S100 calcium binding protein A9

S100 Calcium Binding Protein A9

S100 calcium binding protein A9 (S100A9), also known as calgranulin B, is a protein that in humans is encoded by the S100A9 gene. It is a member of the S100 family of proteins, which are characterized by two distinct EF-hand calcium-binding motifs. S100A9 is involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation.

Structure

S100A9 is a small protein that forms a heterodimer with S100A8, another member of the S100 protein family. This heterodimer is often referred to as calprotectin. The protein is composed of 114 amino acids and has a molecular weight of approximately 13 kDa. The structure of S100A9 includes two EF-hand motifs that bind calcium ions, which are crucial for its function.

Function

S100A9 plays a significant role in the immune response. It is predominantly expressed in neutrophils and monocytes, where it is involved in the regulation of inflammatory processes and immune responses. Upon activation, S100A9 is released into the extracellular space where it can act as a damage-associated molecular pattern (DAMP) molecule, interacting with pattern recognition receptors such as Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE).

S100A9 is also involved in the regulation of myeloid cell function, including the modulation of leukocyte recruitment and adhesion. It has been implicated in various pathological conditions, including cancer, autoimmune diseases, and chronic inflammation.

Clinical Significance

Elevated levels of S100A9 have been associated with several diseases. In rheumatoid arthritis, S100A9 is found in high concentrations in the synovial fluid of affected joints. It is also a marker of disease activity in inflammatory bowel disease and has been studied as a potential biomarker for cystic fibrosis and chronic obstructive pulmonary disease (COPD).

In oncology, S100A9 is overexpressed in various types of cancer, including breast cancer, prostate cancer, and colorectal cancer. It is thought to contribute to tumor progression by promoting inflammation and immune evasion.

Research and Therapeutic Potential

Due to its role in inflammation and cancer, S100A9 is a target of interest for therapeutic intervention. Inhibitors of S100A9 are being investigated for their potential to treat inflammatory diseases and cancer. Understanding the precise mechanisms by which S100A9 contributes to disease pathology is an active area of research.

Also see

• S100 protein family
• Calprotectin
• Inflammation
• Biomarkers