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

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

Written	2003-07	Goran Stenman
		Lundberg Laboratory for Cancer Research, Department of Pathology, Goteborg University, Sahlgrenska University Hospital, SE-413 45 Goteborg, Sweden

(Note : for Links provided by Atlas : click)

Identity

Alias_names	nuclear receptor subfamily 4
Alias_symbol (synonym)	CSMF
	CHN
	NOR1
	MINOR
Other alias	TEC
	NR4A3
HGNC (Hugo)	NR4A3
LocusID (NCBI)	8013
Atlas_Id	75
Location	9q22.33 [Link to chromosome band 9q22]
Location_base_pair	Starts at 99821855 and ends at 99866891 bp from pter ( according to hg19-Feb_2009) [Mapping NR4A3.png]

Fusion genes
(updated 2017)

Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)

EWSR1 (22q12.2) / NR4A3 (9q22.33)	EWSR1 (22q12.2) / NR4A3 (9q31.1)	FUS (16p11.2) / NR4A3 (9q22.33)
FUS (16p11.2) / NR4A3 (9q31.1)	NR4A3 (9q22.33) / ABL2 (1q25.2)	NR4A3 (9q22.33) / EWSR1 (22q12.2)
NR4A3 (9q22.33) / TAF15 (17q12)	NR4A3 (9q22.33) / TCF12 (15q21.3)	NR4A3 (9q22.33) / TFG (3q12.2)
NR4A3 (9q31.1) / EWSR1 (22q12.2)	NR4A3 (9q31.1) / TAF15 (17q12)	STX17 (9q31.1) / NR4A3 (9q22.33)
TAF15 (17q12) / NR4A3 (9q22.33)	TAF15 (17q12) / NR4A3 (9q31.1)	TCF12 (15q21.3) / NR4A3 (9q22.33)
TCF12 (15q21.3) / NR4A3 (9q31.1)	TFG (3q12.2) / NR4A3 (9q22.33)	TFG (3q12.2) / NR4A3 (9q31.1)

DNA/RNA

Description	spans about 46 kb; 9 exons
Transcription	four transcript variants (6382 bp, 5635 bp, 4983bp and 2588 bp)

Protein

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

Note

Entity	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/Mutated Gene	EWSR1-TEC
Abnormal Protein	N-terminal transactivation domain of EWSR1 fused to the entire TEC protein.


Entity	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/Mutated Gene	TAF2N-TEC
Abnormal Protein	N-terminal transactivation domain of TAF2N fused to the entire TEC protein.


Entity	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/Mutated Gene	TCF12-TEC
Abnormal 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

Bibliography

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, Tariq M, Harris M, Coyne JD, Telford N, Varley JM

Oncogene. 1999 ; 18 (52) : 7599-7601.

PMID 10602520

Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor gene superfamily, in a human myxoid chondrosarcoma.

Clark J, Benjamin H, Gill S, Sidhar S, Goodwin G, Crew J, Gusterson BA, Shipley J, Cooper CS

Oncogene. 1996 ; 12 (2) : 229-235.

PMID 8570200

The isolation and characterization of MINOR, a novel mitogen-inducible nuclear orphan receptor.

Hedvat CV, Irving SG

Molecular endocrinology (Baltimore, Md.). 1995 ; 9 (12) : 1692-1700.

PMID 8614405

The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator.

Labelle Y, Bussières J, Courjal F, Goldring MB

Oncogene. 1999 ; 18 (21) : 3303-3308.

PMID 10359536

Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation.

Labelle Y, Zucman J, Stenman G, Kindblom LG, Knight J, Turc-Carel C, Dockhorn-Dworniczak B, Mandahl N, Desmaze C, Peter M

Human molecular genetics. 1995 ; 4 (12) : 2219-2226.

PMID 8634690

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, Filion C, Bridge JA, Ladanyi M, Goldring MB, Labelle Y

Cancer research. 2003 ; 63 (2) : 449-454.

PMID 12543801

The AF2 domain of the orphan nuclear receptor TEC is essential for the transcriptional activity of the oncogenic fusion protein EWS/TEC.

