Nr4a1
Developmental stage
Highest levels are found in the adult with barely detectable levels in pre- and early postnatal tissue.
Domain
The NR LBD domain binds the lipid A moiety of lipopolysaccharide (LPS) in the cytosol.
Function
Orphan nuclear receptor. Binds the NGFI-B response element (NBRE) 5'-AAAGGTCA-3' (PubMed:37001519). Binds 9-cis-retinoic acid outside of its ligand-binding (NR LBD) domain (By similarity). Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation (By similarity). 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) (PubMed:30134173). Inhibits NF-kappa-B signaling by binding to low-affinity NF-kappa-B binding sites, such as at the IL2 promoter (PubMed:30134173). 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 (PubMed:22427340).
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.
Post-translational modifications
Phosphorylated at Ser-354 by RPS6KA1 and RPS6KA3 in response to mitogenic or stress stimuli.
Acetylated by p300/CBP, acetylation increases stability. Deacetylated by HDAC1 (By similarity).
Sequence Similarities
Belongs to the nuclear hormone receptor family. NR4 subfamily.
Tissue Specificity
Expressed in testis, thymus, brain, and heart, and at lower levels in ovaries and spleen.
Cellular localization
- 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 (By similarity).
Alternative names
Gfrp, Hmr, N10, Nur77, Nuclear receptor subfamily 4 group A member 1, Nuclear hormone receptor NUR/77, Nuclear protein N10, Orphan nuclear receptor HMR