Receptor nomenclature NR2F6
Receptor code 4.10.1:OR:2:F6
Other names
Molecular information Hs: 403aa, P10588, chr0.19p131
Rn: 390aa, O09017, chr. 16p14
Mm: 389aa, P43136, chr. 8 B3.32
DNA binding
   Structure Homodimer, heterodimer
   HRE core sequence AGGTCA n AGGTCA (DR-1)
Partners TRβ (physical, functional): heterodimerization with TRβ 1 inhibits TRβ 1 binding to its response element3; COUP-TFII (physical, functional): DNA binding4; CBFA2 (physical, functional): interaction with CBFA2 inhibits activity of CBFA25; ERα (physical)3; GR (physical)3
Coactivators NCOA13
Biologically important isoforms
Tissue distribution Developmental: liver; adult: placenta, heart, muscle, pancreas, kidney, but not in the lung or brain—also expressed in myeloid progenitor cells and epithelial cells {Hs, Mm} [Northern blot, in situ hybridization, immunohistology]16
Functional assays
Main target genes Repressed: renin {Mm},7 LH receptor {Hs, Mm, Rn},8 GRIK5 {Hs, Mm, Rn},9 oxytocin {Hs, Mm, Rn}6
Mutant phenotype EAR2-null mice exhibit defects in the development of the locus coeruleus and in circadian behaviors and circadian gene expression {Mm} [knockout]9
Human disease
  • aa, amino acids; chr., chromosome; HRE, hormone response element; GR, glucocorticoid receptor; LH, luteinizing hormone

  • 1. Miyajima N, Kadowaki Y, Fukushige S, Shimizu S, Semba K, Yamanashi Y, Matsubara K, Toyoshima K, and Yamamoto T (1988) Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other. Nucleic Acids Res 16: 11057-11074

  • 2. Jonk LJ, de Jonge ME, Pals CE, Wissink S, Vervaart JM, Schoorlemmer J, and Kruijer W (1994) Cloning and expression during development of three murine members of the COUP family of nuclear orphan receptors. Mech Dev 47: 81-97

  • 3. Zhu XG, Park KS, Kaneshige M, Bhat MK, Zhu Q, Mariash CN, McPhie P, and Cheng SY (2000) The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function. Mol Cell Biol 20: 2604-2618

  • 4. Avram D, Ishmael JE, Nevrivy DJ, Peterson VJ, Lee SH, Dowell P, and Leid M (1999) Heterodimeric interactions between chicken ovalbumin upstream promoter-transcription factor family members ARP1 and ear2. J Biol Chem 274: 14331-14336

  • 5. Ahn MJ, Nason-Burchenal K, Moasser MM, and Dmitrovsky E (1995) Growth suppression of acute promyelocytic leukemia cells having increased expression of the non-rearranged alleles: RARα or PML. Oncogene 10: 2307-2314

  • 6. Chu K, Boutin JM, Breton C, and Zingg HH (1998) Nuclear orphan receptors COUP-TFII and Ear-2: presence in oxytocin-producing uterine cells and functional interaction with the oxytocin gene promoter. Mol Cell Endocrinol 137: 145-154

  • 7. Liu X, Huang X, and Sigmund CD (2003) Identification of a nuclear orphan receptor (Ear2) as a negative regulator of renin gene transcription. Circ Res 92: 1033-1040

  • 8. Zhang Y and Dufau ML (2001) EAR2 and EAR3/COUP-TFI regulate transcription of the rat LH receptor. Mol Endocrinol 15: 1891-1905

  • 9. Warnecke M, Oster H, Revelli JP, Alvarez-Bolado G, and Eichele G (2005) Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs the functionality of the forebrain clock and affects nociception. Genes Dev 19: 614-625