S100A15
Encyclopedia
Koebnerisin also known as protein S100-A7A (S100A7A), S100 calcium-binding protein A7-like 1 (S100A7L1) or S100 calcium-binding protein A15 (S100A15) is a protein
that in humans is encoded by the S100A7A (alias:S100A15) gene
.
S100 proteins 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
.
Koebnerisin (S100A15) was first identified upregulated in inflammation-prone psoriatic skin, suggesting involvement in the lesional phenotype of the disease, Koebner phenomenon
. Today, the protein is of further interest because of its role in antimicrobial defence, innate immunity, epidermal cell maturation and epithelial tumorigenesis.
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 (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.
and eczema
. It is regulated through Th1 but not Th2 proinflammatory cytokines. When released into the extracellar space, koebnerisin (S100A15) induces inflammation. It acts as a chemoattractant for lymphocytes and myeloid leukocytes through a pertussis toxin sensitive Gi protein coupled receptor. Koebnerisin (S100A15) amplifies inflammation with related psoriasin (S100A7
) that is co-regulated and proinflammatory through RAGE
.
s within the Epidermal Differentiation Complex (EDC, chromosome 1q21) during primate evolution 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, 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.
. It can be used to study the significance of the corresponding human proteins for epidermal maturation, inflammation and carcinogenesis.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the S100A7A (alias:S100A15) gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
S100 proteins 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
Antimicrobial peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides...
.
Koebnerisin (S100A15) was first identified upregulated in inflammation-prone psoriatic skin, suggesting involvement in the lesional phenotype of the disease, Koebner phenomenon
Koebner Phenomenon
The Koebner phenomenon, also called the "Koebner response" or the "isomorphic response", refers to skin lesions appearing on lines of trauma. The Koebner phenomenon may result from either a linear exposure or irritation...
. Today, the protein is of further interest because of its role in antimicrobial defence, innate immunity, epidermal cell maturation and epithelial tumorigenesis.
Epithelial homeostasis and antimicrobial host defence
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 and endothelial cells.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 (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 psoriasisPsoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...
and eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...
. It is regulated through Th1 but not Th2 proinflammatory cytokines. When released into the extracellar space, koebnerisin (S100A15) induces inflammation. It acts as a chemoattractant for lymphocytes and myeloid leukocytes through a pertussis toxin sensitive Gi protein coupled receptor. Koebnerisin (S100A15) amplifies inflammation with related psoriasin (S100A7
S100A7
Protein S100-A7 also known as S100 calcium-binding protein A7 or 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...
) that is co-regulated and proinflammatory through RAGE
RAGE
RAGE, the Receptor for Advanced Glycation Endproducts is a 35kD transmembrane receptor of the immunoglobulin super family which was first characterized in 1992 by Neeper et al. It is also called "AGER"...
.
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.Primate
Koebnerisin (S100A15) has lately evolved by gene duplicationGene duplication
Gene duplication is any duplication of a region of DNA that contains a gene; it may occur as an error in homologous recombination, a retrotransposition event, or duplication of an entire chromosome.The second copy of the gene is often free from selective pressure — that is, mutations of it have no...
s within the Epidermal Differentiation Complex (EDC, chromosome 1q21) during primate evolution 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, 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) geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. It can be used to study the significance of the corresponding human proteins for epidermal maturation, inflammation and carcinogenesis.