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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s found in

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

s characterized by two

calcium Calcium is a chemical element; it has 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 to it ...

-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 has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

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, AH receptor, or as the 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 express ...

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 Eukaryote, eukaryotic cells. It is an intracellular target of the Second messenger system, sec ...

. 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 The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, ...

(

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 glial cell, satellite ...

s, and

melanocyte Melanocytes are melanin-producing neural-crest, neural crest-derived cell (biology), cells located in the bottom layer (the stratum basale) of the skin's epidermis (skin), epidermis, the middle layer of the eye (the uvea), the inner ear, vagina ...

s),

chondrocyte Chondrocytes (, ) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans. Although the word '' chondroblast'' is commonly used to describe an immatu ...

adipocyte Adipocytes, also known as lipocytes and fat cells, are the cell (biology), 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 ...

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 lumen (anatomy), luminal cells. These may be positive for ACTA2, alph ...

macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin once thought to be a resident dendritic cell. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in t ...

dendritic cells A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...

, 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 refer ...

. They may be present in some

breast The breasts are two prominences located on the upper ventral region of the torso among humans and other primates. Both sexes develop breasts from the same embryology, embryological tissues. The relative size and development of the breasts is ...

epithelial cells Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

. 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 is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...

s, 100% of

schwannomas A schwannoma (or neurilemmoma) is a usually benign nerve sheath tumor composed of Schwann cells, which normally produce the insulating myelin sheath covering peripheral nerves. Schwannomas are homogeneous tumors, consisting only of Schwann cells ...

, 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 peripheral nerves. Given its origin and behavior it is classified as a sarcoma. About half the cases are diagnosed in people with neurofi ...

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 pa ...

, and

clear-cell sarcoma Clear cell sarcoma is a sub-type of 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 ...

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 macroscopic, microscopic, biochemical, immunologic and molecular examination ...

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. S10 ...

'', ''

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'', ''

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 The EF hand is a helix–loop–helix structu ...

'', '' S100A5'', '' S100A6'', '' S100A7'' (psoriasin), '' S100A7A'' (koebnerisin), '' S100A8'' (calgranulin A), '' S100A9'' (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 c ...

'', '' S100A11'', '' S100A12'' (calgranulin C), '' S100A13'', '' S100A14'', '' S100A16'' * '' S100B'', ''

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 1, calbindin, calretinin and S100G. They wer ...

'', '' 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 ce ...

'', ''

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