Nuclear receptor subfamily 4 group A member 3

Details

Name

Nuclear receptor subfamily 4 group A member 3

Synonyms

• CHN
• CSMF
• MINOR
• Mitogen-induced nuclear orphan receptor
• Neuron-derived orphan receptor 1
• NOR1
• Nuclear hormone receptor NOR-1
• TEC

Gene Name

NR4A3

Organism

Humans

Amino acid sequence

>lcl|BSEQ0049710|Nuclear receptor subfamily 4 group A member 3
MPCVQAQYSPSPPGSSYAAQTYSSEYTTEIMNPDYTKLTMDLGSTEITATATTSLPSIST
FVEGYSSNYELKPSCVYQMQRPLIKVEEGRAPSYHHHHHHHHHHHHHHQQQHQQPSIPPA
SSPEDEVLPSTSMYFKQSPPSTPTTPAFPPQAGALWDEALPSAPGCIAPGPLLDPPMKAV
PTVAGARFPLFHFKPSPPHPPAPSPAGGHHLGYDPTAAAALSLPLGAAAAAGSQAAALES
HPYGLPLAKRAAPLAFPPLGLTPSPTASSLLGESPSLPSPPSRSSSSGEGTCAVCGDNAA
CQHYGVRTCEGCKGFFKRTVQKNAKYVCLANKNCPVDKRRRNRCQYCRFQKCLSVGMVKE
VVRTDSLKGRRGRLPSKPKSPLQQEPSQPSPPSPPICMMNALVRALTDSTPRDLDYSRYC
PTDQAAAGTDAEHVQQFYNLLTASIDVSRSWAEKIPGFTDLPKEDQTLLIESAFLELFVL
RLSIRSNTAEDKFVFCNGLVLHRLQCLRGFGEWLDSIKDFSLNLQSLNLDIQALACLSAL
SMITERHGLKEPKRVEELCNKITSSLKDHQSKGQALEPTESKVLGALVELRKICTLGLQR
IFYLKLEDLVSPPSIIDKLFLDTLPF

Number of residues

626

Molecular Weight

68229.025

Theoretical pI

Not Available

GO Classification

Functions

core promoter sequence-specific DNA binding / DNA binding / glucocorticoid receptor binding / histone acetyltransferase binding / protein homodimerization activity / protein kinase binding / RNA polymerase II core promoter proximal region sequence-specific DNA binding / steroid hormone receptor activity / thyroid hormone receptor activity / transcription coactivator binding / transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding / zinc ion binding

Processes

adult behavior / animal organ regeneration / axon guidance / cellular respiration / cellular response to catecholamine stimulus / cellular response to corticotropin-releasing hormone stimulus / cellular response to leptin stimulus / common myeloid progenitor cell proliferation / energy homeostasis / fat cell differentiation / gastrulation / hippocampus development / mast cell degranulation / mesoderm formation / negative regulation of hydrogen peroxide-induced neuron death / negative regulation of neuron apoptotic process / negative regulation of transcription from RNA polymerase II promoter / neuromuscular process controlling balance / positive regulation of cardiac muscle hypertrophy / positive regulation of cell cycle / positive regulation of epithelial cell proliferation / positive regulation of fatty acid oxidation / positive regulation of feeding behavior / positive regulation of glucose transport / positive regulation of leukocyte apoptotic process / positive regulation of mast cell activation by Fc-epsilon receptor signaling pathway / positive regulation of mast cell cytokine production / positive regulation of monocyte aggregation / positive regulation of smooth muscle cell proliferation / positive regulation of transcription from RNA polymerase II promoter / pyruvate oxidation / regulation of energy homeostasis / regulation of smooth muscle cell proliferation / regulation of type B pancreatic cell proliferation / response to hydrogen peroxide / semicircular canal morphogenesis / transcription initiation from RNA polymerase II promoter / vestibular reflex

Components

mast cell granule / nucleoplasm / nucleus / transcription factor complex

General Function

Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (By similarity). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (By similarity). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (By similarity). Mediates also survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (By similarity). Plays also a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (By similarity) (PubMed:20558821). In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation (By similarity). Plays also a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (By similarity). Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (PubMed:24022864). Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration. Inhibits adipogenesis (By similarity). Also participates in cardiac hypertrophy by activating PARP1 (By similarity).

