NR4A1
GeneName
NR4A1
Summary
NR4A1, also known as Nur77, N10, or HMR, is a 64kDa nuclear receptor that functions primarily as a transcription factor. It is expressed in various tissues, including the brain, heart, and immune cells, and is localised to the nucleus, cytoplasm, and mitochondria. NR4A1 is involved in the regulation of gene expression through its DNA-binding capabilities, specifically as a transcription activator for RNA polymerase II. It plays a role in diverse biological processes such as apoptosis, cell migration, and inflammatory responses, and is implicated in the detection of lipopolysaccharide and the regulation of endothelial cell proliferation. Its functions are mediated through interactions with various ligands and proteins, including glucocorticoids and lipopolysaccharides.
Importance
NR4A1 is relevant to: - The regulation of immune responses and inflammation, influencing macrophage activation and the cellular response to growth factors. - Cancer biology, where it is involved in apoptosis and cell cycle regulation, potentially impacting tumour growth and progression. - Cardiovascular research, as it plays a role in endothelial cell function and angiogenesis. - Metabolic disorders, given its involvement in fat cell differentiation and pancreatic cell proliferation.
Top Products
For researchers investigating NR4A1, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-NUR77 antibody (ab153914), which has garnered 10 citations and is particularly effective for Western blotting (WB). This product is trusted by many in the field for its reliable performance. Additionally, we offer the recombinant antibody, Anti-NUR77 antibody [EPR23982-85] (ab283264), which has been validated in knockout models and is suitable for a broader range of applications, including WB, flow cytometry (FC), and immunoprecipitation (IP). With 5 citations, this recombinant antibody provides the batch-to-batch consistency that researchers often seek, making it a strong choice for those studying NR4A1.
Abcam Product Citation Summary
The data indicates that the NR4A1 antibody (ab153914) has been effectively used in immunohistochemistry and immunofluorescence applications in mouse models. The studies focus on the role of NR4A1 in macrophage responses to oxidised low-density lipoprotein (ox-LDL) and its involvement in inflammatory processes within atherosclerotic lesions.
Abcam Product Citation Table
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
swissprot:P22736 entrezGene:3164 omim:139139
Other research areas
- Immuno-oncology