Alternative titles; symbols
HGNC Approved Gene Symbol: NR2C1
Cytogenetic location: 12q22 Genomic coordinates (GRCh38): 12:95,020,229-95,073,618 (from NCBI)
Chang and Kokontis (1988) used an oligonucleotide probe based on the zinc finger DNA-binding domain of steroid receptors to isolate a putative steroid receptor, termed TR2, from a human testis cDNA library. Subsequent studies (Chang et al., 1989) showed that several splice variants of TR2 exist and the original TR2 clone was renamed TR2-5. Northern blot analysis by Chang and Kokontis (1988) showed that TR2-5 produced a 2.5-kb transcript that was abundant in androgen-sensitive organs, such as ventral prostate and seminal vesicle. Dot blot hybridization indicated that TR2-5 mRNA levels increased after castration of rats and that this increase was reversed by 5-alpha-dihydrotestosterone injection. Expression of TR2-5 resulted in a 52-kD protein.
Chang et al. (1989) described 4 splice variants of the TR2 gene, TR2-5, TR2-7, TR2-9, and TR2-11, which encode proteins of 483, 184, 467, and 603 amino acids, respectively. All were isolated from human testis or prostate cDNA libraries. The DNA-binding domains of the 4 variants are identical and share 50 to 60% amino acid identity with other steroid receptors. The TR2-7 receptor has no apparent hormone-binding region, whereas the other 3 variants have the same hormone-binding region followed by variant C termini. In vitro transcription and translation of the TR2-11 receptor indicated that this receptor did not bind any known steroids, suggesting to Chang et al. (1989) that this receptor could be steroid independent or dependent on an unknown hormone. The authors noted that the identity of the DNA-binding regions of these receptors suggests that they regulate the same target gene(s), but the differences in the C termini may allow them to bind different ligands or bind the same ligand with differing affinities. By analogy to the splice variants of the thyroid hormone receptor, the authors suggested that the expression ratio of the TR2 splice variants could vary in a tissue-specific or developmental stage-specific manner regulated at the level of RNA splicing.
Using yeast 2-hybrid analysis, Lee et al. (1998) identified an interaction between mouse Tr2 and Rip140 (NRIP1; 602490). By mutation analysis, they determined that the LxxLL motifs of mouse Rip140 interacted with the activation function-2 region of Tr2. Coimmunoprecipitation experiments detected interaction between the 2 proteins in cell extracts. Rip140 repressed binding of Tr2 to target DNA. In the presence of Rip140, Tr2 translocated into the nucleus.
The International Radiation Hybrid Mapping Consortium mapped the NR2C1 gene to chromosome 12 (STS-H68838).
Shyr et al. (2002) detected Tr2 expression in mice at 3 weeks of age, and the expression was restricted mainly to spermatocytes and round spermatids. They found that mice lacking Tr2 were viable with no serious developmental defects. Male mice lacking Tr2 had functional testes, including normal sperm number and motility, and both male and female mice lacking Tr2 were fertile.
Chang, C., Kokontis, J. Identification of a new member of the steroid receptor super-family by cloning and sequence analysis. Biochem. Biophys. Res. Commun. 155: 971-977, 1988. [PubMed: 3421977] [Full Text: https://doi.org/10.1016/s0006-291x(88)80591-6]
Chang, C., Kokontis, J., Acakpo-Satchivi, L., Liao, S., Takeda, H., Chang, Y. Molecular cloning of new human TR2 receptors: a class of steroid receptor with multiple ligand-binding domains. Biochem. Biophys. Res. Commun. 165: 735-741, 1989. [PubMed: 2597158] [Full Text: https://doi.org/10.1016/s0006-291x(89)80028-2]
Lee, C.-H., Chinpaisal, C., Wei, L.-N. Cloning and characterization of mouse RIP140, a corepressor for nuclear orphan receptor TR2. Molec. Cell. Biol. 18: 6745-6755, 1998. [PubMed: 9774688] [Full Text: https://doi.org/10.1128/MCB.18.11.6745]
Shyr, C.-R., Collins, L. L., Mu, X.-M., Platt, K. A., Chang, C. Spermatogenesis and testis development are normal in mice lacking testicular orphan nuclear receptor 2. Molec. Cell. Biol. 22: 4661-4666, 2002. [PubMed: 12052874] [Full Text: https://doi.org/10.1128/MCB.22.13.4661-4666.2002]