TABLE 10

TR2

Receptor nomenclature NR2C1
Receptor code 4.10.1:OR:2:C1
Other names TR2-11
Molecular information Hs: 603aa, Q15625, chr. 12q221
Rn: 590aa, Q8VIJ4, chr. 7q122
Mm: 590aa, Q505F1, chr. 10 C33
DNA binding
   Structure Homodimer, heterodimer
   HRE core sequence AGGTCA n AGGTCA (DR-1, DR-2, DR-3, DR-4, DR-5, DR-6)
Partners TR4 (physical, functional): DNA binding, exerts a stronger repressive activity than expressing either receptor alone2; AR (physical, functional): DNA binding, repression of TR2 target genes3; ER (physical, functional): DNA binding4
Agonists
Antagonists
Coactivators
Corepressors NRIP1, HDAC3, HDAC45,6
Biologically important isoforms TR2–5 {Hs}: shorter LBD1,7; TR2–7 {Hs}: lacking LBD1,7; TR2–9 {Hs}: shorter LBD1,7
Tissue distribution Developmental: testis (seminiferous tubules), kidney, and intestine; adult: prostate, liver, testis, seminal vesicle, and kidney {Mm, Rn} [Northern blot, in situ hybridization]1,7
Functional assays
Main target genes Activated: CNTFRα {Hs},2 aldolase A {Hs}8; repressed: HRH1 {Hs},9 EPO {Hs}10
Mutant phenotype Both male and female TR2 knockout mice are fertile; male mutants have functional testes, including normal sperm number and motility {Mm} [knockout]11
Human disease

  • aa, amino acids; chr., chromosome; HRE, hormone response element; CNTFR, ciliary neurotrophic factor receptor; EPO, erythropoietin

  • ↵1. Chang C, Kokontis J, Acakpo-Satchivi L, Liao S, Takeda H, and Chang Y (1989) Molecular cloning of new human TR2 receptors: a class of steroid receptor with multiple ligand-binding domains. Biochem Biophys Res Commun 165: 735-741

  • ↵2. Mu X and Chang C (2003) TR2 orphan receptor functions as negative modulator for androgen receptor in prostate cancer cells PC-3. Prostate 57: 129-133

  • ↵3. Young WJ, Lee YF, Smith SM, and Chang C (1998) A bidirectional regulation between the TR2/TR4 orphan receptors (TR2/TR4) and the ciliary neurotrophic factor (CNTF) signaling pathway. J Biol Chem 273: 20877-20885

  • ↵4. Hu YC, Shyr CR, Che W, Mu XM, Kim E, and Chang C (2002) Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor. J Biol Chem 277: 33571-33579

  • ↵5. Lee CH, Chinpaisal C, and Wei LN (1998) Cloning and characterization of mouse RIP140, a corepressor for nuclear orphan receptor TR2. Mol Cell Biol 18: 6745-6755

  • ↵6. Li G, Franco PJ, and Wei LN (2003) Identification of histone deacetylase-3 domains that interact with the orphan nuclear receptor TR2. Biochem Biophys Res Commun 310: 384-390

  • ↵7. Chang C and Kokontis J (1988) Identification of a new member of the steroid receptor super-family by cloning and sequence analysis. Biochem Biophys Res Commun 155: 971-977

  • ↵8. Chang C, Lee HJ, and Lee YF (1997) Identification of the human aldolase A gene as the first induced target for the TR2 orphan receptor, a member of the steroid hormone receptor superfamily. Biochem Biophys Res Commun 235: 205-211

  • ↵9. Lee HJ, Lee YF, and Chang C (1999) Identification of the histamine H1 receptor gene as a differentially repressed target of the human TR2 orphan receptor. Mol Cell Biochem 194: 199-207

  • ↵10. Lee HJ, Young WJ, Shih CY, and Chang C (1996) Suppression of the human erythropoietin gene expression by the TR2 orphan receptor, a member of the steroid receptor superfamily. J Biol Chem 271: 10405-10412

  • ↵11. Shyr CR, Collins LL, Mu XM, Platt KA, and Chang C (2002) Spermatogenesis and testis development are normal in mice lacking testicular orphan nuclear receptor 2. Mol Cell Biol 22: 4661-4666