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Protein

Dapper homolog 1

Gene

DACT1

Organism
Homo sapiens (Human)
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. 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 (By similarity). 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. 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: ParkinsonsUK-UCL
  • protein kinase A binding Source: UniProtKB
  • protein kinase C binding Source: UniProtKB
  • RNA polymerase II transcription factor binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • embryonic hindgut morphogenesis Source: UniProtKB
  • negative regulation of beta-catenin-TCF complex assembly Source: ParkinsonsUK-UCL
  • negative regulation of canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • 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: ParkinsonsUK-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • neural tube development Source: ParkinsonsUK-UCL
  • positive regulation of catenin import into nucleus Source: UniProtKB
  • positive regulation of cellular protein catabolic process Source: ParkinsonsUK-UCL
  • positive regulation of protein binding Source: ParkinsonsUK-UCL
  • 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
  • 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

BioCyciZFISH:ENSG00000165617-MONOMER.
ReactomeiR-HSA-4641258. Degradation of DVL.
SIGNORiQ9NYF0.

Names & Taxonomyi

Protein namesi
Recommended name:
Dapper homolog 1
Short name:
hDPR1
Alternative name(s):
Dapper antagonist of catenin 1
Hepatocellular carcinoma novel gene 3 protein
Gene namesi
Name:DACT1
Synonyms:DPR1, HNG3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:17748. DACT1.

Subcellular locationi

  • Cytoplasm
  • Nucleus
  • Cell junctionsynapse By similarity

  • Note: Shuttles between the nucleus and the cytoplasm. Seems to be nuclear in the absence of Wnt signaling and to translocate to the cytoplasm in its presence.

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • nucleoplasm Source: HPA
  • nucleus Source: ParkinsonsUK-UCL
  • synapse Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Nucleus, Synapse

Pathology & Biotechi

Involvement in diseasei

Neural tube defects (NTD)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionCongenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components.
See also OMIM:182940
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06842745R → W in NTD; uncertain pathological significance; does not affect interaction with DVL2; does not affect subcellular location; increases RHOA activation but decreases the ability to activate JNK. 1 PublicationCorresponds to variant rs778976254dbSNPEnsembl.1
Natural variantiVAR_068429356N → K in NTD; does not affect interaction with DVL2; does not affect subcellular location; results in reduced RHOA and JNK activation. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi132L → A: Abolishes nuclear export; when associated with A-136. 1 Publication1
Mutagenesisi136I → A: Abolishes nuclear export; when associated with A-132. 1 Publication1
Mutagenesisi237S → A: Impairs interaction with YWHAB. Abolishes interaction with YWHAB; when associated with A-827. 1
Mutagenesisi622 – 623KK → AA: Partial nuclear accumulation upon LMB treatment. 1 Publication2
Mutagenesisi827S → A: Abolishes interaction with YWHAB; when associated with A-237. 1

Organism-specific databases

DisGeNETi51339.
MalaCardsiDACT1.
MIMi182940. phenotype.
OpenTargetsiENSG00000165617.
Orphaneti63260. Craniorachischisis.
268823. Occipital encephalocele.
PharmGKBiPA134957283.

Polymorphism and mutation databases

BioMutaiDACT1.
DMDMi34098740.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001913531 – 836Dapper homolog 1Add BLAST836

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei237Phosphoserine; by PKA1 Publication1
Modified residuei827Phosphoserine; by PKA1 Publication1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9NYF0.
PaxDbiQ9NYF0.
PeptideAtlasiQ9NYF0.
PRIDEiQ9NYF0.

PTM databases

iPTMnetiQ9NYF0.
PhosphoSitePlusiQ9NYF0.

Expressioni

Gene expression databases

BgeeiENSG00000165617.
CleanExiHS_DACT1.
ExpressionAtlasiQ9NYF0. baseline and differential.
GenevisibleiQ9NYF0. HS.

Organism-specific databases

HPAiHPA003016.

Interactioni

Subunit structurei

Can form homodimers and heterodimers with DACT2 or DACT3. Interacts with CSNK1D, PKA catalytic subunit, PKC-type kinase, CSNK2A1, CSNK2B, DVL1, DVL3, VANGL1, VANGL2, CTNND1 and HDAC1 (By similarity). Interacts with DVL2. Interacts with YWHAB; the interaction is enhanced by PKA phosphorylating DACT1 at Ser-237 and Ser-827. Interacts with CTNNB1 and HDAC1. Interacts with GSK3B; the interaction is indicative for an association of DACT1 with the beta-catenin destruction complex. Interacts with GSK3A.By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CTNNB1P352223EBI-3951744,EBI-491549
DVL2O146416EBI-3951744,EBI-740850
GSK3BP498413EBI-3951744,EBI-373586
YWHABP319464EBI-3951744,EBI-359815

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi119486. 17 interactors.
IntActiQ9NYF0. 22 interactors.
MINTiMINT-8247381.
STRINGi9606.ENSP00000337439.

