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.
| 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 | TOO GENERAL | Summary: Too general. Plasma membrane annotation is more specific. Reason: TOO_GENERAL rather than REMOVE: plasma membrane and recycling endosome membrane, kept in this review, entail this term, so the claim is true but less informative. |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | TOO GENERAL | Summary: Too general. Recycling endosome membrane annotation is more specific. Reason: TOO_GENERAL rather than REMOVE: recycling endosome membrane, kept in this review, entails this term, so the claim is true but less informative. |
| 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 transducersβparticularly DVLβand 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 | TOO GENERAL | Summary: Too general. Wnt receptor activity is more specific. Reason: TOO_GENERAL rather than REMOVE: G protein-coupled receptor activity and Wnt receptor activity, kept in this review, entail this term, so the claim is true but less informative. |
| 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. Reason: The interacting partner recorded for this row is myocilin (MYOC), from a study showing that myocilin modulates Wnt signalling and interacts with several Frizzled receptors (PMID:19188438). Frizzled binding describes the myocilin side of that interaction: it is true of myocilin, which binds FZD7, whereas FZD7 is itself the Frizzled, and the experiment says nothing about FZD7 binding another Frizzled receptor. The term is attached to the wrong side of the interaction and is removed from FZD7; the finding belongs on MYOC as frizzled binding. 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 | TOO GENERAL | Summary: Too general. More specific canonical and non-canonical annotations present. Reason: Wnt signaling pathway is entailed by the canonical and non-canonical Wnt signaling pathway annotations that this review accepts for FZD7 on experimental evidence, so the keyword-derived parent term is true of the receptor but adds nothing to them. A true but less informative term is recorded as too general rather than removed. |
| GO:0007165 signal transduction | IEA GO_REF:0000043 | TOO GENERAL | Summary: Too general. Wnt pathway terms are more specific. Reason: Signal transduction is entailed by the canonical and non-canonical Wnt signaling pathway annotations accepted in this review for FZD7, so the keyword-derived term is true of the receptor but uninformative beside them. A true but less informative term is recorded as too general rather than removed. |
| GO:0007166 cell surface receptor signaling pathway | IEA GO_REF:0000002 | TOO GENERAL | Summary: Too general. Captured by Wnt signaling pathway annotations. Reason: Cell surface receptor signaling pathway is entailed by the canonical and non-canonical Wnt signaling pathway annotations accepted in this review for FZD7, so the signature-derived term is true of the receptor but uninformative beside them. A true but less informative term is recorded as too general rather than removed. |
| GO:0007186 G protein-coupled receptor signaling pathway | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Keyword-derived G protein-coupled receptor signaling term. FZD7 is a class F GPCR that signals mainly through DVL, with limited coupling to heterotrimeric G proteins; treated like the G protein-coupled receptor activity row. Reason: Frizzleds form class F of the G protein-coupled receptor superfamily, and this review keeps G protein-coupled receptor activity for FZD7 as a non-core structural classification; the pathway term follows directly from that activity, so it cannot be removed while the activity is kept. FZD7 signals mainly through Dishevelled, and structural work indicates only limited coupling to heterotrimeric G proteins, which is why the term is peripheral rather than core. It is kept as non-core, in line with the molecular function row. |
| GO:0060828 regulation of canonical Wnt signaling pathway | IMP PMID:9707618 A novel frizzled gene identified in human esophageal carcino... | MODIFY | Summary: Mutant-phenotype evidence that FZD7 (FzE3) drives APC/beta-catenin signalling in oesophageal carcinoma cells; better expressed as canonical Wnt signaling pathway than as regulation of it. Reason: The cited study showed that expressing the receptor (then called FzE3) in oesophageal carcinoma cells stimulates complex formation between APC and beta-catenin and nuclear translocation of beta-catenin, and that a C-terminally truncated receptor blocks it (PMID:9707618). FZD7 is thus a component that transmits the canonical signal rather than an outside regulator of the pathway, so the finding is sound but belongs under the pathway term itself, canonical Wnt signaling pathway, which FZD7 already carries from direct assays. Overlap with those rows is a reason to move this evidence to the same term, not to remove a true experimental annotation. Proposed replacements: 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 ... | MARK AS OVER ANNOTATED | Summary: Loss of OCT4 and altered marker-gene expression after FZD7 knockdown in human ES cells; a downstream consequence of receptor signalling rather than transcriptional regulation by FZD7. Reason: Knockdown of FZD7 in human embryonic stem cells perturbed expression of germ-layer marker genes and caused loss of OCT4 expression (PMID:18681827), so the row records a real mutant phenotype. Changed gene expression after loss of a cell-surface Wnt receptor is a downstream consequence of losing the self-renewal signal, not evidence that FZD7 itself regulates transcription; what the experiment supports is the stem cell population maintenance annotation accepted in this review from the same paper. The transcription term over-reads the phenotype and is marked as an over-annotation; it is not false, and is not removed. 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... | MARK AS OVER ANNOTATED | Summary: Reporter-gene readout of Wnt3a signalling through transfected Fzd7; a downstream consequence of canonical Wnt signalling rather than transcriptional regulation by the receptor. Reason: Transient expression of Fzd7 in H441 lung epithelial cells increased the Wnt3a-driven response of a beta-catenin/TCF luciferase reporter (PMID:18215320), so the observation is real. That reporter measures the output of the canonical Wnt pathway, and the same experiment is already accepted in this review as canonical Wnt signaling pathway; describing a plasma-membrane receptor as a regulator of DNA-templated transcription annotates the downstream consequence of the pathway to its receptor. The term is an over-annotation rather than a false claim, and is not removed. 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... | MODIFY | Summary: Phosphorylation readout (c-Jun) of FZD7/syntenin non-canonical Wnt signalling; more specifically captured as positive regulation of JNK cascade, which the same curators inferred from this row. Reason: The claim is true but less specific than the evidence allows. The cited study of syntenin and Frizzled 7 in non-canonical Wnt signalling reports stimulation of c-Jun phosphorylation as its phosphorylation readout (PMID:18256285), and the curators of this row derived a positive regulation of JNK cascade annotation from it, which this review keeps as non-core. Positive regulation of JNK cascade is therefore the specific, supported form of this row and is proposed as its replacement; a correct but general term is refined rather than removed. Only the abstract of the paper is available here, so the assay details rest on the curators' annotation. Proposed replacements: positive regulation of JNK cascade 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... | TOO GENERAL | Summary: Too general. Plasma membrane is more specific. Reason: TOO_GENERAL rather than REMOVE: plasma membrane and recycling endosome membrane, kept in this review, entail this term, so the claim is true but less informative. 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,... | MARK AS OVER ANNOTATED | Summary: Reduced Wnt target gene expression after FZD7 knockdown in colon cancer cells; a downstream consequence of canonical Wnt signalling rather than transcriptional regulation by the receptor. Reason: Knockdown of FZD7 in colon cancer cells reduced Wnt target gene expression (PMID:19773752), so the row records a real mutant phenotype. The reduced target-gene expression reflects loss of canonical Wnt pathway output, which is already accepted for FZD7 from the same paper as canonical Wnt signaling pathway; a plasma-membrane receptor does not itself regulate DNA-templated transcription. The term annotates the downstream consequence of the pathway to its receptor and is marked as an over-annotation, like the other row for this term, rather than removed. 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 (BallesterosβWeinstein 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. |
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Download this section (compressed HTML)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?
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.
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