S100 protein

S100 protein refers to a family of low-molecular-weight proteins found in vertebrates characterized by two calcium-binding sites of the helix-loop-helix ("EF-hand type") conformation. There are at least 21 different S100 proteins, which are encoded by a cluster of genes located on human chromosome 1q21. These proteins are involved in a variety of intracellular and extracellular functions including regulation of protein phosphorylation, transcription factors, the dynamics of cytoskeleton constituents, Ca2+ homeostasis, inflammation, and the progression and suppression of cancer. S100 proteins are also involved in intracellular and extracellular signaling pathways.

Structure and Function

S100 proteins are small, around 10-12 kDa, and typically form homodimers, heterodimers, or larger oligomeric assemblies, which are crucial for their function. The presence of calcium significantly alters the conformation of S100 proteins, which enables them to interact with target proteins. These interactions often result in changes in cell function, as S100 proteins can influence the activity of their targets. The specific functions of S100 proteins vary widely among different family members and include roles in cell growth, energy metabolism, inflammation, neuroprotection, and the regulation of transcription and cell cycle progression.

Clinical Significance

Several S100 proteins are implicated in human diseases. For example, S100B is found in high concentrations in the brain and has been studied as a potential biomarker for brain injury and neurodegenerative diseases. Elevated levels of S100B are associated with certain types of brain damage and can be detected in the blood, making it a useful tool for assessing patients with head injuries or neurodegenerative conditions.

S100A8 and S100A9, also known as calprotectin, are markers of inflammation and are elevated in diseases such as rheumatoid arthritis, inflammatory bowel disease, and some cancers. Calprotectin levels in feces are used to diagnose and monitor inflammatory bowel diseases.

The expression of certain S100 proteins is also associated with cancer progression. For example, S100A4 is involved in metastasis, and its expression levels can correlate with tumor aggressiveness and poor prognosis in cancer patients.

Genetics

The genes encoding S100 proteins are located on chromosome 1q21, a region known as the "epidermal differentiation complex," which is involved in skin and mucosal membrane development and function. This gene cluster suggests a shared evolutionary history and functional relatedness among the S100 family members.

Research Directions

Research on S100 proteins continues to uncover their roles in various diseases, offering potential new targets for therapy. For instance, inhibiting the interaction between S100 proteins and their targets could be a strategy for treating certain cancers or inflammatory conditions. Additionally, as biomarkers, S100 proteins offer a non-invasive means of diagnosing and monitoring diseases.

See Also

• Calcium-binding protein
• Biomarker
• Inflammation
• Cancer

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