FZD7

UniProt ID: O75084
Organism: Homo sapiens
Review Status: COMPLETE
Aliases:
Frizzled-7 Fz-7 hFz7 FzE3
πŸ“ Provide Detailed Feedback

Gene Description

Frizzled-7 (FZD7) is a seven-transmembrane receptor belonging to the class F G-protein coupled receptor family. It functions as the primary receptor for Wnt ligands, transducing both canonical Wnt/beta-catenin signaling and non-canonical Wnt signaling pathways (planar cell polarity/PCP and Wnt/Ca2+). The receptor contains an extracellular cysteine-rich domain (CRD) that binds Wnt proteins, a seven-transmembrane core, and a C-terminal PDZ-binding motif that recruits Dishevelled (DVL) and other PDZ domain-containing proteins. A 1.9 Γ… cryo-EM structure of inactive human FZD7 (Bous et al. 2024) identified an internal water pocket and a conserved cholesterol-binding site (F3.34/H4.46/W4.50) that is required for FZD7-DVL association and downstream signalosome formation; a R6.32-W7.55 micro-switch acts as a hinge limiter on TM6 opening, biasing the receptor toward DVL coupling over heterotrimeric G proteins. Surface levels of FZD7 are negatively regulated by RNF43-mediated ubiquitination and endocytosis. FZD7 is essential for human embryonic stem cell self-renewal, skeletal muscle satellite stem cell maintenance, and postnatal angiogenesis. It is frequently overexpressed in multiple cancers where it drives tumor progression through Wnt pathway activation. FZD7 also serves as a receptor for C. difficile toxin B in colonic epithelium.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005886 plasma membrane
IDA
PMID:27386966
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports...
ACCEPT
Summary: Direct experimental evidence from microscopy showing FZD7 at plasma membrane. K569 is essential for SDCBP-mediated plasma membrane PIP2 recognition. Multiple independent IDA studies confirm this localization.
Supporting Evidence:
PMID:27386966
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling.
PMID:18256285
2008 Feb 6. The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling.
GO:0055038 recycling endosome membrane
IDA
PMID:27386966
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports...
KEEP AS NON CORE
Summary: FZD7 localizes to recycling endosomes in absence of PIP2/SDCBP interaction. Part of receptor trafficking, not core functional location.
Supporting Evidence:
PMID:27386966
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling.
GO:0016020 membrane
IEA
GO_REF:0000002
REMOVE
Summary: Too general. Plasma membrane annotation is more specific.
GO:0010008 endosome membrane
IEA
GO_REF:0000044
REMOVE
Summary: Too general. Recycling endosome membrane annotation is more specific.
GO:0042813 Wnt receptor activity
IDA
PMID:28733458
Mapping of Wnt-Frizzled interactions by multiplex CRISPR tar...
ACCEPT
Summary: FZD7 is a bona fide Wnt receptor. Demonstrated through CRISPR mapping studies and extensive literature showing Wnt ligand binding and signal transduction. This is the core molecular function of FZD7.
Supporting Evidence:
PMID:28733458
Mapping of Wnt-Frizzled interactions by multiplex CRISPR targeting of receptor gene families.
PMID:9707618
A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals.
PMID:18313787
Feb 7. Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells.
file:human/FZD7/FZD7-deep-research-perplexity.md
file:human/FZD7/FZD7-deep-research-falcon.md
FZD7's primary molecular role is as a plasma-membrane WNT receptor that couples extracellular WNT ligand recognition to intracellular signaling by recruiting transducersβ€”particularly DVLβ€”and in some contexts engaging heterotrimeric G proteins
GO:0017147 Wnt-protein binding
IPI
PMID:18313787
Functional interaction between Wnt3 and Frizzled-7 leads to ...
ACCEPT
Summary: Direct binding to Wnt3 demonstrated by co-immunoprecipitation. The extracellular CRD domain binds Wnt ligands.
Supporting Evidence:
PMID:18313787
Feb 7. Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells.
GO:0030165 PDZ domain binding
IPI
PMID:19388021
Sequence requirement and subtype specificity in the high-aff...
ACCEPT
Summary: FZD7 C-terminal KTXXXW motif binds PDZ domains of DVL, SDCBP/syntenin, NHERF1, and other PDZ proteins. Critical for signal transduction.
Supporting Evidence:
PMID:19388021
Sequence requirement and subtype specificity in the high-affinity interaction between human frizzled and dishevelled proteins.
PMID:18256285
2008 Feb 6. The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling.
GO:0005546 phosphatidylinositol-4,5-bisphosphate binding
IDA
PMID:27386966
