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    NR4A2 nuclear receptor subfamily 4 group A member 2 [ Homo sapiens (human) ]

    Gene ID: 4929, updated on 28-Oct-2024

    Summary

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    Official Symbol
    NR4A2provided by HGNC
    Official Full Name
    nuclear receptor subfamily 4 group A member 2provided by HGNC
    Primary source
    HGNC:HGNC:7981
    See related
    Ensembl:ENSG00000153234 MIM:601828; AllianceGenome:HGNC:7981
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NOT; RNR1; HZF-3; IDLDP; NURR1; TINUR
    Summary
    This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. The encoded protein may act as a transcription factor. Mutations in this gene have been associated with disorders related to dopaminergic dysfunction, including Parkinson disease, schizophernia, and manic depression. Misregulation of this gene may be associated with rheumatoid arthritis. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in adrenal (RPKM 41.8), bone marrow (RPKM 25.5) and 15 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NR4A2 in Genome Data Viewer
    Location:
    2q24.1
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (156324437..156332721, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (156777128..156785409, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (157180949..157189233, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373703 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:156697781-156698549 Neighboring gene VISTA enhancer hs411 Neighboring gene MPRA-validated peak3904 silencer Neighboring gene long intergenic non-protein coding RNA 1876 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:156903772-156904272 Neighboring gene MPRA-validated peak3905 silencer Neighboring gene MPRA-validated peak3906 silencer Neighboring gene HEBP2 pseudogene 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:156939984-156941183 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:157031916-157032139 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_53336 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:157149084-157149974 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16658 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12016 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16659 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:157190964-157191836 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:157197537-157198092 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:157198093-157198646 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12018 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16661 Neighboring gene uncharacterized LOC124906082 Neighboring gene uncharacterized LOC440918

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Nuclear Receptor Nr4a2 Promotes Alternative Polarization of Macrophages and Confers Protection in Sepsis. Mahajan S, et al. J Biol Chem, 2015 Jul 24. PMID 25953901, Free PMC Article
    2. High cytoplasmic expression of the orphan nuclear receptor NR4A2 predicts poor survival in nasopharyngeal carcinoma. Wang J, et al. Asian Pac J Cancer Prev, 2013. PMID 23803035
    3. Nuclear orphan receptor NR4A2 confers chemoresistance and predicts unfavorable prognosis of colorectal carcinoma patients who received postoperative chemotherapy. Han Y, et al. Eur J Cancer, 2013 Nov. PMID 23809767
    4. Expression of orphan nuclear receptor NR4A2 in gastric cancer cells confers chemoresistance and predicts an unfavorable postoperative survival of gastric cancer patients with chemotherapy. Han Y, et al. Cancer, 2013 Oct 1. PMID 23821160
    5. Chemoprevention of skin cancer with 1,1-Bis (3'-indolyl)-1-(aromatic) methane analog through induction of the orphan nuclear receptor, NR4A2 (Nurr1). Boakye CH, et al. PLoS One, 2013. PMID 23950896, Free PMC Article

    See all (229) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.
      Title: Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.
    2. Orphan Nuclear Receptor Family 4A (NR4A) Members NR4A2 and NR4A3 Selectively Modulate Elements of the Monocyte Response to Buffered Hypercapnia.
      Title: Orphan Nuclear Receptor Family 4A (NR4A) Members NR4A2 and NR4A3 Selectively Modulate Elements of the Monocyte Response to Buffered Hypercapnia.
    3. The nuclear receptor Nurr1 is preferentially expressed in human pro-inflammatory macrophages and limits their inflammatory profile.
      Title: The nuclear receptor Nurr1 is preferentially expressed in human pro-inflammatory macrophages and limits their inflammatory profile.
    4. A role of NR4A2 in Graves' disease: regulation of Th17/Treg.
      Title: A role of NR4A2 in Graves' disease: regulation of Th17/Treg.
    5. Evaluation of mRNA Expressions of TOX and NR4As in CD8+ T cells in Acute Leukemia.
      Title: Evaluation of mRNA Expressions of TOX and NR4As in CD8+ T cells in Acute Leukemia.
    6. Nuclear Receptor 4A2 (NR4A2/NURR1) Regulates Autophagy and Chemoresistance in Pancreatic Ductal Adenocarcinoma.
      Title: Nuclear Receptor 4A2 (NR4A2/NURR1) Regulates Autophagy and Chemoresistance in Pancreatic Ductal Adenocarcinoma.
    7. Mechanisms of NURR1 Regulation: Consequences for Its Biological Activity and Involvement in Pathology.
      Title: Mechanisms of NURR1 Regulation: Consequences for Its Biological Activity and Involvement in Pathology.
    8. 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.
      Title: 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.
    9. Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c+ Dendritic Cell Dysregulation in Systemic Sclerosis.
      Title: Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c+ Dendritic Cell Dysregulation in Systemic Sclerosis.
    10. The lncRNA LUCAT1 is elevated in inflammatory disease and restrains inflammation by regulating the splicing and stability of NR4A2.
      Title: The lncRNA LUCAT1 is elevated in inflammatory disease and restrains inflammation by regulating the splicing and stability of NR4A2.
    Submit: New GeneRIF Correction See all GeneRIFs (168)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2022-09-27)

