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.
| Attribute | Value |
|---|---|
| Gene Symbol | S100A6 |
| Chromosomal Location | 1q21.3 |
| NCBI Gene ID | 6277 |
| Ensembl ID | ENSG00000197646 |
| Uniprot ID | P06703 |
| Aliases | CALCYCLIN, S100A6, CACY, SIAS |
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.
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 proteins
The two EF-hands are connected by a central hinge region that undergoes conformational changes upon calcium binding, exposing interaction surfaces for target proteins.
S100A6 participates in multiple cellular processes:
S100A6 interacts with several key proteins:
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 context
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 function
S100A6 is expressed in multiple brain cell types:
S100A6 has been investigated as a potential biomarker: