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Gene Review

NR4A3  -  nuclear receptor subfamily 4, group A,...

Homo sapiens

Synonyms: CHN, CSMF, MINOR, Mitogen-induced nuclear orphan receptor, NOR1, ...
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Disease relevance of NR4A3


Psychiatry related information on NR4A3


High impact information on NR4A3


Chemical compound and disease context of NR4A3


Biological context of NR4A3

  • We report a case of EMC with no detectable NR4A3 gene alterations, as assessed with various molecular techniques including reverse transcription-polymerase chain reaction (RT-PCR), Southern blotting, interphase fluorescence in situ hybridization, and PCR single-strand conformation polymorphism-but with coexpression of native NOR1 and SIX3 [19].
  • These variant sequences share the common exon-intron boundary with NOR-1 mRNA, suggesting that they were generated from a single gene by alternative splicing, with the divergent points conserved between the rat and human [20].
  • CONCLUSIONS: In VSMCs, LDL-induced mitogenesis involves NOR-1 upregulation through a CREB-dependent mechanism [21].
  • The hNOR-1 gene is more than 35 kilobases long and interrupted by seven introns [22].
  • In all junction types, the putative translation product contained the amino-terminal transactivation domain of EWS linked to the entire TEC protein [23].

Anatomical context of NR4A3


Associations of NR4A3 with chemical compounds

  • Moreover, in agreement with these observations, isoprenaline also significantly increased the activity of the NOR-1 promoter [24].
  • The Orphan Nuclear Receptor, NOR-1, Is a Target of {beta}-Adrenergic Signaling in Skeletal Muscle [24].
  • Using glutathione S-transferase fusion protein pull-down assays and transient cotransfections of Neuro-2a cells with expression and reporter vectors, we found that one mutation, c.676C>G (p.L226V), does not alter the properties of SIX3 toward NOR1 [2].
  • The chimeric transcript encodes a protein in which the first 108 amino acids of the NH2-terminus of the basic helix-loop-helix (bHLH) protein TCF12 is linked to the entire TEC protein [15].
  • The NR4A Orphan Nuclear Receptor NOR1 Is Induced by Platelet-derived Growth Factor and Mediates Vascular Smooth Muscle Cell Proliferation [26].

Physical interactions of NR4A3


Regulatory relationships of NR4A3

  • In this study, we investigated the functional consequences of these SIX3 mutations with respect to the ability of the protein to interact with and stimulate the transcriptional activity of the nuclear receptor NOR1 (NR4A3) [2].
  • Antisense oligonucleotides against NOR-1 inhibit DNA synthesis induced by LDL in VSMCs as efficiently as antisense against the protooncogene c-fos [21].
  • Antisense oligonucleotides against NOR-1 inhibited VEGF-induced endothelial cell growth (reduced DNA synthesis, and inhibited cell cycle progression and endothelial cell wound repair after mechanical injury) [28].
  • A differential display analysis has identified the PLAGL1 gene as being down-regulated in the CFK2(EWS/NOR1) cell line compared to native CFK2 cells [29].

Other interactions of NR4A3


Analytical, diagnostic and therapeutic context of NR4A3


  1. The homeotic protein Six3 is a coactivator of the nuclear receptor NOR-1 and a corepressor of the fusion protein EWS/NOR-1 in human extraskeletal myxoid chondrosarcomas. Laflamme, C., Filion, C., Bridge, J.A., Ladanyi, M., Goldring, M.B., Labelle, Y. Cancer Res. (2003) [Pubmed]
  2. Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1. Laflamme, C., Filion, C., Labelle, Y. Hum. Mutat. (2004) [Pubmed]
  3. Early induction of the orphan nuclear receptor NOR-1 during cell death of the human breast cancer cell line MCF-7. Ohkubo, T., Ohkura, N., Maruyama, K., Sasaki, K., Nagasaki, K., Hanzawa, H., Tsukada, T., Yamaguchi, K. Mol. Cell. Endocrinol. (2000) [Pubmed]
  4. Expression of NOR-1 and its closely related members of the steroid/thyroid hormone receptor superfamily in human neuroblastoma cell lines. Maruyama, K., Tsukada, T., Bandoh, S., Sasaki, K., Ohkura, N., Yamaguchi, K. Cancer Lett. (1995) [Pubmed]
  5. Skeletal and extraskeletal myxoid chondrosarcoma: a comparative clinicopathologic, ultrastructural, and molecular study. Antonescu, C.R., Argani, P., Erlandson, R.A., Healey, J.H., Ladanyi, M., Huvos, A.G. Cancer (1998) [Pubmed]
  6. Genetic linkage of region containing the CREB1 gene to depressive disorders in women from families with recurrent, early-onset, major depression. Zubenko, G.S., Hughes, H.B., Maher, B.S., Stiffler, J.S., Zubenko, W.N., Marazita, M.L. Am. J. Med. Genet. (2002) [Pubmed]
  7. Randomized, placebo-controlled trial of fluoxetine for acute treatment of minor depressive disorder. Judd, L.L., Rapaport, M.H., Yonkers, K.A., Rush, A.J., Frank, E., Thase, M.E., Kupfer, D.J., Plewes, J.M., Schettler, P.J., Tollefson, G. The American journal of psychiatry. (2004) [Pubmed]
  8. Minor physical anomalies, dermatoglyphic asymmetries, and cortisol levels in adolescents with schizotypal personality disorder. Weinstein, D.D., Diforio, D., Schiffman, J., Walker, E., Bonsall, R. The American journal of psychiatry. (1999) [Pubmed]
  9. Psychiatric manifestations of systemic lupus erythematosus: clinical features, symptoms, and signs of central nervous system activity in 43 patients. Miguel, E.C., Pereira, R.M., Pereira, C.A., Baer, L., Gomes, R.E., de Sá, L.C., Hirsch, R., de Barros, N.G., de Navarro, J.M., Gentil, V. Medicine (Baltimore) (1994) [Pubmed]
  10. Basal ganglia metabolite abnormalities in minor motor disorders associated with human immunodeficiency virus type 1. von Giesen, H.J., Wittsack, H.J., Wenserski, F., Köller, H., Hefter, H., Arendt, G. Arch. Neurol. (2001) [Pubmed]
  11. Apoptosis of T cells mediated by Ca2+-induced release of the transcription factor MEF2. Youn, H.D., Sun, L., Prywes, R., Liu, J.O. Science (1999) [Pubmed]
  12. Activity of a monoclonal antibody-saporin-6 conjugate against B-lymphoma cells. Bregni, M., Lappi, D.A., Siena, S., Formosa, A., Villa, S., Soria, M., Bonadonna, G., Gianni, A.M. J. Natl. Cancer Inst. (1988) [Pubmed]
  13. World distribution of factor V Leiden. Rees, D.C., Cox, M., Clegg, J.B. Lancet (1995) [Pubmed]
  14. Outcome of patients with ectopia cordis and significant intracardiac defects. Hornberger, L.K., Colan, S.D., Lock, J.E., Wessel, D.L., Mayer, J.E. Circulation (1996) [Pubmed]
  15. Fusion of the NH2-terminal domain of the basic helix-loop-helix protein TCF12 to TEC in extraskeletal myxoid chondrosarcoma with translocation t(9;15)(q22;q21). Sjögren, H., Wedell, B., Meis-Kindblom, J.M., Kindblom, L.G., Stenman, G., Kindblom, J.M. Cancer Res. (2000) [Pubmed]
  16. Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma. Clark, J., Benjamin, H., Gill, S., Sidhar, S., Goodwin, G., Crew, J., Gusterson, B.A., Shipley, J., Cooper, C.S. Oncogene (1996) [Pubmed]
