The S100 proteins are a family of low molecular-weight proteins found in vertebrates characterized by two calcium-binding sites that have helix-loop-helix (" EF-hand-type") conformation. At least 21 different S100 proteins are known. 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 (DAMPs), and knockdown of aryl hydrocarbon receptor downregulates the expression of S100 proteins in THP-1 cells.

Structure

Most S100 proteins consist of two identical polypeptides (homodimeric), which are held together by noncovalent bonds. They are structurally similar to

calmodulin Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the bind ...

. They differ from

, though, 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. In 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 ( Schwann cells, and

melanocyte Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. ...

s),

chondrocyte Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteog ...

adipocyte Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...

s, myoepithelial cells,

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s, Langerhans cells, dendritic cells, and keratinocytes. They may be present in some breast epithelial cells. S100 proteins have been implicated in a variety of intracellular and extracellular functions, such as regulation of protein phosphorylation, transcription factors, Ca²⁺ homeostasis, the dynamics of cytoskeleton constituents, enzyme activities, cell growth and differentiation, and the inflammatory response. S100A7 (psoriasin) 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. They can be found in

melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

s, 100% of schwannomas, 100% of neurofibromas (weaker than schwannomas), 50% of malignant peripheral nerve sheath tumors (may be weak and/or focal), 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

* '' S100A1, S100A2, S100A3, S100A4,

S100A5 S1, S01, S.I, S-1, S.1, Š-1 or S 1 may refer to: Biology and chemistry * S1 nuclease, an enzyme that digests singled-stranded DNA and RNA * S1: Keep locked up, a safety phrase in chemistry * Primary somatosensory cortex, also known as S1 * Tegafu ...

S100A6 S100 calcium-binding protein A6 (S100A6) is a protein that in humans is encoded by the ''S100A6'' gene. Function The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 pro ...

, S100A7'' (psoriasin), '' S100A8'' (calgranulin A), '' S100A9'' (calgranulin B), '' S100A10, S100A11,

S100A12 S100 calcium-binding protein A12 (S100A12) is a protein that in humans is encoded by the ''S100A12'' gene. Human S100A12, also known as calgranulin C, was first described in 1995. The protein encoded by this gene is a member of the S100 family of ...

'' (calgranulin C), '' S100A13,

S100A14 S100 calcium binding protein A14 (S100A14) is a protein that in humans is encoded by the S100A14 gene. Function This gene encodes a member of the S100 protein family which contains an EF-hand motif and binds calcium. The gene is located i ...

, S100A15 ''(koebnerisin), ''

S100A16 S100 calcium-binding protein A16 (S100A16) is a protein that in humans is encoded by the ''S100A16'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." mean ...

'' * '' S100B * '' S100P * ''

S100Z S1, S01, S.I, S-1, S.1, Š-1 or S 1 may refer to: Biology and chemistry * S1 nuclease, an enzyme that digests singled-stranded DNA and RNA * S1: Keep locked up, a safety phrase in chemistry * Primary somatosensory cortex, also known as S1 * Tega ...

'' (), '' CRNN; FLG, FLG2, HRNR,

RPTN Repetin is an extracellular matrix protein expressed in the epidermis. In humans it is encoded by the ''RPTN'' gene. Repetin is part of the S100 fused-type protein family and contains an EF hand structural domain. It functions in the cornified c ...

, S100G, TCHH, THHL1''

Nomenclature

The "S100" symbol prefix denotes 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 HUGO Gene Nomenclature Committee nomenclature, does not use hyphens in symbols.

References

External links

* {{Portal bar, Biology Diagnostic neurology Protein families