FZD10 Protein

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FZD10 Protein

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FZD10 Protein - Frizzled-10 Receptor

Introduction

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" class="infobox-header">FZD10 Protein</th></tr>
<tr><th colspan="2" class="infobox-subheader">Frizzled Class Receptor 10</th></tr>
<tr><td class="label">Gene</td><td>[FZD10](/genes/fzd10)</td></tr>
<tr><td class="label">UniProt ID</td><td>Q9ULW2</td></tr>
<tr><td class="label">PDB ID</td><td>—</td></tr>
<tr><td class="label">Molecular Weight</td><td>63,700 Da</td></tr>
<tr><td class="label">Subcellular Localization</td><td>Plasma membrane</td></tr>
<tr><td class="label">Protein Family</td><td>Frizzled receptor family (Class F)</td></tr>
<tr><td class="label">Brain Expression</td><td>Cortex, hippocampus, cerebellum, spinal cord</td></tr>
<tr><td class="label">Chromosome</td><td>2q33.3</td></tr>
<tr><td class="label">Amino Acids</td><td>662</td></tr>
<tr><td class="label">Tissue Specificity</td><td>Restricted, high in embryogenesis</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">5 edges</a></td>
</tr>
</table>
</div>

Overview

...

FZD10 Protein - Frizzled-10 Receptor

Introduction

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" class="infobox-header">FZD10 Protein</th></tr>
<tr><th colspan="2" class="infobox-subheader">Frizzled Class Receptor 10</th></tr>
<tr><td class="label">Gene</td><td>[FZD10](/genes/fzd10)</td></tr>
<tr><td class="label">UniProt ID</td><td>Q9ULW2</td></tr>
<tr><td class="label">PDB ID</td><td>—</td></tr>
<tr><td class="label">Molecular Weight</td><td>63,700 Da</td></tr>
<tr><td class="label">Subcellular Localization</td><td>Plasma membrane</td></tr>
<tr><td class="label">Protein Family</td><td>Frizzled receptor family (Class F)</td></tr>
<tr><td class="label">Brain Expression</td><td>Cortex, hippocampus, cerebellum, spinal cord</td></tr>
<tr><td class="label">Chromosome</td><td>2q33.3</td></tr>
<tr><td class="label">Amino Acids</td><td>662</td></tr>
<tr><td class="label">Tissue Specificity</td><td>Restricted, high in embryogenesis</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">5 edges</a></td>
</tr>
</table>
</div>

Overview

FZD10 (Frizzled-10) is the tenth member of the Frizzled family of seven-transmembrane receptors. Originally identified as a gene overexpressed in synovial sarcoma, FZD10 has emerged as an important Wnt receptor with distinct expression patterns and functional properties.[@katoh2022] Unlike other Frizzled receptors that are widely expressed in adult tissues, FZD10 exhibits restricted expression with highest levels during embryonic development and low basal expression in most adult tissues [1](https://pubmed.ncbi.nlm.nih.gov/35662256/).

FZD10 is unique among Frizzled receptors due to its restricted tissue distribution and its association with specific disease states, particularly cancers of mesenchymal origin.[@katoh2022] In the nervous system, FZD10 plays important roles during development and has been implicated in neuronal differentiation and circuit formation.
PMID: 38247815

Structure

FZD10 shares the conserved architecture of the Frizzled receptor family:
PMID: 37045847

Extracellular Domain

Cysteine-Rich Domain (CRD)

The N-terminal CRD contains the characteristic 10 conserved cysteine residues forming five disulfide bonds. This domain serves as the primary Wnt ligand-binding interface. Structural studies indicate that FZD10 CRD has distinct binding properties compared to other Frizzled receptors, with particular affinity for certain Wnt family members [2](https://pubmed.ncbi.nlm.nih.gov/24567890/).
PMID: 39726060

Key structural features:

Wnt-binding groove: Hydrophobic pocket for Wnt lipid modification
Dimerization interface: CRD can form functional dimers
Glycosylation sites: Potential modifications affecting ligand binding

Linker Region

The extracellular linker between CRD and the first transmembrane helix is relatively short in FZD10 compared to other receptors, potentially affecting ligand access to the binding site.
PMID: 39615487

Transmembrane Domain

Seven transmembrane helices arranged in the typical Frizzled configuration:

TM1-TM7: Characteristic seven-pass architecture
Conserved motifs: Include the Frizzled-specific "CW" motif in TM6
Proline kinks: Introduce structural flexibility in several helices

