Rev-ErbA alpha

Rev-ErbA alpha (also known as NR1D1 for Nuclear Receptor Subfamily 1, Group D, Member 1) is a nuclear receptor that in humans is encoded by the NR1D1 gene. It is a member of the nuclear receptor family of intracellular transcription factors and plays a critical role in the regulation of circadian rhythms, metabolism, and immune function.

Function

Rev-ErbA alpha functions as a transcriptional repressor and is involved in the regulation of various physiological processes. It is a key component of the circadian clock, where it negatively regulates the expression of BMAL1 (Brain and Muscle ARNT-Like 1), a core clock gene, thereby contributing to the maintenance of circadian rhythm. In addition to its role in the circadian clock, Rev-ErbA alpha influences lipid and glucose metabolism, making it a potential target for the treatment of metabolic disorders such as obesity and diabetes.

Structure

The Rev-ErbA alpha protein contains a DNA-binding domain (DBD) and a ligand-binding domain (LBD). The DBD allows the protein to bind to specific DNA sequences, known as Rev-Drb response elements (RevREs), to regulate gene expression. The LBD can bind to heme, which acts as a ligand, modulating the receptor's activity in response to intracellular heme levels.

Clinical Significance

Alterations in the expression or function of Rev-ErbA alpha have been associated with various health conditions, including metabolic syndrome, cardiovascular diseases, and certain cancers. Its role in the circadian regulation makes it a potential target for the treatment of sleep disorders and the adverse health effects associated with shift work and jet lag.

Research

Research on Rev-ErbA alpha has focused on its potential as a therapeutic target for metabolic and circadian rhythm disorders. Synthetic ligands that selectively target Rev-ErbA alpha have been developed, showing promise in the regulation of metabolism and the enhancement of circadian rhythm synchronization.

See Also

• Nuclear receptor
• Circadian rhythm
• Metabolic disorder
• BMAL1