Specific Function

Core promoter sequence-specific dna binding

Pfam Domain Function

• Hormone_recep (PF00104)
• zf-C4 (PF00105)

Transmembrane Regions

Not Available

Cellular Location

Nucleus

Gene sequence

>lcl|BSEQ0049711|Nuclear receptor subfamily 4 group A member 3 (NR4A3)
ATGCCCTGCGTCCAAGCCCAATATAGCCCTTCCCCTCCAGGTTCCAGTTATGCGGCGCAG
ACATACAGCTCGGAATACACCACGGAGATCATGAACCCCGACTACACCAAGCTGACCATG
GACCTTGGCAGCACTGAGATCACGGCTACAGCCACCACGTCCCTGCCCAGCATCAGTACC
TTCGTGGAGGGCTACTCGAGCAACTACGAACTCAAGCCTTCCTGCGTGTACCAAATGCAG
CGGCCCTTGATCAAAGTGGAGGAGGGGCGGGCGCCCAGCTACCATCACCATCACCACCAC
CACCACCACCACCACCACCATCACCAGCAGCAGCATCAGCAGCCATCCATTCCTCCAGCC
TCCAGCCCGGAGGACGAGGTGCTGCCCAGCACCTCCATGTACTTCAAGCAGTCCCCACCG
TCCACCCCCACCACGCCGGCCTTCCCCCCGCAGGCGGGGGCGTTATGGGACGAGGCACTG
CCCTCGGCGCCCGGCTGCATCGCACCCGGCCCGCTGCTGGACCCGCCGATGAAGGCGGTC
CCCACGGTGGCCGGCGCGCGCTTCCCGCTCTTCCACTTCAAGCCCTCGCCGCCGCATCCC
CCCGCGCCCAGCCCGGCCGGCGGCCACCACCTCGGCTACGACCCGACGGCCGCTGCCGCG
CTCAGCCTGCCGCTGGGAGCCGCAGCCGCCGCGGGCAGCCAGGCCGCCGCGCTTGAGAGC
CACCCGTACGGGCTGCCGCTGGCCAAGAGGGCGGCCCCGCTGGCCTTCCCGCCTCTCGGC
CTCACGCCCTCCCCTACCGCGTCCAGCCTGCTGGGCGAGAGTCCCAGCCTGCCGTCGCCG
CCCAGCAGGAGCTCGTCGTCTGGCGAGGGCACGTGTGCCGTGTGCGGGGACAACGCCGCC
TGCCAGCACTACGGCGTGCGAACCTGCGAGGGCTGCAAGGGCTTTTTCAAGAGAACAGTG
CAGAAAAATGCAAAATATGTTTGCCTGGCAAATAAAAACTGCCCAGTAGACAAGAGACGT
CGAAACCGATGTCAGTACTGTCGATTTCAGAAGTGTCTCAGTGTTGGAATGGTAAAAGAA
GTTGTCCGTACAGATAGTCTGAAAGGGAGGAGAGGTCGTCTGCCTTCCAAACCAAAGAGC
CCATTACAACAGGAACCTTCTCAGCCCTCTCCACCTTCTCCTCCAATCTGCATGATGAAT
GCCCTTGTCCGAGCTTTAACAGACTCAACACCCAGAGATCTTGATTATTCCAGATACTGT
CCCACTGACCAGGCTGCTGCAGGCACAGATGCTGAGCATGTGCAACAATTCTACAACCTC
CTGACAGCCTCCATTGATGTATCCAGAAGCTGGGCAGAAAAGATTCCGGGATTTACTGAT
CTCCCCAAAGAAGATCAGACATTACTTATTGAATCAGCCTTTTTGGAGCTGTTTGTCCTC
AGACTTTCCATCAGGTCAAACACTGCTGAAGATAAGTTTGTGTTCTGCAATGGACTTGTC
CTGCATCGACTTCAGTGCCTTCGTGGATTTGGGGAGTGGCTCGACTCTATTAAAGACTTT
TCCTTAAATTTGCAGAGCCTGAACCTTGATATCCAAGCCTTAGCCTGCCTGTCAGCACTG
AGCATGATCACAGAAAGACATGGGTTAAAAGAACCAAAGAGAGTCGAAGAGCTATGCAAC
AAGATCACAAGCAGTTTAAAAGACCACCAGAGTAAGGGACAGGCTCTGGAGCCCACCGAG
TCCAAGGTCCTGGGTGCCCTGGTAGAACTGAGGAAGATCTGCACCCTGGGCCTCCAGCGC
ATCTTCTACCTGAAGCTGGAAGACTTGGTGTCTCCACCTTCCATCATTGACAAGCTCTTC
CTGGACACCCTACCTTTCTAA

