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

Gene ID: 4929, updated on 3-Apr-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
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Genomic context

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Location:
2q24.1
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (156324437..156332721, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (156777128..156785409, complement)
105.20220307 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
  • 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. NURR1 expression regulates retinal pigment epithelial-mesenchymal transition and age-related macular degeneration phenotypes. Yao PL, et al. Proc Natl Acad Sci U S A, 2022 Jul 12. PMID 35867766, Free PMC Article
  2. Recruitment of the CoREST transcription repressor complexes by Nerve Growth factor IB-like receptor (Nurr1/NR4A2) mediates silencing of HIV in microglial cells. Ye F, et al. PLoS Pathog, 2022 Jul. PMID 35797416, Free PMC Article
  3. The role of NURR1 in metabolic abnormalities of Parkinson's disease. Al-Nusaif M, et al. Mol Neurodegener, 2022 Jun 27. PMID 35761385, Free PMC Article
  4. NR4A2 expression is not altered in placentas from cases of growth restriction or preeclampsia, but is reduced in hypoxic cytotrophoblast. de Alwis N, et al. Sci Rep, 2021 Oct 19. PMID 34667209, Free PMC Article
  5. Working memory deficits in schizophrenia are associated with the rs34884856 variant and expression levels of the NR4A2 gene in a sample Mexican population: a case control study. Ruiz-Sánchez E, et al. BMC Psychiatry, 2021 Feb 9. PMID 33563249, Free PMC Article

See all (219) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. A role of NR4A2 in Graves' disease: regulation of Th17/Treg.
    Title: A role of NR4A2 in Graves' disease: regulation of Th17/Treg.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. A Proposed TUSC7/miR-211/Nurr1 ceRNET Might Potentially be Disturbed by a cer-SNP rs2615499 in Breast Cancer.
    Title: A Proposed TUSC7/miR-211/Nurr1 ceRNET Might Potentially be Disturbed by a cer-SNP rs2615499 in Breast Cancer.
Submit: New GeneRIF Correction See all GeneRIFs (167)

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
  
acts_upstream_of_or_within cellular response to extracellular stimulus IDA
Inferred from Direct Assay
more info
 PubMed 
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 signal transduction NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
part_of 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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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_2023_10

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

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