Maltais A, Filion C, Labelle Y

Cancer letters. 2002 ; 183 (1) : 87-94.

PMID 12049818

Molecular cloning of a novel thyroid/steroid receptor superfamily gene from cultured rat neuronal cells.

Ohkura N, Hijikuro M, Yamamoto A, Miki K

Biochemical and biophysical research communications. 1994 ; 205 (3) : 1959-1965.

PMID 7811288

The EWS/NOR1 fusion gene product gains a novel activity affecting pre-mRNA splicing.

Ohkura N, Yaguchi H, Tsukada T, Yamaguchi K

The Journal of biological chemistry. 2002 ; 277 (1) : 535-543.

PMID 11673470

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, Wedell B, Meis-Kindblom JM, Kindblom LG, Stenman G

Cancer research. 2000 ; 60 (24) : 6832-6835.

PMID 11156374

Citation

This paper should be referenced as such :

Stenman, G

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

Atlas Genet Cytogenet Oncol Haematol. 2003;7(3):176-177.

Free journal version : [ pdf ] [ DOI ]

On line version : http://AtlasGeneticsOncology.org/Genes/TECID75.html

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 7 ]

Bone: Chondrosarcoma
Soft Tissues: Extraskeletal myxoid chondrosarcoma
Soft tissue tumors: an overview
t(3;9)(q12;q22) TFG/NR4A3
t(9;15)(q22;q21) TCF12/NR4A3
t(9;17)(q22;q11) TAF15/NR4A3
t(9;22)(q22;q12) EWSR1/NR4A3