    ClinGen Genome Curation PagePubMed
    Triplosensitivity

    No evidence available (Last evaluated 2022-09-27)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    Genome-wide association of lipid-lowering response to statins in combined study populations.
    EBI GWAS Catalog
    Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
    EBI GWAS Catalog
    Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of nuclear receptor subfamily 4, group A, member 2 (NR4A2) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Vif vif HIV-1 Vif upregulates the expression of nuclear receptor subfamily 4, group A, member 2 (NR4A2) in Vif-expression T cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables DNA-binding transcription activator activity, RNA polymerase II-specific ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
    Inferred from Sequence Alignment
    more info
    		  
    enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables beta-catenin binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables nuclear glucocorticoid receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables nuclear receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables nuclear retinoid X receptor binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein heterodimerization activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables sequence-specific double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in adult locomotory behavior IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in canonical Wnt signaling pathway TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cellular response to corticotropin-releasing hormone stimulus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to corticotropin-releasing hormone stimulus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cellular response to oxidative stress IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in central nervous system neuron differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in central nervous system projection neuron axonogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in dopamine biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in dopaminergic neuron differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in dopaminergic neuron differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in fat cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in general adaptation syndrome IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in habenula development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in intracellular receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in midbrain dopaminergic neuron differentiation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in negative regulation of apoptotic signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in neuron apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuron maturation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neuron migration TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in positive regulation of transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in post-embryonic development IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of dopamine metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of respiratory gaseous exchange IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in response to amphetamine IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in chromatin ISA
    Inferred from Sequence Alignment
    more info
    		  
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    part_of protein-containing complex TAS
    Traceable Author Statement
    more info
    		 PubMed 
    part_of transcription regulator complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    nuclear receptor subfamily 4 group A member 2
    Names
    NGFI-B/nur77 beta-type transcription factor homolog
    T-cell nuclear receptor NOT
    immediate-early response protein NOT
    intermediate-early receptor protein
    nuclear receptor related 1
    nur related protein-1, human homolog of
    orphan nuclear receptor NR4A2
    orphan nuclear receptor NURR1
    transcriptionally inducible nuclear receptor related 1
    transcriptionally-inducible nuclear receptor

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_011821.2 RefSeqGene

      Range
      5000..13284
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_006186.4 → NP_006177.1  nuclear receptor subfamily 4 group A member 2 isoform a

      See identical proteins and their annotated locations for NP_006177.1

      Status: REVIEWED

      Source sequence(s)
      AC074099
      Consensus CDS
      CCDS2201.1
      UniProtKB/Swiss-Prot
      P43354, Q16311, Q53RZ2, Q6NXU0
      UniProtKB/TrEMBL
      F1D8N6, Q53EL4
      Related
      ENSP00000344479.4, ENST00000339562.9
      Conserved Domains (2) summary
      cd07071
      Location:361 → 598
      NR_LBD_Nurr1; The ligand binding domain of Nurr1, a member of conserved family of nuclear receptors
      cd06969
      Location:261 → 335
      NR_DBD_NGFI-B; DNA-binding domain of the orphan nuclear receptor, nerve growth factor-induced-B

