| S100A10 Protein | |
|---|---|
| Protein Name | S100 Calcium Binding Protein A10 |
| Gene Symbol | [S100A10](/genes/s100a10) |
| UniProt ID | [P60903](https://www.uniprot.org/uniprot/P60903) |
| PDB Structures | 1A2P, 1BT6, 1XQX |
| Molecular Weight | 11,297 Da |
| Subcellular Localization | Cytoplasm, Cell membrane, Extracellular |
| Protein Family | S100 family (annexin ligand) |
S100A10 Protein is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
S100A10 (also known as p11) is a small calcium-binding protein belonging to the S100 family. The protein forms a heterotetrameric complex with annexin A2 (ANXA2), which is essential for its biological function. S100A10 lacks calcium-binding ability due to mutations in its EF-hand calcium-binding motifs, but instead serves as a scaffolding protein that recruits annexin A2 to the plasma membrane. The S100A10-ANXA2 complex (also called calpactins) plays crucial roles in membrane organization, endocytosis, and exocytosis.
S100A10[1] is abundantly expressed in the nervous system with multiple neuronal functions:
S100A10 is implicated in AD pathogenesis through multiple mechanisms. The protein interacts with the amyloid precursor protein (APP) and may influence amyloid-beta production. S100A10 expression is elevated in AD brain, particularly around amyloid plaques, where it may participate in inflammatory responses. Additionally, S100A10 modulates beta-secretase (BACE1) activity, linking it to amyloidogenesis. Studies show that S100A10 deficiency in mouse models exacerbates cognitive deficits, suggesting a neuroprotective role.
In PD, S100A10 participates in alpha-synuclein aggregation and toxicity. The protein can bind to alpha-synuclein and may influence its aggregation kinetics. S100A10[1:1] is also involved in microglial activation and neuroinflammation in PD models. The annexin A2 complex regulates dopamine transporter (DAT) trafficking and function, which is relevant to PD pathophysiology.
S100A10 is elevated in ALS and may contribute to disease progression through:
S100A10 plays a protective role in cerebral ischemia through:
S100A10 is being explored as a therapeutic target for neurodegenerative diseases:
Research shows that S100A10 modulators have potential for treating AD, PD, and stroke, though clinical development is still in early stages.
Donato R et al. S100A10: Structure, function and therapeutic potential. Cell Calcium. 2013. ↩︎ ↩︎