Chromosome Location

9

Locus

9q31.1

External Identifiers

Resource	Link
UniProtKB ID	Q92570
UniProtKB Entry Name	NR4A3_HUMAN
HGNC ID	HGNC:7982

General References

1. Ohkura N, Ito M, Tsukada T, Sasaki K, Yamaguchi K, Miki K: Structure, mapping and expression of a human NOR-1 gene, the third member of the Nur77/NGFI-B family. Biochim Biophys Acta. 1996 Sep 11;1308(3):205-14. [Article]
2. Hedvat CV, Irving SG: The isolation and characterization of MINOR, a novel mitogen-inducible nuclear orphan receptor. Mol Endocrinol. 1995 Dec;9(12):1692-700. [Article]
3. Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS: Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma. Oncogene. 1996 Jan 18;12(2):229-35. [Article]
4. Labelle Y, Zucman J, Stenman G, Kindblom LG, Knight J, Turc-Carel C, Dockhorn-Dworniczak B, Mandahl N, Desmaze C, Peter M, et al.: Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation. Hum Mol Genet. 1995 Dec;4(12):2219-26. [Article]
5. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
6. Ohkura N, Ito M, Tsukada T, Sasaki K, Yamaguchi K, Miki K: Alternative splicing generates isoforms of human neuron-derived orphan receptor-1 (NOR-1) mRNA. Gene. 1998 Apr 28;211(1):79-85. [Article]
7. Laflamme C, Filion C, Bridge JA, Ladanyi M, Goldring MB, Labelle Y: 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. 2003 Jan 15;63(2):449-54. [Article]
8. Zhao Y, Howatt DA, Gizard F, Nomiyama T, Findeisen HM, Heywood EB, Jones KL, Conneely OM, Daugherty A, Bruemmer D: Deficiency of the NR4A orphan nuclear receptor NOR1 decreases monocyte adhesion and atherosclerosis. Circ Res. 2010 Aug 20;107(4):501-11. doi: 10.1161/CIRCRESAHA.110.222083. Epub 2010 Jun 17. [Article]
9. Liu Q, Zhu X, Xu L, Fu Y, Garvey WT: 6-Mercaptopurine augments glucose transport activity in skeletal muscle cells in part via a mechanism dependent upon orphan nuclear receptor NR4A3. Am J Physiol Endocrinol Metab. 2013 Nov 1;305(9):E1081-92. doi: 10.1152/ajpendo.00169.2013. Epub 2013 Sep 10. [Article]
10. Medunjanin S, Daniel JM, Weinert S, Dutzmann J, Burgbacher F, Brecht S, Bruemmer D, Kahne T, Naumann M, Sedding DG, Zuschratter W, Braun-Dullaeus RC: DNA-dependent protein kinase (DNA-PK) permits vascular smooth muscle cell proliferation through phosphorylation of the orphan nuclear receptor NOR1. Cardiovasc Res. 2015 Jun 1;106(3):488-97. doi: 10.1093/cvr/cvv126. Epub 2015 Apr 7. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB01254	Dasatinib	approved, investigational	unknown	inhibitor	Details