Receptor nomenclature NR2F2
Receptor code 4.10.1:OR:2:F2
Other names COUPβ, COUP-TFB, ARP1, SVP40
Molecular information Hs: 414aa, P24468, chr. 15q261
Rn: 414aa, O09018, chr. 1q0.31
Mm: 414aa, P43135, chr. 72
DNA binding
   Structure Homodimer, heterodimer
   HRE core sequence A/GGGTCA n AGGGTCA (DR-0, DR-1, DR-3, DR-4, DR-5, DR-6, DR-8, DR-10, DR-11, palindrome, inverted repeats)
Partners RXR (physical): sequesters RXR partners, thereby reducing its availability for use by TR, VDR, RAR, and PPAR receptors35; HNF-4 (physical, functional): transactivation, competition for DNA binding68; EAR2 (physical)9; RAR10; TR10
Coactivators BCL11B, SQSTM111,12
Corepressors NCOR1, NCOR2, BCL11A11,13
Biologically important isoforms
Tissue distribution Developmental: at 7.5 days postcoitum expression identical to that of COUP-TFI except for a set of neuromeres in the diencephalic neuromeres, rhombomeres in the hindbrain, and expression restricted to motorneurons in the neural tube; COUP-TFII expression is greater than that of COUP-TFI in salivary gland, lung, esophagus, stomach, pancreas, kidney, and prostate but less than that of COUP-TFI in the testis, ovary, retina, skin, inner ear, or limb bud {Hs, Mm, Rn} [Northern blot, in situ hybridization, Western blot]1,14
Functional assays
Main target genes Activated: CYP7A {Hs, Mm, Rn},1520 arrestin {Hs, Mm, Rn}21; repressed: Apo AI {Hs, Mm, Rn},1,22,23 MHC class I {Mm}2426
Mutant phenotype Homozygous mutants die around embryonic day 10 with growth retardation, hemorrhage, and edema; histological analysis revealed enlarged blood vessels, lack of normal heart development, and malformed cardinal veins; two-thirds of heterozygous mutants die during the first weeks of life with growth and reproductive defects due to reduced expression of enzymes important for progesterone synthesis in the ovary and defective decidual response in the uterus {Mm} [knockout]2731
Human disease
  • aa, amino acids; chr., chromosome; HRE, hormone response element; VDR, vitamin D receptor; MHC, major histocompatibility class

  • 1. Ladias JA and Karathanasis SK (1991) Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily. Science (Wash DC) 251: 561-565

  • 2. Qiu Y, Cooney AJ, Kuratani S, DeMayo FJ, Tsai SY, and Tsai MJ (1994) Spatiotemporal expression patterns of chicken ovalbumin upstream promoter-transcription factors in the developing mouse central nervous system: evidence for a role in segmental patterning of the diencephalon. Proc Natl Acad Sci USA 91: 4451-4455

  • 3. Kliewer SA, Umesono K, Heyman RA, Mangelsdorf DJ, Dyck JA, and Evans RM (1992) Retinoid X receptor-COUP-TF interactions modulate retinoic acid signaling. Proc Natl Acad Sci USA 89: 1448-1452

  • 4. Cooney AJ, Tsai SY, O'Malley BW, and Tsai MJ (1992) Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors. Mol Cell Biol 12: 4153-4163

  • 5. Tran P, Zhang XK, Salbert G, Hermann T, Lehmann JM, and Pfahl M (1992) COUP orphan receptors are negative regulators of retinoic acid response pathways. Mol Cell Biol 12: 4666-4676

  • 6. Schaeffer E, Guillou F, Part D, and Zakin MM (1993) A different combination of transcription factors modulates the expression of the human transferrin promoter in liver and Sertoli cells. J Biol Chem 268: 23399-23408

  • 7. Ktistaki E and Talianidis I (1997) Chicken ovalbumin upstream promoter transcription factors act as auxiliary cofactors for hepatocyte nuclear factor 4 and enhance hepatic gene expression. Mol Cell Biol 17: 2790-2797

  • 8. Sugiyama T, Wang JC, Scott DK, and Granner DK (2000) Transcription activation by the orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI): definition of the domain involved in the glucocorticoid response of the phosphoenolpyruvate carboxykinase gene. J Biol Chem 275: 3446-3454

  • 9. 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

  • 10. Leng X, Cooney AJ, Tsai SY, and Tsai SY (1996) Molecular mechanisms of COUP-TF-mediated transcriptional repression: evidence for transrepression and active repression. Mol Cell Biol 16: 2332-2340

  • 11. Avram D, Fields A, Pretty On Top K, Nevrivy DJ, Ishmael JE, and Leid M (2000) Isolation of a novel family of C2H2 zinc finger proteins implicated in transcriptional repression mediated by chicken ovalbumin upstream promoter transcription factor (COUP-TF) orphan nuclear receptors. J Biol Chem 275: 10315-10322

  • 12. Marcus SL, Winrow CJ, Capone JP, and Rachubinski RA (1996) A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor. J Biol Chem 271: 27197-27200

