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Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens
Mus musculus
Transcription Factor Encyclopedia  BETA
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The NR2F2 gene locus is mapped to 15q26 close to IGF1R gene located at the terminal side of the chromosome (see Figure 1). In 1995, Qiu et al[1] reported a genomic organization composed of three exons. Nevertheless, the analyses of transcripts suggest alternative forms(see Figure 2 and the Protein tab, under Isoforms). NR2F2 expression is widely distributed but different in mammalian tissues[2][3] and can be regulated by several transcription modulators[4][5][6][7][4][8]. See the "Interactions" and "Expression" tabs for compounds and proteins that regulate NR2F2 and its tissue-specific expression.

It was previously reported that NR2F2 homozygous mutants die around E10, possibly as a result of hemorrhage and edema in the brain and heart. Furthermore, 5% of heterozygote animals at E9.5 presented a similar hemorrhagic phenotype comparing to homozygotes[9]. Other works also supports that even heterozygote animals exhibit remarkable phenotypic changes in specific tissues such as white adipose tissue[10][11] and pancreatic beta cells[12][13] (see Figure 3 for a simplified schematic representation of COUP-TFII connections in a complex regulatory network working in pancreatic beta cells). The phenotypic effects of NR2F2 gene dosage implies in a potential relevance concerning human diseases.

NR2F2 (nuclear receptor subfamily 2, group F, member 2), NR2F1 and NR2F6 are human members of Subfamily 2/Group F of nuclear receptors according to the Unified Nomenclature System[14]. Strong sequence similarities are observed between NR2F2 and NR2F1 and to a lesser extend between one of then and NR2F6. The DNA Binding Domain (DBD, followed by the Ligand Binding Domain LBD) is the domain where the higher fraction of conserved residues is found (see Figure 4).

The phylogenetic conservation of members of this subfamily, even when considering distant organisms, indicates its primitive origin and suggests a relevant adaptative role[15]. The groups A (HNF4s), B (RXRs) and C (TRs) are included the same subfamily (Phylogenetic tree).

  1. Qiu Y et al. Isolation, characterization, and chromosomal localization of mouse and human COUP-TF I and II genes. Genomics, 29(1):240-6. (PMID 8530078)
  2. Gofflot F et al. Systematic gene expression mapping clusters nuclear receptors according to their function in the brain. Cell, 131(2):405-18. (PMID 17956739)
  3. Baroukh N et al. Comparative genomic analysis reveals a distant liver enhancer upstream of the COUP-TFII gene. Mamm. Genome, 16(2):91-5. (PMID 15859353)
  4. Perilhou A et al. The transcription factor COUP-TFII is negatively regulated by insulin and glucose via Foxo1- and ChREBP-controlled pathways. Mol. Cell. Biol., 28(21):6568-79. (PMID 18765640)
  5. Takamoto N et al. COUP-TFII is essential for radial and anteroposterior patterning of the stomach. Development, 132(9):2179-89. (PMID 15829524)
  6. Soosaar A et al. Cell type specific regulation of COUP-TF II promoter activity. FEBS Lett., 391(1-2):95-100. (PMID 8706939)
  7. Moré E et al. Activation of the MAP kinase pathway induces chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) expression in human breast cancer cell lines. J. Endocrinol., 176(1):83-94. (PMID 12525252)
  8. Okamura M et al. COUP-TFII acts downstream of Wnt/beta-catenin signal to silence PPARgamma gene expression and repress adipogenesis. Proc. Natl. Acad. Sci. U.S.A., 106(14):5819-24. (PMID 19307559)
  1. Pereira FA et al. The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development. Genes Dev., 13(8):1037-49. (PMID 10215630)
  2. Bardoux P et al. Essential role of chicken ovalbumin upstream promoter-transcription factor II in insulin secretion and insulin sensitivity revealed by conditional gene knockout. Diabetes, 54(5):1357-63. (PMID 15855320)
  3. Li L et al. The nuclear orphan receptor COUP-TFII plays an essential role in adipogenesis, glucose homeostasis, and energy metabolism. Cell Metab., 9(1):77-87. (PMID 19117548)
  4. Perilhou A et al. The MODY1 gene for hepatocyte nuclear factor 4alpha and a feedback loop control COUP-TFII expression in pancreatic beta cells. Mol. Cell. Biol., 28(14):4588-97. (PMID 18474611)
  5. Boutant M et al. COUP-TFII Controls Mouse Pancreatic β-Cell Mass through GLP-1-β-Catenin Signaling Pathways. PLoS ONE, 7(1):e30847. (PMID 22292058)
  6. . A unified nomenclature system for the nuclear receptor superfamily. Cell, 97(2):161-3. (PMID 10219237)
  7. Escriva H et al. Ligand binding was acquired during evolution of nuclear receptors. Proc. Natl. Acad. Sci. U.S.A., 94(13):6803-8. (PMID 9192646)
FIGURE 1 Genomic map indicating NR2F2 location
The figure represents 3 different zoom levels into the genomoic location of NR2F2 (GENOMIC DATA: Start=94,670,543 bp from pter; End=94,684,496 bp from pter; Size=13,954 bases; Orientation=plus strand)
This figure is from Figure created based in NCBI's Map Viewer images (