Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Dapper homolog 1

Gene

Dact1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in regulation of intracellular signaling pathways during development. Specifically thought to play a role in canonical and/or non-canonical Wnt signaling pathways through interaction with DSH (Dishevelled) family proteins. The activation/inhibition of Wnt signaling may depend on the phosphorylation status. Proposed to regulate the degradation of CTNNB1/beta-catenin, thereby modulating the transcriptional activation of target genes of the Wnt signaling pathway. Its function in stabilizing CTNNB1 may involve inhibition of GSK3B activity. Promotes the membrane localization of CTNNB1. The cytoplasmic form can induce DVL2 degradation via a lysosome-dependent mechanism; the function is inhibited by PKA-induced binding to 14-3-3 proteins, such as YWHAB (By similarity). Seems to be involved in morphogenesis at the primitive streak by regulating VANGL2 and DVL2; the function seems to be independent of canonical Wnt signaling and rather involves the non-canonical Wnt/planar cell polarity (PCP) pathway. The nuclear form may prevent the formation of LEF1:CTNNB1 complex and recruit HDAC1 to LEF1 at target gene promoters to repress transcription thus antagonizing Wnt signaling (By similarity). May be involved in positive regulation of fat cell differentiation. During neuronal differentiation may be involved in excitatory synapse organization, and dendrite formation and establishment of spines.By similarity5 Publications

GO - Molecular functioni

  • beta-catenin binding Source: UniProtKB
  • delta-catenin binding Source: UniProtKB
  • histone deacetylase binding Source: MGI
  • protein kinase A binding Source: UniProtKB
  • protein kinase C binding Source: UniProtKB
  • RNA polymerase II transcription factor binding Source: MGI

GO - Biological processi

  • dendrite morphogenesis Source: MGI
  • embryonic hindgut morphogenesis Source: UniProtKB
  • embryonic morphogenesis Source: MGI
  • gastrulation with mouth forming second Source: MGI
  • negative regulation of beta-catenin-TCF complex assembly Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of G1/S transition of mitotic cell cycle Source: UniProtKB
  • negative regulation of JNK cascade Source: UniProtKB
  • negative regulation of protein binding Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • neural tube development Source: MGI
  • positive regulation of catenin import into nucleus Source: UniProtKB
  • positive regulation of cellular protein catabolic process Source: MGI
  • positive regulation of fat cell differentiation Source: MGI
  • positive regulation of protein binding Source: MGI
  • positive regulation of protein catabolic process Source: MGI
  • positive regulation of Wnt signaling pathway Source: UniProtKB
  • regulation of catenin import into nucleus Source: UniProtKB
  • regulation of protein stability Source: UniProtKB
  • regulation of Wnt signaling pathway, planar cell polarity pathway Source: UniProtKB
  • synapse organization Source: MGI
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Neurogenesis, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-4641258. Degradation of DVL.

Names & Taxonomyi

Protein namesi
Recommended name:
Dapper homolog 1
Alternative name(s):
Dapper antagonist of catenin 1
Frodo homolog
MDpr1
Thymus-expressed novel gene 3 protein
Gene namesi
Name:Dact1
Synonyms:Thyex3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:1891740. Dact1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Nucleus, Synapse

Pathology & Biotechi

Disruption phenotypei

Mice die within a day of birth with malformations involving the spine, genitourinary system and distal digestive tract due to disrupted germ-layer morphogenesis at the primitive streak where cells undergo an epithelial-mesenchymal transition. Urogenital defects due to impaired hindgut formation start at embryonic day 8.25. Dvl2 and Vangl2 are found increased at the primitive streak, associated with abnormal distribution of E-cadherin.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 778778Dapper homolog 1PRO_0000191354Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei769 – 7691Phosphoserine; by PKABy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8R4A3.
PRIDEiQ8R4A3.

PTM databases

iPTMnetiQ8R4A3.
PhosphoSiteiQ8R4A3.

Expressioni

Tissue specificityi

Expressed in multiple tissues including brain, heart, kidney, liver and testis.2 Publications

Developmental stagei

Expression strongly increases from E9.5, peaks between E11.5 and E13.5 and diminishes slowly thereafter. Expressed in the somites during segmentation, limb bud mesenchyme, and developing central nervous system. Expressed in primitive streak mesoderm, neuroectoderm, neural crest, presomitic mesoderm and somites.2 Publications

Gene expression databases

BgeeiENSMUSG00000044548.
ExpressionAtlasiQ8R4A3. baseline and differential.
GenevisibleiQ8R4A3. MM.

