Estrogen-related receptor alpha
), also known as NR3B1
(nuclear receptor subfamily 3, group B, member 1), is a nuclear receptor
which is encoded by the gene (EStrogen Related Receptor Alpha).
ERRα has wide tissue distribution but it is most highly expressed in tissue that preferentially use fatty acids as energy sources such as kidney, heart, cerebellum, intestine, and skeletal muscle.
encoded by this gene is a nuclear receptor
that is closely related to the estrogen receptor
. This protein acts as a site-specific transcription regulator and has been also shown to interact with estrogen and the transcription factor TFIIB
by direct protein-protein contact. The binding and regulatory activities of this protein have been demonstrated in the regulation of a variety of genes including lactoferrin
, medium-chain acyl coenzyme A dehydrogenase (MCAD
) and thyroid hormone receptor
genes. A processed pseudogene
of ESRRA is located on chromosome 13q12.1.
ERRα regulates genes involved in mitochondrial
, oxidative phosphorylation
, and fatty acid metabolism
. Furthermore ERRα knockout mice
display impaired fat metabolism and absorption.
Estrogen receptor alpha
(ERα) and estrogen related receptor alpha (ERRα) have been found to regulate many of the same genes. Furthermore ERRα appears to modulate the activity of ERα in various tissues including breast, uterus, and bone.
No endogenous ligands
of ERRα have been identified to date, hence ERRα is classified as an orphan receptor
. In addition both biochemical and structural studies indicate that ERRα is constitutively active in the absence of ligand.
The isoflavone phytoestrogens genistein and daidzein are non-selective ERR agonists, while XCT790 has been identified as a potent and selective inverse agonist of ERRα.