External links

	Nomenclature
HGNC (Hugo)	NR4A3 7982
	Cards
Atlas	TECID75
Entrez_Gene (NCBI)	NR4A3 8013 nuclear receptor subfamily 4 group A member 3
Aliases	CHN; CSMF; MINOR; NOR1;
	TEC
GeneCards (Weizmann)	NR4A3
Ensembl hg19 (Hinxton)	ENSG00000119508 [Gene_View]
Ensembl hg38 (Hinxton)	ENSG00000119508 [Gene_View] ENSG00000119508 [Sequence] chr9:99821855-99866891 [Contig_View] NR4A3 [Vega]
ICGC DataPortal	ENSG00000119508
TCGA cBioPortal	NR4A3
AceView (NCBI)	NR4A3
Genatlas (Paris)	NR4A3
WikiGenes	8013
SOURCE (Princeton)	NR4A3
Genetics Home Reference (NIH)	NR4A3
	Genomic and cartography
GoldenPath hg38 (UCSC)	NR4A3 - chr9:99821855-99866891 + 9q31.1 [Description] (hg38-Dec_2013)
GoldenPath hg19 (UCSC)	NR4A3 - 9q31.1 [Description] (hg19-Feb_2009)
GoldenPath	NR4A3 - 9q31.1 [CytoView hg19] NR4A3 - 9q31.1 [CytoView hg38]
ImmunoBase	ENSG00000119508
Mapping of homologs : NCBI	NR4A3 [Mapview hg19] NR4A3 [Mapview hg38]
OMIM	600542 612237
	Gene and transcription
Genbank (Entrez)	AK226108 BX649089 D78579 D85241 D85242
RefSeq transcript (Entrez)	NM_006981 NM_173198 NM_173199 NM_173200
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)	NR4A3
Cluster EST : Unigene	Hs.279522 [ NCBI ]
CGAP (NCI)	Hs.279522
Alternative Splicing Gallery	ENSG00000119508
Gene Expression	NR4A3 [ NCBI-GEO ] NR4A3 [ EBI - ARRAY_EXPRESS ] NR4A3 [ SEEK ] NR4A3 [ MEM ]
Gene Expression Viewer (FireBrowse)	NR4A3 [ Firebrowse - Broad ]
SOURCE (Princeton)	Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60]
Genevestigator	Expression in : [tissues] [cell-lines] [cancer] [perturbations]
BioGPS (Tissue expression)	8013
GTEX Portal (Tissue expression)	NR4A3
Human Protein Atlas	ENSG00000119508-NR4A3 [pathology] [cell] [tissue]
	Protein : pattern, domain, 3D structure
UniProt/SwissProt	Q92570 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction]
NextProt	Q92570 [Sequence] [Exons] [Medical] [Publications]
With graphics : InterPro	Q92570
Splice isoforms : SwissVar	Q92570
PhosPhoSitePlus	Q92570
Domaine pattern : Prosite (Expaxy)	NR_LBD (PS51843) NUCLEAR_REC_DBD_1 (PS00031) NUCLEAR_REC_DBD_2 (PS51030)
Domains : Interpro (EBI)	NHR_like_dom_sf NOR1_rcpt Nuc_orph_rcpt Nucl_hrmn_rcpt_lig-bd Nuclear_hrmn_rcpt Znf_hrmn_rcpt Znf_NHR/GATA
Domain families : Pfam (Sanger)	Hormone_recep (PF00104) zf-C4 (PF00105)
Domain families : Pfam (NCBI)	pfam00104 pfam00105
Domain families : Smart (EMBL)	HOLI (SM00430) ZnF_C4 (SM00399)
Conserved Domain (NCBI)	NR4A3
DMDM Disease mutations	8013
Blocks (Seattle)	NR4A3
Superfamily	Q92570
Human Protein Atlas [tissue]	ENSG00000119508-NR4A3 [tissue]
Peptide Atlas	Q92570
HPRD	02766
IPI	IPI00328269 IPI00293038 IPI00334557 IPI00748100
	Protein Interaction databases
DIP (DOE-UCLA)	Q92570
IntAct (EBI)	Q92570
FunCoup	ENSG00000119508
BioGRID	NR4A3
STRING (EMBL)	NR4A3
ZODIAC	NR4A3
	Ontologies - Pathways
QuickGO	Q92570
Ontology : AmiGO	negative regulation of transcription by RNA polymerase II RNA polymerase II regulatory region sequence-specific DNA binding RNA polymerase II proximal promoter sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific transcription coactivator binding DNA-binding transcription activator activity, RNA polymerase II-specific mesoderm formation DNA binding steroid hormone receptor activity nuclear receptor activity protein binding nucleus nucleus nucleoplasm transcription factor complex transcription initiation from RNA polymerase II promoter gastrulation axon guidance zinc ion binding pyruvate oxidation positive regulation of cardiac muscle hypertrophy positive regulation of glucose transmembrane transport protein kinase binding hippocampus development intracellular receptor signaling pathway adult behavior animal organ regeneration positive regulation of mast cell cytokine production histone acetyltransferase binding glucocorticoid receptor binding cAMP response element binding common myeloid progenitor cell proliferation positive regulation of mast cell activation by Fc-epsilon receptor signaling pathway response to