Nuclear receptor 4A3

The nuclear receptor 4A3 (NR4A3) (nuclear receptor subfamily 4, group A, member 3) also known as neuron-derived orphan receptor 1 (NOR1) is a protein that in humans is encoded by the NR4A3 gene.^[5] NR4A3 is a member of the nuclear receptor family of intracellular transcription factors.

NR4A3
Identifiers
Aliases	NR4A3, CHN, CSMF, MINOR, NOR1, TEC, nuclear receptor subfamily 4 group A member 3
External IDs	OMIM: 600542; MGI: 1352457; HomoloGene: 5074; GeneCards: NR4A3; OMA:NR4A3 - orthologs
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q31.1 Start 99,821,855 bp[1] End 99,866,891 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 B1 Start 48,045,153 bp[2] End 48,086,447 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of paranasal sinus mucosa of urinary bladder tail of epididymis gastric mucosa vena cava muscle of thigh gallbladder right ventricle popliteal artery tibial arteries Top expressed in Region I of hippocampus proper seminal vesicula medulla of thymus hippocampus proper adrenal gland dentate gyrus dentate gyrus of hippocampal formation granule cell amygdala subiculum extraocular muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding protein homodimerization activity DNA-binding transcription factor activity zinc ion binding DNA-binding transcription activator activity, RNA polymerase II-specific metal ion binding RNA polymerase II cis-regulatory region sequence-specific DNA binding steroid hormone receptor activity nuclear receptor activity core promoter sequence-specific DNA binding protein binding histone acetyltransferase binding glucocorticoid receptor binding transcription coactivator binding protein kinase binding DNA-binding transcription factor activity, RNA polymerase II-specific cAMP response element binding RNA polymerase II transcription regulatory region sequence-specific DNA binding Cellular component transcription regulator complex mast cell granule nucleoplasm nucleus Biological process negative regulation of neuron apoptotic process cellular response to catecholamine stimulus semicircular canal morphogenesis regulation of transcription, DNA-templated neuromuscular process controlling balance positive regulation of epithelial cell proliferation common myeloid progenitor cell proliferation pyruvate oxidation negative regulation of oxidative stress-induced neuron death mesoderm formation response to peptide hormone negative regulation of apoptotic process positive regulation of leukocyte apoptotic process negative regulation of transcription by RNA polymerase II regulation of smooth muscle cell proliferation cellular response to leptin stimulus transcription, DNA-templated positive regulation of cardiac muscle hypertrophy axon guidance positive regulation of transcription, DNA-templated adult behavior positive regulation of cell cycle negative regulation of hydrogen peroxide-induced neuron death gastrulation positive regulation of mast cell activation by Fc-epsilon receptor signaling pathway animal organ regeneration inner ear morphogenesis positive regulation of mast cell cytokine production cellular respiration vestibular reflex energy homeostasis cellular response to corticotropin-releasing hormone stimulus mast cell degranulation transcription initiation from RNA polymerase II promoter positive regulation of feeding behavior positive regulation of glucose transmembrane transport hippocampus development positive regulation of monocyte aggregation fat cell differentiation response to hydrogen peroxide regulation of type B pancreatic cell proliferation positive regulation of transcription by RNA polymerase II steroid hormone mediated signaling pathway positive regulation of smooth muscle cell proliferation positive regulation of fatty acid oxidation intracellular receptor signaling pathway regulation of megakaryocyte differentiation platelet-derived growth factor receptor signaling pathway positive regulation of vascular associated smooth muscle cell proliferation positive regulation of vascular associated smooth muscle cell migration Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8013 18124 Ensembl ENSG00000119508 ENSMUSG00000028341 UniProt Q92570 Q9QZB6 RefSeq (mRNA) NM_006981 NM_173198 NM_173199 NM_173200 NM_015743 NM_001307989 RefSeq (protein) NP_008912 NP_775291 NP_775292 NP_001294918 NP_056558 Location (UCSC) Chr 9: 99.82 – 99.87 Mb Chr 4: 48.05 – 48.09 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

NR4A3 plays a central regulatory role in cell proliferation, differentiation, mitochondrial respiration,^[6] metabolism^[7][8] and apoptosis^[9]

Interactions

NR4A3 has been shown to interact with SIX3.^[10][11]

