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