Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O14640 (DVL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Segment polarity protein dishevelled homolog DVL-1

Short name=Dishevelled-1
Alternative name(s):
DSH homolog 1
Gene names
Name:DVL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length695 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. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Required for LEF1 activation upon WNT1 and WNT3A signaling. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ).

Subunit structure

Interacts with CXXC4. Interacts (via PDZ domain) with NXN By similarity. Interacts with BRD7 and INVS. Interacts through its PDZ domain with the C-terminal regions of VANGL1, VANGL2 and CCDC88C/DAPLE. Interacts with ARRB1; the interaction is enhanced by phosphorylation of DVL1. Interacts with CYLD By similarity. Interacts (via PDZ domain) with RYK. Self-associates (via DIX domain) and forms higher homooligomers. Interacts (via PDZ domain) with DACT1 and FZD7, where DACT1 and FZD7 compete for the same binding site By similarity. Interacts (via DEP domain) with MUSK; the interaction is direct and mediates the formation a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering By similarity. Interacts (via PDZ domain) with TMEM88. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7

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 By similarity.

Domain

The DIX domain promotes homooligomerization By similarity.

The DEP domain mediates interaction with the cell membrane By similarity.

Post-translational modification

Ubiquitinated; undergoes both 'Lys-48'-linked ubiquitination, leading to its subsequent degradation by the ubiquitin-proteasome pathway, and 'Lys-63'-linked ubiquitination. The interaction with INVS is required for ubiquitination. Deubiquitinated by CYLD, which acts on 'Lys-63'-linked ubiquitin chains 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
   Coding sequence diversityAlternative splicing
   Molecular functionDevelopmental protein
   PTMUbl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway, planar cell polarity pathway

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

axon extension

Inferred from Biological aspect of Ancestor. Source: RefGenome

axon guidance

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from direct assay PubMed 11113207PubMed 14747478PubMed 17593335. Source: BHF-UCL

cochlea morphogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

collateral sprouting

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

cytoplasmic microtubule organization

Inferred from electronic annotation. Source: Ensembl

dendrite morphogenesis

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

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

negative regulation of protein binding

Inferred from direct assay PubMed 19643732. Source: BHF-UCL

negative regulation of protein kinase activity

Inferred from direct assay PubMed 10330181. Source: BHF-UCL

neural tube development

Inferred from expression pattern PubMed 8817329. Source: BHF-UCL

neuromuscular junction development

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

neurotransmitter secretion

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 Wnt signaling pathway

Inferred from direct assay PubMed 11113207. Source: BHF-UCL

positive regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron projection development

Inferred from electronic annotation. Source: Ensembl

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype PubMed 20177058. Source: BHF-UCL

positive regulation of transcription, DNA-templated

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

prepulse inhibition

Inferred from electronic annotation. Source: Ensembl

protein localization to microtubule

Inferred from electronic annotation. Source: Ensembl

protein localization to nucleus

Inferred from mutant phenotype PubMed 10330181. Source: BHF-UCL

receptor clustering

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

regulation of neurotransmitter levels

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

skeletal muscle acetylcholine-gated channel clustering

Inferred from Biological aspect of Ancestor. Source: RefGenome

social behavior

Inferred from electronic annotation. Source: Ensembl

synapse organization

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

transcription from RNA polymerase II promoter

Inferred from direct assay Ref.3. Source: UniProtKB

   Cellular_componentaxon

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell cortex

Inferred from Biological aspect of Ancestor. Source: RefGenome

clathrin-coated vesicle

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasmic membrane-bounded vesicle

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

cytoplasmic vesicle

Inferred from direct assay PubMed 11113207. Source: BHF-UCL

cytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

dendrite

Inferred from Biological aspect of Ancestor. Source: RefGenome

growth cone

Inferred from Biological aspect of Ancestor. Source: RefGenome

microtubule

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuronal cell body

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

synapse

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

   Molecular_functionRac GTPase binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

enzyme binding

Inferred from physical interaction Ref.5. Source: UniProtKB

frizzled binding

Inferred from physical interaction PubMed 19388021. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 10330181. Source: IntAct

protein kinase binding

Inferred from physical interaction PubMed 19643732. Source: BHF-UCL

signal transducer activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14640-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O14640-2)

The sequence of this isoform differs from the canonical sequence as follows:
     378-403: GTSPCSSAVTRTSSSSLTSSVPGAPQ → E

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 695695Segment polarity protein dishevelled homolog DVL-1
PRO_0000145742

Regions

Domain1 – 8585DIX
Domain251 – 32373PDZ
Domain425 – 49975DEP
Compositional bias221 – 2244Poly-Arg

Natural variations

Alternative sequence378 – 40326GTSPC…PGAPQ → E in isoform 2.
VSP_024460

Experimental info

Sequence conflict21A → G in AAB65242. Ref.1
Sequence conflict1571A → P in AAB65242. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 17, 2007. Version 2.
Checksum: B009BDBCC57BD562

FASTA69575,187
        10         20         30         40         50         60 
MAETKIIYHM DEEETPYLVK LPVAPERVTL ADFKNVLSNR PVHAYKFFFK SMDQDFGVVK 

        70         80         90        100        110        120 
EEIFDDNAKL PCFNGRVVSW LVLAEGAHSD AGSQGTDSHT DLPPPLERTG GIGDSRPPSF 

