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Gene Review

Nr2f2  -  nuclear receptor subfamily 2, group F,...

Mus musculus

Synonyms: 2700033K02Rik, 9430015G03Rik, ARP-1, Apolipoprotein AI regulatory protein 1, Aporp1, ...
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Disease relevance of Nr2f2


High impact information on Nr2f2

  • Mediation of Sonic hedgehog-induced expression of COUP-TFII by a protein phosphatase [5].
  • In fact, the expression of Angiopoietin-1, a proangiogenic soluble factor thought to mediate the mesenchymal-endothelial interactions during heart development and vascular remodeling, is down-regulated in COUP-TFII mutants [6].
  • This down-regulation suggests that COUP-TFII may be required for bidirectional signaling between the endothelial and mesenchymal compartments essential for proper angiogenesis and heart development [6].
  • The embryonic expression of COUP-TFII, an orphan nuclear receptor, suggests that it may participate in mesenchymal-epithelial interactions required for organogenesis [6].
  • One of these, COUP-TF II, is expressed in embryonic/fetal erythroid cell lines, murine yolk sac, intra-embryonic splanchnopleura and fetal liver [7].

Biological context of Nr2f2


Anatomical context of Nr2f2


Associations of Nr2f2 with chemical compounds


Physical interactions of Nr2f2

  • The inhibition of MyoD-mediated trans-activation involves the direct binding of the DNA binding domain/C-region and hinge/D-regions [i.e. amino acid (aa) residues 78-213] of COUP-TF II to the N-terminal activation domain of MyoD [18].

Regulatory relationships of Nr2f2

  • Thus, COUP-TFII has a critical role in repressing Notch signalling to maintain vein identity, which suggests that vein identity is under genetic control and is not derived by a default pathway [19].
  • However, this enhancer-bound NF-kappaB failed to up-regulate class I expression because the class I enhancer chromatin remained repressed as a result of histone deacetylation by HDAC in association with COUP-TFII [20].

Other interactions of Nr2f2

  • Full-length FOG-2 markedly enhanced transcriptional repression by GAL4-COUP-TF2(117-414), but not by a COUP-TF2 repression domain mutant [9].
  • The expression patterns of COUP-TF1, ARP-1 and EAR2 during development were investigated by in situ hybridization [13].
  • These results indicate that the PPREs of the CYP4A6 gene are recognized by multiple members of the nuclear receptor family that are likely to contribute to the regulation of CYP4A6 expression in both an agonistic (RXR alpha) and an antagonistic (ARP-1) manner [10].
  • Finally, COUP-TFII expression was detected in pancreas, as judged by co-expression of the beta-gal in some of the glucagon and PDX1 positive-cells at 12.5 dpc and co-expression with insulin positive-cells at 15.5 dpc [14].
  • Significantly, NF-kappaB p50/p52 double-knockout cells enabled us to demonstrate directly that COUP-TFII can completely repress both nonactivated and NF-kappaB-activated MHC class I transcription [1].

Analytical, diagnostic and therapeutic context of Nr2f2


  1. Coup-TFII is up-regulated in adenovirus type 12 tumorigenic cells and is a repressor of MHC class I transcription. Smirnov, D.A., Hou, S., Liu, X., Claudio, E., Siebenlist, U.K., Ricciardi, R.P. Virology (2001) [Pubmed]
  2. Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. You, L.R., Takamoto, N., Yu, C.T., Tanaka, T., Kodama, T., Demayo, F.J., Tsai, S.Y., Tsai, M.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. Haploinsufficiency of chicken ovalbumin upstream promoter transcription factor II in female reproduction. Takamoto, N., Kurihara, I., Lee, K., Demayo, F.J., Tsai, M.J., Tsai, S.Y. Mol. Endocrinol. (2005) [Pubmed]
  4. The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Seo, S., Fujita, H., Nakano, A., Kang, M., Duarte, A., Kume, T. Dev. Biol. (2006) [Pubmed]
  5. Mediation of Sonic hedgehog-induced expression of COUP-TFII by a protein phosphatase. Krishnan, V., Pereira, F.A., Qiu, Y., Chen, C.H., Beachy, P.A., Tsai, S.Y., Tsai, M.J. Science (1997) [Pubmed]
  6. The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development. Pereira, F.A., Qiu, Y., Zhou, G., Tsai, M.J., Tsai, S.Y. Genes Dev. (1999) [Pubmed]
  7. Regulation of embryonic/fetal globin genes by nuclear hormone receptors: a novel perspective on hemoglobin switching. Filipe, A., Li, Q., Deveaux, S., Godin, I., Roméo, P.H., Stamatoyannopoulos, G., Mignotte, V. EMBO J. (1999) [Pubmed]
  8. Regulation of retinoic acid signaling during lung morphogenesis. Malpel, S., Mendelsohn, C., Cardoso, W.V. Development (2000) [Pubmed]
  9. Friend of GATA 2 physically interacts with chicken ovalbumin upstream promoter-TF2 (COUP-TF2) and COUP-TF3 and represses COUP-TF2-dependent activation of the atrial natriuretic factor promoter. Huggins, G.S., Bacani, C.J., Boltax, J., Aikawa, R., Leiden, J.M. J. Biol. Chem. (2001) [Pubmed]
  10. Interaction of the peroxisome proliferator-activated receptor alpha with the retinoid X receptor alpha unmasks a cryptic peroxisome proliferator response element that overlaps an ARP-1-binding site in the CYP4A6 promoter. Palmer, C.N., Hsu, M.H., Muerhoff, A.S., Griffin, K.J., Johnson, E.F. J. Biol. Chem. (1994) [Pubmed]
  11. Down-regulation of acyl-CoA oxidase gene expression in heart of troglitazone-treated mice through a mechanism involving chicken ovalbumin upstream promoter transcription factor II. Cabrero, A., Jové, M., Planavila, A., Merlos, M., Laguna, J.C., Vázquez-Carrera, M. Mol. Pharmacol. (2003) [Pubmed]
  12. The expression profiles of nuclear receptors in the developing and adult kidney. Suh, J.M., Yu, C.T., Tang, K., Tanaka, T., Kodama, T., Tsai, M.J., Tsai, S.Y. Mol. Endocrinol. (2006) [Pubmed]
  13. Cloning and expression during development of three murine members of the COUP family of nuclear orphan receptors. Jonk, L.J., de Jonge, M.E., Pals, C.E., Wissink, S., Vervaart, J.M., Schoorlemmer, J., Kruijer, W. Mech. Dev. (1994) [Pubmed]
  14. Expression of COUP-TFII in metabolic tissues during development. Zhang, P., Bennoun, M., Gogard, C., Bossard, P., Leclerc, I., Kahn, A., Vasseur-Cognet, M. Mech. Dev. (2002) [Pubmed]
  15. Essential role of chicken ovalbumin upstream promoter-transcription factor II in insulin secretion and insulin sensitivity revealed by conditional gene knockout. Bardoux, P., Zhang, P., Flamez, D., Perilhou, A., Lavin, T.A., Tanti, J.F., Hellemans, K., Gomas, E., Godard, C., Andreelli, F., Buccheri, M.A., Kahn, A., Le Marchand-Brustel, Y., Burcelin, R., Schuit, F., Vasseur-Cognet, M. Diabetes (2005) [Pubmed]
  16. The directly repeated RG(G/T)TCA motifs of the rat and mouse cellular retinol-binding protein II genes are promiscuous binding sites for RAR, RXR, HNF-4, and ARP-1 homo- and heterodimers. Nakshatri, H., Chambon, P. J. Biol. Chem. (1994) [Pubmed]
  17. Identification of a regulatory function for an orphan receptor in muscle: COUP-TF II affects the expression of the myoD gene family during myogenesis. Muscat, G.E., Rea, S., Downes, M. Nucleic Acids Res. (1995) [Pubmed]
  18. The orphan nuclear receptor, COUP-TF II, inhibits myogenesis by post-transcriptional regulation of MyoD function: COUP-TF II directly interacts with p300 and myoD. Bailey, P., Sartorelli, V., Hamamori, Y., Muscat, G.E. Nucleic Acids Res. (1998) [Pubmed]
  19. Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity. You, L.R., Lin, F.J., Lee, C.T., DeMayo, F.J., Tsai, M.J., Tsai, S.Y. Nature (2005) [Pubmed]
  20. Chromatin repression by COUP-TFII and HDAC dominates activation by NF-kappaB in regulating major histocompatibility complex class I transcription in adenovirus tumorigenic cells. Zhao, B., Hou, S., Ricciardi, R.P. Virology (2003) [Pubmed]
  21. The COUP-TF nuclear receptors regulate cell migration in the mammalian basal forebrain. Tripodi, M., Filosa, A., Armentano, M., Studer, M. Development (2004) [Pubmed]
  22. COUP-TFII is essential for radial and anteroposterior patterning of the stomach. Takamoto, N., You, L.R., Moses, K., Chiang, C., Zimmer, W.E., Schwartz, R.J., DeMayo, F.J., Tsai, M.J., Tsai, S.Y. Development (2005) [Pubmed]
  23. All-trans retinoic acid affects the expression of orphan receptors COUP-TF I and COUP-TF II in the developing neural tube. Brubaker, K., McMillan, M., Neuman, T., Nornes, H.O. Brain Res. Dev. Brain Res. (1996) [Pubmed]
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