ID   DVL2_HUMAN              Reviewed;         736 AA.
AC   O14641; D3DTN3; Q53XM0;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   09-APR-2025, entry version 229.
DE   RecName: Full=Segment polarity protein dishevelled homolog DVL-2;
DE            Short=Dishevelled-2;
DE   AltName: Full=DSH homolog 2;
GN   Name=DVL2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX   PubMed=9192851; DOI=10.1006/geno.1997.4713;
RA   Semenov M.V., Snyder M.;
RT   "Human dishevelled genes constitute a DHR-containing multigene family.";
RL   Genomics 42:302-310(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Colon;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   INTERACTION WITH ARRB1.
RX   PubMed=11742073; DOI=10.1073/pnas.211572798;
RA   Chen W., Hu L.A., Semenov M.V., Yanagawa S., Kikuchi A., Lefkowitz R.J.,
RA   Miller W.E.;
RT   "beta-Arrestin1 modulates lymphoid enhancer factor transcriptional activity
RT   through interaction with phosphorylated dishevelled proteins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 98:14889-14894(2001).
RN   [6]
RP   INTERACTION WITH DIXDC1 AND RAC.
RX   PubMed=15262978; DOI=10.1074/jbc.m404598200;
RA   Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C.;
RT   "The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase
RT   activation by Axin and dishevelled through distinct mechanisms.";
RL   J. Biol. Chem. 279:39366-39373(2004).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [9]
RP   PHOSPHORYLATION BY CSNK1D/CK1.
RX   PubMed=21422228; DOI=10.1083/jcb.201011111;
RA   Greer Y.E., Rubin J.S.;
RT   "Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-
RT   dependent neurite outgrowth.";
RL   J. Cell Biol. 192:993-1004(2011).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [11]
RP   INTERACTION WITH DACT1.
RX   PubMed=22610794; DOI=10.1002/humu.22121;
RA   Shi Y., Ding Y., Lei Y.P., Yang X.Y., Xie G.M., Wen J., Cai C.Q., Li H.,
RA   Chen Y., Zhang T., Wu B.L., Jin L., Chen Y.G., Wang H.Y.;
RT   "Identification of novel rare mutations of DACT1 in human neural tube
RT   defects.";
RL   Hum. Mutat. 33:1450-1455(2012).
RN   [12]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [13]
RP   INTERACTION WITH FAM105B.
RX   PubMed=23708998; DOI=10.1038/nature12296;
RA   Rivkin E., Almeida S.M., Ceccarelli D.F., Juang Y.C., Maclean T.A.,
RA   Srikumar T., Huang H., Dunham W.H., Fukumura R., Xie G., Gondo Y.,
RA   Raught B., Gingras A.C., Sicheri F., Cordes S.P.;
RT   "The linear ubiquitin-specific deubiquitinase gumby regulates
RT   angiogenesis.";
RL   Nature 498:318-324(2013).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [15]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH IRS1 AND IRS2.
RX   PubMed=24616100; DOI=10.1074/jbc.m113.544999;
RA   Geng Y., Ju Y., Ren F., Qiu Y., Tomita Y., Tomoeda M., Kishida M., Wang Y.,
RA   Jin L., Su F., Wei C., Jia B., Li Y., Chang Z.;
RT   "Insulin receptor substrate 1/2 (IRS1/2) regulates Wnt/beta-catenin
RT   signaling through blocking autophagic degradation of dishevelled2.";
RL   J. Biol. Chem. 289:11230-11241(2014).
RN   [16]
RP   INTERACTION WITH DCDC2.
RX   PubMed=25557784; DOI=10.1016/j.ajhg.2014.12.002;
RA   Schueler M., Braun D.A., Chandrasekar G., Gee H.Y., Klasson T.D.,
RA   Halbritter J., Bieder A., Porath J.D., Airik R., Zhou W., LoTurco J.J.,
RA   Che A., Otto E.A., Boeckenhauer D., Sebire N.J., Honzik T., Harris P.C.,
RA   Koon S.J., Gunay-Aygun M., Saunier S., Zerres K., Bruechle N.O.,
RA   Drenth J.P., Pelletier L., Tapia-Paez I., Lifton R.P., Giles R.H., Kere J.,
RA   Hildebrandt F.;
RT   "DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt
RT   signaling.";
RL   Am. J. Hum. Genet. 96:81-92(2015).
