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Protein

Dapper homolog 1

Gene

DACT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 by RNA polymerase II Source: UniProtKB
  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • neural tube development Source: ParkinsonsUK-UCL
  • positive regulation of canonical Wnt signaling pathway 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 canonical Wnt signaling pathway 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

Keywordsi

Molecular functionDevelopmental protein
Biological processNeurogenesis, Wnt signaling pathway

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000165617.14
HGNCiHGNC:17748 DACT1
MIMi607861 gene
neXtProtiNX_Q9NYF0

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 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 dbSNP:rs778976254Ensembl.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
Townes-Brocks syndrome 2 (TBS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Townes-Brocks syndrome, a rare autosomal dominant disease characterized by the triad of imperforate anus, dysplastic ears, and thumb malformations. Minor features of the condition include hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease.
See also OMIM:617466
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080125419 – 836Missing in TBS2; the mutant protein is stable and expressed. 1 PublicationAdd BLAST418

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

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi51339
MalaCardsiDACT1
MIMi182940 phenotype
617466 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

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

Show more details

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, 19 interactors
IntActiQ9NYF0, 22 interactors
MINTiQ9NYF0
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
KOiK22154
OMAiQWSKESK
OrthoDBiEOG091G02YO
PhylomeDBiQ9NYF0
TreeFamiTF331300

Family and domain databases

InterProiView protein in InterPro
IPR024848 Dact1
IPR024843 Dapper
PANTHERiPTHR15919 PTHR15919, 1 hit
PTHR15919:SF12 PTHR15919:SF12, 1 hit
PfamiView protein in Pfam
PF15268 Dapper, 1 hit

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 dbSNP:rs778976254Ensembl.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_080125419 – 836Missing in TBS2; the mutant protein is stable and expressed. 1 PublicationAdd BLAST418
Natural variantiVAR_053057446D → N. Corresponds to variant dbSNP:rs34015825Ensembl.1
Natural variantiVAR_053058464A → V1 PublicationCorresponds to variant dbSNP:rs17832998Ensembl.1
Natural variantiVAR_053059628S → A. Corresponds to variant dbSNP:rs17094821Ensembl.1
Natural variantiVAR_036462682S → L in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_053060697G → S. Corresponds to variant dbSNP:rs698025Ensembl.1
Natural variantiVAR_068430702V → G Found in a patient with closed spina bifida; sporadic case; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs1028180302Ensembl.1
Natural variantiVAR_068431800D → G1 PublicationCorresponds to variant dbSNP:rs773720154Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiDACT1_HUMAN
AccessioniPrimary (citable) accession number: Q9NYF0
Secondary accession number(s): A8MYJ2, Q86TY0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: August 15, 2003
Last modified: May 23, 2018
This is version 141 of the entry and version 2 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

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health