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Target not currently curated in GtoImmuPdb
Target id: 613
Nomenclature: Testicular receptor 2
Systematic Nomenclature: NR2C1
Family: 2C. Testicular receptors
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 603 | 12q22 | NR2C1 | nuclear receptor subfamily 2 group C member 1 | 2 |
| Mouse | 590 | 10 48.81 cM | Nr2c1 | nuclear receptor subfamily 2, group C, member 1 | 12 |
| Rat | 590 | 7q13 | Nr2c1 | nuclear receptor subfamily 2, group C, member 1 | 10 |
| Previous and Unofficial Names |
| nuclear receptor subfamily 2 | Eenr | orphan nuclear receptor TR2 | orphan receptor, TR2-11 | TR2 |
| Database Links |
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| Alphafold | P13056 (Hs), Q505F1 (Mm), Q8VIJ4 (Rn) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL1961787 (Hs) |
| Ensembl Gene | ENSG00000120798 (Hs), ENSMUSG00000005897 (Mm), ENSRNOG00000006983 (Rn) |
| Entrez Gene | 7181 (Hs), 22025 (Mm), 252924 (Rn) |
| Human Protein Atlas | ENSG00000120798 (Hs) |
| KEGG Gene | hsa:7181 (Hs), mmu:22025 (Mm), rno:252924 (Rn) |
| OMIM | 601529 (Hs) |
| Pharos | P13056 (Hs) |
| RefSeq Nucleotide | NM_003297 (Hs), NM_001127362 (Hs), NM_001032287 (Hs), NM_011629 (Mm), NM_145780 (Rn) |
| RefSeq Protein | NP_001120834 (Hs), NP_003288 (Hs), NP_001027458 (Hs), NP_035759 (Mm), NP_665723 (Rn) |
| UniProtKB | P13056 (Hs), Q505F1 (Mm), Q8VIJ4 (Rn) |
| Wikipedia | NR2C1 (Hs) |
| Natural/Endogenous Ligands |
| Comments: Orphan |
| DNA Binding |
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| DNA Binding Comments | |||||||
| TR2 is able to form heterodimers with TR4 on a DR5 element. TR2 interact with DR element with different spacing with the following preference: DR1>DR2>DR5=DR4=DR6>DR3 | |||||||
| Co-binding Partners |
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| Name | Interaction | Effect | Reference |
| Androgen receptor | Physical, Functional | DNA binding and AR can heterodimerize with TR2, and function as a repressor to down-regulate TR2 target genes by preventing the binding of TR2 to those genes. Reciprocally, TR2 can repress AR target gene expression. | 10 |
| Testicular receptor 4 | Physical, Functional | DNA binding, TR2 and TR4 form heterodimers. The dimerization interface is localized in the ligand-binding domains, and three leucine residues in helix H10 are critical for this interaction. Coexpression of TR2 and TR4 exerts a stronger repressive activity than expressing either receptor alone in a reporter gene assay. | 12 |
| Estrogen receptor-α | Physical, Functional | DNA binding | 5 |
| Main Co-regulators |
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| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| NRIP1 | Co-repressor | No | No | Yes | 6 | |
| HDAC3 | Co-repressor | No | No | No | 9 | |
| HDAC4 | Co-repressor | Yes | No | No | 9 | |
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| Aldolase A | Human | Activated | Transient transfection, EMSA | Aldolase A: TR2 was identified as an M1 site binding protein of the muscle-specific pM promoter in the human aldolase A gene | 3 |
| EPO | Human | Repressed | Transient transfection, EMSA | EPO: A TR2RE-EPO has been identified in the 3 minimal hypoxia-inducible enhancer of the human erythropoietin (EPO) gene. | 8 |
| histamine receptor H1 | Human | Repressed | Transient transfection, EMSA, Other | Histamine H1 receptor: A DNA response element (TR2RE-HR) in the 3 flanking region of the human histamine H1 receptor (HR) gene was identified as a target for human TR2 | 7 |
| CNTFRa | Human | Activated | Transient transfection, EMSA | 12 | |
| Main Target Genes Comments | |||||
| Human papillomavirus type 16:- TR2 can bind to a DR4 response element in the HPV-16 promoter, and potentiate HPV transcriptional activity in a dose-dependent manner [4]. | |||||
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||||
| The first studies on rat TR2 gene expression detected a transcript of 2.5 kb in prostate, liver, testis, seminal vesicle and kidney and suggest that the transcript observed in prostate was negatively regulated by androgens. A prominent testis expression was described in mouse although the expression was also observed in numerous other tissues. The very high expression in testis was confirmed by subsequent studies that also demonstrate that TR2 expression starts at E8.5 days of development, reaches a maximal level at E12.5 and declines at E14.5. The corresponding protein was located in the seminiferous tubules where advanced germ cells reside. In situ hybridisation located TR2 expression in many mouse tissues including kidney and intestine during late embryogenesis. It was shown that TR2 expression is down-regulated by ionising irradiation and that this effect is mediated by p53 which behaves as a down-regulator of TR2 expression. A regulation of TR2 expression by retinoic acid was suggested since mice fed with vitamin-A depleted diet exhibit no germ cells and no TR2 expression in testis. | ||||||||||
| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||
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| Biologically Significant Variants
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1. Chang C, Kokontis J. (1988) Identification of a new member of the steroid receptor super-family by cloning and sequence analysis. Biochem Biophys Res Commun, 155 (2): 971-7. [PMID:3421977]
2. Chang C, Kokontis J, Acakpo-Satchivi L, Liao S, Takeda H, 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 (2): 735-41. [PMID:2597158]
3. Chang C, Lee HJ, 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 (1): 205-11. [PMID:9196064]
4. Collins LL, Lin DL, Mu XM, Chang C. (2001) Feedback regulation between orphan nuclear receptor TR2 and human papilloma virus type 16. J Biol Chem, 276 (29): 27316-21. [PMID:11358973]
5. Hu YC, Shyr CR, Che W, Mu XM, Kim E, Chang C. (2002) Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor. J Biol Chem, 277 (37): 33571-9. [PMID:12093804]
6. Lee CH, Chinpaisal C, Wei LN. (1998) Cloning and characterization of mouse RIP140, a corepressor for nuclear orphan receptor TR2. Mol Cell Biol, 18 (11): 6745-55. [PMID:9774688]
7. Lee HJ, Lee YF, 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 (1-2): 199-207. [PMID:10391141]
8. Lee HJ, Young WJ, Shih CY, 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 (17): 10405-12. [PMID:8626614]
9. Li G, Franco PJ, Wei LN. (2003) Identification of histone deacetylase-3 domains that interact with the orphan nuclear receptor TR2. Biochem Biophys Res Commun, 310 (2): 384-90. [PMID:14521922]
10. Mu X, Chang C. (2003) TR2 orphan receptor functions as negative modulator for androgen receptor in prostate cancer cells PC-3. Prostate, 57 (2): 129-33. [PMID:12949936]
11. Shyr CR, Collins LL, Mu XM, Platt KA, Chang C. (2002) Spermatogenesis and testis development are normal in mice lacking testicular orphan nuclear receptor 2. Mol Cell Biol, 22 (13): 4661-6. [PMID:12052874]
12. Young WJ, Lee YF, Smith SM, 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 (33): 20877-85. [PMID:9694834]
2C. Testicular receptors: Testicular receptor 2. Last modified on 07/08/2019. Accessed on 05/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=613.
