TABLE 6

RORβ

Receptor nomenclature NR1F2
Receptor code 4.10.1:OR:1:F2
Other names RZRβ, RORB
Molecular information Hs: 459aa, Q92753, chr. 9q21
Rn: 459aa, P45446, chr. 1q431
Mm: 459aa, Q8R1B8, chr. 19 B2
DNA binding
   Structure Monomer, homodimer
   HRE core sequence T/A A/T T/A C A/T A/GGGTCA (half-site)
Partners Nm23–2 (physical)3
Agonists
Antagonists ALRT 1550 (39 pM),* all-trans-retinoic acid (150 pM), all-trans-4-oxoretinoic acid (520 pM) [IC50]4
Coactivators NCOA15
Corepressors Nrip2, HR6,7
Biologically important isoforms RORβ2 {Rn}: differing in the N-terminal region, expression found only in the pineal gland and retina, more restricted DNA-binding properties, probably to regulate different sets of genes8
Tissue distribution Developmental: retina; adult: pineal gland, hypothalamus, thalamus, spinal cord, pituitary, eye (retinal progenitor cells), spleen {Hs, Mm, Rn} [Northern blot, in situ hybridization, immunohistology]9–11
Functional assays
Main target genes Activated: Bmal1 {Hs, Mm, Rn}12
Mutant phenotype Knockout mice exhibit duck-like gait, disrupted reproduction in males, disorganization of the retina resulting in blindness, and abnormal circadian rhythm {Mm} [knockout]9
Human disease

  • aa, amino acids; chr., chromosome; HRE, hormone response element; HR, hairless

  • ↵* Radioligand

  • ↵1. Becker-Andre M, Andre E, and DeLamarter JF (1993) Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences. Biochem Biophys Res Commun 194: 1371-1379

  • ↵2. Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, et al. (2002) Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci USA 99: 16899-16903

  • ↵3. Paravicini G, Steinmayr M, Andre E, and Becker-Andre M (1996) The metastasis suppressor candidate nucleotide diphosphate kinase NM23 specifically interacts with members of the ROR/RZR nuclear orphan receptor subfamily. Biochem Biophys Res Commun 227: 82-87

  • ↵4. Stehlin-Gaon C, Willmann D, Zeyer D, Sanglier S, Van Dorsselaer A, Renaud JP, Moras D, and Schule R (2003) All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR β. Nat Struct Biol 10: 820-825

  • ↵5. Stehlin C, Wurtz JM, Steinmetz A, Greiner E, Schule R, Moras D, and Renaud JP (2001) X-ray structure of the orphan nuclear receptor RORβ ligand-binding domain in the active conformation. EMBO (Eur Mol Biol Organ) J 20: 5822-5831

  • ↵6. Greiner EF, Kirfel J, Greschik H, Huang D, Becker P, Kapfhammer JP, and Schule R (2000) Differential ligand-dependent protein-protein interactions between nuclear receptors and a neuronal-specific cofactor. Proc Natl Acad Sci USA 97: 7160-7165

  • ↵7. Moraitis AN, Giguere V, and Thompson CC (2002) Novel mechanism of nuclear receptor corepressor interaction dictated by activation function 2 helix determinants. Mol Cell Biol 22: 6831-6841

  • ↵8. Andre E, Gawlas K, and Becker-Andre M (1998) A novel isoform of the orphan nuclear receptor RORβ is specifically expressed in pineal gland and retina. Gene 216: 277-283

  • ↵9. Andre E, Conquet F, Steinmayr M, Stratton SC, Porciatti V, and Becker-Andre M (1998) Disruption of retinoid-related orphan receptor β changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice. EMBO (Eur Mol Biol Organ) J 17: 3867-3877

  • ↵10. Becker-Andre M, Wiesenberg I, Schaeren-Wiemers N, Andre E, Missbach M, Saurat JH, and Carlberg C (1994) Pineal gland hormone melatonin binds and activates an orphan of the nuclear receptor superfamily. J Biol Chem 269: 28531-28534

  • ↵11. Schaeren-Wiemers N, Andre E, Kapfhammer JP, and Becker-Andre M (1997) The expression pattern of the orphan nuclear receptor RORβ in the developing and adult rat nervous system suggests a role in the processing of sensory information and in circadian rhythm. Eur J Neurosci 9: 2687-2701

  • ↵12. Guillaumond F, Dardente H, Giguere V, and Cermakian N (2005) Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors. J Biol Rhythms 20: 391-403