Rev-ErbA beta
Encyclopedia
Rev-ErbA beta 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 factor
s. Rev-erbβ, like Rev-erbα
, belongs to the nuclear receptor
superfamily and can modulate gene expression
by directly binding to their promoters.
, 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.
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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the NR1D2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Rev-erbβ is a member of the Rev-ErbA
Rev-ErbA
The Rev-ErbA proteins are members of the nuclear receptor family of intracellular transcription factors. There are two forms of the receptor, alpha and beta, each encoded by a separate gene ....
family of transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s. Rev-erbβ, like Rev-erbα
Rev-ErbA alpha
Rev-ErbA alpha also known as NR1D1 , is a protein that in humans is encoded by the NR1D1 gene.Rev-erbα is member of the Rev-ErbA family of nuclear receptors and is a transcriptional repressor...
, belongs to the nuclear receptor
Nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...
superfamily and can modulate gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
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 hemeHeme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
, 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
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...
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
Circadian rhythm
A circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...
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.