NR4A3 Ligand-binding Domain (human, recombinant)

Nuclear receptor subfamily 4 group A member 3 (NR4A3) is a transcription factor and member of the NR4A orphan nuclear receptor family.^1,2 It is composed of an N-terminal activation function-1 (AF-1) transactivation domain, a DNA-binding domain, a variable linker region, and a C-terminal domain comprising a ligand-binding domain and an AF-2 domain. NR4A3 is primarily expressed in the fetal brain and lungs and adult heart and skeletal muscle, with both splice variants showing similar expression patterns.^3,4 It is involved in several biological processes, including apoptosis, differentiation, metabolism, inflammation, cardiac remodeling, and development, and its expression can be induced by several factors such as growth factors, cytokines, and stress.^1,2 Knockout of Nr4a3 inhibits GM-CSF- and IL-4-induced differentiation of primary mouse monocytes into dendritic cells.⁵ Overexpression of NR4A3 reduces infarct size as a percentage of the area at risk in a mouse model of acute myocardial infarction.⁶ Fusion proteins of NR4A3 with Ewing sarcoma protein (EWS) or TAF15 are associated with extraskeletal myxoid chondrosarcoma.⁷

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1. Martínez-González, J., Cañes, L., Alonso, J., et al. NR4A3: A key nuclear receptor in vascular biology, cardiovascular remodeling, and beyond. Int. J. Mol. Sci. 22(21), 11371 (2021).

2. He, S., Jiang, W., Jiang, B., et al. Potential roles of Nr4a3-mediated inflammation in immunological and neurological diseases. Mol. Neurobiol. 61(8), 5958-5973 (2024).

3. Ohkura, N., Ito, M., Tsukada, T., et al. Structure, mapping and expression of a human NOR-1 gene, the third member of the Nur77/NGFI-B family. Biochim. Biophys. Acta 308(3), 205-214 (1996).

4. Ohkura, N., Ito, M., Tsukada, T., et al. Alternative splicing generates isoforms of human neuron-derived orphan receptor-1 (NOR-1) mRNA. Gene 11(1), 79-85 (1998).

5. Boulet, S., Daudelin, J.-F., Odagiu, L., et al. The orphan nuclear receptor NR4A3 controls the differentiation of monocyte-derived dendritic cells following microbial stimulation. Proc. Natl. Acad. Sci. USA 116(30), 15150-15159 (2019).

6. Jiang, Y., Feng, Y.-P., Tang, L.-X., et al. The protective role of NR4A3 in acute myocardial infarction by suppressing inflammatory responses via JAK2-STAT3/NF-κB pathway. Biochem. Biophys. Res. Commun. 517(4), 697-702 (2019).

7. Hisaoka, M., and Hashimoto, H. Extraskeletal myxoid chondrosarcoma: updated clinicopathological and molecular genetic characteristics. Pathol. Int. 55(8), 453-463 (2005).