S100A15 protein

Peptide belonging to the S100 family of calcium binding proteins. As antimicrobial peptides, the peptides belonging to this family regulate basic cellular and extracellular processes such as cell proliferation and differentiation, cell migration and antimicrobial host defense.

By RT-PCR of psoriatic skin, Wolf et al. (2003) cloned 2 splice variants of S100A7A, which they named S100A15 (S100 Calcium Binding Protein A15). Both splice variants encode identical 101-amino acid proteins with a calculated molecular mass of 11.3 kD. S100A15 has an N-terminal S100-type EF-hand motif and a C-terminal canonical EF-hand motif, a bipartite core target sequence, and an N-myristoylation site. S100A15 is 93% identical to S100A7 (600353).

Furthermore, S100A15 functions as an antimicrobial peptide (AMP). The cytokine is significantly involved in antimicrobial host defense of the skin and digestive tract. In the normal epidermis, S100A15 is expressed by basal and differentiated keratinocytes, melanocytes, and Langerhans cells of the epidermis. Within follicles, S100A15 is found in the inner and outer root sheaths and in the basal layer of the sebaceous gland. In the dermis, S100A15 is produced by dendritic cells, smooth muscle cells, endothelial cells, and fibroblasts to control tissue regeneration.

Thus, S100A15 is overexpressed in inflammatory skin diseases such as psoriasis and eczema. It is regulated by proinflammatory Th1 and Th17 but not Th2 cytokines. When released into the extracellular space, S100A15 triggers inflammation. It acts as a chemoattractant for myeloid leukocytes via a G protein-coupled receptor. S100A15 enhances inflammation with the related S100A7 (psoriasin), as it also has inflammatory activity.

1. Al-Sudany NK et al. (2019) Downregulation of S100a7a antimicrobial peptide in acne vulgaris patients after isotretinoin therapy. Dermatol Ther 32:e13136.
2. Marenholz I et al. (2001) Identification of human epidermal differentiation complex (EDC)-encoded genes by subtractive hybridization of entire YACs to a gridded keratinocyte cDNA library. Genome Res 11: 341-355.
3. Wolf R et al. (2003) Molecular cloning and characterization of alternatively spliced mRNA isoforms from psoriatic skin encoding a novel member of the S100 family. FASEB J 17: 1969-1979.
4. Wolf R et al. (2011) Novel S100A7 (psoriasin)/S100A15 (koebnerisin) subfamily: highly homologous but distinct in regulation and function. Amino Acids 41: 789-796.
5. Nasser MW et al (2015) RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment. Cancer Res 75: 974-985.