NR4A1 phospho S351
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:18690216, PubMed:8121493, PubMed:9315652). Binds 9-cis-retinoic acid outside of its ligand-binding (NR LBD) domain (PubMed:18690216). Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation (PubMed:22983157). 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 (PubMed:15466594). 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.
Post-translational modifications
Phosphorylated at Ser-351 by RPS6KA1 and RPS6KA3 in response to mitogenic or stress stimuli.
Acetylated by p300/CBP, acetylation increases stability. Deacetylated by HDAC1.
Sequence Similarities
Belongs to the nuclear hormone receptor family. NR4 subfamily.
Tissue Specificity
Fetal muscle and adult liver, brain and thyroid.
Cellular localization
- Nucleus
- Cytoplasm
- Cytosol
- Mitochondrion
- Nuclear export to the cytosol is XPO1-mediated and positively regulated by IFI27 (PubMed:22427340). Translocation to the mitochondrion upon interaction with RXRA and upon the presence of 9-cis retinoic acid (PubMed:17761950).
Alternative names
GFRP1, HMR, NAK1, NR4A1, Nuclear receptor subfamily 4immunitygroup A member 1, Early response protein NAK1, Nuclear hormone receptor NUR/77, Orphan nuclear receptor HMR, Orphan nuclear receptor TR3, ST-59, Testicular receptor 3, Nur77
Database links
Other research areas
- Immuno-oncology