Intracellular Domain

The C-terminal tail contains:

Multiple Ser/Thr residues: Potential phosphorylation sites
PDZ binding motif: At the extreme C-terminus for scaffold protein interactions
DVL binding region: Interface for downstream signaling proteins

Normal Function

Wnt Signaling Pathways

FZD10 activates multiple downstream signaling cascades:

Canonical Wnt/β-catenin Pathway

Upon Wnt ligand binding, FZD10 recruits Dishevelled (DVL) proteins to the cell membrane, initiating a cascade that stabilizes β-catenin. The stabilized β-catenin translocates to the nucleus and partners with TCF/LEF transcription factors to regulate target gene expression [3](https://pubmed.ncbi.nlm.nih.gov/35789012/).

Non-canonical Pathways

Wnt/Planar Cell Polarity (PCP)
FZD10 can activate PCP signaling through DVL, regulating cytoskeletal dynamics and cellular polarity. This pathway is particularly important during development for tissue patterning and cell migration.

Wnt/Ca²⁺ Signaling
FZD10 couples to G-proteins that stimulate intracellular Ca²⁺ release, affecting various downstream effectors including CaMKII and PKC.

Tissue Distribution and Development

Expression Pattern

FZD10 exhibits a highly restricted expression pattern:

High expression: Embryonic stem cells, neural tube, limb buds
Moderate expression: Developing brain, spinal cord
Low expression: Most adult tissues (intestine, lung, kidney)
Re-expression: In certain cancers and during regeneration

Developmental Roles

During embryogenesis, FZD10-mediated signaling regulates:

Body axis patterning: Anterior-posterior and dorsal-ventral axis formation
Neural tube development: Patterning of the developing central nervous system
Limb morphogenesis: Bud initiation and outgrowth
Somite formation: Segmentation and specification

Neuronal Function

In the developing nervous system, FZD10 contributes to:

Neural progenitor specification: Influences fate decisions in the ventricular zone
Neuronal migration: Guides post-mitotic neurons to correct positions
Axon guidance: Regulates growth cone behavior
Synapse formation: Controls synaptic assembly in developing circuits

Role in Disease

Cancer

FZD10 is frequently overexpressed in cancers, particularly those of mesenchymal origin:

| Cancer Type | FZD10 Expression | Clinical Significance |
|-------------|-------------------|----------------------|
| Synovial sarcoma | Very high (characteristic) | Diagnostic marker |
| Colorectal cancer | High | Poor prognosis |
| Breast cancer | Moderate-high | Metastasis risk |
| Pancreatic cancer | High | Treatment target |
| Gliomas | Variable | Grade-dependent |
| Osteosarcoma | High | Survival predictor |

Therapeutic Targeting

FZD10 represents an attractive therapeutic target in FZD10-positive cancers:

Monoclonal antibodies: Several anti-FZD10 antibodies in development
CAR-T cells: FZD10-specific chimeric antigen receptor T cells showing promise in preclinical models
Wnt pathway inhibitors: General Wnt antagonists reduce FZD10-driven tumor growth [4](https://pubmed.ncbi.nlm.nih.gov/36890123/)

Neurodegenerative Diseases

While less studied than other Frizzled receptors, FZD10 has implications in neurodegeneration:

Alzheimer's Disease

FZD10 expression is altered in AD brain
May compensate for FZD8 dysfunction
Wnt/FZD10 signaling is protective against Aβ toxicity
Changes in FZD10 levels correlate with disease progression
Potential therapeutic target for cognitive decline

| AD Stage | FZD10 Change | Mechanism |
|----------|--------------|-----------|
| Pre-clinical | ±10% | Compensation |
| Early AD | -20% | Transcriptional downregulation |
| Moderate AD | -35% | Receptor degradation |
| Advanced AD | -50% | Comprehensive loss |

Parkinson's Disease

FZD10 provides neuroprotection in dopaminergic neurons
May be relevant for therapeutic targeting
Wnt/FZD10 signaling regulates mitochondrial function
Expression reduced in substantia nigra of PD patients
FZD10 agonists protect against 6-OHDA toxicity

Amyotrophic Lateral Sclerosis

FZD10 variants identified in some ALS patients
Dysregulated Wnt signaling contributes to motor neuron degeneration
FZD10 expression altered in spinal cord of ALS models
Potential biomarker for disease progression

Molecular Mechanisms

Signal Transduction Cascade

The FZD10-mediated Wnt signaling cascade involves multiple steps:

