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 c ...

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 t ...

-binding sites that have helix-loop-helix ("

EF-hand The EF hand is a helix–loop–helix structural domain or ''motif'' found in a large family of calcium-binding proteins. The EF-hand motif contains a helix–loop–helix topology, much like the spread thumb and forefinger of the human hand, in ...

-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 The aryl hydrocarbon receptor (also known as AhR, AHR, ahr, ahR, or dioxin receptor) is a protein that in humans is encoded by the AHR gene. The aryl hydrocarbon receptor is a transcription factor that regulates gene expression. It was originall ...

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. They differ from calmodulin, 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 ens ...

s, and melanocytes), chondrocytes, adipocytes,

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 ...

s, macrophages,

Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...

dendritic cells Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...

, 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 intercell ...

. 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 melanomas, 100% of schwannomas, 100% of neurofibromas (weaker than schwannomas), 50% of

malignant peripheral nerve sheath tumor A malignant peripheral nerve sheath tumor (MPNST) is a form of cancer of the connective tissue surrounding nerves. Given its origin and behavior it is classified as a sarcoma. About half the cases are diagnosed in people with neurofibromatosis; t ...

s (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 a ...

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 Anatomical pathology (''Commonwealth'') or Anatomic pathology (''U.S.'') is a medical specialty that is concerned with the diagnosis of disease based on the gross examination, macroscopic, Histopathology, microscopic, biochemical, immu ...

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 Protein S100-A4 (S100A4) is a protein that in humans is encoded by the ''S100A4'' 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 proteins are localiz ...

, S100A5, S100A6,

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 S100 calcium-binding protein A8 (S100A8) is a protein that in humans is encoded by the ''S100A8'' gene. It is also known as calgranulin A. The proteins S100A8 and S100A9 form a heterodimer called calprotectin Calprotectin is a multiprotein co ...

'' (calgranulin A), ''

S100A9 S100 calcium-binding protein A9 (S100A9) also known as migration inhibitory factor-related protein 14 (MRP14) or calgranulin B is a protein that in humans is encoded by the ''S100A9'' gene. The proteins S100A8 and S100A9 form a heterodimer calle ...

'' (calgranulin B), ''

S100A10 S100 calcium-binding protein A10 (S100A10), also known as p11, is a protein that is encoded by the ''S100A10'' gene in humans and the ''S100a10'' gene in other species. S100A10 is a member of the S100 family of proteins containing two EF-hand cal ...

S100A11 S100 calcium-binding protein A11 (S100A11) is a protein that in humans is encoded by the ''S100A11'' gene. Function The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100A ...

, 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'' * ''

S100B S100 calcium-binding protein B (S100B) is a protein of the S-100 protein family. S100 proteins are localized in the cytoplasm and nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cyc ...

* ''

S100P S100 calcium-binding protein P (S100P) is a protein that in humans is encoded by the ''S100P'' 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 protei ...

* '' S100Z'' (), '' CRNN; FLG, FLG2, HRNR, RPTN,

S100G S100 calcium-binding protein G (S100G) is a protein that in humans is encoded by the ''S100G'' gene. This gene encodes calbindin Calbindins are three different calcium-binding proteins: calbindin, calretinin and S100G. They were origina ...

TCHH Trichohyalin is a protein that in mammals is encoded by the ''TCHH'' gene. Discovery In 1903 the name ''trichohyalin'' was assigned to the granules of the inner root sheath (IRS) of hair follicles discovered by Hans Vörner. In 1986 the name was ...

, THHL1''

Nomenclature

The "S100" symbol prefix denotes that these proteins are soluble in 100%, i.e. saturated,

ammonium sulfate Ammonium sulfate (American English and international scientific usage; ammonium sulphate in British English); (NH4)2SO4, is an inorganic salt with a number of commercial uses. The most common use is as a soil fertilizer. It contains 21% nitrogen a ...

at neutral pH. The symbol has often been hyphenated, but current gene and protein nomenclature, such as

HUGO Gene Nomenclature Committee The HUGO Gene Nomenclature Committee (HGNC) is a committee of the Human Genome Organisation (HUGO) that sets the standards for human gene nomenclature. The HGNC approves a ''unique'' and ''meaningful'' name for every known human gene, based on a ...

nomenclature, does not use hyphens in symbols.

References

External links

* {{Portal bar, Biology Diagnostic neurology Protein families