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports...
ACCEPT
Summary: FZD7 binds PIP2 via SDCBP-mediated interaction at plasma membrane. K569 is essential for this function.
Supporting Evidence:
PMID:27386966
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling.
GO:0004930 G protein-coupled receptor activity
IEA
GO_REF:0000043
KEEP AS NON CORE
Summary: FZD7 is structurally a class F GPCR. However, its primary signaling is through DVL rather than classical G protein coupling. Structural work shows a R6.32-W7.55 micro-switch acting as a hinge limiter that restricts TM6 opening, rationalizing the modest coupling to heterotrimeric G proteins. Keep as structural classification.
Supporting Evidence:
PMID:39198452
the molecular switch R6.32-W7.55 acts as a hinge limiter (Fig. 3c, d) permitting only a restricted TM6 opening (11Β°, 5.5 Γ…). 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
PMID:37516754
prefer coupling to DVL rather than heterotrimeric
GO:0004888 transmembrane signaling receptor activity
IEA
GO_REF:0000002
REMOVE
Summary: Too general. Wnt receptor activity is more specific.
GO:0005109 frizzled binding
IPI
PMID:19188438
Myocilin is a modulator of Wnt signaling
REMOVE
Summary: This annotation reflects that MYOC binds FZD7, not that FZD7 binds other Frizzled receptors. Should be captured on MYOC entry instead.
Supporting Evidence:
PMID:19188438
Feb 2. Myocilin is a modulator of Wnt signaling.
GO:0005515 protein binding
IPI
PMID:27386966
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports...
REMOVE
Summary: Protein binding is uninformative per GO curation guidelines. FZD7 binds multiple proteins including SDCBP, DVL, NHERF1, Wnt3 - captured by more specific terms (PDZ domain binding, Wnt-protein binding).
Supporting Evidence:
PMID:27386966
Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling.
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:28733458
Mapping of Wnt-Frizzled interactions by multiplex CRISPR tar...
ACCEPT
Summary: FZD7 transduces canonical Wnt/beta-catenin signaling. This leads to beta-catenin stabilization, nuclear translocation, and TCF/LEF-mediated transcription. Core biological process.
Supporting Evidence:
PMID:28733458
Mapping of Wnt-Frizzled interactions by multiplex CRISPR targeting of receptor gene families.
PMID:9707618
A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals.
PMID:20802536
Direct interaction between NHERF1 and Frizzled regulates Ξ²-catenin signaling.
PMID:18215320
Ror2 modulates the canonical Wnt signaling in lung epithelial cells through cooperation with Fzd2.
PMID:18313787
Feb 7. Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells.
GO:0035567 non-canonical Wnt signaling pathway
IMP
PMID:19773752
Down-regulation of frizzled-7 expression decreases survival,...
ACCEPT
Summary: FZD7 transduces non-canonical Wnt signaling including JNK/RhoA pathway. FZD7 knockdown decreases RhoA activation and JNK phosphorylation. Core biological process alongside canonical signaling.
Supporting Evidence:
PMID:19773752
2009 Sep 22. Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells.
PMID:18256285
2008 Feb 6. The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling.
PMID:26126266
Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling.
GO:0060071 Wnt signaling pathway, planar cell polarity pathway
NAS
PMID:24431302
Wnt signaling in midbrain dopaminergic neuron development an...
KEEP AS NON CORE
Summary: FZD7 signals through PCP pathway via Vangl2, RhoA/Rac1. Part of non-canonical Wnt signaling. Keep as specific subtype.
Supporting Evidence:
PMID:24431302
Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease.
GO:0016055 Wnt signaling pathway
IEA
GO_REF:0000043
REMOVE
Summary: Too general. More specific canonical and non-canonical annotations present.
GO:0007165 signal transduction
IEA
GO_REF:0000043
REMOVE
Summary: Too general. Wnt pathway terms are more specific.
GO:0007166 cell surface receptor signaling pathway
IEA
GO_REF:0000002
REMOVE
Summary: Too general. Captured by Wnt signaling pathway annotations.
GO:0007186 G protein-coupled receptor signaling pathway
IEA
GO_REF:0000043
REMOVE
Summary: FZD7 signals primarily through DVL, not classical G proteins. Wnt pathway terms are more accurate.
GO:0060828 regulation of canonical Wnt signaling pathway
IMP
PMID:9707618
A novel frizzled gene identified in human esophageal carcino...
REMOVE
Summary: Redundant with GO:0060070 canonical Wnt signaling pathway.
Supporting Evidence:
PMID:9707618
A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals.
GO:0043410 positive regulation of MAPK cascade
IMP
PMID:19773752
Down-regulation of frizzled-7 expression decreases survival,...
KEEP AS NON CORE
Summary: FZD7 knockdown decreases JNK phosphorylation. Part of non-canonical Wnt signaling (JNK/PCP pathway). Downstream effect.
Supporting Evidence:
PMID:19773752
2009 Sep 22. Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells.
GO:0046330 positive regulation of JNK cascade
IC
PMID:18256285
The postsynaptic density 95/disc-large/zona occludens protei...
KEEP AS NON CORE
Summary: Part of non-canonical Wnt signaling. FZD7 activates JNK through DVL/RhoA.
Supporting Evidence:
PMID:18256285
2008 Feb 6. The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling.
PMID:19773752
2009 Sep 22. Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells.
GO:0019827 stem cell population maintenance
IMP
PMID:18681827
The WNT receptor FZD7 contributes to self-renewal signaling ...
ACCEPT
Summary: FZD7 is essential for hESC self-renewal. Knockdown causes rapid loss of OCT4 and differentiation. Critical developmental/stem cell role.
Supporting Evidence:
PMID:18681827
The WNT receptor FZD7 contributes to self-renewal signaling of human embryonic stem cells.
GO:0042666 negative regulation of ectodermal cell fate specification
IMP
PMID:18681827
The WNT receptor FZD7 contributes to self-renewal signaling ...
KEEP AS NON CORE
Summary: FZD7 knockdown in hESCs leads to perturbation of germ layer markers. Part of stem cell maintenance function.
Supporting Evidence:
PMID:18681827
The WNT receptor FZD7 contributes to self-renewal signaling of human embryonic stem cells.
GO:0006355 regulation of DNA-templated transcription
IMP
PMID:18681827
The WNT receptor FZD7 contributes to self-renewal signaling ...
REMOVE
Summary: Downstream consequence of Wnt signaling. Too general.
Supporting Evidence:
PMID:18681827
The WNT receptor FZD7 contributes to self-renewal signaling of human embryonic stem cells.
GO:0045893 positive regulation of DNA-templated transcription
IDA
PMID:18215320
Ror2 modulates the canonical Wnt signaling in lung epithelia...
REMOVE
Summary: Downstream effect of Wnt signaling. Too general.
Supporting Evidence:
PMID:18215320
Ror2 modulates the canonical Wnt signaling in lung epithelial cells through cooperation with Fzd2.
GO:0060231 mesenchymal to epithelial transition
IMP
PMID:17016432
Frizzled-7 dictates three-dimensional organization of colore...
KEEP AS NON CORE
Summary: FZD7 regulates 3D organization in colorectal cancer cells. Context-dependent phenotypic outcome.
Supporting Evidence:
PMID:17016432
Oct 2. Frizzled-7 dictates three-dimensional organization of colorectal cancer cell carcinoids.
GO:0010812 negative regulation of cell-substrate adhesion
IMP
PMID:18156211
Regulation of endothelial cell cytoskeletal reorganization b...
KEEP AS NON CORE
Summary: FZD7 effects on cell adhesion in epithelial cells. Downstream phenotypic effect.
Supporting Evidence:
PMID:18156211
Dec 21. 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.
GO:2000726 negative regulation of cardiac muscle cell differentiation
IGI
PMID:23939491
Overexpression of microRNA-1 promotes cardiomyocyte commitme...
KEEP AS NON CORE
Summary: FZD7 suppresses cardiomyocyte differentiation via Wnt signaling.
Supporting Evidence:
PMID:23939491
2013 Aug 9. Overexpression of microRNA-1 promotes cardiomyocyte commitment from human cardiovascular progenitors via suppressing WNT and FGF signaling pathways.
GO:0060054 positive regulation of epithelial cell proliferation involved in wound healing
IMP
PMID:18313787
Functional interaction between Wnt3 and Frizzled-7 leads to ...
KEEP AS NON CORE
Summary: Wnt3-FZD7 signaling promotes epithelial cell proliferation in HCC context.
Supporting Evidence:
PMID:18313787
Feb 7. Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells.
GO:0042327 positive regulation of phosphorylation
IDA
PMID:18256285
The postsynaptic density 95/disc-large/zona occludens protei...
REMOVE
Summary: Too general. FZD7 activates downstream kinases as part of signaling.
Supporting Evidence:
PMID:18256285
2008 Feb 6. The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling.
GO:0030182 neuron differentiation
ISS
GO_REF:0000024
UNDECIDED
Summary: Inferred from sequence similarity. FZD7 likely involved in neuron differentiation but evidence is indirect.
GO:0071300 cellular response to retinoic acid
ISS
GO_REF:0000024
UNDECIDED
Summary: Inferred from sequence similarity. Indirect evidence only.
GO:0005886 plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: Phylogenetic annotation. Consolidated with IDA evidence above.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-3858482