    2. NM_173173.3 → NP_775265.1  nuclear receptor subfamily 4 group A member 2 isoform d

      Status: REVIEWED

      Source sequence(s)
      AC074099
      Consensus CDS
      CCDS86887.1
      UniProtKB/TrEMBL
      A0A8V8TR19
      Related
      ENSP00000389986.1, ENST00000426264.5
      Conserved Domains (2) summary
      cd07071
      Location:298 → 535
      NR_LBD_Nurr1; The ligand binding domain of Nurr1, a member of conserved family of nuclear receptors
      cd06969
      Location:198 → 272
      NR_DBD_NGFI-B; DNA-binding domain of the orphan nuclear receptor, nerve growth factor-induced-B

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      156324437..156332721 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006712553.5 → XP_006712616.1  nuclear receptor subfamily 4 group A member 2 isoform X2

      UniProtKB/TrEMBL
      B7Z5U7
      Conserved Domains (2) summary
      cd06969
      Location:272 → 346
      NR_DBD_NGFI-B; DNA-binding domain of the orphan nuclear receptor, nerve growth factor-induced-B
      cl11397
      Location:373 → 584
      NR_LBD; The ligand binding domain of nuclear receptors, a family of ligand-activated transcription regulators

    2. XM_011511246.3 → XP_011509548.1  nuclear receptor subfamily 4 group A member 2 isoform X4

      UniProtKB/TrEMBL
      F8W6I3
      Related
      ENSP00000386993.2, ENST00000409108.6
      Conserved Domains (2) summary
      cd06969
      Location:272 → 346
      NR_DBD_NGFI-B; DNA-binding domain of the orphan nuclear receptor, nerve growth factor-induced-B
      cl11397
      Location:378 → 488
      NR_LBD; The ligand binding domain of nuclear receptors, a family of ligand-activated transcription regulators

    3. XM_005246621.5 → XP_005246678.1  nuclear receptor subfamily 4 group A member 2 isoform X1

      UniProtKB/TrEMBL
      B7Z5U7
      Conserved Domains (2) summary
      cd07071
      Location:372 → 609
      NR_LBD_Nurr1; The ligand binding domain of Nurr1, a member of conserved family of nuclear receptors
      cd06969
      Location:272 → 346
      NR_DBD_NGFI-B; DNA-binding domain of the orphan nuclear receptor, nerve growth factor-induced-B

    4. XM_047444554.1 → XP_047300510.1  nuclear receptor subfamily 4 group A member 2 isoform X3

      UniProtKB/TrEMBL
      F1DAL2

    5. XM_047444551.1 → XP_047300507.1  nuclear receptor subfamily 4 group A member 2 isoform X8

      UniProtKB/Swiss-Prot
      P43354, Q16311, Q53RZ2, Q6NXU0
      UniProtKB/TrEMBL
      F1D8N6

    6. XM_047444558.1 → XP_047300514.1  nuclear receptor subfamily 4 group A member 2 isoform X6

      Related
      ENSP00000514865.1, ENST00000700228.1

    7. XM_047444555.1 → XP_047300511.1  nuclear receptor subfamily 4 group A member 2 isoform X3

      UniProtKB/TrEMBL
      F1DAL2
      Related
      ENSP00000514868.1, ENST00000700231.1

    8. XM_047444557.1 → XP_047300513.1  nuclear receptor subfamily 4 group A member 2 isoform X5

    9. XM_047444559.1 → XP_047300515.1  nuclear receptor subfamily 4 group A member 2 isoform X7

      Related
      ENSP00000415632.1, ENST00000417764.5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      156777128..156785409 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054342297.1 → XP_054198272.1  nuclear receptor subfamily 4 group A member 2 isoform X2

    2. XM_054342299.1 → XP_054198274.1  nuclear receptor subfamily 4 group A member 2 isoform X4

    3. XM_054342296.1 → XP_054198271.1  nuclear receptor subfamily 4 group A member 2 isoform X1

    4. XM_054342301.1 → XP_054198276.1  nuclear receptor subfamily 4 group A member 2 isoform X6

    5. XM_054342298.1 → XP_054198273.1  nuclear receptor subfamily 4 group A member 2 isoform X3

    6. XM_054342300.1 → XP_054198275.1  nuclear receptor subfamily 4 group A member 2 isoform X5

    7. XM_054342302.1 → XP_054198277.1  nuclear receptor subfamily 4 group A member 2 isoform X7

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_173171.1: Suppressed sequence

      Description
      NM_173171.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

    2. NM_173172.1: Suppressed sequence

      Description
      NM_173172.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P43354.1 GenPept UniProtKB/Swiss-Prot:P43354

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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