NR4A3 (nuclear receptor subfamily 4, group A, member 3)

2003-07-01   Goran Stenman 

Lundberg Laboratory for Cancer Research, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden

Identity

HGNC
LOCATION
9q22.33
LOCUSID
FUSION GENES

DNA/RNA

Description

spans about 46 kb; 9 exons

Transcription

four transcript variants (6382 bp, 5635 bp, 4983bp and 2588 bp)

Proteins

Description

three isoforms (637 aa, 626 aa and 443 aa); N-terminal activation domain; central bipartite zinc finger DNA-binding domain; C-terminal ligand binding domain.

Expression

most tissues, highest expression levels in the central nervous system.

Localisation

nuclear

Function

orphan nuclear receptor; implicated in the control of cell proliferation as an immediate-early protein and in differentiation and apoptosis; binds as a monomer to the DNA-response element NBRE; activate transcription constitutively when bound to NBRE; the homeotic protein Six3 is a coactivator of TEC.

Homology

belongs to the steroid/thyroid receptor gene super family; highly homologous to the nuclear receptors NGFI-B and NURR1.

Implicated in

Disease
rare type of sarcoma (2.3% of all soft tissue sarcomas) characteristically involving the deep, soft tissues of the extremities; morphological resemblance to embryonic cartilage.
Hybrid gene
EWSR1-TEC
Fusion protein
N-terminal transactivation domain of EWSR1 fused to the entire TEC protein.
Disease
rare type of sarcoma (2.3% of all soft tissue sarcomas) characteristically involving the deep, soft tissues of the extremities; morphological resemblance to embryonic cartilage.
Hybrid gene
TAF2N-TEC
Fusion protein
N-terminal transactivation domain of TAF2N fused to the entire TEC protein.
Entity name
Extraskeletal myxoid chondrosarcoma with t(9;15)(q22;q21).
Disease
rare type of sarcoma (2.3% of all soft tissue sarcomas) characteristically involving the deep, soft tissues of the extremities; morphological resemblance to embryonic cartilage.
Hybrid gene
TCF12-TEC
Fusion protein
N-terminal domain of TCF12 fused to the entire TEC protein; the N-terminal of TCF12 shows no sequence homology to the N-terminals of EWSR1 or TAF2N.

Breakpoints

Atlas Image

Bibliography

Pubmed IDLast YearTitleAuthors
106025201999Identification of a novel fusion gene involving hTAFII68 and CHN from a t(9;17)(q22;q11.2) translocation in an extraskeletal myxoid chondrosarcoma.Attwooll C et al
85702001996Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma.Clark J et al
86144051995The isolation and characterization of MINOR, a novel mitogen-inducible nuclear orphan receptor.Hedvat CV et al
103595361999The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator.Labelle Y et al
86346901995Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation.Labelle Y et al
125438012003The 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 et al
120498182002The AF2 domain of the orphan nuclear receptor TEC is essential for the transcriptional activity of the oncogenic fusion protein EWS/TEC.Maltais A et al
78112881994Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells.Ohkura N et al
116734702002The EWS/NOR1 fusion gene product gains a novel activity affecting pre-mRNA splicing.Ohkura N et al
111563742000Fusion 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 et al

Other Information

Locus ID:

NCBI: 8013
MIM: 600542
HGNC: 7982
Ensembl: ENSG00000119508

Variants:

dbSNP: 8013
ClinVar: 8013
TCGA: ENSG00000119508
COSMIC: NR4A3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000119508ENST00000330847Q92570
ENSG00000119508ENST00000338488Q92570
ENSG00000119508ENST00000395097Q92570
ENSG00000119508ENST00000395097A0A024R168
ENSG00000119508ENST00000618101Q92570

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45

Pathways

PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Nuclear Receptor transcription pathwayREACTOMER-HSA-383280

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
175158972007Abrogation of nuclear receptors Nr4a3 and Nr4a1 leads to development of acute myeloid leukemia.116
159648442005Induction of NR4A orphan nuclear receptor expression in macrophages in response to inflammatory stimuli.87
168737292006Nuclear receptors Nur77, Nurr1, and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses.81
183259992008The orphan nuclear receptor, NOR-1, a target of beta-adrenergic signaling, regulates gene expression that controls oxidative metabolism in skeletal muscle.54
169459222006The NR4A orphan nuclear receptor NOR1 is induced by platelet-derived growth factor and mediates vascular smooth muscle cell proliferation.50
235544592013MicroRNA-638 is highly expressed in human vascular smooth muscle cells and inhibits PDGF-BB-induced cell proliferation and migration through targeting orphan nuclear receptor NOR1.50
145257952003Vascular endothelial growth factor-regulated gene expression in endothelial cells: KDR-mediated induction of Egr3 and the related nuclear receptors Nur77, Nurr1, and Nor1.48
259170812016Nuclear receptor 4A (NR4A) family - orphans no more.39
205588212010Deficiency of the NR4A orphan nuclear receptor NOR1 decreases monocyte adhesion and atherosclerosis.27
149629442004Involvement of neuron-derived orphan receptor-1 (NOR-1) in LDL-induced mitogenic stimulus in vascular smooth muscle cells: role of CREB.20

Citation

Goran Stenman

NR4A3 (nuclear receptor subfamily 4, group A, member 3)

Atlas Genet Cytogenet Oncol Haematol. 2003-07-01

Online version: http://atlasgeneticsoncology.org/gene/75/nr4a3