NR1D2
NR1D2 (nuclear receptor subfamily 1 group D member 2, also known as REV-ERBβ, RVR, BD73, EAR-1r and HZF2) is a heme-regulated transcriptional repressor of the nuclear hormone receptor family. It links the circadian clock to lipid metabolism and inflammatory gene expression. Browse Assay Genie's current range of NR1D2 research reagents below, or read on for the biology behind the target.
NR1D2 is a transcriptional repressor that coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. It forms a critical negative limb of the circadian clock by directly repressing the core clock components BMAL1 and CLOCK. The protein acts as a receptor for heme, which stimulates its interaction with the NCOR1/HDAC3 corepressor complex and enhances repression. It is also a potent competitive repressor of ROR alpha (RORA) function and negatively regulates expression of NR1D1.
NR1D2 recognises two classes of DNA response element in target promoters. It binds as a monomer to a RevRE, built from the half-site 5'-[A/G]GGTCA-3' preceded by an A/T-rich sequence, or as a homodimer to a direct repeat of the core motif spaced by two nucleotides (RevDR-2). In skeletal muscle it represses genes of lipid metabolism and myogenesis, including CD36, FABP3, FABP4, UCP3, SCD1 and MSTN, and it is a key regulator of mitochondrial function. In liver it represses APOC3, and in macrophages it represses gene expression at a distance by inhibiting enhancer-derived RNAs. Although mainly a repressor, it can also activate transcription of SREBF1 and IL-6 in skeletal muscle.
The NR1D2 gene belongs to the NR1 subfamily of the nuclear hormone receptor family, and alternatively spliced transcript variants have been described. The protein is essential for maintaining wakefulness during the active period and may contribute to circadian control of neutrophilic inflammation in the lung. It is closely related to NR1D1, and the mouse and rat orthologues are both named Nr1d2.
NR1D2 directly represses BMAL1 and CLOCK, forming a negative limb of the clock and helping to shape circadian rhythmicity.
It represses lipid-metabolism and myogenesis genes and regulates mitochondrial biogenesis and fatty acid beta-oxidation in skeletal muscle.
NR1D2 regulates hepatic lipid metabolism through APOC3 repression and contributes to wider control of lipid and energy balance.
It regulates inflammatory gene expression, may control circadian neutrophilic inflammation in the lung, and supports wakefulness during the active phase.
NR1D2 is a heme-responsive transcriptional repressor. It represses the core clock genes BMAL1 and CLOCK, and genes in lipid metabolism, myogenesis and inflammation. Heme binding promotes its interaction with the NCOR1/HDAC3 corepressor complex. It can also act as an activator of SREBF1 and IL-6 in skeletal muscle.
NR1D2 is also known as REV-ERBβ (REVERBB), RVR, BD73, EAR-1r and HZF2. The HGNC name is nuclear receptor subfamily 1 group D member 2, previously nuclear receptor subfamily 1, group D, member 2. Alternatively spliced transcript variants of the NR1D2 gene have been described.
Yes. Orthologues exist in mouse and rat, both designated Nr1d2. The protein belongs to the NR1 subfamily of nuclear hormone receptors, alongside NR1D1, with which it shares circadian and metabolic roles. Check the datasheet of any product for its validated reactivity.
Other NR1 subfamily members, nuclear receptors and corepressor-related proteins involved in circadian and metabolic regulation.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q14995; product specifications from Assay Genie datasheets.