FZD10 (Frizzled-10, CD350) is a class F seven-transmembrane receptor of the plasma membrane with an N-terminal extracellular cysteine-rich (Frizzled) domain that binds lipidated Wnt ligands and a cytoplasmic C-terminal tail carrying the Dishevelled-interacting KTxxxW motif and a PDZ-binding motif. Together with its closest paralog FZD9 it forms a distinct Frizzled subfamily. FZD10 transduces Wnt signals into both beta-catenin-dependent signaling (for example with WNT9A and WNT9B) and beta-catenin-independent Dishevelled-Rac1-JNK signaling that remodels the actin cytoskeleton. It is expressed mainly in placenta and fetal kidney, lung and brain, is largely absent from adult tissues, and is strongly overexpressed at the cell surface of synovial sarcomas, where its exposed extracellular domain has been used as an antibody target.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004888 transmembrane signaling receptor activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro 7TM mapping gives generic transmembrane signaling receptor activity. Reason: Correct but too general. FZD10 is a Wnt receptor, a descendant term the gene already carries by IDA and TAS. Proposed replacements: Wnt receptor activity Supporting Evidence: PMID:28733458 Wnt9b induced canonical signaling with FZD5 and FZD8, but also with FZD4 and FZD10 |
| GO:0005515 protein binding | IPI PMID:15930302 Hypoxia-inducible protein 2 (HIG2), a novel diagnostic marke... | REMOVE | Summary: HIG2 (HILPDA) binds the FZD10 extracellular domain. Reason: Bare protein binding is uninformative under the protein-binding policy. The HIG2-FZD10 interaction itself is not disputed, but HIG2 is not established as a canonical receptor ligand, so no more specific receptor MF is asserted from it. Supporting Evidence: PMID:15930302 By binding to an extracellular domain of frizzled homologue 10 (FZD10), HIG2 protein enhanced oncogenic Wnt signaling |
| GO:0005515 protein binding | IPI PMID:19188438 Myocilin is a modulator of Wnt signaling. | REMOVE | Summary: Myocilin binds Frizzled cysteine-rich domains including FZD10. Reason: Bare protein binding is uninformative under the protein-binding policy; the myocilin interaction is a modulatory CRD contact rather than a defined receptor activity. Supporting Evidence: PMID:19188438 Interaction of myocilin with sFRP1, sFRP3, and several Frizzled receptors was confirmed by immunoprecipitation experiments |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding from a high-throughput or interaction assay. Reason: Bare protein binding is uninformative under the protein-binding policy. Removal does not dispute the reported interaction; the informative receptor functions are captured by Wnt receptor activity and Wnt-protein binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding from a high-throughput or interaction assay. Reason: Bare protein binding is uninformative under the protein-binding policy. Removal does not dispute the reported interaction; the informative receptor functions are captured by Wnt receptor activity and Wnt-protein binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding from a high-throughput or interaction assay. Reason: Bare protein binding is uninformative under the protein-binding policy. Removal does not dispute the reported interaction; the informative receptor functions are captured by Wnt receptor activity and Wnt-protein binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding from a high-throughput or interaction assay. Reason: Bare protein binding is uninformative under the protein-binding policy. Removal does not dispute the reported interaction; the informative receptor functions are captured by Wnt receptor activity and Wnt-protein binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding from a high-throughput or interaction assay. Reason: Bare protein binding is uninformative under the protein-binding policy. Removal does not dispute the reported interaction; the informative receptor functions are captured by Wnt receptor activity and Wnt-protein binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein binding from a high-throughput or interaction assay. Reason: Bare protein binding is uninformative under the protein-binding policy. Removal does not dispute the reported interaction; the informative receptor functions are captured by Wnt receptor activity and Wnt-protein binding. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Holdup affinity screen of PDZ domains against PDZ-binding motifs. Reason: The assay measures binding of PDZ domains (DLG4, SCRIB, MPDZ, PATJ, GRIP1 and others) to C-terminal PDZ-binding motif peptides, and FZD10 ends in the Ser/Thr-Xxx-Val motif, so the informative MF is PDZ domain binding rather than bare protein binding. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 PDZ domains and their target PDZ-binding motifs (PBM) PMID:10448064 the C-terminal Ser/Thr-Xxx-Val motif |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | REMOVE | Summary: Extracellular region inherited from the secreted Frizzled-related protein node. Reason: The asserting node PTN002259328 is the sFRP1/sFRP2 clade, where the extracellular location is paired with recorded losses of plasma membrane and Wnt receptor activity (see the PTHR11309 family review). FZD10 is a signal-peptide-bearing seven-transmembrane receptor whose extracellular domain is exposed at the cell surface; it is not a secreted protein, so the term is over-propagated to this receptor. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN002259328 SUPPORTS SOURCE BUT NOT TARGET sFRP1/sFRP2 node asserting extracellular region together with IRD losses of plasma membrane and Wnt receptor activity; appropriate for secreted sFRPs but not for a seven-transmembrane Frizzled receptor. Supporting Evidence: file:human/FZD10/FZD10-uniprot.txt Multi-pass membrane protein PMID:18271942 MAb 92‐13 bound to cell surfaces of four FZD10‐overexpressing synovial sarcoma cell lines |
| GO:0005737 cytoplasm | IDA PMID:16007199 Therapeutic potential of antibodies against FZD 10, a cell-s... | UNDECIDED | Summary: Cytoplasmic staining reported in the synovial sarcoma antibody study. Reason: The cached paper is abstract-only and the abstract describes FZD10 as a cell-surface protein; the cytoplasmic signal presumably comes from tumor immunohistochemistry, which may reflect biosynthetic or endocytic pools. Without the full text the claim cannot be judged. Supporting Evidence: PMID:16007199 Northern blotting and immunohistochemical staining confirmed that expression levels of FZD 10 were very high in nearly all SS tumors |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt subcellular-location mapping places FZD10 in the plasma membrane. Reason: Consistent with the seven-transmembrane topology and cell-surface antibody binding. Supporting Evidence: file:human/FZD10/FZD10-uniprot.txt Multi-pass membrane protein PMID:18271942 MAb 92‐13 bound to cell surfaces of four FZD10‐overexpressing synovial sarcoma cell lines |
| GO:0005886 plasma membrane | TAS PMID:10448064 Molecular cloning of Frizzled-10, a novel member of the Friz... | ACCEPT | Summary: Cloning paper describes FZD10 as a seven-transmembrane receptor. Reason: Plasma membrane is the site of Wnt reception by FZD10. Supporting Evidence: PMID:10448064 human FZD10 gene encodes a seven-transmembrane-receptor of 581 amino acids |
| GO:0007166 cell surface receptor signaling pathway | IEA GO_REF:0000002 | MODIFY | Summary: Generic cell surface receptor signaling from InterPro. Reason: Correct but too general; FZD10 is supported for both canonical and non-canonical Wnt signaling, descendants the gene already carries. Proposed replacements: canonical Wnt signaling pathway non-canonical Wnt signaling pathway Supporting Evidence: PMID:28733458 Wnt9a signaled only via FZD4 and FZD10 PMID:19137009 FZD10 transactivation causes the activation of the non-canonical Dvl-Rac1-JNK pathway |
| GO:0009986 cell surface | IDA PMID:18271942 Radioimmunotherapy of human synovial sarcoma using a monoclo... | ACCEPT | Summary: Anti-FZD10 monoclonal antibody binds live synovial sarcoma cells and is internalized. Reason: Flow cytometry on intact cells shows the extracellular domain exposed at the cell surface. Supporting Evidence: PMID:18271942 MAb 92‐13 bound to cell surfaces of four FZD10‐overexpressing synovial sarcoma cell lines |
| GO:0009986 cell surface | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA cell-surface prediction. Reason: Independently supported by antibody binding to intact cells. Supporting Evidence: PMID:18271942 MAb 92‐13 bound to cell surfaces of four FZD10‐overexpressing synovial sarcoma cell lines |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Generic membrane from InterPro 7TM signatures. Reason: Correct but too general; the specific supported location is plasma membrane, which the gene already carries. Proposed replacements: plasma membrane Supporting Evidence: PMID:10448064 human FZD10 gene encodes a seven-transmembrane-receptor of 581 amino acids |
| GO:0017147 Wnt-protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: Wnt-protein binding inherited from the Frizzled root node. Reason: Wnt binding by the CRD is the ancestral Frizzled property retained by all receptor subfamilies; FZD10 responds to WNT9A/WNT9B in rescue assays. Supporting Evidence: PMID:28733458 Wnt9a signaled only via FZD4 and FZD10 |
| GO:0017147 Wnt-protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of Wnt-protein binding from mouse Fzd10. Reason: Consistent with the conserved CRD and the IBA. Supporting Evidence: PMID:28733458 Wnt9a signaled only via FZD4 and FZD10 |
