S100protein

S100 proteins are a family of small, calcium-binding proteins characterized by two EF-hand motifs. They function as homodimers or heterodimers and participate in intracellular signaling by sensing and regulating intracellular calcium levels. Each S100 subunit is about 10–12 kDa and roughly 90–100 amino acids long. In humans, the S100 family includes multiple members (such as S100A1–A14 and S100B), encoded in a gene cluster on chromosome 1q21. They are expressed in a variety of tissues, including neural, glial, immune, and epithelial cells; certain members show tissue-specific expression patterns (for example, S100B in astrocytes and melanoma cells; S100A8/A9 in neutrophils).

Inside the cell, S100 proteins bind calcium via their EF-hand motifs, undergoing conformational changes that enable interactions with a range of target proteins. Through these interactions they regulate processes such as cytoskeletal organization, cell proliferation and differentiation, enzyme activities (including modulation of NADPH oxidase), and calcium homeostasis. Some S100 proteins also act as calcium buffers or chaperones, helping to shape calcium signaling events.

Extracellularly, S100 proteins can be released by cells and function as damage-associated molecular patterns (DAMPs). They interact with receptors such as RAGE and TLR4 to promote inflammatory signaling, recruit immune cells, and influence tissue repair. This extracellular activity links S100 proteins to inflammation, infection, cancer, and neurodegenerative diseases.

Clinically, certain S100 proteins serve as biomarkers. S100B is used in assessing brain injury and melanoma risk, while S100A8/A9 (calprotectin) and S100A12 serve as inflammatory markers in various diseases. The biology of S100 proteins remains an active area of research, with ongoing work into their diagnostic and therapeutic potential.