Structurei

3D structure databases

ProteinModelPortaliQ9NYF0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni92 – 156Required for self-associationBy similarityAdd BLAST65

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili92 – 156Sequence analysisAdd BLAST65

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi132 – 141Nuclear export signal10
Motifi610 – 623Bipartite nuclear localization signalCuratedAdd BLAST14
Motifi826 – 836PDZ-bindingBy similarityAdd BLAST11

Domaini

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

Sequence similaritiesi

Belongs to the dapper family.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410IGBZ. Eukaryota.
ENOG4110UQH. LUCA.
GeneTreeiENSGT00530000063890.
HOGENOMiHOG000015393.
HOVERGENiHBG051286.
InParanoidiQ9NYF0.
OMAiQWSKESK.
OrthoDBiEOG091G02YO.
PhylomeDBiQ9NYF0.
TreeFamiTF331300.

Family and domain databases

InterProiIPR024848. Dact1.
IPR024843. Dapper.
[Graphical view]
PANTHERiPTHR15919. PTHR15919. 2 hits.
PTHR15919:SF12. PTHR15919:SF12. 2 hits.
PfamiPF15268. Dapper. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NYF0-1) [UniParc]FASTAAdd to basket
Also known as: Alpha, Long

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKPSPAGTAK ELEPPAPARG EQRTAEPEGR WREKGEADTE RQRTRERQEA
60 70 80 90 100
TLAGLAELEY LRQRQELLVR GALRGAGGAG AAAPRAGELL GEAAQRSRLE
110 120 130 140 150
EKFLEENILL LRKQLNCLRR RDAGLLNQLQ ELDKQISDLR LDVEKTSEEH
160 170 180 190 200
LETDSRPSSG FYELSDGASG SLSNSSNSVF SECLSSCHSS TCFCSPLEAT
210 220 230 240 250
LSLSDGCPKS ADLIGLLEYK EGHCEDQASG AVCRSLSTPQ FNSLDVIADV
260 270 280 290 300
NPKYQCDLVS KNGNDVYRYP SPLHAVAVQS PMFLLCLTGN PLREEDRLGN
310 320 330 340 350
HASDICGGSE LDAVKTDSSL PSPSSLWSAS HPSSSKKMDG YILSLVQKKT
360 370 380 390 400
HPVRTNKPRT SVNADPTKGL LRNGSVCVRA PGGVSQGNSV NLKNSKQACL
410 420 430 440 450
PSGGIPSLNN GTFSPPKQWS KESKAEQAES KRVPLPEGCP SGAASDLQSK
460 470 480 490 500
HLPKTAKPAS QEHARCSAIG TGESPKESAQ LSGASPKESP SRGPAPPQEN
510 520 530 540 550
KVVQPLKKMS QKNSLQGVPP ATPPLLSTAF PVEERPALDF KSEGSSQSLE
560 570 580 590 600
EAHLVKAQFI PGQQPSVRLH RGHRNMGVVK NSSLKHRGPA LQGLENGLPT
610 620 630 640 650
VREKTRAGSK KCRFPDDLDT NKKLKKASSK GRKSGGGPEA GVPGRPAGGG
660 670 680 690 700
HRAGSRAHGH GREAVVAKPK HKRTDYRRWK SSAEISYEEA LRRARRGRRE
710 720 730 740 750
NVGLYPAPVP LPYASPYAYV ASDSEYSAEC ESLFHSTVVD TSEDEQSNYT
760 770 780 790 800
TNCFGDSESS VSEGEFVGES TTTSDSEESG GLIWSQFVQT LPIQTVTAPD
810 820 830
LHNHPAKTFV KIKASHNLKK KILRFRSGSL KLMTTV
Length:836
Mass (Da):90,174
Last modified:August 15, 2003 - v2
Checksum:i10B77DC5B7C73485
GO
Isoform 2 (identifier: Q9NYF0-2) [UniParc]FASTAAdd to basket
Also known as: Beta, Short

The sequence of this isoform differs from the canonical sequence as follows:
     213-249: Missing.

Show »
Length:799
Mass (Da):86,212
Checksum:iDD6E27684D714681
GO

Sequence cautioni

The sequence AAF65569 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAD61905 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06842745R → W in NTD; uncertain pathological significance; does not affect interaction with DVL2; does not affect subcellular location; increases RHOA activation but decreases the ability to activate JNK. 1 PublicationCorresponds to variant rs778976254dbSNPEnsembl.1
Natural variantiVAR_036461124G → C in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_068428142D → G Found in a patient with craniorachischisis; sporadic case; unknown pathological significance. 1 Publication1
Natural variantiVAR_068429356N → K in NTD; does not affect interaction with DVL2; does not affect subcellular location; results in reduced RHOA and JNK activation. 1 Publication1
Natural variantiVAR_053057446D → N.Corresponds to variant rs34015825dbSNPEnsembl.1
Natural variantiVAR_053058464A → V.1 PublicationCorresponds to variant rs17832998dbSNPEnsembl.1
Natural variantiVAR_053059628S → A.Corresponds to variant rs17094821dbSNPEnsembl.1
Natural variantiVAR_036462682S → L in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_053060697G → S.Corresponds to variant rs698025dbSNPEnsembl.1
Natural variantiVAR_068430702V → G Found in a patient with closed spina bifida; sporadic case; unknown pathological significance. 1 Publication1
Natural variantiVAR_068431800D → G.1 PublicationCorresponds to variant rs773720154dbSNPEnsembl.1
Natural variantiVAR_068432808T → K Found in a patient with encephalocele; sporadic case; unknown pathological significance. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044198213 – 249Missing in isoform 2. CuratedAdd BLAST37

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL133312 Genomic DNA. No translation available.
BX161433 mRNA. Translation: CAD61905.1. Different initiation.
AF251079 mRNA. Translation: AAF65569.1. Different initiation.
BK000256 mRNA. Translation: DAA00310.1.
CCDSiCCDS41961.1. [Q9NYF0-2]
CCDS9736.1. [Q9NYF0-1]
RefSeqiNP_001072988.1. NM_001079520.1. [Q9NYF0-2]
NP_057735.2. NM_016651.5. [Q9NYF0-1]
XP_006720230.1. XM_006720167.3.
UniGeneiHs.48950.
Hs.714204.

Genome annotation databases

EnsembliENST00000335867; ENSP00000337439; ENSG00000165617. [Q9NYF0-1]
ENST00000395153; ENSP00000378582; ENSG00000165617. [Q9NYF0-2]
GeneIDi51339.
KEGGihsa:51339.
UCSCiuc001xdw.4. human. [Q9NYF0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Dapper antagonist of beta-catenin homolog 1 (Xenopus laevis) (DACT1)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL133312 Genomic DNA. No translation available.
BX161433 mRNA. Translation: CAD61905.1. Different initiation.
AF251079 mRNA. Translation: AAF65569.1. Different initiation.
BK000256 mRNA. Translation: DAA00310.1.
CCDSiCCDS41961.1. [Q9NYF0-2]
CCDS9736.1. [Q9NYF0-1]
RefSeqiNP_001072988.1. NM_001079520.1. [Q9NYF0-2]
NP_057735.2. NM_016651.5. [Q9NYF0-1]
XP_006720230.1. XM_006720167.3.
UniGeneiHs.48950.
Hs.714204.

3D structure databases

ProteinModelPortaliQ9NYF0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119486. 17 interactors.
IntActiQ9NYF0. 22 interactors.
MINTiMINT-8247381.
STRINGi9606.ENSP00000337439.

PTM databases

iPTMnetiQ9NYF0.
PhosphoSitePlusiQ9NYF0.

Polymorphism and mutation databases

BioMutaiDACT1.
DMDMi34098740.

Proteomic databases

EPDiQ9NYF0.
PaxDbiQ9NYF0.
PeptideAtlasiQ9NYF0.
PRIDEiQ9NYF0.

Protocols and materials databases

DNASUi51339.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000335867; ENSP00000337439; ENSG00000165617. [Q9NYF0-1]
ENST00000395153; ENSP00000378582; ENSG00000165617. [Q9NYF0-2]
GeneIDi51339.
KEGGihsa:51339.
UCSCiuc001xdw.4. human. [Q9NYF0-1]

Organism-specific databases

CTDi51339.
DisGeNETi51339.
GeneCardsiDACT1.
HGNCiHGNC:17748. DACT1.
HPAiHPA003016.
MalaCardsiDACT1.
MIMi182940. phenotype.
607861. gene.
neXtProtiNX_Q9NYF0.
OpenTargetsiENSG00000165617.
Orphaneti63260. Craniorachischisis.
268823. Occipital encephalocele.
PharmGKBiPA134957283.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGBZ. Eukaryota.
ENOG4110UQH. LUCA.
GeneTreeiENSGT00530000063890.
HOGENOMiHOG000015393.
HOVERGENiHBG051286.
InParanoidiQ9NYF0.
OMAiQWSKESK.
OrthoDBiEOG091G02YO.
PhylomeDBiQ9NYF0.
TreeFamiTF331300.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165617-MONOMER.
ReactomeiR-HSA-4641258. Degradation of DVL.
SIGNORiQ9NYF0.

Miscellaneous databases

ChiTaRSiDACT1. human.
GenomeRNAii51339.
PROiQ9NYF0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165617.
CleanExiHS_DACT1.
ExpressionAtlasiQ9NYF0. baseline and differential.
GenevisibleiQ9NYF0. HS.

Family and domain databases

InterProiIPR024848. Dact1.
IPR024843. Dapper.
[Graphical view]
PANTHERiPTHR15919. PTHR15919. 2 hits.
PTHR15919:SF12. PTHR15919:SF12. 2 hits.
PfamiPF15268. Dapper. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDACT1_HUMAN
AccessioniPrimary (citable) accession number: Q9NYF0
Secondary accession number(s): A8MYJ2, Q86TY0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: August 15, 2003
Last modified: November 2, 2016
This is version 129 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  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. 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.