Nuclear receptor subfamily 5 group A member 2

Definition:

Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis. Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an essential transcriptional regulator of lipid metabolism. Plays an anti-inflammatory role during the hepatic acute phase response by acting as a corepressor: inhibits the hepatic acute phase response by preventing dissociation of the N-Cor corepressor complex. Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. Activates the transcription of CYP2C38 (By similarity).

References:

[1]. Eric A Ortlund, et al. Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP. Nat Struct Mol Biol. 2005 Apr;12(4):357-63. [Content Brief]

[2]. Weiru Wang, et al. The crystal structures of human steroidogenic factor-1 and liver receptor homologue-1. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7505-10. [Content Brief]

[3]. Irina N Krylova, et al. Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1. Cell. 2005 Feb 11;120(3):343-55. [Content Brief]

[4]. Isaac H Solomon, et al. Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity. J Mol Biol. 2005 Dec 16;354(5):1091-102. [Content Brief]

[5]. Nicolas Venteclef, et al. GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXRbeta in the hepatic acute phase response. Genes Dev. 2010 Feb 15;24(4):381-95. [Content Brief]

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