hydrogen peroxide mast cell granule protein homodimerization activity mast cell degranulation steroid hormone mediated signaling pathway negative regulation of neuron apoptotic process sequence-specific DNA binding cellular response to leptin stimulus cellular respiration fat cell differentiation regulation of megakaryocyte differentiation positive regulation of cell cycle positive regulation of transcription by RNA polymerase II positive regulation of fatty acid oxidation platelet-derived growth factor receptor signaling pathway regulation of smooth muscle cell proliferation positive regulation of smooth muscle cell proliferation semicircular canal morphogenesis positive regulation of epithelial cell proliferation neuromuscular process controlling balance vestibular reflex regulation of type B pancreatic cell proliferation cellular response to corticotropin-releasing hormone stimulus cellular response to corticotropin-releasing hormone stimulus cellular response to catecholamine stimulus energy homeostasis positive regulation of monocyte aggregation negative regulation of hydrogen peroxide-induced neuron death positive regulation of vascular smooth muscle cell proliferation positive regulation of vascular associated smooth muscle cell migration positive regulation of leukocyte apoptotic process positive regulation of feeding behavior
Ontology : EGO-EBI	negative regulation of transcription by RNA polymerase II RNA polymerase II regulatory region sequence-specific DNA binding RNA polymerase II proximal promoter sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific transcription coactivator binding DNA-binding transcription activator activity, RNA polymerase II-specific mesoderm formation DNA binding steroid hormone receptor activity nuclear receptor activity protein binding nucleus nucleus nucleoplasm transcription factor complex transcription initiation from RNA polymerase II promoter gastrulation axon guidance zinc ion binding pyruvate oxidation positive regulation of cardiac muscle hypertrophy positive regulation of glucose transmembrane transport protein kinase binding hippocampus development intracellular receptor signaling pathway adult behavior animal organ regeneration positive regulation of mast cell cytokine production histone acetyltransferase binding glucocorticoid receptor binding cAMP response element binding common myeloid progenitor cell proliferation positive regulation of mast cell activation by Fc-epsilon receptor signaling pathway response to hydrogen peroxide mast cell granule protein homodimerization activity mast cell degranulation steroid hormone mediated signaling pathway negative regulation of neuron apoptotic process sequence-specific DNA binding cellular response to leptin stimulus cellular respiration fat cell differentiation regulation of megakaryocyte differentiation positive regulation of cell cycle positive regulation of transcription by RNA polymerase II positive regulation of fatty acid oxidation platelet-derived growth factor receptor signaling pathway regulation of smooth muscle cell proliferation positive regulation of smooth muscle cell proliferation semicircular canal morphogenesis positive regulation of epithelial cell proliferation neuromuscular process controlling balance vestibular reflex regulation of type B pancreatic cell proliferation cellular response to corticotropin-releasing hormone stimulus cellular response to corticotropin-releasing hormone stimulus cellular response to catecholamine stimulus energy homeostasis positive regulation of monocyte aggregation negative regulation of hydrogen peroxide-induced neuron death positive regulation of vascular smooth muscle cell proliferation positive regulation of vascular associated smooth muscle cell migration positive regulation of leukocyte apoptotic process positive regulation of feeding behavior
Pathways : KEGG	Transcriptional misregulation in cancer
REACTOME	Q92570 [protein]
REACTOME Pathways	R-HSA-8936459 [pathway]
