S100A16 is a member of the S100 family of calcium-binding proteins, which are small, dimeric proteins characterized by two conserved EF-hand Ca²⁺-binding motifs. Unlike most S100 proteins, only the C-terminal EF-hand of S100A16 is functional, while the N-terminal domain lacks Ca²⁺-binding capacity (1,2).
Its expression is regulated by intracellular Ca²⁺ levels. Subcellularly, S100A16 localizes to the cytoplasm, nucleus, and membrane, and can shuttle between these compartments in a Ca²⁺-dependent manner (2,3). In the adult brain, for example, S100A16 is found in the nuclei, somata, and neurites of astrocytes, exhibiting region- and astrocyte-type-specific subcellular distributions (2).
S100A16 is widely expressed in normal tissues, including skin, esophagus, and adipose tissue. Elevated expression has been linked to poor prognosis in several cancers (3–8). Functionally, S100A16 overexpression promotes proliferation, migration, and invasiveness. Mechanistically, it is involved in protein processing, gene regulation, and cell cycle control, contributing to cytoskeletal remodeling and cellular differentiation.
