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Target not currently curated in GtoImmuPdb
Target id: 631
Nomenclature: Neuron-derived orphan receptor 1
Systematic Nomenclature: NR4A3
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 626 | 9q22 | NR4A3 | nuclear receptor subfamily 4 group A member 3 | 6,8 |
| Mouse | 627 | 4 B1 | Nr4a3 | nuclear receptor subfamily 4, group A, member 3 | 22 |
| Rat | 628 | 5q22 | Nr4a3 | nuclear receptor subfamily 4, group A, member 3 | 14 |
| Previous and Unofficial Names |
| CHN | MINOR | mitogen-induced nuclear orphan receptor | Neuron-derived orphan receptor | NOR1 | neuron-derived orphan receptor 1 | neuron-derived orphan receptor 1/2 | nuclear hormone receptor NOR-1/NOR-2 | TEC | CSMF | nuclear receptor subfamily 4 |
| Database Links |
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| Alphafold | Q92570 (Hs), Q9QZB6 (Mm), P51179 (Rn) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL1961792 (Hs) |
| Ensembl Gene | ENSG00000119508 (Hs), ENSMUSG00000028341 (Mm), ENSRNOG00000005964 (Rn) |
| Entrez Gene | 8013 (Hs), 18124 (Mm), 58853 (Rn) |
| Human Protein Atlas | ENSG00000119508 (Hs) |
| KEGG Gene | hsa:8013 (Hs), mmu:18124 (Mm), rno:58853 (Rn) |
| OMIM | 600542 (Hs) |
| Orphanet | ORPHA361071 (Hs) |
| Pharos | Q92570 (Hs) |
| RefSeq Nucleotide | NM_173199 (Hs), NM_006981 (Hs), NM_173200 (Hs), NM_015743 (Mm), NM_017352 (Rn), NM_031628 (Rn) |
| RefSeq Protein | NP_008912 (Hs), NP_775291 (Hs), NP_775292 (Hs), NP_056558 (Mm), NP_113816 (Rn) |
| UniProtKB | Q92570 (Hs), Q9QZB6 (Mm), P51179 (Rn) |
| Wikipedia | NR4A3 (Hs) |
| Natural/Endogenous Ligands |
| Comments: Orphan |
Download all structure-activity data for this target as a CSV file 
| Agonists |
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| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Based on alignment with the related NR4A subfamilly members and on 3D structure analysis of the LBD, NR4A3 as the others NR4A receptors have been shown to be unable to interact with ligands due to the lack of a ligand binding pocket (LBP) [1,4,19]. | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Immuno Process Associations | ||
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| DNA Binding |
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| DNA Binding Comments | |||||||
| NR4A3 is able to interact with DNA in various manner. As monomers, NR4A3 as other N4R4A subfamily members interact with the so-called NBRE sequence (AAAGGTCA). NR4A1 is also able to homodimerize and to heterodimerize with other NR4A family members and bind the so-called NuRE sequence which has the structure of an ER10 (two AGGTCA elements as everted repeats spaced by 10 bp, the two immediate 5’ bases of each element being As). | |||||||
| Co-binding Partners |
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| Name | Interaction | Effect | Reference |
| Nuclear receptor related 1 | Physical | DNA binding | 11 |
| Neuron-derived orphan receptor 1 | Physical | DNA binding | 11 |
| Main Co-regulators |
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| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| SIX3 | Co-activator | Yes | No | No | SIX3 seems to act as a coactivator for NR4A3 dependent transcriptional activation but as a corepressor for the fusion protein EWS/NOR-1 in human extraskeletal myxoid chondrosarcomas. SIX3 interacts with the DNA Binding domain of Nor1. | 9,16 |
| MED1 | Co-activator | No | No | No | TRAP220 interacts with the NR4A1-3 subgroup in an AF-1-dependent manner in a cellular context. | 21 |
| EP300 | Co-activator | No | No | No | SRC-2 recruitment allows interaction with p300 | 20 |
| NCOA2 | Co-activator | No | No | No | NR4A3 seems to interact with SRC-2 via its a/B domain. SRC-2 modulates the activity of the N-terminal AF-1 domain.-terminal AF-1 domain. | 20 |
| KAT2B | Co-activator | No | No | No | SRC-2 recruitment allows interaction with pCAF | 20 |
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| POMC | Human | Activated | Transient transfection, EMSA, Other | NR4A3 like NR4A1 is able to stimulate the expression of the POMC gene via its interaction with the NuRE element in the POMC promoter. (All species) | 10,13 |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| NR4A3 is expressed as a complex pattern of transcripts (6.5 kb, 5.0 kb, 2.0 kb) in skeletal muscles, fetal heart as well as at lower levels in other tissues. The three NR4A subfamily members are expressed in a complex pattern in the nervous system where they are induced as part of the immediate early response to stimuli such as growth factors, membrane depolarisation and seizure. Their expression pattern outside the nervous system is quite large. NR4A3 is expressed in the pituitary, adrenal, heart, muscle, thymus and kidney. (NB: similar expression patterns observed in rodents). | ||||||||
| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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1. Baker KD, Shewchuk LM, Kozlova T, Makishima M, Hassell A, Wisely B, Caravella JA, Lambert MH, Reinking JL, Krause H, Thummel CS, Willson TM, Mangelsdorf DJ. (2003) The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathway. Cell, 113 (6): 731-42. [PMID:12809604]
2. Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS. (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]
3. DeYoung RA, Baker JC, Cado D, Winoto A. (2003) The orphan steroid receptor Nur77 family member Nor-1 is essential for early mouse embryogenesis. J Biol Chem, 278 (47): 47104-9. [PMID:13129926]
4. Flaig R, Greschik H, Peluso-Iltis C, Moras D. (2005) Structural basis for the cell-specific activities of the NGFI-B and the Nurr1 ligand-binding domain. J Biol Chem, 280 (19): 19250-8. [PMID:15716272]
5. Gill S, McManus AP, Crew AJ, Benjamin H, Sheer D, Gusterson BA, Pinkerton CR, Patel K, Cooper CS, Shipley JM. (1995) Fusion of the EWS gene to a DNA segment from 9q22-31 in a human myxoid chondrosarcoma. Genes Chromosomes Cancer, 12 (4): 307-10. [PMID:7539287]
6. Hedvat CV, Irving SG. (1995) The isolation and characterization of MINOR, a novel mitogen-inducible nuclear orphan receptor. Mol Endocrinol, 9 (12): 1692-700. [PMID:8614405]
7. Labelle Y, Bussières J, Courjal F, Goldring MB. (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. [PMID:10359536]
8. Labelle Y, Zucman J, Stenman G, Kindblom LG, Knight J, Turc-Carel C, Dockhorn-Dworniczak B, Mandahl N, Desmaze C, Peter M. (1995) Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation. Hum Mol Genet, 4 (12): 2219-26. [PMID:8634690]
9. Laflamme C, Filion C, Bridge JA, Ladanyi M, Goldring MB, Labelle Y. (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 Res, 63 (2): 449-54. [PMID:12543801]
10. Maira M, Martens C, Batsché E, Gauthier Y, Drouin J. (2003) Dimer-specific potentiation of NGFI-B (Nur77) transcriptional activity by the protein kinase A pathway and AF-1-dependent coactivator recruitment. Mol Cell Biol, 23 (3): 763-76. [PMID:12529383]
11. Maira M, Martens C, Philips A, Drouin J. (1999) Heterodimerization between members of the Nur subfamily of orphan nuclear receptors as a novel mechanism for gene activation. Mol Cell Biol, 19 (11): 7549-57. [PMID:10523643]
12. Maltais A, Labelle Y. (2000) Structure and expression of the mouse gene encoding the orphan nuclear receptor TEC. DNA Cell Biol, 19 (2): 121-30. [PMID:10701778]
13. Martens C, Bilodeau S, Maira M, Gauthier Y, Drouin J. (2005) Protein-protein interactions and transcriptional antagonism between the subfamily of NGFI-B/Nur77 orphan nuclear receptors and glucocorticoid receptor. Mol Endocrinol, 19 (4): 885-97. [PMID:15591535]
14. Ohkura N, Hijikuro M, Yamamoto A, Miki K. (1994) Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells. Biochem Biophys Res Commun, 205 (3): 1959-65. [PMID:7811288]
15. Ohkura N, Ito M, Tsukada T, Sasaki K, Yamaguchi K, Miki K. (1998) Alternative splicing generates isoforms of human neuron-derived orphan receptor-1 (NOR-1) mRNA. Gene, 211 (1): 79-85. [PMID:9573341]
16. Ohkura N, Ohkubo T, Maruyama K, Tsukada T, Yamaguchi K. (2001) The orphan nuclear receptor NOR-1 interacts with the homeobox containing protein Six3. Dev Neurosci, 23 (1): 17-24. [PMID:11173923]
17. Ponnio T, Burton Q, Pereira FA, Wu DK, Conneely OM. (2002) The nuclear receptor Nor-1 is essential for proliferation of the semicircular canals of the mouse inner ear. Mol Cell Biol, 22 (3): 935-45. [PMID:11784868]
18. Stiller T, Merk D. (2023) Exploring Fatty Acid Mimetics as NR4A Ligands. J Med Chem, 66 (22): 15362-15369. [PMID:37918435]
19. Wang Z, Benoit G, Liu J, Prasad S, Aarnisalo P, Liu X, Xu H, Walker NP, Perlmann T. (2003) Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors. Nature, 423 (6939): 555-60. [PMID:12774125]
20. Wansa KD, Harris JM, Muscat GE. (2002) The activation function-1 domain of Nur77/NR4A1 mediates trans-activation, cell specificity, and coactivator recruitment. J Biol Chem, 277 (36): 33001-11. [PMID:12082103]
21. Wansa KD, Harris JM, Yan G, Ordentlich P, Muscat GE. (2003) The AF-1 domain of the orphan nuclear receptor NOR-1 mediates trans-activation, coactivator recruitment, and activation by the purine anti-metabolite 6-mercaptopurine. J Biol Chem, 278 (27): 24776-90. [PMID:12709428]
22. Zetterström RH, Solomin L, Mitsiadis T, Olson L, Perlmann T. (1996) Retinoid X receptor heterodimerization and developmental expression distinguish the orphan nuclear receptors NGFI-B, Nurr1, and Nor1. Mol Endocrinol, 10 (12): 1656-66. [PMID:8961274]
4A. Nerve growth factor IB-like receptors: Neuron-derived orphan receptor 1. Last modified on 03/11/2023. Accessed on 18/01/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=631.
