TABLE 7

RORγ

Receptor nomenclature NR1F3
Receptor code 4.10.1:OR:1:F3
Other names TOR, RORC
Molecular information Hs: 518aa, P51449, chr. 1q211
Rn: 508aa, chr. 2q34
Mm: 516aa, P51450, chr. 3 F22
DNA binding
   Structure Homodimer
   HRE core sequence AGGTCA nnnnn AGGTCA (DR-4, DR-5, half-site)
Partners Mi-2β (physical, functional): inhibition of RORγ transcriptional activity3
Agonists
Antagonists ALRT 1550, 4 all-trans-retinoic acid4
Coactivators NCOA15
Corepressors HR6
Biologically important isoforms RORγb {Hs, Mm}: differs in the 5′-UTR and coding region; resulting isoform is shorter and has a distinct N terminus7
Tissue distribution Skeletal muscle, thymus, testis, pancreas, prostate, heart, liver, tongue, diaphragm; no expression found in the spleen or bone marrow {Hs, Mm, Rn} [Northern blot, in situ hybridization, immunohistology]1,2,8,9
Functional assays
Main target genes
Mutant phenotype Homozygous mutants lack peripheral and mesenteric lymph nodes and Peyer's patches, reduced numbers of thymocytes and increased apoptosis with loss of thymic expression of antiapoptotic factor Bcl-xL {Mm} [knockout]10
Human disease

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

  • ↵1. Hirose T, Smith RJ, and Jetten AM (1994) RORγ: the third member of ROR/RZR orphan receptor subfamily that is highly expressed in skeletal muscle. Biochem Biophys Res Commun 205: 1976-1983

  • ↵2. Ortiz MA, Piedrafita FJ, Pfahl M, and Maki R (1995) TOR: a new orphan receptor expressed in the thymus that can modulate retinoid and thyroid hormone signals. Mol Endocrinol 9: 1679-1691

  • ↵3. Johnson DR, Lovett JM, Hirsch M, Xia F, and Chen JD (2004) NuRD complex component Mi-2β binds to and represses RORγ -mediated transcriptional activation. Biochem Biophys Res Commun 318: 714-718

  • ↵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 RORβ. Nat Struct Biol 10: 820-825

  • ↵5. Kurebayashi S, Nakajima T, Kim SC, Chang CY, McDonnell DP, Renaud JP, and Jetten AM (2004) Selective LXXLL peptides antagonize transcriptional activation by the retinoid-related orphan receptor RORγ. Biochem Biophys Res Commun 315: 919-927

  • ↵6. 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

  • ↵7. He YW, Deftos ML, Ojala EW, and Bevan MJ (1998) RORγ t, a novel isoform of an orphan receptor, negatively regulates Fas ligand expression and IL-2 production in T cells. Immunity 9: 797-806

  • ↵8. Eberl G, and Littman DR (2003) The role of the nuclear hormone receptor RORgammat in the development of lymph nodes and Peyer's patches. Immunol Rev 195: 81-90

  • ↵9. Eberl G, Marmon S, Sunshine MJ, Rennert PD, Choi Y, and Littman DR (2004) An essential function for the nuclear receptor RORγt in the generation of fetal lymphoid tissue inducer cells. Nat Immunol 5: 64-73

  • ↵10. Sun Z, Unutmaz D, Zou YR, Sunshine MJ, Pierani A, Brenner-Morton S, Mebius RE, and Littman DR (2000) Requirement for RORγ in thymocyte survival and lymphoid organ development. Science (Wash DC) 288: 2369-2373