S100 protein


The S100 proteins are a family of low-molecular-weight proteins found in vertebrates and characterized by two calcium-binding sites that have helix-loop-helix conformation. There are at least 21 different S100 proteins. They are encoded by a family of genes whose symbols use the S100 prefix, for example, S100A1, S100A2, S100A3.
They are also considered as Damage-associated molecular pattern molecules and knockdown of AHR downregulates the expression of S100 proteins in THP-1 cells.

Structure

Most S100 proteins are homodimeric, consisting of two identical polypeptides, which are held together by non-covalent bonds. S100 proteins are structurally similar to calmodulin. On the other hand, they differ from calmodulin on the other features. For instance, their expression pattern is cell-specific, i.e. they are expressed in particular cell types. Their expression depends on environmental factors. To contrast, calmodulin is a ubiquitous and universal intracellular Ca2+ receptor widely expressed in many cells.

Normal function

S100 proteins are normally present in cells derived from the neural crest, chondrocytes, adipocytes, myoepithelial cells, macrophages, Langerhans cells, dendritic cells, and keratinocytes. It may be present in some breast epithelial cells.
S100 proteins have been implicated in a variety of intracellular and extracellular functions. S100 proteins are involved in regulation of protein phosphorylation, transcription factors, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, enzyme activities, cell growth and differentiation, and the inflammatory response. S100A7 and S100A15 have been found to act as cytokines in inflammation, particularly in autoimmune skin conditions such as psoriasis.

Pathology

Several members of the S100 protein family are useful as markers for certain tumors and epidermal differentiation. It can be found in melanomas, 100% of schwannomas, 100% of neurofibromas, 50% of malignant peripheral nerve sheath tumors, paraganglioma stromal cells, histiocytoma and clear cell sarcomas. Further, S100 proteins are markers for inflammatory diseases and can mediate inflammation and act as antimicrobials.
S100 proteins have been used in the lab as cell markers for anatomic pathology.

Human genes

CRNN; FLG; FLG2; HRNR; RPTN; S100G; TCHH; THHL1;

Nomenclature

The "S100" symbol prefix is derived from the fact that these proteins are soluble in 100%, i.e. saturated, ammonium sulfate at neutral pH. The symbol has often been hyphenated, but current gene and protein nomenclature, such as HGNC nomenclature, does not use hyphens in symbols.