Interactioni

Subunit structurei

Can form homodimers and heterodimers with DACT2 or DACT3. Interacts with CSNK1D, PKA catalytic subunit, PKC-type kinase, CSNK2A1, CSNK2B, DVL1, DLV2, DVAL3, VANGL1, VANGL2, CTNND1 and HDAC1. Interacts with GSK3B; the interaction is indicative for an association of DACT1 with the beta-catenin destruction complex. Interacts with GSK3A. Interacts with YWHAB; the interaction is enhanced by PKA phosphorylating DACT1 at Ser-769. Interacts with CTNNB1 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Dact3Q0PHV72EBI-3870250,EBI-6392520
Dvl1P511414EBI-3870250,EBI-1538407
Dvl2Q608383EBI-3870250,EBI-641940
Vangl2Q91ZD43EBI-3870250,EBI-1750744

GO - Molecular functioni

  • beta-catenin binding Source: UniProtKB
  • delta-catenin binding Source: UniProtKB
  • histone deacetylase binding Source: MGI
  • protein kinase A binding Source: UniProtKB
  • protein kinase C binding Source: UniProtKB
  • RNA polymerase II transcription factor binding Source: MGI

Protein-protein interaction databases

IntActiQ8R4A3. 20 interactions.
STRINGi10090.ENSMUSP00000117169.

Structurei

3D structure databases

ProteinModelPortaliQ8R4A3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni85 – 14965Required for self-associationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili85 – 14965Sequence analysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi125 – 13410Nuclear export signalBy similarity
Motifi551 – 56414Bipartite nuclear localization signalBy similarityAdd
BLAST
Motifi768 – 77811PDZ-bindingAdd
BLAST

Domaini

The C-terminal PDZ-binding motif mediates interaction with the PDZ domains of DSH (Dishevelled) family proteins.1 Publication

Sequence similaritiesi

Belongs to the dapper family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IGBZ. Eukaryota.
ENOG4110UQH. LUCA.
GeneTreeiENSGT00530000063890.
HOGENOMiHOG000015393.
HOVERGENiHBG051286.
InParanoidiQ8R4A3.
PhylomeDBiQ8R4A3.

Family and domain databases

InterProiIPR024848. Dact1.
IPR024843. Dapper.
[Graphical view]
PANTHERiPTHR15919. PTHR15919. 2 hits.
PTHR15919:SF12. PTHR15919:SF12. 2 hits.
PfamiPF15268. Dapper. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8R4A3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKPDAAREPE PLSPGRGAEA EGRWRERGEA DTERQRTRER QEATLAGLAE
60 70 80 90 100
LGYLRQRQEL LVRGALRCSG TVGTVAPRSG ELRGDAAQRS RLEEKFLEEN
110 120 130 140 150
ILLLRRQLNC LRRRDAGLLN QLQELDKQIS DLRLDVEKTS EEHLETDSRP
160 170 180 190 200
SSGFYELSDG ASGSLSNSSN SVFSECLSSC HSSTCFCSPL EAALTISDGC
210 220 230 240 250
PKSADVNPKY QCDLVSKNGN DVYRYPSPLH AVAVQSPMFL LCLTGNTLRE
260 270 280 290 300
EEGLGSHASD ICIGSELNAT KTDNSLPSPS SLWSASHPAS SKKMDGYILS
310 320 330 340 350
LVQKKTHPVR TNKPRTSVNA DPTKGLLRNG SVCVRAPSGV PPGSSVNFKN
360 370 380 390 400
TKQMCLPAGG ITSLENGPFS PPKQRSKDSK TDQLESKRLA LPESCSAGAA
410 420 430 440 450
MEPQSKHVPK AAKAASQELT RCQAGLGESM KESNQASAVS PKTSPGRGPV
460 470 480 490 500
APAESKALQL PKKMSQKNSL QAVPALDRPA LDFKSEGSSQ SLEEGHLVKA
510 520 530 540 550
QFIPGQQAAA RPHRAHRNPG VARSATLKAR GQAAMEHGLP TVREKPRAAG
560 570 580 590 600
KKCRFPDDSD TNKKFRKTSA KGRRSGGLQD AGLPGRALGT GGHRAGSRAH
610 620 630 640 650
AHGREPVVAK PKHKRTDYRR WKSSAEVSYE EALRRARRAR REHGAAYRVA
660 670 680 690 700
VALPYASPYA YVPSDSEYSA ECESLFHSTV VDTSEDEQSN YTTNCFGDSE
710 720 730 740 750
SSVSEGDFVG ESTTTSDSEE SGGLIWSQFV QTLPIQTVTA PDLHTRPTKT
760 770
FVKIKASHNL KKKILRFRSG SLKLMTTV
Length:778
Mass (Da):84,306
Last modified:June 1, 2002 - v1
Checksum:i31EAD7E9BBA77DE7
GO

