Rev-ErbA beta


Rev-ErbA beta also known as NR1D2 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

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 has been resolved 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 shows a substantial movement of helices 1 and 11 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.