O14640 (DVL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Segment polarity protein dishevelled homolog DVL-1
Short name=Dishevelled-1

Alternative name(s):
DSH homolog 1

Gene names

Name:

DVL1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	695 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.3 Ref.4 Ref.5 Ref.6
Subcellular location	Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cytoplasm › cytosol 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 process	Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Cytoplasmic vesicle Membrane
Coding sequence diversity	Alternative splicing
Molecular function	Developmental protein
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon extension Inferred from Biological aspect of Ancestor. Source: RefGenome axon guidance Inferred from Biological aspect of Ancestor. Source: RefGenome canonical Wnt receptor 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: Compara cytoplasmic microtubule organization Inferred from electronic annotation. Source: Compara 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 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 receptor signaling pathway Inferred from direct assay PubMed 11113207. Source: BHF-UCL positive regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of neuron projection development Inferred from electronic annotation. Source: Compara positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype PubMed 20177058. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from direct assay PubMed 12805222PubMed 17593335. Source: BHF-UCL prepulse inhibition Inferred from electronic annotation. Source: Compara protein localization to microtubule Inferred from electronic annotation. Source: Compara protein localization to nucleus Inferred from mutant phenotype PubMed 10330181. Source: BHF-UCL skeletal muscle acetylcholine-gated channel clustering Inferred from Biological aspect of Ancestor. Source: RefGenome social behavior Inferred from electronic annotation. Source: Compara transcription from RNA polymerase II promoter Inferred from direct assay Ref.3. Source: UniProtKB
Cellular_component	axon 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 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_function	Rac GTPase binding Inferred from Biological aspect of Ancestor. Source: RefGenome signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
LRRK2	Q5S007	7	EBI-6504027,EBI-5323863

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 695	695	Segment polarity protein dishevelled homolog DVL-1		PRO_0000145742
Regions
	Domain	1 – 85	85	DIX
	Domain	251 – 323	73	PDZ
	Domain	425 – 499	75	DEP
	Compositional bias	221 – 224	4	Poly-Arg
Amino acid modifications
	Modified residue	559	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	378 – 403	26	GTSPC…PGAPQ → E in isoform 2.		VSP_024460
Experimental info
	Sequence conflict	2	1	A → G in AAB65242. Ref.1
	Sequence conflict	157	1	A → P in AAB65242. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 17, 2007. Version 2. Checksum: B009BDBCC57BD562	FASTA	695	75,187
	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
	Isoform 2 [UniParc]. Checksum: CF31534E784A80A2	FASTA	670	72,881
	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 TGALPRYELE EAPLTVKSDM SAVVRVMQLP DSGLEIRDRM WLKITIANAV 430 440 450 460 470 480 IGADVVDWLY THVEGFKERR EARKYASSLL KHGFLRHTVN KITFSEQCYY VFGDLCSNLA 490 500 510 520 530 540 TLNLNSGSSG TSDQDTLAPL PHPAAPWPLG QGYPYQYPGP PPCFPPAYQD PGFSYGSGST 550 560 570 580 590 600 GSQQSEGSKS SGSTRSSRRA PGREKERRAA GAGGSGSESD HTAPSGVGSS WRERPAGQLS 610 620 630 640 650 660 RGSSPRSQAS ATAPGLPPPH PTTKAYTVVG GPPGGPPVRE LAAVPPELTG SRQSFQKAMG 670 NPCEFFVDIM

References

	« Hide 'large scale' referencesShow '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. , 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.
+	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.
IPI	IPI00023100. IPI00643229.
RefSeq	NP_004412.2. NM_004421.2.
UniGene	Hs.741165.
3D structure databases
ProteinModelPortal	O14640.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-40773N.
IntAct	O14640. 5 interactions.
MINT	MINT-100885.
STRING	9606.ENSP00000368169.
PTM databases
PhosphoSite	O14640.
Proteomic databases
PRIDE	O14640.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000378888; ENSP00000368166; ENSG00000107404. ENST00000378891; ENSP00000368169; ENSG00000107404.
GeneID	1855.
KEGG	hsa:1855.
UCSC	uc001aer.4. human. uc002quu.3. human.
Organism-specific databases
CTD	1855.
GeneCards	GC01M001262.
HGNC	HGNC:3084. DVL1.
HPA	CAB011538.
MIM	601365. gene.
neXtProt	NX_O14640.
PharmGKB	PA27540.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HOG000017084.
HOVERGEN	HBG005542.
InParanoid	O14640.
KO	K02353.
OMA	PLHPLTK.
Enzyme and pathway databases
Pathway_Interaction_DB	wnt_canonical_pathway. Canonical Wnt signaling pathway. ps1pathway. Presenilin action in Notch and Wnt signaling.
Gene expression databases
ArrayExpress	O14640.
Bgee	O14640.
CleanEx	HS_DVL1.
Genevestigator	O14640.
GermOnline	ENSG00000107404. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR000591. 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]
PANTHER	PTHR10878. PTHR10878. 1 hit. PTHR10878:SF5. PTHR10878:SF5. 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.
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...
Other
ChEMBL	CHEMBL6027.
GenomeRNAi	1855.
NextBio	7599.
SOURCE	Search...

Entry information

Entry name

DVL1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.