O14641 (DVL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Segment polarity protein dishevelled homolog DVL-2
Short name=Dishevelled-2

Alternative name(s):
DSH homolog 2

Gene names

Name:

DVL2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	736 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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. 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.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 By similarity. 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 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.7 Ref.9 Ref.10
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	Polymorphism
Molecular function	Developmental protein
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	canonical Wnt receptor signaling pathway involved in regulation of cell proliferation Inferred from direct assay. Source: BHF-UCL cell migration in hindbrain Inferred from Biological aspect of Ancestor. Source: RefGenome cochlea morphogenesis Inferred from Biological aspect of Ancestor. Source: RefGenome intracellular signal transduction Inferred from electronic annotation. Source: InterPro neural tube closure Inferred from sequence or structural similarity. 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. Source: BHF-UCL positive regulation of protein phosphorylation Inferred from mutant phenotype. Source: BHF-UCL positive regulation of sequence-specific DNA binding transcription factor activity Inferred from direct assay. Source: BHF-UCL positive regulation of transcription, DNA-dependent Inferred from direct assay. 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 component	apical part of cell 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 nucleus Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular function	frizzled binding Inferred from physical interaction. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: IntAct signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-740850,EBI-740850
Pard6a	Q9Z101	6	EBI-740850,EBI-81732	From a different organism.
Smurf2	A2A5Z6	8	EBI-740850,EBI-2348309	From a different organism.
TRIM29	Q14134	5	EBI-740850,EBI-702370
ZNF165	P49910	2	EBI-740850,EBI-741694

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 736

735

Segment polarity protein dishevelled homolog DVL-2

PRO_0000145746

Regions

Domain

11 – 93

83

DIX

Domain

267 – 339

73

PDZ

Domain

433 – 507

75

DEP

Compositional bias

7 – 12

6

Poly-Gly

Compositional bias

235 – 240

6

Poly-Arg

Compositional bias

686 – 694

9

Poly-Pro

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8

Modified residue

211

1

Phosphoserine Ref.9

Modified residue

228

1

Phosphoserine Ref.7

Modified residue

275

1

Phosphotyrosine Ref.9

Natural variations

Natural variant

282

1

I → T Found in a renal cell carcinoma case; somatic mutation. Ref.13

VAR_064708

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

736

Helix Strand Turn

Details...

Beta strand

265 – 270

6

Beta strand

280 – 284

5

Beta strand

294 – 299

6

Helix

305 – 308

4

Beta strand

316 – 320

5

Helix

330 – 341

12

Beta strand

343 – 345

3

Beta strand

347 – 352

6

Sequences

	Sequence		Length	Mass (Da)
	O14641 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 4BAD95B6C3FE531B	FASTA	736	78,948
	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

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: 9192851] [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. , 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: 15489334] [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: 11742073] [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: 15262978] [Abstract] Cited for: INTERACTION WITH DIXDC1 AND RAC.
[7]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-228, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[9]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211 AND TYR-275, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[10]	"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: 21422228] [Abstract] Cited for: PHOSPHORYLATION BY CSNK1D/CK1.
[11]	"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: 19252499] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF 264-353, FUNCTION.
[12]	"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.
[13]	"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. , 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: 21248752] [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.

IPI

IPI00023103.

RefSeq

NP_004413.1. NM_004422.2.

UniGene

Hs.118640.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2REY	X-ray	1.55	A	261-354	[»]
3CBX	X-ray	1.70	A/B	264-353	[»]
3CBY	X-ray	1.50	A/B	264-353	[»]
3CBZ	X-ray	1.38	A	264-353	[»]
3CC0	X-ray	1.75	A/B/C	264-353	[»]

ProteinModelPortal

O14641.

SMR

O14641. Positions 13-90, 263-582.

ModBase

Search...

Protein-protein interaction databases

IntAct

O14641. 58 interactions.

MINT

MINT-1435227.

STRING

O14641.

PTM databases

PhosphoSite

O14641.

Proteomic databases

PRIDE

O14641.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000005340; ENSP00000005340; ENSG00000004975.

GeneID

1856.

KEGG

hsa:1856.

UCSC

uc002gez.1. human.

Organism-specific databases

CTD

1856.

GeneCards

GC17M007128.

H-InvDB

HIX0013489.

HGNC

HGNC:3086. DVL2.

HPA

CAB009312.
HPA022914.

MIM

602151. gene.

neXtProt

NX_O14641.

PharmGKB

PA27542.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13534.

GeneTree

ENSGT00390000013552.

HOGENOM

HBG717800.

HOVERGEN

HBG005542.

InParanoid

O14641.

OMA

GAGGHRP.

OrthoDB

EOG4SQWWJ.

PhylomeDB

O14641.

Gene expression databases

ArrayExpress

O14641.

Bgee

O14641.

CleanEx

HS_DVL2.

Genevestigator

O14641.

GermOnline

ENSG00000004975. Homo sapiens.

Family and domain databases

InterPro

IPR000591. DEP_dom.
IPR008339. Dishevelled.
IPR008341. Dishevelled_2.
IPR024580. Dishevelled_C-dom.
IPR003351. Dishevelled_protein_dom.
IPR001158. DIX.
IPR015506. Dsh.
IPR001478. PDZ/DHR/GLGF.
IPR011991. WHTH_trsnscrt_rep_DNA-bd.
[Graphical view]

Gene3D

G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.

KO

K02353.

PANTHER

PTHR10878. Dsh. 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.
PR01762. DISHEVELLED2.

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

NextBio

7605.

SOURCE

Search...

Entry information

Entry name

DVL2_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 118 of the entry and version 1 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.