  17. Dose-dense adjuvant chemotherapy in node-positive breast cancer: docetaxel followed by epirubicin/cyclophosphamide (T/EC), or the reverse sequence (EC/T), every 2 weeks, versus docetaxel, epirubicin and cyclophosphamide (TEC) every 3 weeks. AERO B03 randomized phase II study. Piedbois, P., Serin, D., Priou, F., Laplaige, P., Greget, S., Angellier, E., Teissier, E., Berdah, J.F., Fabbro, M., Valenza, B., Herait, P., Jehl, V., Buyse, M. Ann. Oncol. (2007) [Pubmed]
  18. A randomized prospective comparison of clarithromycin versus amoxycillin in combination with omeprazole for eradication of Helicobacter pylori. Katelaris, P.H., Patchett, S.E., Zhang, Z.W., Domizio, P., Farthing, M.J. Aliment. Pharmacol. Ther. (1995) [Pubmed]
  19. Coexpression of NOR1 and SIX3 proteins in extraskeletal myxoid chondrosarcomas without detectable NR4A3 fusion genes. Hisaoka, M., Okamoto, S., Yokoyama, K., Hashimoto, H. Cancer Genet. Cytogenet. (2004) [Pubmed]
  20. Alternative splicing generates isoforms of human neuron-derived orphan receptor-1 (NOR-1) mRNA. Ohkura, N., Ito, M., Tsukada, T., Sasaki, K., Yamaguchi, K., Miki, K. Gene (1998) [Pubmed]
  21. Involvement of neuron-derived orphan receptor-1 (NOR-1) in LDL-induced mitogenic stimulus in vascular smooth muscle cells: role of CREB. Rius, J., Martínez-González, J., Crespo, J., Badimon, L. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  22. Structure, mapping and expression of a human NOR-1 gene, the third member of the Nur77/NGFI-B family. Ohkura, N., Ito, M., Tsukada, T., Sasaki, K., Yamaguchi, K., Miki, K. Biochim. Biophys. Acta (1996) [Pubmed]
  23. Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation. Labelle, Y., Zucman, J., Stenman, G., Kindblom, L.G., Knight, J., Turc-Carel, C., Dockhorn-Dworniczak, B., Mandahl, N., Desmaze, C., Peter, M. Hum. Mol. Genet. (1995) [Pubmed]
  24. The Orphan Nuclear Receptor, NOR-1, Is a Target of {beta}-Adrenergic Signaling in Skeletal Muscle. Pearen, M.A., Ryall, J.G., Maxwell, M.A., Ohkura, N., Lynch, G.S., Muscat, G.E. Endocrinology (2006) [Pubmed]
  25. Nuclear Receptors Nur77, Nurr1, and NOR-1 Expressed in Atherosclerotic Lesion Macrophages Reduce Lipid Loading and Inflammatory Responses. Bonta, P.I., van Tiel, C.M., Vos, M., Pols, T.W., van Thienen, J.V., Ferreira, V., Arkenbout, E.K., Seppen, J., Spek, C.A., van der Poll, T., Pannekoek, H., de Vries, C.J. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  26. The NR4A Orphan Nuclear Receptor NOR1 Is Induced by Platelet-derived Growth Factor and Mediates Vascular Smooth Muscle Cell Proliferation. Nomiyama, T., Nakamachi, T., Gizard, F., Heywood, E.B., Jones, K.L., Ohkura, N., Kawamori, R., Conneely, O.M., Bruemmer, D. J. Biol. Chem. (2006) [Pubmed]
  27. 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]
  28. NOR-1 is involved in VEGF-induced endothelial cell growth. Rius, J., Martínez-González, J., Crespo, J., Badimon, L. Atherosclerosis (2006) [Pubmed]
  29. The PLAGL1 gene is down-regulated in human extraskeletal myxoid chondrosarcoma tumors. Poulin, H., Labelle, Y. Cancer Lett. (2005) [Pubmed]
  30. Fusion of the RBP56 and CHN genes in extraskeletal myxoid chondrosarcomas with translocation t(9;17)(q22;q11). Panagopoulos, I., Mencinger, M., Dietrich, C.U., Bjerkehagen, B., Saeter, G., Mertens, F., Mandahl, N., Heim, S. Oncogene (1999) [Pubmed]
  31. TFG is a novel fusion partner of NOR1 in extraskeletal myxoid chondrosarcoma. Hisaoka, M., Ishida, T., Imamura, T., Hashimoto, H. Genes Chromosomes Cancer (2004) [Pubmed]
  32. Nitric oxide donors suppress chemokine production by keratinocytes in vitro and in vivo. Giustizieri, M.L., Albanesi, C., Scarponi, C., De Pità, O., Girolomoni, G. Am. J. Pathol. (2002) [Pubmed]
  33. Molecular analysis of the fusion of EWS to an orphan nuclear receptor gene in extraskeletal myxoid chondrosarcoma. Brody, R.I., Ueda, T., Hamelin, A., Jhanwar, S.C., Bridge, J.A., Healey, J.H., Huvos, A.G., Gerald, W.L., Ladanyi, M. Am. J. Pathol. (1997) [Pubmed]
  34. Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells. Ohkura, N., Hijikuro, M., Yamamoto, A., Miki, K. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
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