The S100 protein family consists of 24 members functionally distributed into three main subgroups:
those that only exert intracellular regulatory effects, those with intracellular and extracellular functions and
those which mainly exert extracellular regulatory effects. S100 proteins are only expressed in vertebrates and
show cell-specific expression patterns. In some instances, a particular S100 protein can be induced in
pathological circumstances in a cell type that does not express it in normal physiological conditions. Within
cells, S100 proteins are involved in aspects of regulation of proliferation, differentiation, apoptosis, Ca2+
homeostasis, energy metabolism, inflammation and migration/invasion through interactions with a variety of
target proteins including enzymes, cytoskeletal subunits, receptors, transcription factors and nucleic acids.
Some S100 proteins are secreted or released and regulate cell functions in an autocrine and paracrine manner
via activation of surface receptors (e.g. the receptor for advanced glycation end-products and toll-like receptor
4), G-protein-coupled receptors, scavenger receptors, or heparan sulfate proteoglycans and N-glycans.
Extracellular S100A4 and S100B also interact with epidermal growth factor and basic fibroblast growth factor,
respectively, thereby enhancing the activity of the corresponding receptors. Thus, extracellular S100 proteins
exert regulatory activities on monocytes/macrophages/microglia, neutrophils, lymphocytes, mast cells, articular
chondrocytes, endothelial and vascular smooth muscle cells, neurons, astrocytes, Schwann cells, epithelial
cells, myoblasts and cardiomyocytes, thereby participating in innate and adaptive immune responses, cell
migration and chemotaxis, tissue development and repair, and leukocyte and tumor cell invasion.