Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Nr4a1. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. The encoded protein acts as a nuclear transcription factor. Translocation of the protein from the nucleus to mitochondria induces apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Nr4a1
  • participates in the following biological processes:
    • cellular response to organic substance ^[3]
    • induction of apoptosis ^[7]
    • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process ^[10]
    • positive regulation of transcription from RNA polymerase II promoter ^{[2, 9, 11]}
    • positive regulation of transcription, DNA-dependent ^{[7, 11]}
  • performs the following molecular functions:
    • DNA binding ^[8]
    • protein homodimerization activity ^[4]
    • RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription ^[2]
    • sequence-specific DNA binding ^{[4, 11]}
  • is located in the following cellular components:
    • nucleus ^{[5, 8, 10]}
    • transcription factor complex ^[2]
• The gene product of Nr4a1 has been shown to bind to the gene products of Ncoa1, Rb1. ^{[1, 9]} Researchers have inferred, based on physical interactions, that the gene product of Nr4a1
  • performs the following molecular functions:
    • protein heterodimerization activity ^[11]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Nr4a1
  • participates in the following biological processes:
    • apoptotic process ^[5]
    • skeletal muscle cell differentiation ^[6]
• Researchers have inferred, based on genetic interactions, that the gene product of Nr4a1
  • participates in the following biological processes:
    • positive regulation of transcription from RNA polymerase II promoter based on interactions with Ncoa1, Neurod1, Nr0b1, Rb1 ^{[1, 9]}

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Nr4a1:
  • participates in the following biological processes:
    • cell migration involved in sprouting angiogenesis
    • cellular response to fibroblast growth factor stimulus
    • cellular response to vascular endothelial growth factor stimulus
    • endothelial cell chemotaxis
    • positive regulation of endothelial cell proliferation
    • response to inorganic substance
  • is located in the following cellular components:
    • nucleus

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Summary text based on GO annotations supported by structural data

• Nr4a1 encodes a protein or proteins that contain the following InterPro domains: Nuclear hormone receptor, ligand-binding, Nuclear hormone receptor, ligand-binding, core, Orphan nuclear receptor, Orphan nuclear receptor, HMR type, Steroid hormone receptor, Zinc finger, NHR/GATA-type, Zinc finger, nuclear hormone receptor-type, indicating that the gene product:
  • participates in the following biological processes:
    • intracellular receptor mediated signaling pathway
    • regulation of transcription, DNA-dependent
    • steroid hormone mediated signaling pathway
  • performs the following molecular functions:
    • ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity
    • sequence-specific DNA binding transcription factor activity
    • steroid hormone receptor activity
    • zinc ion binding

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Nr4a1 indicates that it:
  • participates in the following biological processes:
    • regulation of transcription, DNA-dependent
    • transcription, DNA-dependent
  • performs the following molecular functions:
    • metal ion binding

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References

1. Batsche E et al. (2005) Retinoblastoma and the related pocket protein p107 act as coactivators of NeuroD1 to enhance gene transcription. J Biol Chem, 280:16088-95. (PubMed:15701640)
2. Cheng LE et al. (1997) Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis. EMBO J, 16:1865-75. (PubMed:9155013)
3. Gimferrer I et al. (2011) Regulation of GATA-3 Expression during CD4 Lineage Differentiation. J Immunol, 186:3892-8. (PubMed:21357543)
4. Lavoie PL et al. (2008) Developmental Dependence on NurRE and EboxNeuro for Expression of Pituitary Proopiomelanocortin. Mol Endocrinol, 22:1647-57. (PubMed:18388149)
5. Lee KW et al. (2007) Contribution of the orphan nuclear receptor Nur77 to the apoptotic action of IGFBP-3. Carcinogenesis, 28:1653-1658. (PubMed:17434920)
6. Rajan S et al. (2011) Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation. Physiol Genomics, null:null. (PubMed:22147266)
7. Rajpal A et al. (2003) Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor. EMBO J, 22:6526-6536. (PubMed:14657025)
8. Smith AG et al. (2008) Melanocortin-1 receptor signaling markedly induces the expression of the NR4A nuclear receptor subgroup in melanocytic cells. J Biol Chem, 283:12564-70. (PubMed:18292087)
9. Song KH et al. (2004) The atypical orphan nuclear receptor DAX-1 interacts with orphan nuclear receptor Nur77 and represses its transactivation. Mol Endocrinol, 18:1929-40. (PubMed:15155786)
10. Suzuki S et al. (2003) Nur77 as a survival factor in tumor necrosis factor signaling. Proc Natl Acad Sci U S A, 100:8276-80. (PubMed:12815108)
11. Zetterstrom RH et al. (1996) Retinoid X receptor heterodimerization and developmental expression distinguish the orphan nuclear receptors NGFI-B, Nurr1, and Nor1. Mol Endocrinol, 10:1656-66. (PubMed:8961274)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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