Protein: Dapper homolog 1 (hDPR1) (Dapper antagonist of catenin 1) (Hepatocellular carcinoma novel gene 3 protein) (Q9NYF0)
Organism: Homo sapiens (Human)
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.
Subcellular location: Cytoplasm. Nucleus. Synapse {ECO:0000250}. 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.
Sequence: MKPSPAGTAKELEPPAPARGEQRTAEPEGRWREKGEADTERQRTRERQEATLAGLAELEYLRQRQELLVRGALRGAGGAGAAAPRAGELLGEAAQRSRLEEKFLEENILLLRKQLNCLRRRDAGLLNQLQELDKQISDLRLDVEKTSEEHLETDSRPSSGFYELSDGASGSLSNSSNSVFSECLSSCHSSTCFCSPLEATLSLSDGCPKSADLIGLLEYKEGHCEDQASGAVCRSLSTPQFNSLDVIADVNPKYQCDLVSKNGNDVYRYPSPLHAVAVQSPMFLLCLTGNPLREEDRLGNHASDICGGSELDAVKTDSSLPSPSSLWSASHPSSSKKMDGYILSLVQKKTHPVRTNKPRTSVNADPTKGLLRNGSVCVRAPGGVSQGNSVNLKNSKQACLPSGGIPSLNNGTFSPPKQWSKESKAEQAESKRVPLPEGCPSGAASDLQSKHLPKTAKPASQEHARCSAIGTGESPKESAQLSGASPKESPSRGPAPPQENKVVQPLKKMSQKNSLQGVPPATPPLLSTAFPVEERPALDFKSEGSSQSLEEAHLVKAQFIPGQQPSVRLHRGHRNMGVVKNSSLKHRGPALQGLENGLPTVREKTRAGSKKCRFPDDLDTNKKLKKASSKGRKSGGGPEAGVPGRPAGGGHRAGSRAHGHGREAVVAKPKHKRTDYRRWKSSAEISYEEALRRARRGRRENVGLYPAPVPLPYASPYAYVASDSEYSAECESLFHSTVVDTSEDEQSNYTTNCFGDSESSVSEGEFVGESTTTSDSEESGGLIWSQFVQTLPIQTVTAPDLHNHPAKTFVKIKASHNLKKKILRFRSGSLKLMTTV
InterPro domains: - IPR024843: Dapper (family) [25-836]
Interaction partners: - Segment polarity protein dishevelled homolog DVL-2
- Segment polarity protein dishevelled homolog DVL-1
- Vang-like protein 2
- Segment polarity protein dishevelled homolog DVL-3
- Catenin beta-1
- SEC14 domain and spectrin repeat-containing protein 1
- Vang-like protein 1
- Catenin delta-1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0019899 (enzyme binding), GO:0051018 (protein kinase A binding), GO:0019900 (kinase binding), GO:0019901 (protein kinase binding), GO:0005080 (protein kinase C binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0048519 (negative regulation of biological process), GO:0023057 (negative regulation of signaling), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0023051 (regulation of signaling), GO:0048523 (negative regulation of cellular process), GO:0048585 (negative regulation of response to stimulus), GO:0009968 (negative regulation of signal transduction), GO:0010648 (negative regulation of cell communication), GO:0010646 (regulation of cell communication), GO:0080134 (regulation of response to stress), GO:0080135 (regulation of cellular response to stress), GO:0009966 (regulation of signal transduction), GO:0070302 (regulation of stress-activated protein kinase signaling cascade), GO:1902532 (negative regulation of intracellular signal transduction), GO:1902531 (regulation of intracellular signal transduction), GO:0043408 (regulation of MAPK cascade), GO:0070303 (negative regulation of stress-activated protein kinase signaling cascade), GO:0032872 (regulation of stress-activated MAPK cascade), GO:0043409 (negative regulation of MAPK cascade), GO:0032873 (negative regulation of stress-activated MAPK cascade), GO:0046328 (regulation of JNK cascade), GO:0046329 (negative regulation of JNK cascade)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043229 (intracellular organelle), GO:0043233 (organelle lumen), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)