Estrogen-related receptor alpha (ERR-α), also known as NR3B1 (nuclear receptor subfamily 3, group B, member 1), is a nuclear receptor that in humans is encoded by the ESRRA (EStrogen Related Receptor Alpha) gene.[1][2]
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ERR-α 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.[3]
The protein encoded by this gene is a nuclear receptor that is closely related to the estrogen receptor. This protein acts as a site-specific (consensus TNAAGGTCA) 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, osteopontin, medium-chain acyl coenzyme A dehydrogenase (MCAD) and thyroid hormone receptor genes. A processed pseudogene of ESRRA is located on chromosome 13q12.1.[1]
ERR-α regulates genes involved in mitochondrial biogenesis,[4] gluconeogenesis,[5] oxidative phosphorylation,[6] and fatty acid metabolism.[7] Furthermore ERR-α knockout mice display impaired fat metabolism and absorption.[8]
Estrogen receptor alpha (ER-α) and estrogen related receptor alpha (ERR-α) have been found to regulate many of the same genes.[9][10] Furthermore ERR-α appears to modulate the activity of ER-α in various tissues including breast, uterus, and bone.[11]
No endogenous ligands of ERR-α have been identified to date, hence ERR-α is classified as an orphan receptor. In addition both biochemical and structural studies indicate that ERR-α is constitutively active in the absence of ligand.[12]ERR-α does, however, interact with the metabolic-inducible coactivator PGC1-α in its AF2 region which is sometimes referred to as the "protein ligand" of ERR-α.
The isoflavone phytoestrogens genistein and daidzein are non-selective ERR agonists,[13] while XCT790 has been identified as a potent and selective inverse agonist of ERR-α.[14]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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