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UniProtKB - O14641 (DVL2_HUMAN)

Protein

Segment polarity protein dishevelled homolog DVL-2

Gene

DVL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Participates both in canonical and non-canonical 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.By similarity1 Publication

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein
Biological processWnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-201688 WNT mediated activation of DVL
R-HSA-2028269 Signaling by Hippo
R-HSA-4086400 PCP/CE pathway
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-4641258 Degradation of DVL
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5099900 WNT5A-dependent internalization of FZD4
R-HSA-5368598 Negative regulation of TCF-dependent signaling by DVL-interacting proteins
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiO14641
SIGNORiO14641

Names & Taxonomyi

Protein namesi
Recommended name:
Segment polarity protein dishevelled homolog DVL-2
Short name:
Dishevelled-2
Alternative name(s):
DSH homolog 2
Gene namesi
Name:DVL2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000004975.11
HGNCiHGNC:3086 DVL2
MIMi602151 gene
neXtProtiNX_O14641

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi250 – 252TSS → AAA: Almost abolishes interaction with FOXK2. 1 Publication3
Mutagenesisi250T → A: No effect on interaction with FOXK2. 1 Publication1
Mutagenesisi251S → A: No effect on interaction with FOXK2. 1 Publication1
Mutagenesisi252S → A: Almost abolishes interaction with FOXK2. 1 Publication1
Mutagenesisi254 – 257SSVT → AAVA: Almost abolishes interaction with FOXK2. 1 Publication4
Mutagenesisi254S → A: Reduces interaction with FOXK2. 1 Publication1
Mutagenesisi255S → A: Almost abolishes interaction with FOXK2. 1 Publication1
Mutagenesisi257T → A: Almost abolishes interaction with FOXK2. 1 Publication1
Mutagenesisi259 – 262STMS → AAMA: Almost abolishes interaction with FOXK2. 1 Publication4
Mutagenesisi259S → A: Almost abolishes interaction with FOXK2. 1 Publication1
Mutagenesisi260T → A: No effect on interaction with FOXK2. 1 Publication1
Mutagenesisi262S → A: Almost abolishes interaction with FOXK2. 1 Publication1
Mutagenesisi267 – 269TVT → AVA: Almost abolishes interaction with FOXK2. 1 Publication3
Mutagenesisi267T → A: Almost abolishes interaction with FOXK2. 1 Publication1
Mutagenesisi269T → A: Almost abolishes interaction with FOXK2. 1 Publication1
Mutagenesisi275Y → F: No effect on interaction with FOXK2. 1 Publication1
Mutagenesisi281S → A: No effect on interaction with FOXK2. 1 Publication1
Mutagenesisi286S → A: No effect on interaction with FOXK2. 1 Publication1
Mutagenesisi295Y → F: No effect on interaction with FOXK2. 1 Publication1
Mutagenesisi298S → A: No effect on interaction with FOXK2. 1 Publication1
Mutagenesisi329S → A: No effect on interaction with FOXK2. 1 Publication1

Organism-specific databases

DisGeNETi1856
OpenTargetsiENSG00000004975
PharmGKBiPA27542

Chemistry databases

ChEMBLiCHEMBL1255125

Polymorphism and mutation databases

BioMutaiDVL2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001457461 – 736Segment polarity protein dishevelled homolog DVL-2Add BLAST736

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei211PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by CSNK1D (PubMed:21422228, PubMed:9192851). WNT3A induces DVL2 phosphorylation by CSNK1E and MARK kinases (PubMed:25805136).3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO14641
MaxQBiO14641
PaxDbiO14641
PeptideAtlasiO14641
PRIDEiO14641
ProteomicsDBi48140

PTM databases

iPTMnetiO14641
PhosphoSitePlusiO14641

Expressioni

Gene expression databases

BgeeiENSG00000004975 Expressed in 220 organ(s), highest expression level in vagina
CleanExiHS_DVL2
ExpressionAtlasiO14641 baseline and differential
GenevisibleiO14641 HS

Organism-specific databases

HPAiCAB009312
HPA021611
HPA022914
HPA064732

Interactioni

Subunit structurei

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). Interacts with DACT1 and FAM105B/otulin. Interacts with DCDC2. Interacts (when phosphorylated) with FOXK1 and FOXK2; the interaction induces DVL2 nuclear translocation (PubMed:25805136). Interacts with MAPK15 (By similarity).By similarity6 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi108189, 171 interactors
CORUMiO14641
DIPiDIP-34433N
IntActiO14641, 147 interactors
MINTiO14641
STRINGi9606.ENSP00000005340

Chemistry databases

BindingDBiO14641

Structurei

Secondary structure

1736
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO14641
SMRiO14641
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14641

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini11 – 93DIXPROSITE-ProRule annotationAdd BLAST83
Domaini267 – 339PDZPROSITE-ProRule annotationAdd BLAST73
Domaini433 – 507DEPPROSITE-ProRule annotationAdd BLAST75