  • 13. Shibata H, Nawaz Z, Tsai SY, O'Malley BW, and Tsai MJ (1997) Gene silencing by chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI) is mediated by transcriptional corepressors, nuclear receptor-corepressor (N-CoR) and silencing mediator for retinoic acid receptor and thyroid hormone receptor (SMRT). Mol Endocrinol 11: 714-724

  • 14. Lutz B, Kuratani S, Cooney AJ, Wawersik S, Tsai SY, Eichele G, and Tsai MJ (1994) Developmental regulation of the orphan receptor COUP-TF II gene in spinal motor neurons. Development 120: 25-36

  • 15. De Martino MU, Alesci S, Chrousos GP, and Kino T (2004) Interaction of the glucocorticoid receptor and the chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII): implications for the actions of glucocorticoids on glucose, lipoprotein, and xenobiotic metabolism. Ann NY Acad Sci 1024: 72-85

  • 16. Kang S, Spann NJ, Hui TY, and Davis RA (2003) ARP-1/COUP-TF II determines hepatoma phenotype by acting as both a transcriptional repressor of microsomal triglyceride transfer protein and an inducer of CYP7A1. J Biol Chem 278: 30478-30486

  • 17. Stroup D and Chiang JY (2000) HNF4 and COUP-TFII interact to modulate transcription of the cholesterol 7α -hydroxylase gene (CYP7A1). J Lipid Res 41: 1-11

  • 18. Chen J, Cooper AD, and Levy-Wilson B (1999) Hepatocyte nuclear factor 1 binds to and transactivates the human but not the rat CYP7A1 promoter. Biochem Biophys Res Commun 260: 829-834

  • 19. Crestani M, Sadeghpour A, Stroup D, Galli G, and Chiang JY (1998) Transcriptional activation of the cholesterol 7α -hydroxylase gene (CYP7A) by nuclear hormone receptors. J Lipid Res 39: 2192-2200

  • 20. Stroup D, Crestani M, and Chiang JY (1997) Orphan receptors chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and retinoid X receptor (RXR) activate and bind the rat cholesterol 7α -hydroxylase gene (CYP7A). J Biol Chem 272: 9833-9839

  • 21. Lu XP, Salbert G, and Pfahl M (1994) An evolutionary conserved COUP-TF binding element in a neural-specific gene and COUP-TF expression patterns support a major role for COUP-TF in neural development. Mol Endocrinol 8: 1774-1788

  • 22. Ge R, Rhee M, Malik S, and Karathanasis SK (1994) Transcriptional repression of apolipoprotein AI gene expression by orphan receptor ARP-1. J Biol Chem 269: 13185-13192

  • 23. Widom RL, Rhee M, and Karathanasis SK (1992) Repression by ARP-1 sensitizes apolipoprotein AI gene responsiveness to RXRα and retinoic acid. Mol Cell Biol 12: 3380-3389

  • 24. Zhao B, Hou S, and Ricciardi RP (2003) Chromatin repression by COUP-TFII and HDAC dominates activation by NF-κ B in regulating major histocompatibility complex class I transcription in adenovirus tumorigenic cells. Virology 306: 68-76

  • 25. Smirnov DA, Hou S, Liu X, Claudio E, Siebenlist UK, and Ricciardi RP (2001) Coup-TFII is up-regulated in adenovirus type 12 tumorigenic cells and is a repressor of MHC class I transcription. Virology 284: 13-19

  • 26. Kushner DB, Pereira DS, Liu X, Graham FL, and Ricciardi RP (1996) The first exon of Ad12 E1A excluding the transactivation domain mediates differential binding of COUP-TF and NF-κ B to the MHC class I enhancer in transformed cells. Oncogene 12: 143-151

  • 27. Pereira FA, Qiu Y, Zhou G, Tsai MJ, and Tsai SY (1999) The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development. Genes Dev 13: 1037-1049

  • 28. You LR, Takamoto N, Yu CT, Tanaka T, Kodama T, Demayo FJ, Tsai SY, and Tsai MJ (2005) Mouse lacking COUP-TFII as an animal model of Bochdalek-type congenital diaphragmatic hernia. Proc Natl Acad Sci USA 102: 16351-16356

  • 29. Takamoto N, You LR, Moses K, Chiang C, Zimmer WE, Schwartz RJ, DeMayo FJ, Tsai MJ, and Tsai SY (2005) COUP-TFII is essential for radial and anteroposterior patterning of the stomach. Development 132: 2179-2189

  • 30. Takamoto N, Kurihara I, Lee K, Demayo FJ, Tsai MJ, and Tsai SY (2005) Haploinsufficiency of chicken ovalbumin upstream promoter transcription factor II in female reproduction. Mol Endocrinol 19: 2299-2308

  • 31. Lee CT, Li L, Takamoto N, Martin JF, Demayo FJ, Tsai MJ, and Tsai SY (2004) The nuclear orphan receptor COUP-TFII is required for limb and skeletal muscle development. Mol Cell Biol 24: 10835-10843