TABLE 4

Rev-erbβ

Receptor nomenclature NR1D2
Receptor code 4.10.1:OR:1:D2
Other names EAR1β BD73, RVR, HZF-2
Molecular information Hs: 579aa, Q14995, chr. 3p241
Rn: 578aa, Q635042,3
Mm: 576aa, Q60674, chr. 14 B4,5
DNA binding
   Structure Monomer, homodimer
   HRE core sequence A/T A A/T N T PuGGTCA (DR-2, half-site)
Partners Rev-erbβ (physical, functional): DNA binding6
Agonists Homology modeling of the LBD of the NR1D subgroup suggests that the pocket is occupied by bulky side chains and cannot accommodate a classic ligand7
Antagonists
Coactivators NCOA58
Corepressors NCOR1, NCOA5810
Biologically important isoforms
Tissue distribution Heart, brain, lung, liver, skeletal muscle, kidney, spleen, testis, CNS (cerebellar cortex, dentate gyrus, hippocampus) {Hs, Mm} [Northern blot, Q-PCR, in situ hybridization, Western blot, immunohistology]13,11
Functional assays
Main target genes Repressed: Rev-erbα {Hs, Mm, Rn},12 N-Myc {Hs, Mm, Rn}13
Mutant phenotype
Human disease
  • aa, amino acids; chr., chromosome; HRE, hormone response element; CNS, central nervous system; Q-PCR, quantitative polymerase chain reaction

  • 1. Dumas B, Harding HP, Choi HS, Lehmann KA, Chung M, Lazar MA, and Moore DD (1994) A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb. Mol Endocrinol 8: 996-1005

  • 2. Forman BM, Chen J, Blumberg B, Kliewer SA, Henshaw R, Ong ES, and Evans RM (1994) Cross-talk among ROR α 1 and the Rev-erb family of orphan nuclear receptors. Mol Endocrinol 8: 1253-1261

  • 3. Retnakaran R, Flock G, and Giguere V (1994) Identification of RVR, a novel orphan nuclear receptor that acts as a negative transcriptional regulator. Mol Endocrinol 8: 1234-1244

  • 4. Enmark E, Kainu T, Pelto-Huikko M, and Gustafsson JA (1994) Identification of a novel member of the nuclear receptor superfamily which is closely related to Rev-ErbA. Biochem Biophys Res Commun 204: 49-56

  • 5. Pena de Ortiz S, Cannon MM, and Jamieson GA Jr (1994) Expression of nuclear hormone receptors within the rat hippocampus: identification of novel orphan receptors. Brain Res Mol Brain Res 23: 278-283

  • 6. Harding HP and Lazar MA (1995) The monomer-binding orphan receptor Rev-Erb represses transcription as a dimer on a novel direct repeat. Mol Cell Biol 15: 4791-4802

  • 7. Renaud JP, Harris JM, Downes M, Burke LJ, and Muscat GE (2000) Structure-function analysis of the Rev-erbA, and RVR ligand-binding domains reveals a large hydrophobic surface that mediates corepressor binding and a ligand cavity occupied by side chains. Mol Endocrinol 14: 700-717

  • 8. Sauve F, McBroom LD, Gallant J, Moraitis AN, Labrie F, and Giguere V (2001) CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant. Mol Cell Biol 21: 343-353

  • 9. Downes M, Burke LJ, Bailey PJ, and Muscat GE (1996) Two receptor interaction domains in the corepressor, N-CoR/RIP13, are required for an efficient interaction with Rev-erbAα and RVR: physical association is dependent on the E region of the orphan receptors. Nucleic Acids Res 24: 379-386

  • 10. Burke LJ, Downes M, Laudet V, and Muscat GE (1998) Identification and characterization of a novel corepressor interaction region in RVR and Rev-erbAα. Mol Endocrinol 12: 248-262

  • 11. Enmark E, Kainu T, Pelto-Huikko M, and Gustafsson JA (1994) Identification of a novel member of the nuclear receptor superfamily which is closely related to Rev-ErbA. Biochem Biophys Res Commun 204: 49-56

  • 12. Adelmant G, Begue A, Stehelin D, and Laudet V (1996) A functional Rev-erb α responsive element located in the human Rev-erb α promoter mediates a repressing activity. Proc Natl Acad Sci USA 93: 3553-3558

  • 13. Dussault I and Giguere V (1997) Differential regulation of the N-myc proto-oncogene by RORα and RVR, two orphan members of the superfamily of nuclear hormone receptors. Mol Cell Biol 17: 1860-1867