Rev-ErbA beta (Rev-erbβ) also known as NR1D2 (nuclear receptor subfamily 1, group D, member 2) is a protein that in humans is encoded by the NR1D2 gene.Rev-erbβ is a member of the Rev-ErbA family of transcription factors. Rev-erbβ, like Rev-erbα, belongs to the nuclear receptor superfamily and can modulate gene expression by directly binding to their promoters.

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An Overview of NR1D2

NR1D2 (Rev-erb β), the nuclear receptor subfamily 1, group D, member 2, is a member of the nuclear receptor superfamily and regulates gene expression by directly binding its promoter. NR1D2 generally acts as a transcriptional repressor in its protein structure. It’s originally characterized as a repressor of genes involved in circadian rhythms whose mRNA showed rhythmic expression in vivo and in serum synchronized cell culture. It can target the circadian clock genes Bmal1 (brain and muscle ARNT-like protein 1) and clock (circadian locomotor output cycles kaput). NR1D2 is involved in the control of lipid and energy homeostasis in skeletal muscle. However, it is unclear to what extent Rev-erbβ contributes to the oscillation of the core circadian clock.

Agonists of NR1D2

NR1D2 agonists can regulate the expression of core clock proteins driving rhythms in activity and metabolism. Administration of synthetic agonists, SR9011 and SR9009 (Fig. 1), can alter circadian behavior and the circadian pattern of core clock gene expression in the hypothalami of mice. It is reported that the agonists increase energy expenditure and decrease fat mass, plasma triglycerides and cholesterol levels, suggesting that these agonists may be useful in the treatment of metabolic diseases.

Chemical structure of SR9011 and SR9009

Fig. 1 Chemical structure of SR9011 and SR9009.

NR1D2 and diseases

NR1D2 can affect the differentiation and function of fat cells and is associated with metabolic disorders, plasmin system abnormalities, and the onset of cardiovascular disease. It also regulates the rhythm of retinal photoreceptor cells. The physiological clock is considered to be an adaptive response to predict daily environmental changes and is the most basic adjustment unit of the body. It affects many aspects of the body's behavior and physiology, including sleep/wake cycle, blood pressure, body temperature, energy metabolism. Destruction of normal circadian rhythms often leads to an increase in the incidence of many diseases, such as metabolic diseases, mental illnesses and cancer.


Solt, L. A., Wang, Y. J., Banerjee, S., Hughes, T., Kojetin, D. J., Lundasen J., Shin, Y., Liu, J., Cameron, M. D., Noel, R., Yoo, S. H., Takahashi, J. S., Butler, A. A., Kamenecka T. M., Burris, T. P. (2012) Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. 485: 62–68