Q9NYF0 · DACT1_HUMAN
- ProteinDapper homolog 1
- GeneDACT1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids836 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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
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
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDapper homolog 1
- Short nameshDPR1
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9NYF0
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Involvement in disease
Neural tube defects (NTD)
- Note
- 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 alsoMIM:182940
Natural variants in NTD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_068427 | 45 | R>W | in NTD; uncertain significance; does not affect interaction with DVL2; does not affect subcellular location; increases RHOA activation but decreases the ability to activate JNK; dbSNP:rs778976254 | |
VAR_068429 | 356 | N>K | in NTD; does not affect interaction with DVL2; does not affect subcellular location; results in reduced RHOA and JNK activation |
Townes-Brocks syndrome 2 (TBS2)
- Note
- 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 alsoMIM:617466
Natural variants in TBS2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_080125 | 419-836 | missing | in TBS2; the mutant protein is stable and expressed |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_068427 | 45 | in NTD; uncertain significance; does not affect interaction with DVL2; does not affect subcellular location; increases RHOA activation but decreases the ability to activate JNK; dbSNP:rs778976254 | |||
Sequence: R → W | ||||||
Natural variant | VAR_036461 | 124 | in a colorectal cancer sample; somatic mutation | |||
Sequence: G → C | ||||||
Mutagenesis | 132 | Abolishes nuclear export; when associated with A-136. | ||||
Sequence: L → A | ||||||
Mutagenesis | 136 | Abolishes nuclear export; when associated with A-132. | ||||
Sequence: I → A | ||||||
Natural variant | VAR_068428 | 142 | found in a patient with craniorachischisis; uncertain significance | |||
Sequence: D → G | ||||||
Mutagenesis | 237 | Impairs interaction with YWHAB. Abolishes interaction with YWHAB; when associated with A-827. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_068429 | 356 | in NTD; does not affect interaction with DVL2; does not affect subcellular location; results in reduced RHOA and JNK activation | |||
Sequence: N → K | ||||||
Natural variant | VAR_080125 | 419-836 | in TBS2; the mutant protein is stable and expressed | |||
Sequence: Missing | ||||||
Natural variant | VAR_053057 | 446 | in dbSNP:rs34015825 | |||
Sequence: D → N | ||||||
Natural variant | VAR_053058 | 464 | in dbSNP:rs17832998 | |||
Sequence: A → V | ||||||
Mutagenesis | 622-623 | Partial nuclear accumulation upon LMB treatment. | ||||
Sequence: KK → AA | ||||||
Natural variant | VAR_053059 | 628 | in dbSNP:rs17094821 | |||
Sequence: S → A | ||||||
Natural variant | VAR_036462 | 682 | in a colorectal cancer sample; somatic mutation; dbSNP:rs1198900887 | |||
Sequence: S → L | ||||||
Natural variant | VAR_053060 | 697 | in dbSNP:rs698025 | |||
Sequence: G → S | ||||||
Natural variant | VAR_068430 | 702 | found in a patient with closed spina bifida; uncertain significance; dbSNP:rs1028180302 | |||
Sequence: V → G | ||||||
Natural variant | VAR_068431 | 800 | in dbSNP:rs773720154 | |||
Sequence: D → G | ||||||
Natural variant | VAR_068432 | 808 | found in a patient with encephalocele; uncertain significance | |||
Sequence: T → K | ||||||
Mutagenesis | 827 | Abolishes interaction with YWHAB; when associated with A-237. | ||||
Sequence: S → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,180 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000191353 | 1-836 | Dapper homolog 1 | |||
Sequence: MKPSPAGTAKELEPPAPARGEQRTAEPEGRWREKGEADTERQRTRERQEATLAGLAELEYLRQRQELLVRGALRGAGGAGAAAPRAGELLGEAAQRSRLEEKFLEENILLLRKQLNCLRRRDAGLLNQLQELDKQISDLRLDVEKTSEEHLETDSRPSSGFYELSDGASGSLSNSSNSVFSECLSSCHSSTCFCSPLEATLSLSDGCPKSADLIGLLEYKEGHCEDQASGAVCRSLSTPQFNSLDVIADVNPKYQCDLVSKNGNDVYRYPSPLHAVAVQSPMFLLCLTGNPLREEDRLGNHASDICGGSELDAVKTDSSLPSPSSLWSASHPSSSKKMDGYILSLVQKKTHPVRTNKPRTSVNADPTKGLLRNGSVCVRAPGGVSQGNSVNLKNSKQACLPSGGIPSLNNGTFSPPKQWSKESKAEQAESKRVPLPEGCPSGAASDLQSKHLPKTAKPASQEHARCSAIGTGESPKESAQLSGASPKESPSRGPAPPQENKVVQPLKKMSQKNSLQGVPPATPPLLSTAFPVEERPALDFKSEGSSQSLEEAHLVKAQFIPGQQPSVRLHRGHRNMGVVKNSSLKHRGPALQGLENGLPTVREKTRAGSKKCRFPDDLDTNKKLKKASSKGRKSGGGPEAGVPGRPAGGGHRAGSRAHGHGREAVVAKPKHKRTDYRRWKSSAEISYEEALRRARRGRRENVGLYPAPVPLPYASPYAYVASDSEYSAECESLFHSTVVDTSEDEQSNYTTNCFGDSESSVSEGEFVGESTTTSDSEESGGLIWSQFVQTLPIQTVTAPDLHNHPAKTFVKIKASHNLKKKILRFRSGSLKLMTTV | ||||||
Modified residue | 237 | Phosphoserine; by PKA | ||||
Sequence: S | ||||||
Modified residue | 827 | Phosphoserine; by PKA | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
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
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
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9NYF0 | CTNNB1 P35222 | 3 | EBI-3951744, EBI-491549 | |
BINARY | Q9NYF0 | DVL2 O14641 | 6 | EBI-3951744, EBI-740850 | |
BINARY | Q9NYF0 | GSK3B P49841 | 3 | EBI-3951744, EBI-373586 | |
BINARY | Q9NYF0 | YWHAB P31946 | 4 | EBI-3951744, EBI-359815 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, coiled coil, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-47 | Disordered | ||||
Sequence: MKPSPAGTAKELEPPAPARGEQRTAEPEGRWREKGEADTERQRTRER | ||||||
Compositional bias | 23-47 | Basic and acidic residues | ||||
Sequence: RTAEPEGRWREKGEADTERQRTRER | ||||||
Region | 92-156 | Required for self-association | ||||
Sequence: EAAQRSRLEEKFLEENILLLRKQLNCLRRRDAGLLNQLQELDKQISDLRLDVEKTSEEHLETDSR | ||||||
Coiled coil | 92-156 | |||||
Sequence: EAAQRSRLEEKFLEENILLLRKQLNCLRRRDAGLLNQLQELDKQISDLRLDVEKTSEEHLETDSR | ||||||
Motif | 132-141 | Nuclear export signal | ||||
Sequence: LDKQISDLRL | ||||||
Region | 316-335 | Disordered | ||||
Sequence: TDSSLPSPSSLWSASHPSSS | ||||||
Region | 350-374 | Disordered | ||||
Sequence: THPVRTNKPRTSVNADPTKGLLRNG | ||||||
Compositional bias | 401-421 | Polar residues | ||||
Sequence: PSGGIPSLNNGTFSPPKQWSK | ||||||
Region | 401-521 | Disordered | ||||
Sequence: PSGGIPSLNNGTFSPPKQWSKESKAEQAESKRVPLPEGCPSGAASDLQSKHLPKTAKPASQEHARCSAIGTGESPKESAQLSGASPKESPSRGPAPPQENKVVQPLKKMSQKNSLQGVPPA | ||||||
Compositional bias | 473-487 | Polar residues | ||||
Sequence: ESPKESAQLSGASPK | ||||||
Compositional bias | 504-521 | Polar residues | ||||
Sequence: QPLKKMSQKNSLQGVPPA | ||||||
Region | 588-679 | Disordered | ||||
Sequence: GPALQGLENGLPTVREKTRAGSKKCRFPDDLDTNKKLKKASSKGRKSGGGPEAGVPGRPAGGGHRAGSRAHGHGREAVVAKPKHKRTDYRRW | ||||||
Compositional bias | 604-625 | Basic and acidic residues | ||||
Sequence: KTRAGSKKCRFPDDLDTNKKLK | ||||||
Motif | 610-623 | Bipartite nuclear localization signal | ||||
Sequence: KKCRFPDDLDTNKK | ||||||
Compositional bias | 656-670 | Basic and acidic residues | ||||
Sequence: RAHGHGREAVVAKPK | ||||||
Motif | 826-836 | PDZ-binding | ||||
Sequence: RSGSLKLMTTV |
Domain
The C-terminal PDZ-binding motif mediates interaction with the PDZ domains of DSH (Dishevelled) family proteins.
Sequence similarities
Belongs to the dapper family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9NYF0-1
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.
- Name1
- SynonymsAlpha, Long
- Length836
- Mass (Da)90,174
- Last updated2003-08-15 v2
- Checksum10B77DC5B7C73485
Q9NYF0-2
- Name2
- SynonymsBeta, Short
- Differences from canonical
- 213-249: Missing
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 23-47 | Basic and acidic residues | ||||
Sequence: RTAEPEGRWREKGEADTERQRTRER | ||||||
Alternative sequence | VSP_044198 | 213-249 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 401-421 | Polar residues | ||||
Sequence: PSGGIPSLNNGTFSPPKQWSK | ||||||
Compositional bias | 473-487 | Polar residues | ||||
Sequence: ESPKESAQLSGASPK | ||||||
Compositional bias | 504-521 | Polar residues | ||||
Sequence: QPLKKMSQKNSLQGVPPA | ||||||
Compositional bias | 604-625 | Basic and acidic residues | ||||
Sequence: KTRAGSKKCRFPDDLDTNKKLK | ||||||
Compositional bias | 656-670 | Basic and acidic residues | ||||
Sequence: RAHGHGREAVVAKPK |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL133312 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BX161433 EMBL· GenBank· DDBJ | CAD61905.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AF251079 EMBL· GenBank· DDBJ | AAF65569.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BK000256 EMBL· GenBank· DDBJ | DAA00310.1 EMBL· GenBank· DDBJ | mRNA |