ACCEPT
Summary: Reactome pathway annotation. Consolidated with IDA evidence above.
GO:0005886 plasma membrane
IEA
GO_REF:0000120
ACCEPT
Summary: Electronic annotation. Consolidated with IDA evidence above.
GO:0016020 membrane
TAS
PMID:9707618
A novel frizzled gene identified in human esophageal carcino...
REMOVE
Summary: Too general. Plasma membrane is more specific.
Supporting Evidence:
PMID:9707618
A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals.
GO:0042813 Wnt receptor activity
IEA
GO_REF:0000120
ACCEPT
Summary: Electronic annotation. Consolidated with IDA evidence above.
GO:0042813 Wnt receptor activity
IBA
GO_REF:0000033
ACCEPT
Summary: Phylogenetic annotation. Consolidated with IDA evidence above.
GO:0042813 Wnt receptor activity
NAS
PMID:24431302
Wnt signaling in midbrain dopaminergic neuron development an...
ACCEPT
Summary: Author statement. Consolidated with IDA evidence above.
Supporting Evidence:
PMID:24431302
Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease.
GO:0017147 Wnt-protein binding
IBA
GO_REF:0000033
ACCEPT
Summary: Phylogenetic annotation. Consolidated with IPI evidence above.
GO:0017147 Wnt-protein binding
NAS
PMID:24431302
Wnt signaling in midbrain dopaminergic neuron development an...
ACCEPT
Summary: Author statement. Consolidated with IPI evidence above.
Supporting Evidence:
PMID:24431302
Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease.
GO:0017147 Wnt-protein binding
IEA
GO_REF:0000107
ACCEPT
Summary: Electronic annotation. Consolidated with IPI evidence above.
GO:0030165 PDZ domain binding
IEA
GO_REF:0000117
ACCEPT
Summary: ARBA rule annotation. Consolidated with IPI evidence above.
GO:0030165 PDZ domain binding
IPI
PMID:18256285
The postsynaptic density 95/disc-large/zona occludens protei...
ACCEPT
Summary: Interaction with syntenin. Consolidated with IPI evidence above.
Supporting Evidence:
PMID:18256285
2008 Feb 6. The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling.
GO:0060070 canonical Wnt signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: Phylogenetic annotation. Consolidated with IDA evidence above.
GO:0060070 canonical Wnt signaling pathway
IEA
GO_REF:0000117
ACCEPT
Summary: ARBA rule annotation. Consolidated with IDA evidence above.
GO:0060070 canonical Wnt signaling pathway
IMP
PMID:19773752
Down-regulation of frizzled-7 expression decreases survival,...
ACCEPT
Summary: Mutant phenotype. Consolidated with IDA evidence above.
Supporting Evidence:
PMID:19773752
2009 Sep 22. Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells.
GO:0060070 canonical Wnt signaling pathway
IMP
PMID:18313787
Functional interaction between Wnt3 and Frizzled-7 leads to ...
ACCEPT
Summary: Mutant phenotype. Consolidated with IDA evidence above.
Supporting Evidence:
PMID:18313787
Feb 7. Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells.
GO:0035567 non-canonical Wnt signaling pathway
IBA
GO_REF:0000033
ACCEPT
Summary: Phylogenetic annotation. Consolidated with IMP evidence above.
GO:0010812 negative regulation of cell-substrate adhesion
IEA
GO_REF:0000107
KEEP AS NON CORE
Summary: Electronic annotation. Consolidated with IMP evidence above.
GO:0045893 positive regulation of DNA-templated transcription
IMP
PMID:19773752
Down-regulation of frizzled-7 expression decreases survival,...
REMOVE
Summary: Downstream effect of Wnt signaling. Too general.
Supporting Evidence:
PMID:19773752
2009 Sep 22. Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9673284
ACCEPT
Summary: Reactome pathway annotation. Consolidated with IDA evidence.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9673288
ACCEPT
Summary: Reactome pathway annotation. Consolidated with IDA evidence.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9673296
ACCEPT
Summary: Reactome pathway annotation. Consolidated with IDA evidence.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9673349
ACCEPT
Summary: Reactome pathway annotation. Consolidated with IDA evidence.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9673794
ACCEPT
Summary: Reactome pathway annotation. Consolidated with IDA evidence.
GO:0005886 plasma membrane
TAS
Reactome:R-HSA-9673797
ACCEPT
Summary: Reactome pathway annotation. Consolidated with IDA evidence.
GO:0005886 plasma membrane
TAS
Reactome:R-NUL-1504194
ACCEPT
Summary: Reactome pathway annotation. Consolidated with IDA evidence.
GO:0005886 plasma membrane
IDA
PMID:18256285
The postsynaptic density 95/disc-large/zona occludens protei...
ACCEPT
Summary: Direct assay evidence. Consolidated with other IDA evidence.
Supporting Evidence:
PMID:18256285