Sequence cautioni

The sequence AAF65568 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC36958 differs from that shown. Reason: Frameshift at position 633. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti18 – 192AE → SN in AAO49712 (PubMed:16278878).Curated
Sequence conflicti333 – 3331C → F in AAO49712 (PubMed:16278878).Curated
Sequence conflicti343 – 3431G → V in AAF65568 (Ref. 4) Curated
Sequence conflicti430 – 4301M → I in AAO49712 (PubMed:16278878).Curated
Sequence conflicti510 – 5101A → G in AAF65568 (Ref. 4) Curated
Sequence conflicti511 – 5111R → S in AAO49712 (PubMed:16278878).Curated
Sequence conflicti681 – 6811V → G in AAF65568 (Ref. 4) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF488775 mRNA. Translation: AAM12547.1.
AY208970 mRNA. Translation: AAO49712.1.
AK077691 mRNA. Translation: BAC36958.1. Sequence problems.
AF251078 mRNA. Translation: AAF65568.1. Different initiation.
CCDSiCCDS25963.1.
RefSeqiNP_067507.2. NM_021532.4.
UniGeneiMm.46662.

Genome annotation databases

EnsembliENSMUST00000061273; ENSMUSP00000058943; ENSMUSG00000044548.
GeneIDi59036.
KEGGimmu:59036.
UCSCiuc007nup.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF488775 mRNA. Translation: AAM12547.1.
AY208970 mRNA. Translation: AAO49712.1.
AK077691 mRNA. Translation: BAC36958.1. Sequence problems.
AF251078 mRNA. Translation: AAF65568.1. Different initiation.
CCDSiCCDS25963.1.
RefSeqiNP_067507.2. NM_021532.4.
UniGeneiMm.46662.

3D structure databases

ProteinModelPortaliQ8R4A3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8R4A3. 20 interactions.
STRINGi10090.ENSMUSP00000117169.

PTM databases

iPTMnetiQ8R4A3.
PhosphoSiteiQ8R4A3.

Proteomic databases

PaxDbiQ8R4A3.
PRIDEiQ8R4A3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000061273; ENSMUSP00000058943; ENSMUSG00000044548.
GeneIDi59036.
KEGGimmu:59036.
UCSCiuc007nup.2. mouse.

Organism-specific databases

CTDi51339.
MGIiMGI:1891740. Dact1.

Phylogenomic databases

eggNOGiENOG410IGBZ. Eukaryota.
ENOG4110UQH. LUCA.
GeneTreeiENSGT00530000063890.
HOGENOMiHOG000015393.
HOVERGENiHBG051286.
InParanoidiQ8R4A3.
PhylomeDBiQ8R4A3.

Enzyme and pathway databases

ReactomeiR-MMU-4641258. Degradation of DVL.

Miscellaneous databases

PROiQ8R4A3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000044548.
ExpressionAtlasiQ8R4A3. baseline and differential.
GenevisibleiQ8R4A3. MM.

Family and domain databases

InterProiIPR024848. Dact1.
IPR024843. Dapper.
[Graphical view]
PANTHERiPTHR15919. PTHR15919. 2 hits.
PTHR15919:SF12. PTHR15919:SF12. 2 hits.
PfamiPF15268. Dapper. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDACT1_MOUSE
AccessioniPrimary (citable) accession number: Q8R4A3
Secondary accession number(s): Q80VG9, Q8BP49, Q9JK89
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: June 1, 2002
Last modified: September 7, 2016
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.