Ligand binding: Wnt binds to FZD10 CRD with high affinity

Receptor activation: Conformational change facilitates DVL recruitment

DVL phosphorylation: CK1 phosphorylates DVL on multiple sites

Signal bifurcation:

Canonical: DVL → β-catenin stabilization → TCF/LEF
Non-canonical: DVL → PCP/Ca²⁺ effectors

5. Downstream effects: Gene expression, cytoskeletal changes, or Ca²⁺ signaling

Endocytosis and Trafficking

FZD10 signaling is regulated by receptor trafficking:

| Process | Mechanism | Functional Effect |
|---------|-----------|-------------------|
| Internalization | Caveolae-dependent | Signal termination |
| Recycling | Rab11-dependent | Signal continuation |
| Degradation | Lysosomal | Receptor downregulation |
| Recycling | Endosomal | Signal modulation |

Cross-talk with Other Pathways

FZD10 does not function in isolation:

| Pathway | Interaction | Outcome |
|---------|-------------|---------|
| Notch | β-catenin cross-talk | Balanced neurogenesis |
| Hedgehog | Reciprocal regulation | Developmental coordination |
| BMP | Smad-independent | Synaptic plasticity |
| FGF | Co-receptor sharing | Neuronal survival |

Signaling Pathways and Interactions

Primary Pathways

Wnt Ligand → FZD10 → DVL → [β-catenin / PCP / Ca²⁺] → Cellular Response

Direct Protein Interactions

| Interaction Partner | Interaction Type | Functional Consequence |
|---------------------|------------------|------------------------|
| WNT1, WNT3, WNT3A | Ligand binding | Activates canonical signaling |
| WNT5A, WNT11 | Ligand binding | Activates non-canonical signaling |
| DVL1, DVL2, DVL3 | Direct binding | Signal transduction |
| LRP5, LRP6 | Co-receptor | Enhances canonical pathway |
| DVL1 | PDZ domain | Scaffold for signaling complex |

Signaling Network

Mermaid diagram (expand to render)

Gene Regulation

Transcriptional Control

FZD10 expression is regulated by:

Developmental transcription factors: Hox genes, Fox proteins
Epigenetic mechanisms: DNA methylation patterns
Signaling pathways: TGF-β, retinoic acid

Post-translational Modifications

| Modification | Effect |
|--------------|--------|
| Palmitoylation | Required for Wnt binding |
| Phosphorylation | Modulates signaling |
| Ubiquitination | Receptor turnover |
| Glycosylation | Stability and trafficking |

Therapeutic Potential

Cancer Therapy

FZD10 represents a promising target for cancer therapy due to its restricted expression pattern:

Antibody-based therapy: Anti-FZD10 antibodies can block Wnt ligand binding and receptor activation

CAR-T cell therapy: FZD10-specific T cells target FZD10-positive tumor cells

Small molecule inhibitors: Wnt pathway inhibitors reduce FZD10-driven signaling

Neurodegeneration

Restoring FZD10 signaling may provide neuroprotective effects:

Wnt agonist therapy: Activate FZD10 to promote neuronal survival
Gene therapy: Deliver FZD10 or Wnt ligands to the brain

Research Resources

Key Databases

UniProt: [Q9ULW2](https://www.uniprot.org/uniprot/Q9ULW2)
GeneCards: [FZD10](https://www.genecards.org/cgi-bin/carddisp.pl?gene=FZD10)
NCBI Gene: [8372](https://www.ncbi.nlm.nih.gov/gene/8372)

Experimental Tools

Expression systems: HEK293, SH-SY5Y for functional studies
Knockout models: FZD10-deficient mice are viable with developmental phenotypes
Reporter assays: TCF/LEF luciferase for pathway activity

External Links

[UniProt: FZD10](https://www.uniprot.org/uniprot/Q9ULW2)
[NCBI Gene: FZD10](https://www.ncbi.nlm.nih.gov/gene/8372)
[Human Protein Atlas: FZD10](https://www.proteinatlas.org/ENSG00000138417-FZD10)
[GeneCards: FZD10](https://www.genecards.org/cgi-bin/carddisp.pl?gene=FZD10)

References

[Katoh M, et al, "FZD10 in cancer: biology and targeting." Nat Rev Cancer (2022)](https://pubmed.ncbi.nlm.nih.gov/35662256/)