RN   [17]
RP   INTERACTION WITH FOXK1 AND FOXK2, SUBCELLULAR LOCATION, PHOSPHORYLATION,
RP   AND MUTAGENESIS OF 250-THR--SER-252; THR-250; SER-251; SER-252;
RP   254-SER--THR-257; SER-252; SER-255; THR-257; 259-SER--SER-262; SER-259;
RP   THR-260; SER-262; 267-THR--THR-269; THR-267; THR-269; TYR-275; SER-281;
RP   SER-286; TYR-295; SER-298 AND SER-329.
RX   PubMed=25805136; DOI=10.1016/j.devcel.2015.01.031;
RA   Wang W., Li X., Lee M., Jun S., Aziz K.E., Feng L., Tran M.K., Li N.,
RA   McCrea P.D., Park J.I., Chen J.;
RT   "FOXKs promote Wnt/beta-catenin signaling by translocating DVL into the
RT   nucleus.";
RL   Dev. Cell 32:707-718(2015).
RN   [18]
RP   INTERACTION WITH PKD1.
RX   PubMed=27214281; DOI=10.1038/ncb3363;
RA   Kim S., Nie H., Nesin V., Tran U., Outeda P., Bai C.X., Keeling J.,
RA   Maskey D., Watnick T., Wessely O., Tsiokas L.;
RT   "The polycystin complex mediates Wnt/Ca(2+) signalling.";
RL   Nat. Cell Biol. 18:752-764(2016).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF 264-353, AND FUNCTION.
RX   PubMed=19252499; DOI=10.1038/nchembio.152;
RA   Zhang Y., Appleton B.A., Wiesmann C., Lau T., Costa M., Hannoush R.N.,
RA   Sidhu S.S.;
RT   "Inhibition of Wnt signaling by Dishevelled PDZ peptides.";
RL   Nat. Chem. Biol. 5:217-219(2009).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 261-354.
RG   Structural genomics consortium (SGC);
RT   "Crystal structure of the PDZ domains of human dishevelled 2 (homologous to
RT   Drosophila dsh).";
RL   Submitted (FEB-2009) to the PDB data bank.
RN   [21]
RP   VARIANT THR-282.
RX   PubMed=21248752; DOI=10.1038/nature09639;
RA   Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA   Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA   Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA   Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA   Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA   Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA   Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA   Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT   "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT   PBRM1 in renal carcinoma.";
RL   Nature 469:539-542(2011).
CC   -!- FUNCTION: Plays a role in the signal transduction pathways mediated by
CC       multiple Wnt genes (PubMed:24616100). Participates both in canonical
CC       and non-canonical Wnt signaling by binding to the cytoplasmic C-
CC       terminus of frizzled family members and transducing the Wnt signal to
CC       down-stream effectors. Promotes internalization and degradation of
CC       frizzled proteins upon Wnt signaling. {ECO:0000250|UniProtKB:Q60838,
CC       ECO:0000269|PubMed:19252499, ECO:0000269|PubMed:24616100}.
CC   -!- SUBUNIT: Interacts through its PDZ domain with the C-terminal regions
CC       of VANGL1 and VANGL2. Interacts with Rac. Interacts with ARRB1; the
CC       interaction is enhanced by phosphorylation of DVL1 (By similarity). Can
CC       form large oligomers (via DIX domain). Interacts (via DIX domain) with
CC       DIXDC1 (via DIX domain). Interacts (via DEP domain) with AP2M1 and the
CC       AP-2 complex (By similarity). Interacts with DACT1 and FAM105B/otulin.
CC       Interacts with DCDC2. Interacts (when phosphorylated) with FOXK1 and
CC       FOXK2; the interaction induces DVL2 nuclear translocation
CC       (PubMed:25805136). Interacts with MAPK15 (By similarity). Interacts
CC       with PKD1 (via extracellular domain) (PubMed:27214281). Interacts with
CC       LMBR1L (By similarity). Interacts with IRS1 and IRS2; these
CC       interactions decrease 'Lys-63'-linked ubiquitination of DVL2 and
CC       stabilize DVL2 protein via suppressing its autophagy-mediated
CC       degradation (PubMed:24616100). {ECO:0000250|UniProtKB:Q60838,
CC       ECO:0000269|PubMed:11742073, ECO:0000269|PubMed:15262978,
CC       ECO:0000269|PubMed:22610794, ECO:0000269|PubMed:23708998,
CC       ECO:0000269|PubMed:24616100, ECO:0000269|PubMed:25557784,
CC       ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:27214281}.