NDEx Network	NR4A3
Atlas of Cancer Signalling Network	NR4A3
Wikipedia pathways	NR4A3
	Orthology - Evolution
OrthoDB	8013
GeneTree (enSembl)	ENSG00000119508
Phylogenetic Trees/Animal Genes : TreeFam	NR4A3
HOGENOM	Q92570
Homologs : HomoloGene	NR4A3
Homology/Alignments : Family Browser (UCSC)	NR4A3
	Gene fusions - Rearrangements
Fusion : Mitelman	EWSR1/NR4A3 [22q12.2/9q22.33] [t(9;22)(q31;q12)]
Fusion : Mitelman	FUS/NR4A3 [16p11.2/9q22.33] [t(9;16)(q31;p11)]
Fusion : Mitelman	TCF12/NR4A3 [15q21.3/9q22.33] [t(9;15)(q31;q21)]
Fusion : Mitelman	TFG/NR4A3 [3q12.2/9q22.33] [t(3;9)(q12;q31)]
Fusion : COSMIC	EWSR1 [22q12.2] - NR4A3 [9q31.1] [fusion_352] [fusion_353] [fusion_355] [fusion_356] [fusion_358] [fusion_359] [fusion_361]
	[fusion_364] [fusion_365] [fusion_366] [fusion_367] [fusion_369] [fusion_370] [fusion_371] [fusion_374] [fusion_375] [fusion_376]
	[fusion_378] [fusion_380] [fusion_381] [fusion_397] [fusion_398] [fusion_399] [fusion_400] [fusion_496]
Fusion : COSMIC	NR4A3 [9q31.1] - EWSR1 [22q12.2] [fusion_386] [fusion_401] [fusion_402]
Fusion : COSMIC	NR4A3 [9q31.1] - TAF15 [17q12] [fusion_960] [fusion_961]
Fusion : COSMIC	TAF15 [17q12] - NR4A3 [9q31.1] [fusion_589] [fusion_657] [fusion_658] [fusion_957] [fusion_958] [fusion_959]
Fusion : COSMIC	TCF12 [15q21.3] - NR4A3 [9q31.1] [fusion_754] [fusion_755]
Fusion : COSMIC	TFG [3q12.2] - NR4A3 [9q31.1] [fusion_1187] [fusion_610]
Fusion : TICdb	EWSR1 [22q12.2] - NR4A3 [9q22.33]
Fusion : TICdb	TAF15 [17q12] - NR4A3 [9q22.33]
Fusion : TICdb	TFG [3q12.2] - NR4A3 [9q22.33]
Fusion : FusionGDB	12238 24811 2879 36636 37077 37553 37851
Fusion : Fusion_Hub	AR--NR4A3 CLYBL--NR4A3 ERG--NR4A3 EWS--NR4A3 EWSR1--NR4A3 FUS--NR4A3 GREB1--NR4A3 HSPA8--NR4A3 KDM4C--NR4A3 NR4A3--ABL2 NR4A3--ACTB NR4A3--ADH1B NR4A3--BCAT2 NR4A3--EWS NR4A3--EWSR1
	NR4A3--FAM195B NR4A3--FNDC3B NR4A3--FUS NR4A3--NFIL3 NR4A3--PIK3R1 NR4A3--RBP56 NR4A3--RNPC3 NR4A3--TAF15 NR4A3--TAFII68 NR4A3--TCF12 NR4A3--TFG PTPRE--NR4A3 STX17--NR4A3 TAF15--NR4A3 TCF12--NR4A3
	TFG--NR4A3
Fusion : Quiver	NR4A3
	Polymorphisms : SNP and Copy number variants
NCBI Variation Viewer	NR4A3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)	NR4A3
dbVar	NR4A3
ClinVar	NR4A3
1000_Genomes	NR4A3
Exome Variant Server	NR4A3
ExAC (Exome Aggregation Consortium)	ENSG00000119508
GNOMAD Browser	ENSG00000119508
Varsome Browser	NR4A3
Genetic variants : HAPMAP	8013
Genomic Variants (DGV)	NR4A3 [DGVbeta]
DECIPHER	NR4A3 [patients] [syndromes] [variants] [genes]
CONAN: Copy Number Analysis	NR4A3
	Mutations
ICGC Data Portal	NR4A3
TCGA Data Portal	NR4A3
Broad Tumor Portal	NR4A3
OASIS Portal	NR4A3 [ Somatic mutations - Copy number]
Mutations and Diseases : HGMD	NR4A3
LOVD (Leiden Open Variation Database)	Whole genome datasets
LOVD (Leiden Open Variation Database)	LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)	LOVD 3.0 shared installation
BioMuta	search NR4A3
DgiDB (Drug Gene Interaction Database)	NR4A3
DoCM (Curated mutations)	NR4A3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)	NR4A3 (select a term)
intoGen	NR4A3
NCG5 (London)	NR4A3
Cancer3D	NR4A3(select the gene name)
Impact of mutations	[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
	Diseases
OMIM	600542 612237
Orphanet	18668
DisGeNET	NR4A3
Medgen	NR4A3
Genetic Testing Registry	NR4A3
NextProt	Q92570 [Medical]
TSGene	8013
GENETests	NR4A3
Target Validation	NR4A3
Huge Navigator	NR4A3 [HugePedia]
snp3D : Map Gene to Disease	8013
BioCentury BCIQ	NR4A3
ClinGen	NR4A3
	Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD	8013
Chemical/Pharm GKB Gene	PA31763
Clinical trial	NR4A3
	Miscellaneous
canSAR (ICR)	NR4A3 (select the gene name)
DataMed Index	NR4A3
	Probes
	Litterature
PubMed	87 Pubmed reference(s) in Entrez
GeneRIFs	Gene References Into Functions (Entrez)
CoreMine	NR4A3
EVEX	NR4A3
GoPubMed	NR4A3
iHOP	NR4A3

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Search in all EBI NCBI

indexed on : Mon Jul 8 15:23:42 CEST 2019

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