Rev-ErbA beta

Rev-ErbA beta (Rev-erbβ) also known as NR1D2 (nuclear receptor subfamily 1, group D, member 2) is a is_associated_with::protein that in humans is encoded by the NR1D2 is_associated_with::gene.

Rev-erbβ is a member of the is_associated_with::Rev-ErbA family of is_associated_with::transcription factors. Rev-erbβ, like Rev-erbα, belongs to the is_associated_with::nuclear receptor superfamily and can modulate is_associated_with::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 (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 is_associated_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 (is_associated_with::N-terminus ) and 11 (is_associated_with::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 is_associated_with::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.