Rev-ErbA beta

Nuclear receptor subfamily 1, group D, member 2
Structure of the ligand binding domain (LBD) of the Rev-erb? receptor based on PDB: 2v0v​. Depicted here is a dimer of comprising two LBD protein molecules.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2V0V, 2V7C, 3CQV, 4N73
Identifiers
Symbols	NR1D2 ; BD73; EAR-1R; RVR
External IDs	OMIM: 602304 MGI: 2449205 HomoloGene: 3763 IUPHAR: 597 GeneCards: NR1D2 Gene
Gene ontology Molecular function • core promoter sequence-specific DNA binding • steroid hormone receptor activity • RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding • protein binding • zinc ion binding Cellular component • nucleus • nucleoplasm Biological process • regulation of transcription, DNA-templated • transcription initiation from RNA polymerase II promoter • gene expression • regulation of lipid metabolic process • intracellular receptor signaling pathway • regulation of circadian rhythm • steroid hormone mediated signaling pathway • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • rhythmic process • regulation of inflammatory response • lipid homeostasis • regulation of energy homeostasis • regulation of skeletal muscle cell differentiation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	9975	353187
Ensembl	ENSG00000174738	ENSMUSG00000021775
UniProt	Q14995	Q60674
RefSeq (mRNA)	NM_001145425	NM_011584
RefSeq (protein)	NP_001138897	NP_035714
Location (UCSC)	Chr 3: 23.95 – 23.98 Mb	Chr 14: 18.2 – 18.24 Mb
PubMed search	[1]	[2]

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.

Structure

Cartoon diagram of the ligand binding domain of Rev-ErbA beta (rainbow colored, N-terminus = blue, C-terminus = red) complexed with heme (space-filling model, carbon atoms = white, nitrogen = blue, oxygen = red, iron = magenta) based on the PDB: 3CQV​ crystallographic coordinates.

Rev-erbβ is similar to Rev-erbα in its protein structure and function as a transcriptional repressor. The crystal structure of an unliganded Rev-erbβ ligand-binding domain (LBD) has been resolved (see figure to the right) and shows an extremely small ligand-binding pocket. However, Rev-erbβ has been shown to interact with heme, which appears important for its function.

The structure of Rev-erbβ complexed with heme (see figure to the left) shows a substantial movement of helices 1 (N-terminus ) and 11 (C-terminus ) which opens up a large binding pocket in the interior of the protein that is able to accommodate this ligand.

Function

Rev-erbβ has been implicated in the control of lipid and energy homoeostasis in skeletal muscle.

Rev-erbβ is also a circadian regulated gene; its mRNA displays rhythmic expression in vivo and in serum-synchronized cell cultures. However, it is currently unknown to what extent Rev-erbβ contributes to oscillations of the core circadian clock. However it has been shown heme suppresses hepatic gluconeogenic gene expression and glucose output through the related Rev-erbα receptor which mediates gene repression. Hence, the Rev-erbα receptor detects heme and thereby coordinates the cellular clock, glucose homeostasis, and energy metabolism.

External links

• NR1D2 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)