Forkhead-associated domain

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PDB 2csw EBI

Forkhead-associated domain (FHA domain) is a protein domain that is involved in protein-protein interactions. It is named after its similarity to the forkhead box (FOX) proteins, although it is not directly related to them. FHA domains are found in a variety of proteins, particularly those involved in DNA repair, cell cycle control, and signal transduction.

Structure

The FHA domain typically consists of approximately 65-100 amino acids and adopts a beta sandwich structure. This structure is composed of two beta sheets that pack against each other, forming a stable fold. The FHA domain is known for its ability to recognize and bind to phosphothreonine-containing motifs, which is crucial for its role in signaling pathways.

Function

FHA domains are primarily involved in mediating interactions between proteins. They play a critical role in the cellular response to DNA damage by recognizing and binding to phosphorylated threonine residues on target proteins. This interaction is essential for the recruitment of DNA repair proteins to sites of damage and for the activation of cell cycle checkpoints.

Biological Significance

The FHA domain is found in a wide range of proteins across different species, indicating its evolutionary conservation and importance. In humans, proteins containing FHA domains are involved in key processes such as DNA repair, apoptosis, and cell cycle regulation. Mutations or malfunctions in FHA domain-containing proteins can lead to various diseases, including cancer.

Examples of FHA Domain-Containing Proteins

• Chk2: A protein kinase involved in the DNA damage response.
• Rad53: A key regulator of the DNA damage checkpoint in Saccharomyces cerevisiae.
• Nbs1: A component of the MRN complex involved in DNA double-strand break repair.

Research and Clinical Implications

Understanding the structure and function of FHA domains can provide insights into the mechanisms of DNA repair and cell cycle control. This knowledge is valuable for developing therapeutic strategies for diseases related to DNA damage and cell cycle dysregulation, such as cancer.

See Also

• Protein domain
• DNA repair
• Cell cycle
• Signal transduction
• Phosphorylation