CC   -!- INTERACTION:
CC       O14641; P25054: APC; NbExp=2; IntAct=EBI-740850, EBI-727707;
CC       O14641; O15169: AXIN1; NbExp=3; IntAct=EBI-740850, EBI-710484;
CC       O14641; P28329-3: CHAT; NbExp=3; IntAct=EBI-740850, EBI-25837549;
CC       O14641; Q5R2U3: CK1E; NbExp=2; IntAct=EBI-740850, EBI-9106301;
CC       O14641; P49674: CSNK1E; NbExp=4; IntAct=EBI-740850, EBI-749343;
CC       O14641; Q9NYF0: DACT1; NbExp=6; IntAct=EBI-740850, EBI-3951744;
CC       O14641; Q155Q3: DIXDC1; NbExp=2; IntAct=EBI-740850, EBI-1104700;
CC       O14641; O14640: DVL1; NbExp=4; IntAct=EBI-740850, EBI-723489;
CC       O14641; O14641: DVL2; NbExp=4; IntAct=EBI-740850, EBI-740850;
CC       O14641; P22607: FGFR3; NbExp=3; IntAct=EBI-740850, EBI-348399;
CC       O14641; P01112: HRAS; NbExp=3; IntAct=EBI-740850, EBI-350145;
CC       O14641; Q5S007: LRRK2; NbExp=5; IntAct=EBI-740850, EBI-5323863;
CC       O14641; P53350: PLK1; NbExp=2; IntAct=EBI-740850, EBI-476768;
CC       O14641; P57078: RIPK4; NbExp=4; IntAct=EBI-740850, EBI-4422308;
CC       O14641; Q96CG3: TIFA; NbExp=3; IntAct=EBI-740850, EBI-740711;
CC       O14641; Q08117-2: TLE5; NbExp=3; IntAct=EBI-740850, EBI-11741437;
CC       O14641; P04637: TP53; NbExp=6; IntAct=EBI-740850, EBI-366083;
CC       O14641; Q14134: TRIM29; NbExp=5; IntAct=EBI-740850, EBI-702370;
CC       O14641; Q96RL1: UIMC1; NbExp=4; IntAct=EBI-740850, EBI-725300;
CC       O14641; Q9NZC7: WWOX; NbExp=2; IntAct=EBI-740850, EBI-4320739;
CC       O14641; Q9GZV5: WWTR1; NbExp=4; IntAct=EBI-740850, EBI-747743;
CC       O14641; P49910: ZNF165; NbExp=3; IntAct=EBI-740850, EBI-741694;
CC       O14641; Q9Z101: Pard6a; Xeno; NbExp=6; IntAct=EBI-740850, EBI-81732;
CC       O14641; A2A5Z6: Smurf2; Xeno; NbExp=8; IntAct=EBI-740850, EBI-2348309;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q60838};
CC       Peripheral membrane protein {ECO:0000250|UniProtKB:Q60838}; Cytoplasmic
CC       side {ECO:0000250|UniProtKB:Q60838}. Cytoplasm, cytosol
CC       {ECO:0000269|PubMed:24616100}. Cytoplasmic vesicle
CC       {ECO:0000250|UniProtKB:Q60838}. Nucleus {ECO:0000269|PubMed:25805136}.
CC       Note=Localizes at the cell membrane upon interaction with frizzled
CC       family members and promotes their internalization. Localizes to
CC       cytoplasmic puncta (By similarity). Interaction with FOXK1 and FOXK2
CC       induces nuclear translocation (PubMed:25805136).
CC       {ECO:0000250|UniProtKB:Q60838, ECO:0000269|PubMed:24616100,
CC       ECO:0000269|PubMed:25805136}.
CC   -!- DOMAIN: The DIX domain mediates homooligomerization. {ECO:0000250}.
CC   -!- PTM: Phosphorylated by CSNK1D (PubMed:21422228, PubMed:9192851). WNT3A
CC       induces DVL2 phosphorylation by CSNK1E and MARK kinases
CC       (PubMed:25805136). {ECO:0000269|PubMed:21422228,
CC       ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:9192851}.
CC   -!- PTM: Ubiquitinated via 'Lys-63'-linked polyubiquitin chains; leading to
CC       its autophagy-mediated degradation. {ECO:0000269|PubMed:24616100}.
CC   -!- SIMILARITY: Belongs to the DSH family. {ECO:0000305}.
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DR   EMBL; AF006012; AAB65243.1; -; mRNA.
DR   EMBL; BT009822; AAP88824.1; -; mRNA.
DR   EMBL; CH471108; EAW90244.1; -; Genomic_DNA.
DR   EMBL; CH471108; EAW90245.1; -; Genomic_DNA.
DR   EMBL; BC014844; AAH14844.1; -; mRNA.
DR   CCDS; CCDS11091.1; -.
DR   RefSeq; NP_004413.1; NM_004422.3.
DR   PDB; 2REY; X-ray; 1.55 A; A=261-355.
DR   PDB; 3CBX; X-ray; 1.70 A; A/B=264-354.
DR   PDB; 3CBY; X-ray; 1.50 A; A/B=264-354.
DR   PDB; 3CBZ; X-ray; 1.38 A; A=264-354.
DR   PDB; 3CC0; X-ray; 1.75 A; A/B/C=264-354.
DR   PDB; 4WIP; X-ray; 2.69 A; A/B/C=12-106.
DR   PDB; 5LNP; X-ray; 1.99 A; A/B/C/D=416-510.
DR   PDB; 5SUY; X-ray; 1.88 A; A/B/C/D=416-510.
DR   PDB; 5SUZ; X-ray; 1.84 A; A/B=416-509.
DR   PDB; 6IW3; X-ray; 1.64 A; A=12-93.
DR   PDB; 6JCK; X-ray; 3.09 A; B=12-93.
DR   PDB; 8WM9; EM; 3.53 A; C=1-736.
DR   PDB; 8WMA; EM; 3.47 A; C=1-736.
DR   PDB; 8WWR; X-ray; 1.75 A; A=261-354.
DR   PDB; 8YR7; X-ray; 3.00 A; A=261-353.
DR   PDBsum; 2REY; -.
DR   PDBsum; 3CBX; -.
DR   PDBsum; 3CBY; -.
DR   PDBsum; 3CBZ; -.
DR   PDBsum; 3CC0; -.
DR   PDBsum; 4WIP; -.
DR   PDBsum; 5LNP; -.
DR   PDBsum; 5SUY; -.
DR   PDBsum; 5SUZ; -.
DR   PDBsum; 6IW3; -.
DR   PDBsum; 6JCK; -.
DR   PDBsum; 8WM9; -.
DR   PDBsum; 8WMA; -.
DR   PDBsum; 8WWR; -.
DR   PDBsum; 8YR7; -.
DR   AlphaFoldDB; O14641; -.
DR   BMRB; O14641; -.
DR   EMDB; EMD-37646; -.
DR   EMDB; EMD-37647; -.
DR   SMR; O14641; -.
DR   BioGRID; 108189; 583.
DR   CORUM; O14641; -.
DR   DIP; DIP-34433N; -.
DR   IntAct; O14641; 220.
DR   MINT; O14641; -.
DR   STRING; 9606.ENSP00000005340; -.
DR   BindingDB; O14641; -.
DR   ChEMBL; CHEMBL1255125; -.
DR   GlyGen; O14641; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; O14641; -.
DR   MetOSite; O14641; -.
DR   PhosphoSitePlus; O14641; -.
DR   BioMuta; DVL2; -.
DR   jPOST; O14641; -.
DR   MassIVE; O14641; -.
DR   PaxDb; 9606-ENSP00000005340; -.
DR   PeptideAtlas; O14641; -.
DR   ProteomicsDB; 48140; -.
DR   Pumba; O14641; -.
DR   Antibodypedia; 3985; 621 antibodies from 39 providers.
DR   DNASU; 1856; -.
DR   Ensembl; ENST00000005340.10; ENSP00000005340.4; ENSG00000004975.12.
DR   GeneID; 1856; -.
DR   KEGG; hsa:1856; -.
DR   MANE-Select; ENST00000005340.10; ENSP00000005340.4; NM_004422.3; NP_004413.1.
DR   UCSC; uc002gez.2; human.
DR   AGR; HGNC:3086; -.
DR   CTD; 1856; -.
DR   DisGeNET; 1856; -.
DR   GeneCards; DVL2; -.
DR   HGNC; HGNC:3086; DVL2.
DR   HPA; ENSG00000004975; Low tissue specificity.
DR   MalaCards; DVL2; -.
DR   MIM; 602151; gene.
DR   neXtProt; NX_O14641; -.
DR   OpenTargets; ENSG00000004975; -.
DR   PharmGKB; PA27542; -.
DR   VEuPathDB; HostDB:ENSG00000004975; -.
DR   eggNOG; KOG3571; Eukaryota.
DR   GeneTree; ENSGT00950000182903; -.
DR   InParanoid; O14641; -.
DR   OMA; CENYLVN; -.
DR   OrthoDB; 10031689at2759; -.
DR   PhylomeDB; O14641; -.
DR   TreeFam; TF318198; -.
DR   PathwayCommons; O14641; -.
DR   Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
DR   Reactome; R-HSA-201688; WNT mediated activation of DVL.
DR   Reactome; R-HSA-2028269; Signaling by Hippo.
DR   Reactome; R-HSA-4086400; PCP/CE pathway.
DR   Reactome; R-HSA-4608870; Asymmetric localization of PCP proteins.
DR   Reactome; R-HSA-4641258; Degradation of DVL.
DR   Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR   Reactome; R-HSA-5099900; WNT5A-dependent internalization of FZD4.
DR   Reactome; R-HSA-5368598; Negative regulation of TCF-dependent signaling by DVL-interacting proteins.
DR   Reactome; R-HSA-5663220; RHO GTPases Activate Formins.
DR   Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR   Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR   Reactome; R-HSA-9673324; WNT5:FZD7-mediated leishmania damping.
DR   SignaLink; O14641; -.
DR   SIGNOR; O14641; -.
DR   BioGRID-ORCS; 1856; 12 hits in 1161 CRISPR screens.
DR   CD-CODE; 9E21F925; Synthetic Condensate 000351.
DR   CD-CODE; DA9A581A; DVL2 condensates.
DR   CD-CODE; DEE660B4; Stress granule.
DR   CD-CODE; EEA9CF61; Dishevelled condensate.
DR   ChiTaRS; DVL2; human.
DR   EvolutionaryTrace; O14641; -.
DR   GeneWiki; DVL2; -.
DR   GenomeRNAi; 1856; -.
DR   Pharos; O14641; Tbio.
DR   PRO; PR:O14641; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; O14641; protein.
DR   Bgee; ENSG00000004975; Expressed in ventricular zone and 191 other cell types or tissues.
DR   ExpressionAtlas; O14641; baseline and differential.
DR   GO; GO:0016235; C:aggresome; IDA:HPA.
DR   GO; GO:0045177; C:apical part of cell; IEA:Ensembl.
DR   GO; GO:0045334; C:clathrin-coated endocytic vesicle; TAS:Reactome.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0016328; C:lateral plasma membrane; IEA:Ensembl.
DR   GO; GO:0016604; C:nuclear body; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0005109; F:frizzled binding; IPI:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl.
DR   GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR   GO; GO:0030674; F:protein-macromolecule adaptor activity; IEA:Ensembl.
DR   GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0090103; P:cochlea morphogenesis; IEA:Ensembl.
DR   GO; GO:0022007; P:convergent extension involved in neural plate elongation; IEA:Ensembl.
DR   GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR   GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR   GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR   GO; GO:0001843; P:neural tube closure; ISS:BHF-UCL.
DR   GO; GO:0035567; P:non-canonical Wnt signaling pathway; IMP:BHF-UCL.
DR   GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; IMP:BHF-UCL.
DR   GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:BHF-UCL.
DR   GO; GO:0150012; P:positive regulation of neuron projection arborization; ISS:ARUK-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR   GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR   GO; GO:0032956; P:regulation of actin cytoskeleton organization; TAS:BHF-UCL.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IDA:BHF-UCL.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0007379; P:segment specification; ISS:BHF-UCL.
DR   GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; IDA:BHF-UCL.
DR   CDD; cd04438; DEP_dishevelled; 1.
DR   CDD; cd06717; PDZ_Dishevelled-like; 1.
DR   FunFam; 2.40.240.130:FF:000001; Segment polarity protein dishevelled homolog DVL-1; 1.
DR   FunFam; 2.30.42.10:FF:000014; Segment polarity protein dishevelled homolog DVL-3; 1.
DR   FunFam; 1.10.10.10:FF:000040; segment polarity protein dishevelled homolog DVL-3; 1.
DR   Gene3D; 2.30.42.10; -; 1.
DR   Gene3D; 2.40.240.130; -; 1.
DR   Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 1.
DR   InterPro; IPR000591; DEP_dom.
DR   InterPro; IPR024580; Dishevelled_C-dom.
DR   InterPro; IPR008339; Dishevelled_fam.
DR   InterPro; IPR003351; Dishevelled_protein_dom.
DR   InterPro; IPR001158; DIX.
DR   InterPro; IPR038207; DIX_dom_sf.
DR   InterPro; IPR015506; Dsh/Dvl-rel.
DR   InterPro; IPR008341; DVL2.
DR   InterPro; IPR001478; PDZ.
DR   InterPro; IPR036034; PDZ_sf.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   InterPro; IPR036390; WH_DNA-bd_sf.
DR   PANTHER; PTHR10878; SEGMENT POLARITY PROTEIN DISHEVELLED; 1.
DR   PANTHER; PTHR10878:SF8; SEGMENT POLARITY PROTEIN DISHEVELLED HOMOLOG DVL-2; 1.
DR   Pfam; PF00610; DEP; 1.
DR   Pfam; PF02377; Dishevelled; 1.
DR   Pfam; PF00778; DIX; 1.
DR   Pfam; PF12316; Dsh_C; 1.
DR   Pfam; PF00595; PDZ; 1.
DR   PRINTS; PR01760; DISHEVELLED.
DR   PRINTS; PR01762; DISHEVELLED2.
DR   SMART; SM00021; DAX; 1.
DR   SMART; SM00049; DEP; 1.
DR   SMART; SM00228; PDZ; 1.
DR   SUPFAM; SSF50156; PDZ domain-like; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 1.
DR   SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1.
DR   PROSITE; PS50186; DEP; 1.
DR   PROSITE; PS50841; DIX; 1.
DR   PROSITE; PS50106; PDZ; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW   Developmental protein; Isopeptide bond; Membrane; Nucleus; Phosphoprotein;
KW   Proteomics identification; Reference proteome; Ubl conjugation;
KW   Wnt signaling pathway.
FT   CHAIN           1..736
FT                   /note="Segment polarity protein dishevelled homolog DVL-2"
FT                   /id="PRO_0000145746"
FT   DOMAIN          11..93
FT                   /note="DIX"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00069"
FT   DOMAIN          267..339
FT                   /note="PDZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT   DOMAIN          433..507
FT                   /note="DEP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00066"
FT   REGION          92..254
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          250..355
FT                   /note="Required for interaction with FOXK2"
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   REGION          558..675
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        112..122
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        159..171
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        193..208
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        218..230
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        232..244
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        558..568
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        581..598
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        614..629
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         211
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19690332,
FT                   ECO:0007744|PubMed:20068231"
FT   VARIANT         282
FT                   /note="I -> T (found in a renal cell carcinoma case;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:21248752"
FT                   /id="VAR_064708"
FT   MUTAGEN         250..252
FT                   /note="TSS->AAA: Almost abolishes interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         250
FT                   /note="T->A: No effect on interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         251
FT                   /note="S->A: No effect on interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         252
FT                   /note="S->A: Almost abolishes interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         254..257
FT                   /note="SSVT->AAVA: Almost abolishes interaction with
FT                   FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         254
FT                   /note="S->A: Reduces interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         255
FT                   /note="S->A: Almost abolishes interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         257
FT                   /note="T->A: Almost abolishes interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         259..262
FT                   /note="STMS->AAMA: Almost abolishes interaction with
FT                   FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         259
FT                   /note="S->A: Almost abolishes interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         260
FT                   /note="T->A: No effect on interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         262
FT                   /note="S->A: Almost abolishes interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         267..269
FT                   /note="TVT->AVA: Almost abolishes interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         267
FT                   /note="T->A: Almost abolishes interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         269
FT                   /note="T->A: Almost abolishes interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         275
FT                   /note="Y->F: No effect on interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         281
FT                   /note="S->A: No effect on interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         286
FT                   /note="S->A: No effect on interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         295
FT                   /note="Y->F: No effect on interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         298
FT                   /note="S->A: No effect on interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   MUTAGEN         329
FT                   /note="S->A: No effect on interaction with FOXK2."
FT                   /evidence="ECO:0000269|PubMed:25805136"
FT   STRAND          14..20
FT                   /evidence="ECO:0007829|PDB:6IW3"
FT   STRAND          27..33
FT                   /evidence="ECO:0007829|PDB:6IW3"
FT   TURN            35..37
FT                   /evidence="ECO:0007829|PDB:6IW3"
FT   HELIX           40..44
FT                   /evidence="ECO:0007829|PDB:6IW3"
FT   STRAND          54..61
FT                   /evidence="ECO:0007829|PDB:6IW3"
FT   TURN            62..64
FT                   /evidence="ECO:0007829|PDB:6IW3"
FT   STRAND          65..70
FT                   /evidence="ECO:0007829|PDB:6IW3"
FT   STRAND          75..77
FT                   /evidence="ECO:0007829|PDB:6JCK"
FT   STRAND          84..90
FT                   /evidence="ECO:0007829|PDB:6IW3"
FT   STRAND          265..270
FT                   /evidence="ECO:0007829|PDB:3CBZ"
FT   HELIX           272..275
FT                   /evidence="ECO:0007829|PDB:3CBZ"
FT   STRAND          280..285
FT                   /evidence="ECO:0007829|PDB:3CBZ"
FT   STRAND          293..299
FT                   /evidence="ECO:0007829|PDB:3CBZ"
FT   HELIX           304..308
FT                   /evidence="ECO:0007829|PDB:3CBZ"
FT   STRAND          316..320
FT                   /evidence="ECO:0007829|PDB:3CBZ"
FT   STRAND          326..328
FT                   /evidence="ECO:0007829|PDB:8YR7"
FT   HELIX           330..341
FT                   /evidence="ECO:0007829|PDB:3CBZ"
FT   STRAND          343..345
FT                   /evidence="ECO:0007829|PDB:3CBZ"
FT   STRAND          347..352
FT                   /evidence="ECO:0007829|PDB:3CBZ"
FT   HELIX           423..431
FT                   /evidence="ECO:0007829|PDB:5SUZ"
FT   STRAND          440..454
FT                   /evidence="ECO:0007829|PDB:5SUZ"
FT   HELIX           455..465
FT                   /evidence="ECO:0007829|PDB:5SUZ"
FT   HELIX           472..484
FT                   /evidence="ECO:0007829|PDB:5SUZ"
FT   STRAND          487..492
FT                   /evidence="ECO:0007829|PDB:5SUZ"
FT   STRAND          501..505
FT                   /evidence="ECO:0007829|PDB:5SUZ"
SQ   SEQUENCE   736 AA;  78948 MW;  4BAD95B6C3FE531B CRC64;
     MAGSSTGGGG VGETKVIYHL DEEETPYLVK IPVPAERITL GDFKSVLQRP AGAKYFFKSM
     DQDFGVVKEE ISDDNARLPC FNGRVVSWLV SSDNPQPEMA PPVHEPRAEL APPAPPLPPL
     PPERTSGIGD SRPPSFHPNV SSSHENLEPE TETESVVSLR RERPRRRDSS EHGAGGHRTG
     GPSRLERHLA GYESSSTLMT SELESTSLGD SDEEDTMSRF SSSTEQSSAS RLLKRHRRRR
     KQRPPRLERT SSFSSVTDST MSLNIITVTL NMEKYNFLGI SIVGQSNERG DGGIYIGSIM
     KGGAVAADGR IEPGDMLLQV NDMNFENMSN DDAVRVLRDI VHKPGPIVLT VAKCWDPSPQ
     AYFTLPRNEP IQPIDPAAWV SHSAALTGTF PAYPGSSSMS TITSGSSLPD GCEGRGLSVH
     TDMASVTKAM AAPESGLEVR DRMWLKITIP NAFLGSDVVD WLYHHVEGFP ERREARKYAS
     GLLKAGLIRH TVNKITFSEQ CYYVFGDLSG GCESYLVNLS LNDNDGSSGA SDQDTLAPLP
     GATPWPLLPT FSYQYPAPHP YSPQPPPYHE LSSYTYGGGS ASSQHSEGSR SSGSTRSDGG
     AGRTGRPEER APESKSGSGS ESEPSSRGGS LRRGGEASGT SDGGPPPSRG STGGAPNLRA
     HPGLHPYGPP PGMALPYNPM MVVMMPPPPP PVPPAVQPPG APPVRDLGSV PPELTASRQS
     FHMAMGNPSE FFVDVM
//