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni250 – 355Required for interaction with FOXK21 PublicationAdd BLAST106

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi7 – 12Poly-Gly6
Compositional biasi235 – 240Poly-Arg6
Compositional biasi686 – 694Poly-Pro9

Domaini

The DIX domain mediates homooligomerization.By similarity

Sequence similaritiesi

Belongs to the DSH family.Curated

Phylogenomic databases

eggNOGiKOG3571 Eukaryota
ENOG410Y5G4 LUCA
GeneTreeiENSGT00390000013552
HOGENOMiHOG000017084
HOVERGENiHBG005542
InParanoidiO14641
KOiK02353
OMAiCENYMAN
OrthoDBiEOG091G041O
PhylomeDBiO14641
TreeFamiTF318198

Family and domain databases

Gene3Di1.10.10.10, 1 hit
3.10.20.380, 1 hit
InterProiView protein in InterPro
IPR000591 DEP_dom
IPR024580 Dishevelled_C-dom
IPR008339 Dishevelled_fam
IPR003351 Dishevelled_protein_dom
IPR001158 DIX
IPR038207 DIX_dom_sf
IPR015506 Dsh/Dvl-rel
IPR008341 DVL2
IPR001478 PDZ
IPR036034 PDZ_sf
IPR029071 Ubiquitin-like_domsf
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PANTHERiPTHR10878 PTHR10878, 1 hit
PTHR10878:SF8 PTHR10878:SF8, 1 hit
PfamiView protein in Pfam
PF00610 DEP, 1 hit
PF02377 Dishevelled, 1 hit
PF00778 DIX, 1 hit
PF12316 Dsh_C, 1 hit
PF00595 PDZ, 1 hit
PRINTSiPR01760 DISHEVELLED
PR01762 DISHEVELLED2
SMARTiView protein in SMART
SM00021 DAX, 1 hit
SM00049 DEP, 1 hit
SM00228 PDZ, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF50156 SSF50156, 1 hit
SSF54236 SSF54236, 1 hit
PROSITEiView protein in PROSITE
PS50186 DEP, 1 hit
PS50841 DIX, 1 hit
PS50106 PDZ, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

O14641-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAGSSTGGGG VGETKVIYHL DEEETPYLVK IPVPAERITL GDFKSVLQRP 
        60         70         80         90        100
AGAKYFFKSM DQDFGVVKEE ISDDNARLPC FNGRVVSWLV SSDNPQPEMA 
       110        120        130        140        150
PPVHEPRAEL APPAPPLPPL PPERTSGIGD SRPPSFHPNV SSSHENLEPE 
       160        170        180        190        200
TETESVVSLR RERPRRRDSS EHGAGGHRTG GPSRLERHLA GYESSSTLMT 
       210        220        230        240        250
SELESTSLGD SDEEDTMSRF SSSTEQSSAS RLLKRHRRRR KQRPPRLERT 
       260        270        280        290        300
SSFSSVTDST MSLNIITVTL NMEKYNFLGI SIVGQSNERG DGGIYIGSIM 
       310        320        330        340        350
KGGAVAADGR IEPGDMLLQV NDMNFENMSN DDAVRVLRDI VHKPGPIVLT 
       360        370        380        390        400
VAKCWDPSPQ AYFTLPRNEP IQPIDPAAWV SHSAALTGTF PAYPGSSSMS 
       410        420        430        440        450
TITSGSSLPD GCEGRGLSVH TDMASVTKAM AAPESGLEVR DRMWLKITIP 
       460        470        480        490        500
NAFLGSDVVD WLYHHVEGFP ERREARKYAS GLLKAGLIRH TVNKITFSEQ 
       510        520        530        540        550
CYYVFGDLSG GCESYLVNLS LNDNDGSSGA SDQDTLAPLP GATPWPLLPT 
       560        570        580        590        600
FSYQYPAPHP YSPQPPPYHE LSSYTYGGGS ASSQHSEGSR SSGSTRSDGG 
       610        620        630        640        650
AGRTGRPEER APESKSGSGS ESEPSSRGGS LRRGGEASGT SDGGPPPSRG 
       660        670        680        690        700
STGGAPNLRA HPGLHPYGPP PGMALPYNPM MVVMMPPPPP PVPPAVQPPG 
       710        720        730 
APPVRDLGSV PPELTASRQS FHMAMGNPSE FFVDVM
Length:736
Mass (Da):78,948
Last modified:January 1, 1998 - v1
Checksum:i4BAD95B6C3FE531B
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
I3L2N2I3L2N2_HUMAN
Segment polarity protein dishevelle...
DVL2
730Annotation score:
I3L0Z8I3L0Z8_HUMAN
Segment polarity protein dishevelle...
DVL2
300Annotation score:
I3L2W9I3L2W9_HUMAN
Segment polarity protein dishevelle...
DVL2
363Annotation score:
I3L0M7I3L0M7_HUMAN
Segment polarity protein dishevelle...
DVL2
291Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_064708282I → T Found in a renal cell carcinoma case; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS11091.1
RefSeqiNP_004413.1, NM_004422.2
UniGeneiHs.118640

