Q92997 (DVL3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Segment polarity protein dishevelled homolog DVL-3
Short name=Dishevelled-3

Alternative name(s):
DSH homolog 3

Gene names

Name:	DVL3
Synonyms:	KIAA0208

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	716 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May play a role in the signal transduction pathway mediated by multiple Wnt genes.
Subunit structure	Interacts (via the PDZ domain) with the C-terminal regions of VANGL1 and VANGL2 By similarity. Interacts (via the region containing both the PDZ and DEP domains) with LRRFIP2; the DIX domain may inhibit this interaction. Interacts with CYLD, CEP164 and DAB2. Ref.7 Ref.8 Ref.10 Ref.13
Subcellular location	Cytoplasm By similarity.
Post-translational modification	Ubiquitinated. Deubiquitinated by CYLD, which acts on 'Lys-63'-linked ubiquitin chains. Ref.10 Phosphorylated by CSNK1D. Ref.11 Ref.14
Sequence similarities	Belongs to the DSH family. Contains 1 DEP domain. Contains 1 DIX domain. Contains 1 PDZ (DHR) domain.
Sequence caution	The sequence BAA13199.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Wnt signaling pathway
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Developmental protein
PTM	Methylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	canonical Wnt receptor signaling pathway Inferred from direct assay PubMed 17593335. Source: BHF-UCL cochlea morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome convergent extension Inferred from Biological aspect of Ancestor. Source: RefGenome intracellular signal transduction Inferred from electronic annotation. Source: InterPro non-canonical Wnt receptor signaling pathway via JNK cascade Inferred from sequence or structural similarity. Source: BHF-UCL outflow tract septum morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome 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 mutant phenotype PubMed 19137009. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from direct assay PubMed 10644691Ref.7PubMed 17593335. Source: BHF-UCL response to drug Inferred from electronic annotation. Source: Compara
Cellular_component	cell cortex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	beta-catenin binding Inferred from direct assay PubMed 10644691. Source: BHF-UCL protein heterodimerization activity Inferred from direct assay PubMed 19137009. Source: BHF-UCL signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CEP164	Q9UPV0	5	EBI-739789,EBI-3937015
Dab2	P98078	2	EBI-739789,EBI-1391846	From a different organism.
LRRFIP2	Q9Y608	2	EBI-739789,EBI-1023718
LRRK2	Q5S007	4	EBI-739789,EBI-5323863
PRPF3	O43395	2	EBI-739789,EBI-744322

