNA. Translation: EAW90245.1.
BC014844 mRNA. Translation: AAH14844.1.
CCDSCCDS11091.1.
RefSeqNP_004413.1. NM_004422.2.
UniGeneHs.118640.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2REYX-ray1.55A261-355[»]
3CBXX-ray1.70A/B264-354[»]
3CBYX-ray1.50A/B264-354[»]
3CBZX-ray1.38A264-354[»]
3CC0X-ray1.75A/B/C264-354[»]
ProteinModelPortalO14641.
SMRO14641. Positions 13-90, 263-353, 422-582.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108189. 63 interactions.
DIPDIP-34433N.
IntActO14641. 83 interactions.
MINTMINT-1435227.
STRING9606.ENSP00000005340.

Chemistry

ChEMBLCHEMBL1255125.

PTM databases

PhosphoSiteO14641.

Proteomic databases

MaxQBO14641.
PaxDbO14641.
PRIDEO14641.

Protocols and materials databases

DNASU1856.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000005340; ENSP00000005340; ENSG00000004975.
GeneID1856.
KEGGhsa:1856.
UCSCuc002gez.1. human.

Organism-specific databases

CTD1856.
GeneCardsGC17M007128.
HGNCHGNC:3086. DVL2.
HPACAB009312.
HPA022914.
MIM602151. gene.
neXtProtNX_O14641.
PharmGKBPA27542.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG322275.
HOGENOMHOG000017084.
HOVERGENHBG005542.
InParanoidO14641.
KOK02353.
OMAFHLAMGN.
OrthoDBEOG7BP82N.
PhylomeDBO14641.
TreeFamTF318198.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkO14641.

Gene expression databases

ArrayExpressO14641.
BgeeO14641.
CleanExHS_DVL2.
GenevestigatorO14641.

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

ChiTaRSDVL2. human.
EvolutionaryTraceO14641.
GeneWikiDVL2.
GenomeRNAi1856.
NextBio7605.
PROO14641.
SOURCESearch...

Entry information

Entry nameDVL2_HUMAN
AccessionPrimary (citable) accession number: O14641
Secondary accession number(s): D3DTN3, Q53XM0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM