A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals
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FZD7 (originally named FzE3) expression stimulates APC-beta-catenin complex formation and nuclear translocation of beta-catenin
"transfection and expression of the FzE3 cDNA in esophageal carcinoma cells stimulates complex formation between adenomatous polyposis coli (APC) and beta-catenin followed by nuclear translocation of beta-catenin"
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Coexpression with Lef-1 enhances beta-catenin translocation to nucleus
"coexpression of FzE3 with Lef-1 transcription factor enhanced beta-catenin translocation to the nucleus"
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C-terminal truncation completely inhibits APC-beta-catenin interaction
"cotransfection of a mutant construct encoding a FzE3 protein with a C-terminal truncation completely inhibited the interaction of APC with beta-catenin in cells"
Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling
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CCDC88C/DAPLE binds FZD7 following ligand activation
"Daple preferentially binds the cytoplasmic tail of the FZD7R"
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DAPLE binding displaces DVL1 from FZD7
"Daple competes with Dvl for binding to FZDRs and antagonizes Wnt signaling via the β-catenin/TCF/LEF pathway"
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This leads to inhibition of canonical Wnt signaling and activation of non-canonical Wnt responses
"This triggers non-canonical Wnt responses, that is, suppresses the β-catenin/TCF/LEF pathway and tumorigenesis, but enhances PI3K-Akt and Rac1 signals"
Frizzled proteins are colonic epithelial receptors for C. difficile toxin B
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FZD7 acts as a receptor for C. difficile toxin TcdB in colonic epithelium
"TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7"
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Frizzled proteins constitute the major host receptors for TcdB
"These findings establish FZDs as physiologically relevant receptors for TcdB in the colonic epithelium"
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling
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FZD7 binds SDCBP/syntenin via its C-terminal PDZ-binding motif
"The PDZ domains of syntenin also interact for example with certain Frizzled receptors (for example, Frizzled 3, -7 and -8)"
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Interaction is enhanced by inositol trisphosphate (IP3)
"The presence of 0.5 mM IP3 increases the apparent affinity of syntenin PDZ2 for Frizzled 7"
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K569 is essential for SDCBP-mediated PIP2 recognition at plasma membrane
"We determine that asparagine 215, and lysines 214 and 250 in the PDZ2 domain, and lysine 569 in Frizzled 7 (further referred to as lysine-5 in the carboxy-terminal fragment) are essential for membrane PIP2-specific recognition"
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FZD7 localizes to plasma membrane with PIP2 or recycling endosomes otherwise
"When co-expressed, Frizzled 7 and eYFP-PDZ1-PDZ2 strongly localize to the plasma membrane"
Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells
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FZD7 knockdown decreases c-Jun expression, JNK phosphorylation, and RhoA activation
"the band intensities of c-Jun, p-JNK and p-c-Jun were decreased by FZD7_siRNA"
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FZD7 mediates both canonical and non-canonical (JNK/RhoA) Wnt signaling in colon cancer
"FZD7 may be involved in enhancement of survival, invasion and metastatic capabilities of colon cancer cells through non-canonical Wnt signalling pathways as well as the canonical pathway"
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Higher FZD7 expression correlates with poor prognosis in colorectal cancer
"overall survival was shorter in those patients with higher FZD7 expression (P<0.001)"
Direct interaction between NHERF1 and Frizzled regulates β-catenin signaling.
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NHERF1 directly binds FZD7 via its PDZ2 domain
"Fzd4 interacts preferentially with PDZ2"
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NHERF1 binding inhibits canonical Wnt/beta-catenin signaling
"Fzds 2, 4 and 7 showed impaired Wnt-induced β-catenin activation in the presence of NHERF1 (76%, 86% and 74% decrease, respectively)"
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NHERF1 interferes with FZD7-DVL binding and reduces receptor internalization
"the binding of NHERF1 to Fzd should reduce Fzd-Dvl pre-coupling and result in impaired Wnt-induced Fzd internalization"
The WNT receptor FZD7 contributes to self-renewal signaling of human embryonic stem cells
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FZD7 is 200-fold higher in hESCs compared to differentiated cells
"FZD7 mRNA levels in human ES cells are up to 200-fold higher compared to differentiated cell types"
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FZD7 knockdown causes rapid loss of OCT4 expression and stem cell morphology
"ShRNA-mediated knockdown of FZD7 in human ES cells induced dramatic changes in the morphology of ES cell colonies, perturbation of expression levels of germ layer-specific marker genes, and a rapid loss of expression of the ES cell-specific transcription factor OCT4"
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FZD7 is essential for ES cell self-renewal capacity
"These findings identify the WNT receptor FZD7 as a novel ES cell-specific surface antigen with a likely important role in the maintenance of ES cell self-renewal capacity"
Mapping of Wnt-Frizzled interactions by multiplex CRISPR targeting of receptor gene families
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Systematic mapping of Wnt-FZD interactions using CRISPR screening
"we generated cell lines with multiplex mutant alleles of FZD1, FZD2, and FZD7 and demonstrate that these cells are unresponsive to canonical Wnt ligands"
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FZD7 demonstrated Wnt receptor activity in canonical pathway activation
"we performed genetic rescue experiments with combinations of FZDs and canonical Wnts to create a functional ligand-receptor interaction map"
Myocilin is a modulator of Wnt signaling
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MYOC interacts with FZD7
"Interaction of myocilin with sFRP1, sFRP3, and several Frizzled receptors was confirmed by immunoprecipitation experiments"
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This interaction modulates Wnt signaling
"Treatment of NIH 3T3 cells with myocilin and its fragments induced intracellular redistribution of beta-catenin"
The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling.
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Syntenin/SDCBP directly binds FZD7 C-terminus via PDZ domain
"syntenin also interacts with the C-terminal PDZ binding motif of several Frizzled Wnt receptors"
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Supports non-canonical Wnt signaling via JNK pathway
"Syntenin stimulates c-jun phosphorylation and modulates Frizzled 7 signaling, in particular the PKCalpha/CDC42 noncanonical Wnt signaling cascade"
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FZD7 localizes to plasma membrane
"syntenin-Frizzled 7 binding mode indicates syntenin can accommodate Frizzled 7-syndecan complexes"
Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells
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Wnt3 physically binds FZD7
"a specific Wnt3-FZD7 interaction was observed by co-immunoprecipitation experiments, which suggest that the action of Wnt3 was mediated via FZD7"
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FZD7-Wnt3 interaction activates canonical Wnt/beta-catenin signaling in HCC
"Activation of the Wnt/beta-catenin pathway in FOCUS-Wnt3 cells was demonstrated by beta-catenin accumulation, enhanced TCF transcriptional activity and proliferation rate"
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Promotes epithelial cell proliferation in wound healing
"The activation of Wnt/beta-catenin signaling in FOCUS-Wnt3 was abolished by a knockdown of FZD7 expression by siRNA"
Sequence requirement and subtype specificity in the high-affinity interaction between human frizzled and dishevelled proteins
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FZD7 C-terminal KTXXXW motif mediates high-affinity DVL binding via PDZ domain
"The Dvl PDZ domain is known to interact directly with a peptide derived from the KTXXXW motif of Fz7, which is conserved in all known Fz subtypes"
Ror2 modulates the canonical Wnt signaling in lung epithelial cells through cooperation with Fzd2
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FZD7 participates in canonical Wnt signaling in lung epithelial cells
"we transiently expressed Fzd 2 and Fzd7, two receptors shown to mediate Wnt3a signaling in 293 cells"
Overexpression of microRNA-1 promotes cardiomyocyte commitment from human cardiovascular progenitors via suppressing WNT and FGF signaling pathways
Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease.
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FZD7 involved in planar cell polarity Wnt signaling
"Wnt signaling regulates multiple cellular functions and cell systems, including the development and maintenance of midbrain dopaminergic (mDA) neurons"
Frizzled-7 dictates three-dimensional organization of colorectal cancer cell carcinoids.
Regulation of endothelial cell cytoskeletal reorganization by a secreted frizzled-related protein-1 and frizzled 4- and frizzled 7-dependent pathway: role in neovessel formation.
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FZD7 affects cell-substrate adhesion in endothelial cells
"sFRP-1 can interact with Wnt receptors Frizzled 4 and 7 on endothelial cells to transduce downstream to cellular machineries requiring Rac-1 activity"
Deep research synthesis for FZD7
Falcon deep research synthesis for FZD7
Structural basis of frizzled 7 activation and allosteric regulation.
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Cryo-EM structure of inactive human FZD7 at 1.9 Å reveals an internal water pocket and a conserved cholesterol-binding site.
"Here, we apply state-of-the-art cryo-EM to elucidate the apo structure of FZD7 with an overall resolution of 1.9 Å (FSC 0.143)."
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A conserved cholesterol-binding site is critical for FZD7-DVL association and downstream WNT/β-catenin signalosome formation.
"we identified a conserved cholesterol-binding site, which displays a key role in FZD7 association with a transducer protein, Disheveled (DVL), and initiation of downstream signaling and signalosome formation."
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Disrupting cholesterol-interacting residues (F345/H382/W386) abrogates DEP recruitment by FZD7 and reduces WNT-3A-induced TOPFlash signaling without affecting constitutive Gs coupling.
"The double mutants completely abrogated FZD7-DEP recruitment, suggesting that cholesterol plays a key role in constitutive DVL recruitment by FZDs"
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FZD7 shows selectivity towards DVL over heterotrimeric G proteins owing to a R6.32-W7.55 hinge limiter that restricts TM6 opening.
"the molecular switch R6.32-W7.55 acts as a hinge limiter (Fig. 3c, d) permitting only a restricted TM6 opening (11°, 5.5 Å). Hence, the open conformation of FZDs remains suboptimal for G protein coupling providing a rational explanation for the limited capacity of FZDs to couple to heterotrimeric G proteins and their propensity to display selectivity towards DVL over heterotrimeric G proteins"
Pathway selectivity in Frizzleds is achieved by conserved micro-switches defining pathway-determining, active conformations.
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Frizzleds prefer DVL over heterotrimeric G proteins and conserved active-state micro-switches in the receptor determine transducer selection.
"FZDs prefer coupling to DVL rather than heterotrimeric G proteins and that distinct active state micro-switches in the receptor are essential for pathway selection arguing for conformational changes in the receptor protein defining transducer selectivity."
E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled receptors.
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RNF43 preferentially down-regulates FZD1/FZD5/FZD7 via endocytosis, controlling FZD7 surface abundance.
"We find that RNF43 preferentially down-regulates FZD1/FZD5/FZD7, whereas ZNRF3 displays a preference towards FZD6."
Inferred from Sequence Similarity
UniProt Keywords to GO mapping
UniProt Subcellular Location to GO mapping
Phylogenetic annotation based on PANTHER
Automatic annotation by UniProt ARBA
Ensembl to GO automatic annotation
Phylogenetic annotation from UniProt
Reactome pathway annotation
Reactome pathway annotation
Reactome pathway annotation
Reactome pathway annotation
Reactome pathway annotation
Reactome pathway annotation
Reactome pathway annotation
Reactome pathway annotation
Towards a proteome-scale map of the human protein-protein interaction network.
Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin.
Systematic protein-protein interaction mapping for clinically relevant human GPCRs.
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Quantitative fragmentomics allow affinity mapping of interactomes.
Multimodal cell maps as a foundation for structural and functional genomics.