| Property | Value |
|---|---|
| Protein Name | Nuclear Receptor Subfamily 1 Group D Member 2 |
| Gene | NR1D2/REV-ERBβ |
| UniProt ID | Q9UGL9 |
| Molecular Weight | ~51 kDa |
| Subcellular Localization | Nucleus |
| Protein Family | Nuclear receptor family, REV-ERB subfamily |
NR1D2 (Nuclear Receptor Subfamily 1 Group D Member 2), also known as REV-ERBβ, is a nuclear receptor that functions as a transcriptional repressor and plays important roles in circadian rhythm regulation, metabolism, and neuronal function[1]. It is closely related to NR1D1 (REV-ERBα), and both proteins are key components of the molecular circadian clock that drives 24-hour rhythms in physiology and behavior.
NR1D2 has the characteristic nuclear receptor architecture with distinct functional domains[2]:
DNA-binding domain (DBD): The central region contains two C4-type zinc fingers that recognize and bind to specific DNA sequences called Rev-Erb response elements (RREs), consisting of the consensus motif AGGTCA with a variable spacer.
Hinge region: This flexible linker connects the DBD to the ligand-binding domain and often contains sequences important for protein-protein interactions and nuclear localization.
Ligand-binding domain (LBD): The C-terminal domain binds heme as an endogenous ligand, which is crucial for the receptor's transcriptional repressive function. The LBD also contains the AF-2 activation domain that mediates interactions with co-repressors.
N-terminal domain: Contains a transcriptional activation function (AF-1) that can modulate receptor activity in a cell-type specific manner.
NR1D2 is a core component of the circadian clock machinery[1:1][3]:
NR1D2 modulates various metabolic processes:
In the nervous system, NR1D2 influences multiple processes:
Small molecule REV-ERB agonists have been developed as therapeutic agents[4]:
Burris, T.P. (2008). Nuclear receptor REV-ERB: its role in circadian regulation. Current Opinion in Pharmacology, 8(5), 569-575. 2008. ↩︎ ↩︎
Woo, E.J. et al. (2019). Structural basis of Rev-erb recognition. Molecular Cell, 76(2), 359-370. 2019. ↩︎
Everett, L.J. & Lazar, M.A. (2014). Nuclear receptor Rev-erb: an orphan with strategic timing. Molecular Endocrinology, 28(4), 503-517. 2014. ↩︎
Kojetin, D.J. & Burris, T.P. (2014). REV-ERB and ROR nuclear receptors as drug targets. Nature Reviews Drug Discovery, 13(3), 197-216. 2014. ↩︎