       130        140        150        160        170        180 
HPNVASSRDG MDNETGTESM VSHRRERARR RNREEAARTN GHPRGDRRRD VGLPPDSAST 

       190        200        210        220        230        240 
ALSSELESSS FVDSDEDGST SRLSSSTEQS TSSRLIRKHK RRRRKQRLRQ ADRASSFSSI 

       250        260        270        280        290        300 
TDSTMSLNIV TVTLNMERHH FLGISIVGQS NDRGDGGIYI GSIMKGGAVA ADGRIEPGDM 

       310        320        330        340        350        360 
LLQVNDVNFE NMSNDDAVRV LREIVSQTGP ISLTVAKCWD PTPRSYFTVP RADPVRPIDP 

       370        380        390        400        410        420 
AAWLSHTAAL TGALPRYGTS PCSSAVTRTS SSSLTSSVPG APQLEEAPLT VKSDMSAVVR 

       430        440        450        460        470        480 
VMQLPDSGLE IRDRMWLKIT IANAVIGADV VDWLYTHVEG FKERREARKY ASSLLKHGFL 

       490        500        510        520        530        540 
RHTVNKITFS EQCYYVFGDL CSNLATLNLN SGSSGTSDQD TLAPLPHPAA PWPLGQGYPY 

       550        560        570        580        590        600 
QYPGPPPCFP PAYQDPGFSY GSGSTGSQQS EGSKSSGSTR SSRRAPGREK ERRAAGAGGS 

       610        620        630        640        650        660 
GSESDHTAPS GVGSSWRERP AGQLSRGSSP RSQASATAPG LPPPHPTTKA YTVVGGPPGG 

       670        680        690 
PPVRELAAVP PELTGSRQSF QKAMGNPCEF FVDIM 

« Hide

Isoform 2 [UniParc].

Checksum: CF31534E784A80A2
Show »

FASTA67072,881

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] (ISOFORM 2).
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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.
[4]"Identification and characterization of a novel Dvl-binding protein that suppresses Wnt signalling pathway."
Oshita A., Kishida S., Kobayashi H., Michiue T., Asahara T., Asashima M., Kikuchi A.
Genes Cells 8:1005-1017(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CCDC88C.
[5]"Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth."
Lu W., Yamamoto V., Ortega B., Baltimore D.
Cell 119:97-108(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RYK.
[6]"Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways."
Simons M., Gloy J., Ganner A., Bullerkotte A., Bashkurov M., Kroenig C., Schermer B., Benzing T., Cabello O.A., Jenny A., Mlodzik M., Polok B., Driever W., Obara T., Walz G.
Nat. Genet. 37:537-543(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH INVS.
[7]"Identification of transmembrane protein 88 (TMEM88) as a dishevelled-binding protein."
Lee H.J., Finkelstein D., Li X., Wu D., Shi D.L., Zheng J.J.
J. Biol. Chem. 285:41549-41556(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TMEM88.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF006011 mRNA. Translation: AAB65242.1.
AL139287 Genomic DNA. Translation: CAI23185.1.
AL139287 Genomic DNA. Translation: CAI23187.1.
RefSeqNP_004412.2. NM_004421.2.
XP_005244788.1. XM_005244731.1.
UniGeneHs.731450.

3D structure databases

ProteinModelPortalO14640.
SMRO14640. Positions 3-84, 250-499.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108188. 31 interactions.
DIPDIP-40773N.
IntActO14640. 20 interactions.
MINTMINT-100885.
STRING9606.ENSP00000368169.

Chemistry

ChEMBLCHEMBL6027.

PTM databases

PhosphoSiteO14640.

Proteomic databases

PRIDEO14640.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000378888; ENSP00000368166; ENSG00000107404. [O14640-1]
ENST00000378891; ENSP00000368169; ENSG00000107404. [O14640-2]
GeneID1855.
KEGGhsa:1855.
UCSCuc001aer.4. human. [O14640-2]
uc002quu.3. human. [O14640-1]

Organism-specific databases

CTD1855.
GeneCardsGC01M001262.
HGNCHGNC:3084. DVL1.
HPACAB011538.
MIM601365. gene.
neXtProtNX_O14640.
PharmGKBPA27540.
GenAtlasSearch...

Phylogenomic databases

HOGENOMHOG000017084.
HOVERGENHBG005542.
InParanoidO14640.
KOK02353.
OMASESDHTA.
OrthoDBEOG7BP82N.
PhylomeDBO14640.
TreeFamTF318198.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkO14640.

Gene expression databases

ArrayExpressO14640.
BgeeO14640.
CleanExHS_DVL1.
GenevestigatorO14640.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
2.30.42.10. 1 hit.
InterProIPR000591. DEP_dom.
IPR008340. Dishevelled_1.
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:SF5. PTHR10878:SF5. 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.
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

GeneWikiDVL1.
GenomeRNAi1855.
NextBio7599.
PROO14640.
SOURCESearch...

Entry information

Entry nameDVL1_HUMAN
AccessionPrimary (citable) accession number: O14640
Secondary accession number(s): Q5TA33, Q5TA35
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: April 17, 2007
Last modified: April 16, 2014
This is version 143 of the entry and version 2 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

MIM cross-references

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

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM