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Gene Review

Nr4a2  -  nuclear receptor subfamily 4, group A,...

Rattus norvegicus

Synonyms: Hzf-3, NUR-related factor 1, Nuclear orphan receptor HZF-3, Nuclear receptor subfamily 4 group A member 2, Nurr1, ...
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Disease relevance of Nr4a2


High impact information on Nr4a2

  • Here we demonstrate the presence of endogenous RXR ligands in the embryonic central nervous system (CNS) and show that they can activate heterodimers formed between RXR and the orphan NR Nurr1 in vivo [5].
  • Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes [6].
  • This process requires both the overexpression of the nuclear receptor Nurr1 and factors derived from local type 1 astrocytes [6].
  • Here we use undifferentiated progenitors to probe the events leading to the dopaminergic phenotype and find that the influences of Nurr1 can be temporally and mechanistically uncoupled from the patterning influences of sonic hedgehog and FGF-8 or the more generic process of neuronal differentiation itself [7].
  • In gain-of-function experiments, Nurr1 is able to activate transcription of the tyrosine hydroxylase gene by binding a response element within a region of the tyrosine hydroxylase promoter necessary for midbrain-specific expression [7].

Biological context of Nr4a2


Anatomical context of Nr4a2

  • A full-length cDNA clone of RNR-1 encodes a 66-kDa, 597-amino acid protein as verified by in vitro translation in reticulocyte lysate [8].
  • In particular, the NGFI-B ligand-binding domain (LBD) exhibits only modest activity in cell lines in which the Nurr1 LBD strongly activates transcription [9].
  • The transcription factor/nuclear receptor Nurr1 is essential for the differentiation of midbrain dopaminergic neurones [11].
  • Rapid increase of Nurr1 expression in the substantia nigra after 6-hydroxydopamine lesion in the striatum of the rat [12].
  • Additionally, we found that Nurr1 is expressed in brain regions that have not been previously reported, such as striatum, septum, and superior colliculus [12].

Associations of Nr4a2 with chemical compounds


Regulatory relationships of Nr4a2

  • In the present study, we first demonstrate in the adult rat that the orphan nuclear receptor Nurr1 is coexpressed in latexin-expressing neurons located in layer V, sublayer VIa, and the white matter of the lateral sector of the neocortex, and also in latexin-negative early born neurons in sublayer VIb of the entire neocortex [14].

Other interactions of Nr4a2


Analytical, diagnostic and therapeutic context of Nr4a2


  1. Association of homozygous 7048G7049 variant in the intron six of Nurr1 gene with Parkinson's disease. Xu, P.Y., Liang, R., Jankovic, J., Hunter, C., Zeng, Y.X., Ashizawa, T., Lai, D., Le, W.D. Neurology (2002) [Pubmed]
  2. Early induction of the NGFI-B/Nur77 family genes in nephritis induced by anti-glomerular basement membrane antibody. Hayashi, K., Ohkura, N., Miki, K., Osada, S., Tomino, Y. Mol. Cell. Endocrinol. (1996) [Pubmed]
  3. Nurr1 mRNA expression in neonatal and adult rat brain following kainic acid-induced seizure activity. Crispino, M., Tocco, G., Feldman, J.D., Herschman, H.R., Baudry, M. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  4. Expression, purification, and initial structural characterization of rat orphan nuclear receptor NOR-1 LBD domain. Razzera, G., Vernal, J., Portugal, R.V., Calgaro, M.R., Fernandez, P., Zakin, M.M., Polikarpov, I., Terenzi, H. Protein Expr. Purif. (2004) [Pubmed]
  5. Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells. Wallen-Mackenzie, A., Mata de Urquiza, A., Petersson, S., Rodriguez, F.J., Friling, S., Wagner, J., Ordentlich, P., Lengqvist, J., Heyman, R.A., Arenas, E., Perlmann, T. Genes Dev. (2003) [Pubmed]
  6. Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes. Wagner, J., Akerud, P., Castro, D.S., Holm, P.C., Canals, J.M., Snyder, E.Y., Perlmann, T., Arenas, E. Nat. Biotechnol. (1999) [Pubmed]
  7. Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain. Sakurada, K., Ohshima-Sakurada, M., Palmer, T.D., Gage, F.H. Development (1999) [Pubmed]
  8. RNR-1, a nuclear receptor in the NGFI-B/Nur77 family that is rapidly induced in regenerating liver. Scearce, L.M., Laz, T.M., Hazel, T.G., Lau, L.F., Taub, R. J. Biol. Chem. (1993) [Pubmed]
  9. Structural basis for the cell-specific activities of the NGFI-B and the Nurr1 ligand-binding domain. Flaig, R., Greschik, H., Peluso-Iltis, C., Moras, D. J. Biol. Chem. (2005) [Pubmed]
  10. Dopaminergic neuronal differentiation from rat embryonic neural precursors by Nurr1 overexpression. Kim, J.Y., Koh, H.C., Lee, J.Y., Chang, M.Y., Kim, Y.C., Chung, H.Y., Son, H., Lee, Y.S., Studer, L., McKay, R., Lee, S.H. J. Neurochem. (2003) [Pubmed]
  11. Modulation of nurr1 gene expression in mesencephalic dopaminergic neurones. Volpicelli, F., Perrone-Capano, C., Da Pozzo, P., Colucci-D'Amato, L., di Porzio, U. J. Neurochem. (2004) [Pubmed]
  12. Rapid increase of Nurr1 expression in the substantia nigra after 6-hydroxydopamine lesion in the striatum of the rat. Ojeda, V., Fuentealba, J.A., Galleguillos, D., Andrés, M.E. J. Neurosci. Res. (2003) [Pubmed]
  13. Requirements for heterodimerization between the orphan nuclear receptor Nurr1 and retinoid X receptors. Sacchetti, P., Dwornik, H., Formstecher, P., Rachez, C., Lefebvre, P. J. Biol. Chem. (2002) [Pubmed]
  14. Organization and development of corticocortical associative neurons expressing the orphan nuclear receptor Nurr1. Arimatsu, Y., Ishida, M., Kaneko, T., Ichinose, S., Omori, A. J. Comp. Neurol. (2003) [Pubmed]
  15. Induction of orphan nuclear receptor Nur77 gene expression and its role in cadmium-induced apoptosis in lung. Shin, H.J., Lee, B.H., Yeo, M.G., Oh, S.H., Park, J.D., Park, K.K., Chung, J.H., Moon, C.K., Lee, M.O. Carcinogenesis (2004) [Pubmed]
  16. Stress induces zinc finger immediate early genes in the rat adrenal gland. Honkaniemi, J., Zhang, J.S., Longo, F.M., Sharp, F.R. Brain Res. (2000) [Pubmed]
  17. Nurr1 affects pRL-TK but not phRG-B internal control plasmid in genetic reporter system. Matuszyk, J., Ziolo, E., Cebrat, M., Kochel, I., Strzadala, L. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  18. Early induction of nerve growth factor-induced genes after liver resection-reperfusion injury. Ohkubo, T., Sugawara, Y., Sasaki, K., Maruyama, K., Ohkura, N., Makuuchi, M. J. Hepatol. (2002) [Pubmed]
  19. Nuclear orphan receptor Nurr1 directly transactivates the osteocalcin gene in osteoblasts. Pirih, F.Q., Tang, A., Ozkurt, I.C., Nervina, J.M., Tetradis, S. J. Biol. Chem. (2004) [Pubmed]
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