S100 calcium binding protein A8

Human protein and gene

S100 calcium-binding protein A8 (S100A8), also known as myeloid-related protein 8 (MRP8) or calgranulin A, is a protein that in humans is encoded by the S100A8 gene.

Structure

S100A8 is a member of the S100 protein family, which is characterized by the presence of two EF-hand calcium-binding motifs. These motifs allow the protein to bind calcium ions, which can induce conformational changes that affect its function. S100A8 typically forms a heterodimer with S100A9, another member of the S100 family, to form the complex known as calprotectin.

Function

S100A8 plays a crucial role in the regulation of inflammatory processes and immune response. It is predominantly expressed in neutrophils and monocytes, and its expression is upregulated during inflammation. The protein is involved in the recruitment of leukocytes to sites of inflammation and can act as a damage-associated molecular pattern (DAMP) molecule, signaling through receptors such as Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE).

S100A8, as part of the calprotectin complex, has antimicrobial properties and can sequester essential metal ions, such as zinc and manganese, thereby limiting their availability to pathogens and inhibiting microbial growth.

Clinical significance

Elevated levels of S100A8/A9 (calprotectin) are associated with various inflammatory diseases, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. It is used as a biomarker for disease activity in these conditions. Additionally, S100A8/A9 has been implicated in cancer, where it may play a role in tumor progression and metastasis.

Research

Research into S100A8 continues to explore its role in inflammation and its potential as a therapeutic target. Studies are investigating how modulation of S100A8/A9 activity could be used to treat inflammatory diseases and cancer.

Also see

• S100 protein family
• Calprotectin
• Inflammation
• Neutrophil
• Toll-like receptor 4