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

2003-07-01 Goran Stenman Affiliation

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

Identity

HGNC

NR4A3

LOCATION

9q22.33

LOCUSID

8013

FUSION GENES

Show Gene Fusions

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

Entity name

Extraskeletal myxoid chondrosarcoma with t(9;22)(q22;q12).

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.

Entity name

Extraskeletal myxoid chondrosarcoma with t(9;17)(q22;q11).

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

Article Bibliography

Pubmed ID	Last Year	Title	Authors
10602520	1999	Identification 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
8570200	1996	Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma.	Clark J et al
8614405	1995	The isolation and characterization of MINOR, a novel mitogen-inducible nuclear orphan receptor.	Hedvat CV et al
10359536	1999	The 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
8634690	1995	Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation.	Labelle Y et al
12543801	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.	Laflamme C et al
12049818	2002	The 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
7811288	1994	Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells.	Ohkura N et al
11673470	2002	The EWS/NOR1 fusion gene product gains a novel activity affecting pre-mRNA splicing.	Ohkura N et al
11156374	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).	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 ID	Transcript ID	Uniprot
ENSG00000119508	ENST00000330847	Q92570
ENSG00000119508	ENST00000338488	Q92570
ENSG00000119508	ENST00000395097	Q92570
ENSG00000119508	ENST00000395097	A0A024R168
ENSG00000119508	ENST00000618101	Q92570

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Transcriptional misregulation in cancer	KEGG	ko05202
Transcriptional misregulation in cancer	KEGG	hsa05202
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Nuclear Receptor transcription pathway	REACTOME	R-HSA-383280

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
37690706	2024	Upregulation of NOR-1 in calcified human vascular tissues: impact on osteogenic differentiation and calcification.	2
37905340	2024	RP11-495P10.1 promotes HCC cell proliferation by regulating reprogramming of glucose metabolism and acetylation of the NR4A3 promoter via the PDK1/PDH axis.	0
38261254	2024	Potential Roles of Nr4a3-Mediated Inflammation in Immunological and Neurological Diseases.	0
38474099	2024	Orphan Nuclear Receptor Family 4A (NR4A) Members NR4A2 and NR4A3 Selectively Modulate Elements of the Monocyte Response to Buffered Hypercapnia.	0
38629274	2024	Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation.	1
37690706	2024	Upregulation of NOR-1 in calcified human vascular tissues: impact on osteogenic differentiation and calcification.	2
37905340	2024	RP11-495P10.1 promotes HCC cell proliferation by regulating reprogramming of glucose metabolism and acetylation of the NR4A3 promoter via the PDK1/PDH axis.	0
38261254	2024	Potential Roles of Nr4a3-Mediated Inflammation in Immunological and Neurological Diseases.	0
38474099	2024	Orphan Nuclear Receptor Family 4A (NR4A) Members NR4A2 and NR4A3 Selectively Modulate Elements of the Monocyte Response to Buffered Hypercapnia.	0
38629274	2024	Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation.	1
36469101	2023	A minority of cases of acinic cell carcinoma of the salivary glands are driven by an NR4A2 rearrangement: the diagnostic utility of the assessment of NR4A2 and NR4A3 alterations in salivary gland tumors.	0
36482877	2023	Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c+ Dendritic Cell Dysregulation in Systemic Sclerosis.	3
36524687	2023	NR4A3 fusions characterize a distinctive peritoneal mesothelial neoplasm of uncertain biological potential with pure adenomatoid/microcystic morphology.	1
36828363	2023	NR4A3 Expression Is Consistently Absent in Acinic Cell Carcinomas of the Breast: A Potential Nosologic Shift.	1
37389860	2023	Loss of NOR-1 represses muscle metabolism through mTORC1-mediated signaling and mitochondrial gene expression in C2C12 myotubes.	1

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-(nuclear-receptor-subfamily-4-group-a-member-3)