2008 Feb 6. The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling.
GO:0005886 plasma membrane
IDA
GO_REF:0000054
ACCEPT
Summary: LIFEdb annotation. Consolidated with IDA evidence.
GO:0015485 cholesterol binding
IDA
PMID:39198452
Structural basis of frizzled 7 activation and allosteric reg...
NEW
Summary: Bous et al. 2024 identified a conserved cholesterol-binding site on the FZD7 surface (TM2-TM4; F3.34/H4.46/W4.50) by cryo-EM and demonstrated with double mutants that disruption abolishes DEP recruitment and reduces WNT-3A-induced TOPFlash, indicating a direct functional role for cholesterol binding in DVL recruitment and signaling. Proposed new annotation.
Supporting Evidence:
PMID:39198452
we identified a conserved cholesterol-binding site involving W4.50 (Ballesteros–Weinstein numbering)
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:20802536
Direct interaction between NHERF1 and Frizzled regulates Ξ²-c...
ACCEPT
Summary: Direct assay evidence. Consolidated with other IDA evidence.
Supporting Evidence:
PMID:20802536
Direct interaction between NHERF1 and Frizzled regulates Ξ²-catenin signaling.
GO:0060070 canonical Wnt signaling pathway
IDA
PMID:18215320
Ror2 modulates the canonical Wnt signaling in lung epithelia...
ACCEPT
Summary: Direct assay evidence. Consolidated with other IDA evidence.
Supporting Evidence:
PMID:18215320
Ror2 modulates the canonical Wnt signaling in lung epithelial cells through cooperation with Fzd2.
GO:0005515 protein binding
IPI
PMID:26126266
Daple is a novel non-receptor GEF required for trimeric G pr...
REMOVE
Summary: Interaction with DAPLE. Protein binding uninformative per GO guidelines.
Supporting Evidence:
PMID:26126266
Daple is a novel non-receptor GEF required for trimeric G protein activation in Wnt signaling.
GO:0005515 protein binding
IPI
PMID:18256285
The postsynaptic density 95/disc-large/zona occludens protei...
REMOVE
Summary: Interaction with syntenin. Protein binding uninformative per GO guidelines.
Supporting Evidence:
PMID:18256285
2008 Feb 6. The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling.
GO:0005515 protein binding
IPI
PMID:18313787
Functional interaction between Wnt3 and Frizzled-7 leads to ...
REMOVE
Summary: Interaction with Wnt3. Protein binding uninformative per GO guidelines.
Supporting Evidence:
PMID:18313787
Feb 7. Functional interaction between Wnt3 and Frizzled-7 leads to activation of the Wnt/beta-catenin signaling pathway in hepatocellular carcinoma cells.
GO:0005515 protein binding
IPI
PMID:27680706
Frizzled proteins are colonic epithelial receptors for C. di...
REMOVE
Summary: Interaction with TcdB toxin. Protein binding uninformative per GO guidelines.
Supporting Evidence:
PMID:27680706
Frizzled proteins are colonic epithelial receptors for C.
GO:0005515 protein binding
IPI
PMID:16189514
Towards a proteome-scale map of the human protein-protein in...
REMOVE
Summary: Protein binding uninformative per GO guidelines.
Supporting Evidence:
PMID:16189514
Towards a proteome-scale map of the human protein-protein interaction network.
GO:0005515 protein binding
IPI
PMID:21314951
Soluble Frizzled-7 receptor inhibits Wnt signaling and sensi...
REMOVE
Summary: Protein binding uninformative per GO guidelines.
Supporting Evidence:
PMID:21314951
Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin.
GO:0005515 protein binding
IPI
PMID:28298427
Systematic protein-protein interaction mapping for clinicall...
REMOVE
Summary: Protein binding uninformative per GO guidelines.
Supporting Evidence:
PMID:28298427
Systematic protein-protein interaction mapping for clinically relevant human GPCRs.
GO:0005515 protein binding
IPI
PMID:31515488
Extensive disruption of protein interactions by genetic vari...
REMOVE
Summary: Protein binding uninformative per GO guidelines.
Supporting Evidence:
PMID:31515488
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Protein binding uninformative per GO guidelines. Multiple interactions from same study.
Supporting Evidence:
PMID:32296183
Apr 8. A reference map of the human binary protein interactome.
GO:0005515 protein binding
IPI
PMID:36115835
Quantitative fragmentomics allow affinity mapping of interac...
REMOVE
Summary: Protein binding uninformative per GO guidelines.
Supporting Evidence:
PMID:36115835
Quantitative fragmentomics allow affinity mapping of interactomes.
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func...
REMOVE
Summary: Protein binding uninformative per GO guidelines.
Supporting Evidence:
PMID:40205054
Apr 9. Multimodal cell maps as a foundation for structural and functional genomics.

