ID:DVL1_HUMAN DESCRIPTION: RecName: Full=Segment polarity protein dishevelled homolog DVL-1; Short=Dishevelled-1; AltName: Full=DSH homolog 1; FUNCTION: Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Required for LEF1 activation upon WNT1 and WNT3A signaling. DVL1 and PAK1 form a ternary complex with MUSK which is important for MUSK-dependent regulation of AChR clustering during the formation of the neuromuscular junction (NMJ). SUBUNIT: Interacts with CXXC4. Interacts (via PDZ domain) with NXN (By similarity). Interacts with BRD7 and INVS. Interacts through its PDZ domain with the C-terminal regions of VANGL1, VANGL2 and CCDC88C/DAPLE. Interacts with ARRB1; the interaction is enhanced by phosphorylation of DVL1. Interacts with CYLD (By similarity). Interacts (via PDZ domain) with RYK. Self-associates (via DIX domain) and forms higher homooligomers. Interacts (via PDZ domain) with DACT1 and FZD7, where DACT1 and FZD7 compete for the same binding site (By similarity). Interacts (via DEP domain) with MUSK; the interaction is direct and mediates the formation a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering (By similarity). SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Cytoplasm, cytosol (By similarity). Cytoplasmic vesicle (By similarity). Note=Localizes at the cell membrane upon interaction with frizzled family members (By similarity). DOMAIN: The DIX domain promotes homooligomerization (By similarity). DOMAIN: The DEP domain mediates interaction with the cell membrane (By similarity). PTM: Ubiquitinated; undergoes both 'Lys-48'-linked ubiquitination, leading to its subsequent degradation by the ubiquitin-proteasome pathway, and 'Lys-63'-linked ubiquitination. The interaction with INVS is required for ubiquitination. Deubiquitinated by CYLD, which acts on 'Lys-63'-linked ubiquitin chains (By similarity). SIMILARITY: Belongs to the DSH family. SIMILARITY: Contains 1 DEP domain. SIMILARITY: Contains 1 DIX domain. SIMILARITY: Contains 1 PDZ (DHR) domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14640
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC017225 - Homo sapiens dishevelled, dsh homolog 1 (Drosophila), mRNA (cDNA clone IMAGE:4299758), partial cds. AF006011 - Homo sapiens dishevelled 1 (DVL1) mRNA, complete cds. BC025292 - Homo sapiens cDNA clone IMAGE:4554266, containing frame-shift errors. BC050454 - Homo sapiens dishevelled, dsh homolog 1 (Drosophila), mRNA (cDNA clone MGC:54245 IMAGE:6201003), complete cds. AK093189 - Homo sapiens cDNA FLJ35870 fis, clone TESTI2007998, highly similar to SEGMENT POLARITY PROTEIN DISHEVELLED HOMOLOG DVL-1. AX747980 - Sequence 1505 from Patent EP1308459. AK095867 - Homo sapiens cDNA FLJ38548 fis, clone HCHON2001768, highly similar to Segment polarity protein dishevelled homolog DVL-1. AB209210 - Homo sapiens mRNA for dishevelled 1 isoform a variant protein. JD481672 - Sequence 462696 from Patent EP1572962. BC111419 - Homo sapiens cDNA clone IMAGE:40023756. JD495614 - Sequence 476638 from Patent EP1572962. AK300063 - Homo sapiens cDNA FLJ56879 complete cds, highly similar to Segment polarity protein dishevelled homolog DVL-1. AK293286 - Homo sapiens cDNA FLJ56847 complete cds, highly similar to Segment polarity protein dishevelled homologDVL-1. JD401344 - Sequence 382368 from Patent EP1572962. U46461 - Human dishevelled homolog (DVL) mRNA, complete cds. KJ901396 - Synthetic construct Homo sapiens clone ccsbBroadEn_10790 DVL1 gene, encodes complete protein. AB385564 - Synthetic construct DNA, clone: pF1KB8019, Homo sapiens DVL1 gene for segment polarity protein dishevelled homolog DVL-1, complete cds, without stop codon, in Flexi system. CU690690 - Synthetic construct Homo sapiens gateway clone IMAGE:100021370 5' read DVL1 mRNA. JD476318 - Sequence 457342 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_alkPathway - ALK in cardiac myocytes h_hesPathway - Segmentation Clock h_pitx2Pathway - Multi-step Regulation of Transcription by Pitx2 h_agrPathway - Agrin in Postsynaptic Differentiation h_ps1Pathway - Presenilin action in Notch and Wnt signaling h_gsk3Pathway - Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages h_wntPathway - WNT Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein O14640 (Reactome details) participates in the following event(s):
R-HSA-4641155 DVL1 is bound by the HECT ubiquitin ligase HECW1 R-HSA-4641159 DVL1 is ubiquitinated by HECW1 R-HSA-201717 CSNK2-mediated phosphorylation of DVL R-HSA-1504213 DVL is bound by the CUL3:KLHL12:RBX1 ubiquitin ligase complex R-HSA-5368582 CXXC4 binds DVL to prevent AXIN binding R-NUL-5368583 Cxxc4 binds DVL to prevent AXIN binding R-NUL-5368587 DVL binds Ccdc88c R-HSA-5368588 DVL binds CCDC88C R-HSA-3772435 WNT signaling stimulates CSNK1-dependent phosphorylation of DVL R-HSA-3858482 DVL is recruited to the receptor R-HSA-1504188 FZD recruits DVL to the receptor complex R-HSA-3772434 Phosphorylated DVL recruits PIP5K1B to the plasma membrane R-HSA-3858475 ppDVL recruits RAC R-HSA-3858489 ppDVL binds DAAM1 R-HSA-3858480 WNT-dependent phosphorylation of DVL R-HSA-1504190 DVL is ubiquitinated by CUL3:KLHL12:RBX1 R-HSA-201691 Phosphorylation of LRP5/6 cytoplasmic domain by CSNKI R-NUL-1458902 frog CK1gamma phosphorylates LRP5/6 R-HSA-201677 Phosphorylation of LRP5/6 cytoplasmic domain by membrane-associated GSK3beta R-HSA-1504186 DVL recruits GSK3beta:AXIN1 to the receptor complex R-HSA-3858495 DAAM1 recruits GTP-bound RHOA R-HSA-3965450 DAAM1 recruits PFN1 R-HSA-3772436 DVL-associated PIP5K1B phosphorylates PI4P to PI(4,5)P2 R-HSA-4641258 Degradation of DVL R-HSA-201688 WNT mediated activation of DVL R-HSA-5368598 Negative regulation of TCF-dependent signaling by DVL-interacting proteins R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-4086400 PCP/CE pathway R-HSA-5663220 RHO GTPases Activate Formins R-HSA-195721 Signaling by WNT R-HSA-3858494 Beta-catenin independent WNT signaling R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane R-HSA-195258 RHO GTPase Effectors R-HSA-162582 Signal Transduction R-HSA-194315 Signaling by Rho GTPases