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 716	716	Segment polarity protein dishevelled homolog DVL-3		PRO_0000145749
Regions
	Domain	1 – 82	82	DIX
	Domain	249 – 321	73	PDZ
	Domain	422 – 496	75	DEP
Amino acid modifications
	Modified residue	27	1	Omega-N-methylarginine Ref.14
	Modified residue	48	1	Phosphoserine Ref.12
	Modified residue	192	1	Phosphoserine Ref.9 Ref.14
	Modified residue	212	1	Omega-N-methylarginine Ref.14
	Modified residue	342	1	Omega-N-methylarginine Ref.14
	Modified residue	346	1	Phosphothreonine Ref.14
	Modified residue	698	1	Dimethylated arginine; alternate Ref.14
	Modified residue	698	1	Omega-N-methylarginine; alternate Ref.14
	Modified residue	700	1	Phosphoserine Ref.14
Natural variations
	Natural variant	216	1	R → T in a breast cancer sample; somatic mutation. Ref.15		VAR_036116
	Natural variant	433	1	W → L. Ref.6 Corresponds to variant rs17853048 [ dbSNP | Ensembl ].		VAR_025519
Experimental info
	Sequence conflict	2	1	G → D in AAB47447. Ref.1
	Sequence conflict	76	1	S → Y in AAB84228. Ref.2
	Sequence conflict	102	1	P → S in AAB47447. Ref.1
	Sequence conflict	151	1	G → W in AAB47447. Ref.1
	Sequence conflict	182	1	S → R in AAB47447. Ref.1
	Sequence conflict	218	1	K → N in AAB47447. Ref.1
	Sequence conflict	222	1	R → W in AAB47447. Ref.1
	Sequence conflict	230	1	E → D in AAB47447. Ref.1
	Sequence conflict	233	1	S → C in AAB47447. Ref.1
	Sequence conflict	236	1	S → T in AAB47447. Ref.1
	Sequence conflict	239	1	T → S in AAB47447. Ref.1
	Sequence conflict	242	1	T → A in AAB47447. Ref.1
	Sequence conflict	303	1	N → K in AAB47447. Ref.1
	Sequence conflict	431	1	R → C in AAB47447. Ref.1
	Sequence conflict	450	1	W → C in AAB47447. Ref.1
	Sequence conflict	465	1	R → P in AAB47447. Ref.1
	Sequence conflict	472	1	L → V in AAB47447. Ref.1
	Sequence conflict	543	1	P → R in AAB65244. Ref.3
	Sequence conflict	553 – 554	2	FP → LG in AAB65244. Ref.3
	Sequence conflict	629	1	A → T in AAB47447. Ref.1
	Sequence conflict	633	1	S → I in AAB47447. Ref.1
	Sequence conflict	682 – 716	35	PPGRD…FVDVM → LRAATWPQCPRN in BAA13199. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q92997 [UniParc]. Last modified May 30, 2000. Version 2. Checksum: B1A55EBF9507D06E	FASTA	716	78,055
	10 20 30 40 50 60 MGETKIIYHL DGQETPYLVK LPLPAERVTL ADFKGVLQRP SYKFFFKSMD DDFGVVKEEI 70 80 90 100 110 120 SDDNAKLPCF NGRVVSWLVS AEGSHPDPAP FCADNPSELP PPMERTGGIG DSRPPSFHPH 130 140 150 160 170 180 AGGGSQENLD NDTETDSLVS AQRERPRRRD GPEHATRLNG TAKGERRREP GGYDSSSTLM 190 200 210 220 230 240 SSELETTSFF DSDEDDSTSR FSSSTEQSSA SRLMRRHKRR RRKQKVSRIE RSSSFSSITD 250 260 270 280 290 300 STMSLNIITV TLNMEKYNFL GISIVGQSNE RGDGGIYIGS IMKGGAVAAD GRIEPGDMLL 310 320 330 340 350 360 QVNEINFENM SNDDAVRVLR EIVHKPGPIT LTVAKCWDPS PRGCFTLPRS EPIRPIDPAA 370 380 390 400 410 420 WVSHTAAMTG TFPAYGMSPS LSTITSTSSS ITSSIPDTER LDDFHLSIHS DMAAIVKAMA 430 440 450 460 470 480 SPESGLEVRD RMWLKITIPN AFIGSDVVDW LYHNVEGFTD RREARKYASN LLKAGFIRHT 490 500 510 520 530 540 VNKITFSEQC YYIFGDLCGN MANLSLHDHD GSSGASDQDT LAPLPHPGAA PWPMAFPYQY 550 560 570 580 590 600 PPPPHPYNPH PGFPELGYSY GGGSASSQHS EGSRSSGSNR SGSDRRKEKD PKAGDSKSGG 610 620 630 640 650 660 SGSESDHTTR SSLRGPRERA PSERSGPAAS EHSHRSHHSL ASSLRSHHTH PSYGPPGVPP 670 680 690 700 710 LYGPPMLMMP PPPAAMGPPG APPGRDLASV PPELTASRQS FRMAMGNPSE FFVDVM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA characterization and chromosomal mapping of two human homologues of the Drosophila dishevelled polarity gene." Pizzuti A., Amati F., Calabrese G., Mari A., Colosimo A., Silani V., Giardino L., Ratti A., Penso D., Calza L., Palka G., Scarlato G., Novelli G., Dallapiccola B. Hum. Mol. Genet. 5:953-958(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"cDNA cloning of a human dishevelled DVL-3 gene, mapping to 3q27, and expression in human breast and colon carcinomas." Bui T.D., Beier D.R., Jonssen M., Smith K., Dorrington S.M., Kaklamanis L., Kearney L., Regan R., Sussman D.J., Harris A.L. Biochem. Biophys. Res. Commun. 239:510-516(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[3]	"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].
[4]	"Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain." Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O., Tanaka A., Kotani H., Miyajima N., Nomura N. DNA Res. 3:321-329(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow.
[5]	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. , 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].
