S100A7A

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Protein-coding gene in the species Homo sapiens

title: "S100A7A" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["s100-proteins"] description: "Protein-coding gene in the species Homo sapiens" topic_path: "general/s100-proteins" source: "https://en.wikipedia.org/wiki/S100A7A" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Protein S100-A7A (S100A7A), also known as koebnerisin, 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 (S100A7A) 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.

Function

Epithelial homeostasis and antimicrobial host defense

Skin: In normal epidermis, koebnerisin (S100A7A) is expressed by epidermal basal and differentiated keratinocytes, melanocytes, and Langerhans cells. Within the pilosebaceous unit, S100A7A is found in the inner and external root sheath and the basal layer of the sebaceous gland. In the dermis, koebnerisin (S100A7A) is produced by dendritic cells, smooth muscle cells, endothelial cells, as well as fibroblasts to control tissue regeneration.

Breast: Koebnerisin (S100A7A) is expressed by alveolar and small duct luminal cells and by epithelial-derived myoepithelial cells around acini and by surrounding blood vessels.

Koebnerisin (S100A7A) functions as an antimicrobial peptide (AMP) reducing survival of E. coli and was strongly regulated by several bacterial components, such as Pseudomonas aeruginosa and Staphylococcus 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 (S100A7A) is overexpressed in ER/PR negative tumors suggesting a regulation with tumor progression. The secreted koebnerisin (S100A7A) acts as a chemoattractant, enhances inflammation and thus could drive breast carcinogenesis.

Inflammation

Koebnerisin (S100A7A) is overexpressed in inflammatory skin diseases, such as psoriasis and eczema. It is regulated through Th1 and Th17 but not Th2 proinflammatory cytokines. When released into the extracellar space, koebnerisin (S100A7A) induces inflammation. It acts as a chemoattractant for myeloid leukocytes through a pertussis toxin sensitive Gi protein coupled receptor. Koebnerisin (S100A7A) amplifies inflammation with related psoriasin (S100A7) that is co-regulated and proinflammatory through RAGE.

Genomic organization and mRNA splice variants

Koebnerisin (S100A7A) 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 (S100A7A-short (S): 0.5 kb vs. hS100A7A-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 (S100A7A) is basic.

Evolution

Primate

Koebnerisin (S100A7A) has lately evolved by gene duplications 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 (S100A7A) 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 S100A7A (koebnerisin) and S100A7 (psoriasin) in epithelial homeostasis, inflammation and cancer.

Rodent

Koebnerisin (S100A7A) and psoriasin (S100A7) share a common protein in mice encoded by the S100a7a15 (alias: mS100A7, mS100A15, mS100a7a) gene. It can be used to study the significance of the corresponding human proteins for epidermal maturation, inflammation and epithelial carcinogenesis.

References

References

  1. "Entrez Gene: S100 calcium binding protein A7A".
  2. (2003). "Molecular cloning and characterization of alternatively spliced mRNA isoforms from psoriatic skin encoding a novel member of the S100 family". FASEB J..
  3. (2011). "Novel S100A7 (psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function". Amino Acids.
  4. (2012). "[Friend or Foe?--Psoriasin and Koebnerisin: multifunctional defence molecules in skin differentiation, tumorigenesis and inflammation]". Dtsch. Med. Wochenschr..
  5. (2014). "The Antimicrobial Peptides Psoriasin (S100A7) and Koebnerisin (S100A15) Suppress Extracellular Matrix Production and Proliferation of Human Fibroblasts". Skin Pharmacol Physiol.
  6. (2008). "Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15". J. Immunol..
  7. (Sep 2013). "Identification of danger signals in nevirapine-induced skin rash". Chemical Research in Toxicology.
  8. (2014). "The secreted protein S100A7 (psoriasin) is induced by telomere dysfunction in human keratinocytes independently of a DNA damage response and cell cycle regulators". Longevity & Healthspan.
  9. (2009). "Highly homologous hS100A15 and hS100A7 proteins are distinctly expressed in normal breast tissue and breast cancer". Cancer Lett..
  10. (2007). "S100A15, an antimicrobial protein of the skin: regulation by E. coli through Toll-like receptor 4". J. Invest. Dermatol..
  11. (2010). "Gene from a psoriasis susceptibility locus primes the skin for inflammation". Sci Transl Med.
  12. (2007). "Human S100A15 splice variants are differentially expressed in inflammatory skin diseases and regulated through Th1 cytokines and calcium". Exp. Dermatol..
  13. (2012). "Vitamin D analog calcipotriol suppresses the Th17 cytokine-induced proinflammatory S100 "alarmins" psoriasin (S100A7) and koebnerisin (S100A15) in psoriasis". J. Invest. Dermatol..
  14. (2003). "Genomic and phylogenetic analysis of the S100A7 (Psoriasin) gene duplications within the region of the S100 gene cluster on human chromosome 1q21". J. Mol. Evol..
  15. (2006). "The mouse S100A15 ortholog parallels genomic organization, structure, gene expression, and protein-processing pattern of the human S100A7/A15 subfamily during epidermal maturation". J. Invest. Dermatol..
  16. (2012). "Structural characterization of S100A7A reveals a novel zinc coordination site among S100 proteins and altered surface chemistry with functional implications for receptor binding". BMC Struct. Biol..
  17. (2006). "Purification, crystallization and preliminary X-ray diffraction of human S100A15". Acta Crystallographica Section F.
  18. "Entrez Gene: S100a7a S100 calcium binding protein".
  19. (2013). "Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos". Genes Dev..
  20. (2012). "S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways". Cancer Res..
  21. (2015). "RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment". Cancer Res..

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