S100 calcium-binding protein A15 (S100A15), also known as koebnerisin and S100 calcium-binding protein A7A (S100A7A), is a

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, respo ...

that in humans is encoded by the ''S100A7A'' (alias:''S100A15'')

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 ba ...

S100 proteins 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 enc ...

are a diverse calcium-binding family that regulate fundamental cellular and extracellular processes including cell proliferation and differentiation, cell migration, and the antimicrobial host defense as

antimicrobial peptides Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for a ...

. Koebnerisin (S100A15) was first identified upregulated in inflammation-prone psoriatic skin, suggesting involvement in the lesional phenotype of the disease,

Koebner phenomenon The Koebner phenomenon or Köbner phenomenon (, ), also called the Koebner response or the isomorphic response, attributed to Heinrich Köbner, is the appearance of skin lesions on lines of trauma. The Koebner phenomenon may result from either a ...

. Today, the protein is of further interest because of its role in antimicrobial defence, innate immunity, epidermal cell maturation and epithelial tumorigenesis.

Function

Epithelial homeostasis and antimicrobial host defense

''Skin'': In normal epidermis, koebnerisin (S100A15) is expressed by epidermal basal and differentiated keratinocytes, melanocytes, and Langerhans cells. Within the pilosebaceous unit, S100A15 is found in the inner and external root sheath and the basal layer of the sebaceous gland. In the dermis, koebnerisin (S100A15) is produced by dendritic cells, smooth muscle cells, endothelial cells, as well as fibroblasts to control tissue regeneration. ''Breast'': Koebnerisin (S100A15) is expressed by alveolar and small duct luminal cells and by epithelial-derived myoepithelial cells around acini and by surrounding blood vessels. Koebnerisin (S100A15) functions as an

antimicrobial peptide Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for an ...

(AMP) reducing survival of E. coli and was strongly regulated by several bacterial components, such as P. aeruginosa and S. aureus. Thus, koebnerisin participates in the antimicrobial host defence of the skin and in the digestive tract of breast-feeding newborns.

Epithelial carcinogenesis

''Breast cancer:'' Koebnerisin (S100A15) is overexpressed in ER/PR negative tumors suggesting a regulation with tumor progression. The secreted koebnerisin (S100A15) acts as a chemoattractant, enhances inflammation and thus could drive breast carcinogenesis.

Inflammation

Koebnerisin (S100A15) is overexpressed in inflammatory skin diseases, such as

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

and

eczema Dermatitis is inflammation of the Human skin, skin, typically characterized by itchiness, erythema, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become lichenification, thick ...

. It is regulated through Th1 and Th17 but not Th2 proinflammatory cytokines. When released into the extracellar space, koebnerisin (S100A15) induces inflammation. It acts as a chemoattractant for myeloid leukocytes through a pertussis toxin sensitive Gi protein coupled receptor. Koebnerisin (S100A15) amplifies inflammation with related psoriasin (

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 prot ...

) that is co-regulated and proinflammatory through RAGE.

Genomic organization and mRNA splice variants

Koebnerisin (S100A15) maps to the S100 gene cluster within the epidermal differentiation complex (EDC, chromosome 1q21) and reveals an unusual genomic organization compared to other S100 members. The two alternative mRNA-isoforms of koebnerisin share the same coding region, but show differences in composition and length of adjacent untranslated regions (S100A15-short (S): 0.5 kb vs. hS100A15-long (L): 4.4 kb). Both splice variants are differently regulated in inflammatory skin diseases suggesting usage of alternate promoters.

Protein

The amino acid sequence reveals a conserved C-terminal and a variant N-terminal EF-hand typical for S100 proteins (101 amino acids, 11.305 Da, calculated pI of 7.57 kDa). Compared to most S100 proteins, koebnerisin (S100A15) is basic.

Evolution

Primate

Koebnerisin (S100A15) has lately evolved by

gene duplication Gene duplication (or chromosomal duplication or gene amplification) is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. ...

s within the Epidermal Differentiation Complex (EDC, chromosome 1q21) during

primate evolution The evolutionary history of the primates can be traced back 57-85/90 million years. One of the oldest known primate-like mammal species, ''Plesiadapis'', came from North America; another, ''Archicebus'', came from China. Other similar basal prima ...

forming a novel S100 subfamily together with Psoriasin (S100A7). Therefore, koebnerisin is almost identical to psoriasin in sequence (>90%). Despite their high homology, koebnerisin (S100A15) and psoriasin (S100A7) are distinct in tissue distribution, regulation, structure and function and, thus exemplary for the diversity within the S100 family. Their different properties are compelling reasons to discriminate S100A15 (koebnerisin) and S100A7 (psoriasin) in epithelial homeostasis, inflammation and cancer.

Rodent

Koebnerisin (S100A15) and psoriasin (S100A7) share a common protein in mice encoded by the S100a7a15 (alias: mS100A7, mS100A15, mS100a7a)

. It can be used to study the significance of the corresponding human proteins for epidermal maturation, inflammation and epithelial carcinogenesis.

References

External links

* {{PDB Gallery, geneid=338324 S100 proteins