The S100 proteins are a family of low molecular-weight

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s found in

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...

s characterized by two

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...

-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

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

s 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 bin ...

. 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 Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...

(

Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory en ...

s, 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 hear ...

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 prote ...

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 ...

myoepithelial cell Myoepithelial cells (sometimes referred to as myoepithelium) are cells usually found in glandular epithelium as a thin layer above the basement membrane but generally beneath the luminal cells. These may be positive for alpha smooth muscle actin a ...

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 ce ...

s, Langerhans cells, dendritic cells, and

keratinocytes Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...

. They may be present in some

breast The breast is one of two prominences located on the upper ventral region of a primate's torso. Both females and males develop breasts from the same embryological tissues. In females, it serves as the mammary gland, which produces and sec ...

epithelial cells Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...

. 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 A histiocytoma is a tumour consisting of histiocytes. Histiocytes are cells that are a part of the mononuclear phagocytic system, a part of the body's immune system that consists of phagocytic cells, which are responsible for engulfing solid parti ...

, and

clear-cell sarcoma Clear cell sarcoma is a rare form of cancer called a sarcoma. It is known to occur mainly in the soft tissues and dermis. Rare forms were thought to occur in the gastrointestinal tract before they were discovered to be different and redesignated ...

s. 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 Protein S100-A1, also known as S100 calcium-binding protein A1 is a protein which in humans is encoded by the ''S100A1'' gene. S100A1 is highly expressed in cardiac and skeletal muscle, and localizes to Z-discs and sarcoplasmic reticulum. S100A1 ...

S100A2 S100 calcium-binding protein A2 (S100A2) is a protein that in humans is encoded by the ''S100A2'' gene and it is located on chromosome 1q21 with other S100 proteins. Tissue and subcellular distribution S100A2, also known as CaN19 or S100L was ...

S100A3 S100 calcium-binding protein A3 (S100A3) is a protein that in humans is encoded by the ''S100A3'' gene. The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are ...

, S100A4, S100A5,

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 p ...

S100A7 S100 calcium-binding protein A7 (S100A7), also known as psoriasin, is a protein that in humans is encoded by the ''S100A7'' gene. Function S100A7 is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 pro ...

'' (psoriasin), '' S100A8'' (calgranulin A), '' S100A9'' (calgranulin B), '' S100A10, S100A11, S100A12'' (calgranulin C), ''

S100A13 S100 calcium-binding protein A13 (S100A13) is a protein that in humans is encoded by the ''S100A13'' 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 ...

, S100A14,

S100A15 S100 calcium-binding protein A15 (S100A15), also known as koebnerisin and S100 calcium-binding protein A7A (S100A7A), is a protein that in humans is encoded by the ''S100A7A'' (alias:''S100A15'') gene. S100 proteins are a diverse calcium-bindin ...

''(koebnerisin), ''

S100A16 S100 calcium-binding protein A16 (S100A16) is a protein that in humans is encoded by the ''S100A16'' gene. References Further reading * * * * * * * {{gene-1-stub S100 proteins ...

'' * '' S100B * '' S100P * '' S100Z'' (), '' 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