S100A6 Gene
Overview
Mermaid diagram (expand to render)
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">S100A6 Gene</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>S100A6</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>1q21.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>6277</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000197646</td>
</tr>
<tr>
<td class="label">Uniprot ID</td>
<td>P06703</td>
</tr>
<tr>
<td class="label">Aliases</td>
<td>CALCYCLIN, S100A6, CACY, SIAS</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/infection" style="color:#ef9a9a">Infection</a>, <a href="/wiki/tumor" style="color:#ef9a9a">Tumor</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">22 edges</a></td>
</tr>
</table>
S100A6 (S100 Calcium Binding Protein A6), also known as Calcyclin, is a member of the S100 family of small calcium-binding proteins. The S100 family consists of at least 25 members in humans, characterized by their ability to bind calcium through EF-hand motifs. S100A6 is a 91-amino acid protein that participates in numerous cellular processes including cell proliferation, differentiation, motility, and intracellular signaling.
S100A6 is expressed in a tissue-specific manner, with high expression in the brain, particularly in neurons and glial cells. The protein has been implicated in various physiological and pathological processes, including neurodegenerative diseases, cancer progression, and inflammatory responses.
Genomic Structure
The S100A6 gene is located on chromosome 1q21.3, within the S100 gene cluster, a region containing multiple S100 family members. The gene consists of 3 exons encoding a protein of 91 amino acids with a molecular weight of approximately 10.2 kDa.
Protein Structure and Function
Structural Domains
S100A6 contains two EF-hand calcium-binding motifs:
N-terminal EF-hand (residues 18-54): Low-affinity calcium-binding site with unique properties compared to classical EF-hands
C-terminal EF-hand (residues 62-89): High-affinity calcium-binding site typical of S100 proteinsThe two EF-hands are connected by a central hinge region that undergoes conformational changes upon calcium binding, exposing interaction surfaces for target proteins.
Calcium Binding and Activation
- Calcium binding: S100A6 undergoes significant conformational changes upon calcium binding
- Target interaction: Calcium-bound S100A6 interacts with various target proteins
- Zinc binding: S100A6 can also bind zinc, potentially modulating its function
Cellular Functions
S100A6 participates in multiple cellular processes:
Cell proliferation: Regulates cell cycle progression through interaction with various targets
Cytoskeletal dynamics: Binds to and modulates cytoskeletal proteins including tubulin and actin
Signal transduction: Participates in calcium-dependent signaling cascades
Secretory pathway: Can be secreted and may function extracellularly
Apoptosis regulation: Modulates programmed cell death pathwaysInteraction Partners
S100A6 interacts with several key proteins:
- Annexins: Calcium-dependent phospholipid binding proteins
- S100A4: Partner in forming heterodimers
- CacyBP: Calcyclin-binding protein (CacyBP/SIP), a key interaction partner
- p53: Tumor suppressor protein
- Vimentin: Intermediate filament protein
- Tropomyosin: Cytoskeletal regulatory protein
- Rab5: Endocytic vesicle protein
Role in Neurodegenerative Diseases
Alzheimer's Disease
S100A6 has been implicated in Alzheimer's disease pathogenesis:
Amyloid-beta interaction: S100A6 can bind to amyloid-beta peptides and potentially influence Aβ aggregation and toxicity
Calcium dysregulation: As a calcium-binding protein, S100A6 may contribute to or be affected by calcium dysregulation in AD
Tau pathology: S100A6 expression is altered in tauopathies including AD
Neuroinflammation: S100A6 is released from glial cells during neuroinflammatory responses
Neuronal survival: S100A6 has both protective and toxic effects on neurons depending on contextParkinson's Disease
In Parkinson's disease:
Alpha-synuclein interaction: S100A6 may interact with alpha-synuclein and influence its aggregation
Dopaminergic neuron function: S100A6 is expressed in dopaminergic neurons and may affect their function and survival
Oxidative stress: S100A6 expression is modulated by oxidative stress, a key mechanism in PD
Mitochondrial function: S100A6 may influence mitochondrial dynamics and functionOther Neurodegenerative Conditions
- Amyotrophic lateral sclerosis (ALS): Altered S100A6 expression in motor neurons
- Multiple sclerosis: Involvement in neuroinflammatory processes
- Huntington's disease: Changes in S100 protein expression
Expression Patterns
Brain Expression
S100A6 is expressed in multiple brain cell types:
- Neurons: Moderate to high expression in various neuronal populations
- Astrocytes: High expression in astrocytes, particularly reactive astrocytes
- Microglia: Expression in microglial cells
- Oligodendrocytes: Lower expression in oligodendrocytes
Regional Distribution
- Cortex: High expression in cerebral cortex
- Hippocampus: Particularly high expression in hippocampus
- Cerebellum: Moderate expression
- Substantia nigra: Expression in dopaminergic neurons
Clinical Significance
Disease Associations
- Alzheimer's disease: Elevated S100A6 in brain tissue and CSF
- Parkinson's disease: Altered expression in PD brain
- Cancer: Overexpression in various cancers (pancreatic, breast, colorectal)
- Inflammatory disorders: Role in inflammatory responses
Biomarker Potential
S100A6 has been investigated as a potential biomarker:
- CSF biomarker: S100A6 levels in cerebrospinal fluid
- Peripheral biomarker: Blood S100A6 measurement
- Disease progression: Correlation with disease severity
Research Directions
Current Understanding
- S100A6 is a calcium-binding protein with multiple cellular functions
- It participates in both protective and pathogenic processes in neurodegeneration
- The protein has both intracellular and potential extracellular roles
Knowledge Gaps
- Precise mechanisms of S100A6 in neurodegenerative diseases
- Therapeutic targeting potential
- Biomarker validation studies
Related Pages
- [Alzheimer's Disease](/diseases/alzheimers-disease) - Primary disease association
- [Parkinson's Disease](/diseases/parkinsons-disease) - Primary disease association
- [Calcium Dysregulation](/mechanisms/calcium-dysregulation) - Related mechanism
- [Alpha-Synuclein](/proteins/alpha-synuclein) - PD protein with potential S100A6 interaction
- [Amyloid-Beta](/proteins/amyloid-beta) - AD protein with potential S100A6 interaction
- [Astrocytes](/cell-types/astrocytes) - Cell type expressing S100A6
See Also
- [ Protein](/proteins/alpha-synuclein)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Calcium Dysregulation](/mechanisms/calcium-dysregulation)
External Links
- [Ensembl: ENSG00000197646](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000197646)
Pathway Diagram
The following diagram shows the key molecular relationships involving S100A6 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)