CASS4 Protein
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CASS4 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>CASS4</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[CASS4](/genes/cass4)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q9H6S3](https://www.uniprot.org/uniprot/Q9H6S3)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>49 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, plasma membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>CAS family (CT10 Regulated Inositol Polyphosphate 4-phosphatase Type I)</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Strategy</td>
</tr>
<tr>
<td class="label">Kinase inhibitors</td>
<td>Target CASS4 phosphorylation</td>
</tr>
<tr>
<td class="label">Protein-protein interaction modulators</td>
<td>Disrupt CAS interactions</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Modulate expression</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's disease</a></td>
</tr>
<tr>
<td class="label"
...CASS4 Protein
Introduction
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">CASS4 Protein</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>CASS4</td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[CASS4](/genes/cass4)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>[Q9H6S3](https://www.uniprot.org/uniprot/Q9H6S3)</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>49 kDa</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Cytoplasm, plasma membrane</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>CAS family (CT10 Regulated Inositol Polyphosphate 4-phosphatase Type I)</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Strategy</td>
</tr>
<tr>
<td class="label">Kinase inhibitors</td>
<td>Target CASS4 phosphorylation</td>
</tr>
<tr>
<td class="label">Protein-protein interaction modulators</td>
<td>Disrupt CAS interactions</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Modulate expression</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">Alzheimer's disease</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">40 edges</a></td>
</tr>
</table>
Cass4 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
CASS4 (CAS Scaffold Protein Family Member 4) is a member of the CAS family of scaffold proteins involved in cellular signaling, adhesion, and migration. It has emerged as a significant protein in Alzheimer's disease through genome-wide association studies and functional studies. [@karch2012]
Overview
Mermaid diagram (expand to render)
CASS4 (Cas Scaffold Protein Family Member 4) is a signaling adapter protein that regulates T cell activation and is expressed in neurons and immune cells. CASS4 participates in various signaling pathways including those involved in cell migration, adhesion, and immune responses. [@liu2017]
This protein is involved in: [@holler2017]
- Cell signaling: Adapter protein for signaling cascades
- Immune function: Regulates T cell activation
- Cytoskeletal organization: Modulates cell migration
- Disease associations: Alzheimer's disease, psoriasis, autoimmunity
Protein Overview
Structure
CASS4 has a characteristic CAS family domain architecture:
- N-terminal SH3 Domain: Binds to proline-rich motifs in partner proteins
- Central Substrate Domain: Contains multiple YXXP motifs that are phosphorylated
- C-terminal Focal Adhesion Targeting (FAT) Domain: Mediates localization to focal adhesions
- Phosphorylation Sites: Multiple tyrosine residues for signaling regulation
Normal Function
CASS4 participates in cellular processes:
Cell Adhesion: Links integrins to cytoskeletal signaling
Cell Migration: Modulates lamellipodia formation
Survival Signaling: Activates PI3K/Akt pathway
Cytoskeletal Dynamics: Coordinates actin reorganization
Developmental Processes: Important for neural developmentRole in Disease
Alzheimer's Disease
CASS4 is genetically and functionally linked to AD:
- Genetic Association: GWAS identified CASS4 as an AD risk gene (rs72745872)
- [Tau](/proteins/tau) Pathology: Interacts with [tau](/proteins/tau) phosphorylation pathways
- Synaptic Function: Expressed in synapses, may affect plasticity
- Immune Response: Regulates microglial signaling
- Neuronal Survival: Modulates apoptotic pathways
Other Neurodegenerative Diseases
CASS4 may play roles in:
- Parkinson's Disease: Potential involvement in dopaminergic neuron signaling
- FTD: Possible role in frontotemporal lobar degeneration
Molecular Mechanisms
Signaling Pathways
CASS4 interfaces with multiple signaling cascades:
- PI3K/Akt: Promotes cell survival through Akt activation
- ERK/MAPK: Regulates cell proliferation and differentiation
- FAK Signaling: Coordinates focal adhesion dynamics
- p53 Pathway: May modulate apoptotic responses
Protein Interactions
Key interacting proteins include:
- FAK (Focal Adhesion Kinase)
- Src family kinases
- PTEN
- 14-3-3 proteins
- Actin cytoskeleton components
Therapeutic Targeting
Research Directions
Functional Studies: Elucidate precise molecular functions in [neurons](/entities/neurons)
Therapeutic Development: Identify brain-penetrant modulators
Biomarker Potential: Evaluate CASS1 as disease biomarker
Interaction Networks: Map CASS4 protein-protein interactionsKey Publications
Naj AC, et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat Genet. 2011;43(5):436-441.
Karch CM, et al. Expression of novel Alzheimer's disease risk genes in control and AD brains. PLoS One. 2012;7(11):e50976.
Liu C, et al. The role of CASS4 in Alzheimer's disease. Mol Neurobiol. 2017;54(7):5074-5084.
Holler CJ, et al. Genetic evidence for CASS4 in Alzheimer's disease. Neurobiol Aging. 2017;51:137.e1-137.e8.Background
The study of Cass4 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
- [CASS4 Gene](/institutions/cas)
- [Proteins Index](/proteins)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Tau Pathology](/mechanisms/tau-pathology)
- [GWAS Genes](/content/genes)
- [Microglia](/cell-types/microglia)
- [PI3K/Akt Signaling](/mechanisms/pi3k-akt-neurodegeneration)
External Links
- [UniProt - CASS4](https://www.uniprot.org/uniprot/Q9H6S3)
- [AlphaFold - CASS4](https://alphafold.ebi.ac.uk/entry/Q9H6S3)
- [Human Protein Atlas - CASS4](https://www.proteinatlas.org/ENSG00000125995-CASS4)
References
Naj AC, et al, Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease (2011)
Karch CM, et al, Expression of novel Alzheimer's disease risk genes in control and AD brains (2012)
Liu C, et al, The role of CASS4 in Alzheimer's disease (2017)
Holler CJ, et al, Genetic evidence for CASS4 in Alzheimer's disease (2017)Pathway Diagram
The following diagram shows the key molecular relationships involving CASS4 Protein discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)