[6]	"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], VARIANT LEU-433. Tissue: Brain.
[7]	"Regulation of the Wnt signaling pathway by disabled-2 (Dab2)." Howe P.H. EMBO J. 22:3084-3094(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DAB2.
[8]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH LRRFIP2.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-192, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Loss of the tumor suppressor CYLD enhances Wnt/beta-catenin signaling through K63-linked ubiquitination of Dvl." Tauriello D.V., Haegebarth A., Kuper I., Edelmann M.J., Henraat M., Canninga-van Dijk M.R., Kessler B.M., Clevers H., Maurice M.M. Mol. Cell 37:607-619(2010) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION, INTERACTION WITH CYLD.
[11]	"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.
[12]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48, MASS SPECTROMETRY.
[13]	"Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling." Chaki M., Airik R., Ghosh A.K., Giles R.H., Chen R., Slaats G.G., Wang H., Hurd T.W., Zhou W., Cluckey A., Gee H.Y., Ramaswami G., Hong C.J., Hamilton B.A., Cervenka I., Ganji R.S., Bryja V., Arts H.H. , van Reeuwijk J., Oud M.M., Letteboer S.J., Roepman R., Husson H., Ibraghimov-Beskrovnaya O., Yasunaga T., Walz G., Eley L., Sayer J.A., Schermer B., Liebau M.C., Benzing T., Le Corre S., Drummond I., Janssen S., Allen S.J., Natarajan S., O'Toole J.F., Attanasio M., Saunier S., Antignac C., Koenekoop R.K., Ren H., Lopez I., Nayir A., Stoetzel C., Dollfus H., Massoudi R., Gleeson J.G., Andreoli S.P., Doherty D.G., Lindstrad A., Golzio C., Katsanis N., Pape L., Abboud E.B., Al-Rajhi A.A., Lewis R.A., Omran H., Lee E.Y., Wang S., Sekiguchi J.M., Saunders R., Johnson C.A., Garner E., Vanselow K., Andersen J.S., Shlomai J., Nurnberg G., Nurnberg P., Levy S., Smogorzewska A., Otto E.A., Hildebrandt F. Cell 150:533-548(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CEP164.
[14]	"Delicate analysis of post-translational modifications on Dishevelled 3." Wu C., Wei W., Li C., Li Q., Sheng Q., Zeng R. J. Proteome Res. 11:3829-3837(2012) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-192; THR-346 AND SER-700, METHYLATION AT ARG-27; ARG-212; ARG-342 AND ARG-698.
[15]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-216.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U49262 mRNA. Translation: AAB47447.1. U75651 mRNA. Translation: AAB84228.1. AF006013 mRNA. Translation: AAB65244.1. D86963 mRNA. Translation: BAA13199.2. Different initiation. CH471052 Genomic DNA. Translation: EAW78295.1. CH471052 Genomic DNA. Translation: EAW78296.1. BC032459 mRNA. Translation: AAH32459.1.
IPI	IPI00643141.
PIR	JC5763.
RefSeq	NP_004414.3. NM_004423.3.
UniGene	Hs.388116.
3D structure databases
ProteinModelPortal	Q92997.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92997. 35 interactions.
MINT	MINT-1186858.
STRING	9606.ENSP00000316054.
PTM databases
PhosphoSite	Q92997.
Polymorphism databases
DMDM	6919875.
Proteomic databases
PaxDb	Q92997.
PRIDE	Q92997.
Protocols and materials databases
DNASU	1857.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000313143; ENSP00000316054; ENSG00000161202.
GeneID	1857.
KEGG	hsa:1857.
UCSC	uc003fms.3. human.
Organism-specific databases
CTD	1857.
GeneCards	GC03P183873.
HGNC	HGNC:3087. DVL3.
HPA	CAB046486.
MIM	601368. gene.
neXtProt	NX_Q92997.
PharmGKB	PA27543.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG322275.
HOGENOM	HOG000017084.
HOVERGEN	HBG005542.
InParanoid	Q92997.
KO	K02353.
OrthoDB	EOG4TQM8S.
Gene expression databases
ArrayExpress	Q92997.
Bgee	Q92997.
CleanEx	HS_DVL3.
Genevestigator	Q92997.
GermOnline	ENSG00000161202. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.10. 1 hit.
InterPro	IPR000591. DEP_dom. IPR008342. Dishevelled_3. 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:SF6. PTHR10878:SF6. 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. PR01763. DISHEVELLED3.
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	CHEMBL6028.
ChiTaRS	DVL3. human.
GenomeRNAi	1857.
NextBio	7609.
SOURCE	Search...

Entry information

Entry name

DVL3_HUMAN

Accession

Primary (citable) accession number: Q92997
Secondary accession number(s): D3DNT0 , O14642, Q13531, Q8N5E9, Q92607

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	May 30, 2000
Last modified:	May 1, 2013
This is version 129 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.