See also

• NUR nuclear receptor family

References

1. GRCh38: Ensembl release 89: ENSG00000119508 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000028341 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Hedvat CV, Irving SG (Dec 1995). "The isolation and characterization of MINOR, a novel mitogen-inducible nuclear orphan receptor". Molecular Endocrinology. 9 (12): 1692–700. doi:10.1210/mend.9.12.8614405. PMID 8614405.
6. Reynolds MS, Hancock CR, Ray JD, Kener KB, Draney C, Garland K, Hardman J, Bikman BT, Tessem JS (July 2016). "β-Cell deletion of Nr4a1 and Nr4a3 nuclear receptors impedes mitochondrial respiration and insulin secretion". Am J Physiol Endocrinol Metab. 311 (1): E186–201. doi:10.1152/ajpendo.00022.2016. PMID 27221116.
7. Pearen MA, Ryall JG, Maxwell MA, Ohkura N, Lynch GS, Muscat GE (Nov 2006). "The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle". Endocrinology. 147 (11): 5217–27. doi:10.1210/en.2006-0447. PMID 16901967.
8. Pearen MA, Myers SA, Raichur S, Ryall JG, Lynch GS, Muscat GE (Jun 2008). "The orphan nuclear receptor, NOR-1, a target of beta-adrenergic signaling, regulates gene expression that controls oxidative metabolism in skeletal muscle". Endocrinology. 149 (6): 2853–65. doi:10.1210/en.2007-1202. PMID 18325999.
9. Nomiyama T, Nakamachi T, Gizard F, Heywood EB, Jones KL, Ohkura N, Kawamori R, Conneely OM, Bruemmer D (Nov 2006). "The NR4A orphan nuclear receptor NOR1 is induced by platelet-derived growth factor and mediates vascular smooth muscle cell proliferation". The Journal of Biological Chemistry. 281 (44): 33467–76. doi:10.1074/jbc.M603436200. PMC 1829169. PMID 16945922.
10. Laflamme C, Filion C, Bridge JA, Ladanyi M, Goldring MB, Labelle Y (Jan 2003). "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". Cancer Research. 63 (2): 449–54. PMID 12543801.
11. Ohkura N, Ohkubo T, Maruyama K, Tsukada T, Yamaguchi K (2001). "The orphan nuclear receptor NOR-1 interacts with the homeobox containing protein Six3". Developmental Neuroscience. 23 (1): 17–24. doi:10.1159/000048692. PMID 11173923. S2CID 84167063.

Further reading

• Ohkura N, Hijikuro M, Yamamoto A, Miki K (Dec 1994). "Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells". Biochemical and Biophysical Research Communications. 205 (3): 1959–65. doi:10.1006/bbrc.1994.2900. PMID 7811288.
• Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS (Jan 1996). "Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma". Oncogene. 12 (2): 229–35. PMID 8570200.
• Labelle Y, Zucman J, Stenman G, Kindblom LG, Knight J, Turc-Carel C, Dockhorn-Dworniczak B, Mandahl N, Desmaze C, Peter M (Dec 1995). "Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation". Human Molecular Genetics. 4 (12): 2219–26. doi:10.1093/hmg/4.12.2219. PMID 8634690.
• Ohkura N, Ito M, Tsukada T, Sasaki K, Yamaguchi K, Miki K (Sep 1996). "Structure, mapping and expression of a human NOR-1 gene, the third member of the Nur77/NGFI-B family". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1308 (3): 205–14. doi:10.1016/0167-4781(96)00101-7. PMID 8809112.
• Ohkura N, Ito M, Tsukada T, Sasaki K, Yamaguchi K, Miki K (Apr 1998). "Alternative splicing generates isoforms of human neuron-derived orphan receptor-1 (NOR-1) mRNA". Gene. 211 (1): 79–85. doi:10.1016/S0378-1119(98)00095-X. PMID 9573341.
• Labelle Y, Bussières J, Courjal F, Goldring MB (May 1999). "The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator". Oncogene. 18 (21): 3303–8. doi:10.1038/sj.onc.1202675. PMID 10359536. S2CID 21623156.
• Panagopoulos I, Mencinger M, Dietrich CU, Bjerkehagen B, Saeter G, Mertens F, Mandahl N, Heim S (Dec 1999). "Fusion of the RBP56 and CHN genes in extraskeletal myxoid chondrosarcomas with translocation t(9;17)(q22;q11)". Oncogene. 18 (52): 7594–8. doi:10.1038/sj.onc.1203155. PMID 10602519. S2CID 31905291.
• Sjögren H, Wedell B, Meis-Kindblom JM, Kindblom LG, Stenman G, Kindblom JM (Dec 2000). "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)". Cancer Research. 60 (24): 6832–5. PMID 11156374.
• Liu D, Jia H, Holmes DI, Stannard A, Zachary I (Nov 2003). "Vascular endothelial growth factor-regulated gene expression in endothelial cells: KDR-mediated induction of Egr3 and the related nuclear receptors Nur77, Nurr1, and Nor1". Arteriosclerosis, Thrombosis, and Vascular Biology. 23 (11): 2002–7. doi:10.1161/01.ATV.0000098644.03153.6F. PMID 14525795.
• Rius J, Martínez-González J, Crespo J, Badimon L (Apr 2004). "Involvement of neuron-derived orphan receptor-1 (NOR-1) in LDL-induced mitogenic stimulus in vascular smooth muscle cells: role of CREB". Arteriosclerosis, Thrombosis, and Vascular Biology. 24 (4): 697–702. doi:10.1161/01.ATV.0000121570.00515.dc. PMID 14962944.
• Hisaoka M, Okamoto S, Yokoyama K, Hashimoto H (Jul 2004). "Coexpression of NOR1 and SIX3 proteins in extraskeletal myxoid chondrosarcomas without detectable NR4A3 fusion genes". Cancer Genetics and Cytogenetics. 152 (2): 101–7. doi:10.1016/j.cancergencyto.2003.11.011. PMID 15262426.
• Laflamme C, Filion C, Labelle Y (Dec 2004). "Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1". Human Mutation. 24 (6): 502–8. doi:10.1002/humu.20102. PMID 15523651. S2CID 42925900.
• Rius J, Martínez-González J, Crespo J, Badimon L (Feb 2006). "NOR-1 is involved in VEGF-induced endothelial cell growth". Atherosclerosis. 184 (2): 276–82. doi:10.1016/j.atherosclerosis.2005.04.008. PMID 15949808.
• Pei L, Castrillo A, Chen M, Hoffmann A, Tontonoz P (Aug 2005). "Induction of NR4A orphan nuclear receptor expression in macrophages in response to inflammatory stimuli". The Journal of Biological Chemistry. 280 (32): 29256–62. doi:10.1074/jbc.M502606200. PMID 15964844.
• Bonta PI, van Tiel CM, Vos M, Pols TW, van Thienen JV, Ferreira V, Arkenbout EK, Seppen J, Spek CA, van der Poll T, Pannekoek H, de Vries CJ (Oct 2006). "Nuclear receptors Nur77, Nurr1, and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses". Arteriosclerosis, Thrombosis, and Vascular Biology. 26 (10): 2288–94. doi:10.1161/01.ATV.0000238346.84458.5d. PMID 16873729.
• Pearen MA, Ryall JG, Maxwell MA, Ohkura N, Lynch GS, Muscat GE (Nov 2006). "The orphan nuclear receptor, NOR-1, is a target of beta-adrenergic signaling in skeletal muscle". Endocrinology. 147 (11): 5217–27. doi:10.1210/en.2006-0447. PMID 16901967.
• Pearen MA, Myers SA, Raichur S, Ryall JG, Lynch GS, Muscat GE (Jun 2008). "The orphan nuclear receptor, NOR-1, a target of beta-adrenergic signaling, regulates gene expression that controls oxidative metabolism in skeletal muscle". Endocrinology. 149 (6): 2853–65. doi:10.1210/en.2007-1202. PMID 18325999.
• Vacca M, Murzilli S, Salvatore L, Di Tullio G, D'Orazio A, Lo Sasso G, Graziano G, Pinzani M, Chieppa M, Mariani-Costantini R, Palasciano G, Moschetta A (Jun 2013). "Neuron-derived orphan receptor 1 promotes proliferation of quiescent hepatocytes". Gastroenterology. 144 (7): 1518–1529.e3. doi:10.1053/j.gastro.2013.02.027. PMID 23462179.

External links

• NR4A3+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)