Core Functions

FZD7 functions as a transmembrane Wnt receptor at the plasma membrane, binding Wnt ligands via its extracellular cysteine-rich domain and transducing signals through recruitment of intracellular adaptor proteins including Dishevelled (DVL).

Supporting Evidence:

FZD7 recruits DVL and other PDZ domain-containing proteins (SDCBP/syntenin, NHERF1) via its C-terminal KTXXXW motif. This PDZ-mediated interaction is essential for signal transduction from the receptor to downstream pathways and DVL recruitment seeds the WNT/Ξ²-catenin signalosome.

Molecular Function:
PDZ domain binding
Cellular Locations:
Supporting Evidence:

A conserved cholesterol-binding site on the TM2-TM4 receptor surface (residues F3.34/H4.46/W4.50, with F/Y2.46 and F/Y3.34 enriched in aromatic character across class F GPCRs) binds cholesterol and stabilizes a conformation competent for DVL recruitment. Disruption of this site abolishes DEP-domain recruitment and reduces WNT-3A-induced Ξ²-catenin signaling without affecting constitutive Gs coupling, indicating a direct functional role of cholesterol binding in FZD7 signaling.

Molecular Function:
cholesterol binding
Cellular Locations:
Supporting Evidence:

References

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Suggested Questions for Experts

Q: What is the relative contribution of FZD7 to canonical versus non-canonical Wnt signaling in different cell types? Are there cell-type-specific co-factors that determine pathway choice?

Suggested Experiments

Experiment: Systematic comparison of Wnt ligand binding affinities to FZD7 using surface plasmon resonance or isothermal calorimetry to determine which Wnts preferentially activate FZD7.

Hypothesis: Different Wnt ligands may preferentially activate canonical or non-canonical pathways through FZD7, but quantitative binding data is limited.

Deep Research

Falcon

(FZD7-deep-research-falcon.md)

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Perplexity

(FZD7-deep-research-perplexity.md)

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