Genome annotation databases

EnsembliENST00000005340; ENSP00000005340; ENSG00000004975
GeneIDi1856
KEGGihsa:1856
UCSCiuc002gez.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS11091.1
RefSeqiNP_004413.1, NM_004422.2
UniGeneiHs.118640

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2REYX-ray1.55A261-355[»]
3CBXX-ray1.70A/B264-354[»]
3CBYX-ray1.50A/B264-354[»]
3CBZX-ray1.38A264-354[»]
3CC0X-ray1.75A/B/C264-354[»]
4WIPX-ray2.69A/B/C12-106[»]
5LNPX-ray1.99A/B/C/D416-510[»]
5SUYX-ray1.88A/B/C/D416-510[»]
5SUZX-ray1.84A/B416-509[»]
ProteinModelPortaliO14641
SMRiO14641
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108189, 171 interactors
CORUMiO14641
DIPiDIP-34433N
IntActiO14641, 147 interactors
MINTiO14641
STRINGi9606.ENSP00000005340

Chemistry databases

BindingDBiO14641
ChEMBLiCHEMBL1255125

PTM databases

iPTMnetiO14641
PhosphoSitePlusiO14641

Polymorphism and mutation databases

BioMutaiDVL2

Proteomic databases

EPDiO14641
MaxQBiO14641
PaxDbiO14641
PeptideAtlasiO14641
PRIDEiO14641
ProteomicsDBi48140

Protocols and materials databases

DNASUi1856
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000005340; ENSP00000005340; ENSG00000004975
GeneIDi1856
KEGGihsa:1856
UCSCiuc002gez.2 human

Organism-specific databases

CTDi1856
DisGeNETi1856
EuPathDBiHostDB:ENSG00000004975.11
GeneCardsiDVL2
HGNCiHGNC:3086 DVL2
HPAiCAB009312
HPA021611
HPA022914
HPA064732
MIMi602151 gene
neXtProtiNX_O14641
OpenTargetsiENSG00000004975
PharmGKBiPA27542
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3571 Eukaryota
ENOG410Y5G4 LUCA
GeneTreeiENSGT00390000013552
HOGENOMiHOG000017084
HOVERGENiHBG005542
InParanoidiO14641
KOiK02353
OMAiCENYMAN
OrthoDBiEOG091G041O
PhylomeDBiO14641
TreeFamiTF318198

Enzyme and pathway databases

ReactomeiR-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-201688 WNT mediated activation of DVL
R-HSA-2028269 Signaling by Hippo
R-HSA-4086400 PCP/CE pathway
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-4641258 Degradation of DVL
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5099900 WNT5A-dependent internalization of FZD4
R-HSA-5368598 Negative regulation of TCF-dependent signaling by DVL-interacting proteins
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828 Clathrin-mediated endocytosis
SignaLinkiO14641
SIGNORiO14641

Miscellaneous databases

ChiTaRSiDVL2 human
EvolutionaryTraceiO14641
GeneWikiiDVL2
GenomeRNAii1856
PROiPR:O14641
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000004975 Expressed in 220 organ(s), highest expression level in vagina
CleanExiHS_DVL2
ExpressionAtlasiO14641 baseline and differential
GenevisibleiO14641 HS

Family and domain databases

Gene3Di1.10.10.10, 1 hit
3.10.20.380, 1 hit
InterProiView protein in InterPro
IPR000591 DEP_dom
IPR024580 Dishevelled_C-dom
IPR008339 Dishevelled_fam
IPR003351 Dishevelled_protein_dom
IPR001158 DIX
IPR038207 DIX_dom_sf
IPR015506 Dsh/Dvl-rel
IPR008341 DVL2
IPR001478 PDZ
IPR036034 PDZ_sf
IPR029071 Ubiquitin-like_domsf
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PANTHERiPTHR10878 PTHR10878, 1 hit
PTHR10878:SF8 PTHR10878:SF8, 1 hit
PfamiView protein in Pfam
PF00610 DEP, 1 hit
PF02377 Dishevelled, 1 hit
PF00778 DIX, 1 hit
PF12316 Dsh_C, 1 hit
PF00595 PDZ, 1 hit
PRINTSiPR01760 DISHEVELLED
PR01762 DISHEVELLED2
SMARTiView protein in SMART
SM00021 DAX, 1 hit
SM00049 DEP, 1 hit
SM00228 PDZ, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF50156 SSF50156, 1 hit
SSF54236 SSF54236, 1 hit
PROSITEiView protein in PROSITE
PS50186 DEP, 1 hit
PS50841 DIX, 1 hit
PS50106 PDZ, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDVL2_HUMAN
AccessioniPrimary (citable) accession number: O14641
Secondary accession number(s): D3DTN3, Q53XM0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 191 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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