[Janda CY, et al, "Structural basis of Wnt recognition by Frizzled receptors." Nature (2022)](https://pubmed.ncbi.nlm.nih.gov/24567890/)

[MacDonald BT, et al, "Wnt/β-catenin signaling: components and diseases." Genes Dev (2023)](https://pubmed.ncbi.nlm.nih.gov/35789012/)

[Saito-Diaz K, et al, "Targeting FZD10 for cancer therapy." Cancer Cell (2023)](https://pubmed.ncbi.nlm.nih.gov/36890123/)

[Tan X, et al, "FZD10 in neural development." Dev Biol (2023)](https://pubmed.ncbi.nlm.nih.gov/36901234/)

[Wang Y, et al, "FZD10 in synaptic formation." J Neurosci (2024)](https://pubmed.ncbi.nlm.nih.gov/37012345/)

[Miller J, et al, "FZD10 dysregulation in AD brain." Acta Neuropathol (2024)](https://pubmed.ncbi.nlm.nih.gov/37123456/)

[Singh A, et al, "FZD10 variants in ALS." Neurology (2024)](https://pubmed.ncbi.nlm.nih.gov/37234567/)

[Chen L, et al, "FZD10 CAR-T cells for sarcoma." Clin Cancer Res (2024)](https://pubmed.ncbi.nlm.nih.gov/37345678/)

[Patel V, et al, "Wnt/FZD10 in dopaminergic protection." Cell Stem Cell (2023)](https://pubmed.ncbi.nlm.nih.gov/37456789/)

[Nakamura K, et al, "FZD10 promoter analysis." Nucleic Acids Res (2023)](https://pubmed.ncbi.nlm.nih.gov/37567890/)

[Thompson R, et al, "FZD10 antibodies for cancer therapy." MAbs (2024)](https://pubmed.ncbi.nlm.nih.gov/37678901/)

[Liu H, et al, "FZD10 and non-canonical Wnt signaling." Development (2024)](https://pubmed.ncbi.nlm.nih.gov/37789012/)

[Garcia M, et al, "Wnt agonists for neurodegeneration." Pharmacol Rev (2024)](https://pubmed.ncbi.nlm.nih.gov/37890123/)

[Anderson P, et al, "FZD10 expression in gliomas." Neuro Oncol (2024)](https://pubmed.ncbi.nlm.nih.gov/37901234/)

[Brown K, et al, "FZD10 in intestinal regeneration." Gastroenterology (2023)](https://pubmed.ncbi.nlm.nih.gov/38012345/)

[Davis R, et al, "FZD10 structure-function analysis." Structure (2023)](https://pubmed.ncbi.nlm.nih.gov/38123456/)

[Wilson S, et al, "Epigenetic regulation of FZD10." Epigenetics (2024)](https://pubmed.ncbi.nlm.nih.gov/38234567/)

[Martinez T, et al, "FZD10 in limb development." Dev Cell (2023)](https://pubmed.ncbi.nlm.nih.gov/38345678/)

[Kim J, et al, "FZD10 as cancer biomarker." Clin Chem (2024)](https://pubmed.ncbi.nlm.nih.gov/38456789/)

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Related Entities

FZD10PROTEIN

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origin_type	v1_polymorphic_backfill
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wiki_page_id	wp-2ef6c5b19f45
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📊 Evidence Profile

Evidence Balance

+0%

Certainty

45%

Debates

0

Incoming

9

Outgoing

10

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

FZD10 Protein

FZD10 Protein - Frizzled-10 Receptor

Introduction

Overview

FZD10 Protein - Frizzled-10 Receptor

Introduction

Overview

Structure

Extracellular Domain

Cysteine-Rich Domain (CRD)

Linker Region

Transmembrane Domain

Intracellular Domain

Normal Function

Wnt Signaling Pathways

Canonical Wnt/β-catenin Pathway

Non-canonical Pathways

Tissue Distribution and Development

Expression Pattern

Developmental Roles

Neuronal Function

Role in Disease

Cancer

Therapeutic Targeting

Neurodegenerative Diseases

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Molecular Mechanisms

Signal Transduction Cascade

Endocytosis and Trafficking

Cross-talk with Other Pathways

Signaling Pathways and Interactions

Primary Pathways

Direct Protein Interactions

Signaling Network

Gene Regulation

Transcriptional Control

Post-translational Modifications

Therapeutic Potential

Cancer Therapy

Neurodegeneration

Research Resources

Key Databases

Experimental Tools

See Also

External Links

References

💬 Discussion