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S100 Proteins

S100 proteins are a group of small (molecular weight 10-12 kDa), dimeric Ca2+-binding proteins that share a similar sequence and structure. They are found in a wide variety of tissues with cell- and tissue-specific expression patterns. Due to their broad range of extracellular and intracellular interaction partners, S100 proteins are involved in a plethora of extra- and intracellular functions, including regulation of inflammation, cell differentiation and proliferation, migration, tissue repair, apoptosis, and protein phosphorylation.

Extracellular S100 proteins are secreted actively or passively in response to cell stress and inflammation e.g., by inflammatory cells and other granulocytes, macrophages, epithelial cells, or cancer cells. Upon release, they act at damage associated patterns (DAMPs) and interact with a range of pattern recognition receptors such as toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (RAGE), thus leading to the activation of proinflammatory signaling pathways such as the NF-kB and p38 pathways. S100 proteins also trigger immune cell migration, invasion, and differentiation.

Because of their association with various pathologies and the ease to identify them in body fluids, several S100 proteins can serve as biomarkers for certain diseases. These include e.g. Alzheimer’s disease (S100A7), inflammatory arthritis (S100A8/A9 heterodimers), or diabetes (S100A12). Many S100 proteins play a role in cancer prognosis or and some of them are suggested as biomarkers to certain types of cancer. Systemic upregulation of S100A8/A9 has also been shown to be a feature of COVID-19.

Related pathways:


  • Leclerc E et al. Binding of S100 proteins to RAGE: an update. Biochim. Biophys. Acta (2009) PMID 19121341
  • Xia C et al. S100 Proteins As an Important Regulator of Macrophage Inflammation. Front. Immunol. (2017) PMID 29379499
  • Gonzalez LL et al. Role of S100 proteins in health and disease. Biochim. Biophys. Acta. Mol. Cell Res. (2020) PMID 32057918
  • Ren X et al. COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas. Cell (2021) PMID 33657410
  • Land WG et al. Role of DAMPs in respiratory virus-induced acute respiratory distress syndrome-with a preliminary reference to SARS-CoV-2 pneumonia. Genes Immun (2021) PMID 34140652
  • Sattar Z et al. The S100 Protein Family as Players and Therapeutic Targets in Pulmonary Diseases. Pulm. Med. (2021) PMID 34239729

S100 Proteins

S100A8 (S100 Calcium Binding Protein A8):

S100A9 (S100 Calcium Binding Protein A9):

S100A10 (S100 Calcium Binding Protein A10):

S100A7 (S100 Calcium Binding Protein A7):

S100A1 (S100 Calcium Binding Protein A1):

S100G (S100 Calcium Binding Protein G):

S100A13 (S100 Calcium Binding Protein A13):

S100A2 (S100 Calcium Binding Protein A2):

S100A3 (S100 Calcium Binding Protein A3):

S100A6 (S100 Calcium Binding Protein A6):

S100B (S100 Calcium Binding Protein B):

S100A14 (S100 Calcium Binding Protein A14):

S100A5 (S100 Calcium Binding Protein A5):

S100A12 (S100 Calcium Binding Protein A12):

S100A11 (S100 Calcium Binding Protein A11):

S100P (S100 Calcium Binding Protein P):

S100Z (S100 Calcium Binding Protein Z):

S100A16 (S100 Calcium Binding Protein A16):

S100A7A (S100 Calcium Binding Protein A7A):

S100A/B (S100A/B):

S100A8/A9 - S100A8/A9 Complex (Calprotectin):

S100 Protein Receptors

NF-kappaB Signaling

CARD10 (Caspase Recruitment Domain Family, Member 10):

MALT1 (Mucosa Associated Lymphoid Tissue Lymphoma Translocation Gene 1):

TRAF2 (TNF Receptor-Associated Factor 2):

IKBKB (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase beta):

IKBKG (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase gamma):

NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1):

p38 Signaling

MAPK14 (Mitogen-Activated Protein Kinase 14):

MAPK12 (Mitogen-Activated Protein Kinase 12):

MAPK11 (Mitogen-Activated Protein Kinase 11):

MAPK13 (Mitogen-Activated Protein Kinase 13):

JNK Signaling

Erk Signaling

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