| GO:0030182 neuron differentiation | ISS GO_REF:0000024 | REMOVE | Summary: Neuron differentiation transferred by sequence similarity from WNT7B. Reason: The WITH/FROM donor UniProtKB:P56706 is human WNT7B, a Wnt ligand that is not homologous to FZD10, so a sequence-similarity transfer from it is not valid. No FZD10-specific neuronal differentiation evidence was found in the cached literature. |
| GO:0032956 regulation of actin cytoskeleton organization | IMP PMID:19137009 Activation of the non-canonical Dvl-Rac1-JNK pathway by Friz... | KEEP AS NON CORE | Summary: FZD10 overexpression disrupts actin stress fibers via Rac1/RhoA in synovial sarcoma cells. Reason: A downstream consequence of non-canonical Dvl-Rac1 signaling; supported but peripheral to the receptor function. Supporting Evidence: PMID:19137009 FZD10 overexpression also caused the destruction of the actin cytoskeleton structure, probably through the downregulation of the RhoA activity |
| GO:0035567 non-canonical Wnt signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Non-canonical Wnt signaling inherited from the Frizzled receptor node. Reason: Consistent with direct FZD10 evidence for Dvl-Rac1-JNK activation; FZD10 appearing among its own descendants is expected. Supporting Evidence: PMID:19137009 FZD10 transactivation causes the activation of the non-canonical Dvl-Rac1-JNK pathway |
| GO:0035567 non-canonical Wnt signaling pathway | IMP PMID:19137009 Activation of the non-canonical Dvl-Rac1-JNK pathway by Friz... | ACCEPT | Summary: FZD10 activates the Dvl-Rac1-JNK pathway in synovial sarcoma cells. Reason: Direct experimental support for beta-catenin-independent signaling by FZD10. Supporting Evidence: PMID:19137009 FZD10 transactivation causes the activation of the non-canonical Dvl-Rac1-JNK pathway |
| GO:0042813 Wnt receptor activity | IDA PMID:28733458 Mapping of Wnt-Frizzled interactions by multiplex CRISPR tar... | ACCEPT | Summary: Re-expression of FZD10 in FZD-depleted cells restores Wnt9a/Wnt9b reporter signaling. Reason: Core receptor activity, demonstrated in a systematic Wnt-FZD rescue map. Supporting Evidence: PMID:28733458 Wnt9b induced canonical signaling with FZD5 and FZD8, but also with FZD4 and FZD10 |
| GO:0042813 Wnt receptor activity | TAS PMID:10448064 Molecular cloning of Frizzled-10, a novel member of the Friz... | ACCEPT | Summary: Cloning paper states Frizzled genes encode Wnt receptors. Reason: Consistent with later experimental evidence. Supporting Evidence: PMID:10448064 The Frizzled genes encode WNT receptors. |
| GO:0046330 positive regulation of JNK cascade | IMP PMID:19137009 Activation of the non-canonical Dvl-Rac1-JNK pathway by Friz... | KEEP AS NON CORE | Summary: FZD10 overexpression activates the Rac1-JNK cascade. Reason: Downstream output of the non-canonical pathway; supported but peripheral. Supporting Evidence: PMID:19137009 activation of the Rac1-JNK cascade in synovial sarcoma cells in which FZD10 was overexpressed |
| GO:0060070 canonical Wnt signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Canonical Wnt signaling inherited from the Frizzled receptor node. Reason: Supported directly for FZD10 by Wnt9a/Wnt9b TCF reporter rescue. Supporting Evidence: PMID:28733458 Wnt9a signaled only via FZD4 and FZD10 |
| GO:0060070 canonical Wnt signaling pathway | IDA PMID:28733458 Mapping of Wnt-Frizzled interactions by multiplex CRISPR tar... | ACCEPT | Summary: FZD10 mediates canonical beta-catenin reporter signaling by Wnt9a and Wnt9b. Reason: Direct experimental evidence. Supporting Evidence: PMID:28733458 Wnt9b induced canonical signaling with FZD5 and FZD8, but also with FZD4 and FZD10 |
| GO:0071300 cellular response to retinoic acid | ISS GO_REF:0000024 | REMOVE | Summary: Cellular response to retinoic acid transferred by sequence similarity from WNT7B. Reason: The donor UniProtKB:P56706 is WNT7B, not a FZD10 homolog, so the ISS basis is invalid; a transcriptional response to retinoic acid would in any case not be a core receptor process. |
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Download this section (compressed HTML)Q: Which Wnt ligands engage FZD10 in its physiological sites of expression (placenta, fetal kidney, cerebellum), and with which co-receptors (LRP5/6, ROR, RYK)?
Q: Is the cytoplasmic FZD10 signal reported in tumor tissue an endocytic pool, a biosynthetic pool, or an antibody artifact?
Experiment: Surface biotinylation and live-cell antibody uptake assays in synovial sarcoma cells to quantify the surface versus internal pools of endogenous FZD10 and its constitutive endocytosis rate.
Experiment: Direct binding assays (BLI/SPR) of purified FZD10 CRD with WNT9A, WNT9B and WNT7A to establish ligand affinities underlying the reporter-based selectivity.
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