Orphan nuclear receptor. Binds the NGFI-B response element (NBRE) 5'-AAAGGTCA-3' ( ). Binds 9-cis-retinoic acid outside of its ligand-binding (NR LBD) domain . Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation . Regulates the inflammatory response in macrophages by regulating metabolic adaptations during inflammation, including repressing the transcription of genes involved in the citric acid cycle (TCA) (By similarity). Inhibits NF-kappa-B signaling by binding to low-affinity NF-kappa-B binding sites, such as at the IL2 promoter . May act concomitantly with NR4A2 in regulating the expression of delayed-early genes during liver regeneration (By similarity). Plays a role in the vascular response to injury (By similarity).
In the cytosol, upon its detection of both bacterial lipopolysaccharide (LPS) and NBRE-containing mitochondrial DNA released by GSDMD pores during pyroptosis, it promotes non-canonical NLRP3 inflammasome activation by stimulating association of NLRP3 and NEK7.
Subcellular locations: Nucleus, Cytoplasm, Cytosol, Mitochondrion
Nuclear export to the cytosol is XPO1-mediated and positively regulated by IFI27 . Translocation to the mitochondrion upon interaction with RXRA and upon the presence of 9-cis retinoic acid .
Fetal muscle and adult liver, brain and thyroid.