Germ cell nuclear factor
Target id: 634
Nomenclature: Germ cell nuclear factor
Systematic Nomenclature: NR6A1
Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Natural/Endogenous Ligands
- DNA Binding
- Co-binding Partners
- Main Co-regulators
- Main Target Genes
- Tissue Distribution
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Biologically Significant Variants
- References
- How to cite this page
Gene and Protein Information  |
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| Species | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 480 | 9q33.3 | NR6A1 | nuclear receptor subfamily 6 group A member 1 | 1,14,19-20,22 |
| Mouse | 495 | 2 B | Nr6a1 | nuclear receptor subfamily 6, group A, member 1 | 23-24,29 |
| Rat | 438 | 3q12 | Nr6a1 | nuclear receptor subfamily 6, group A, member 1 | 29 |
| Previous and Unofficial Names |
| GCNF1 | GCNF | RTR | NCNF | retinoid receptor-related testis-specific receptor | nuclear receptor subfamily 6 |
| Database Links |
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| Alphafold | Q15406 (Hs), Q64249 (Mm), E9PSV7 (Rn) |
| CATH/Gene3D | 3.30.50.10 |
| ChEMBL Target | CHEMBL1961793 (Hs) |
| Ensembl Gene | ENSG00000148200 (Hs), ENSMUSG00000063972 (Mm), ENSRNOG00000013232 (Rn) |
| Entrez Gene | 2649 (Hs), 14536 (Mm), 362125 (Rn) |
| Human Protein Atlas | ENSG00000148200 (Hs) |
| KEGG Gene | hsa:2649 (Hs), mmu:14536 (Mm), rno:362125 (Rn) |
| OMIM | 602778 (Hs) |
| Pharos | Q15406 (Hs) |
| RefSeq Nucleotide | NM_001489 (Hs), NM_010264 (Mm), NM_001159548 (Mm), NM_001159549 (Mm) |
| RefSeq Protein | NP_201591 (Hs), NP_034394 (Mm) |
| UniProtKB | Q15406 (Hs), Q64249 (Mm), E9PSV7 (Rn) |
| Wikipedia | NR6A1 (Hs) |
| Natural/Endogenous Ligands |
| Comments: Orphan |
| DNA Binding |
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| DNA Binding Comments | |||||||
| GCNF has been shown to bind to DNA on extended half site sequences identical to the SF-1 response element (SFRE : TCA AGGTCA) [3,8,13,24]). Binding to DRO element (AGGTCA AGGTCA ; which also encompasses the SFRE) was also observed, apparently with a better affinity [8,13,24,27]. PCR-coupled EMSA selection of specific binding sites indicated that the preferential target sequence is : TCA AG(G/T)TCA [27]. Although recombinant GCNF has been shown to bind DNA as a homodimer, endogenous GCNF binds DNA as hexamer first identified as the TRIF complex in P19 and ES cells [2,5-7,10]. No interaction with RXR has been detected [2,5]. | |||||||
| Co-binding Partners |
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| Name | Interaction | Effect | Reference |
| Steroidogenic factor 1 | Functional | DNA binding | 3,5-6 |
| Estrogen-related receptor-α | Functional | DNA binding | 12 |
| Estrogen-related receptor-β | Functional | DNA binding | 12 |
| Estrogen-related receptor-γ | Functional | DNA binding | 12 |
| COUP-TF1 | Functional | DNA binding | 6 |
| COUP-TF2 | Functional | DNA binding | 6 |
| Liver receptor homolog-1 | Functional | DNA binding | 9 |
| CREM tau | Functional | DNA binding | 12 |
| Main Co-regulators |
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| Name | Activity | Specific | Ligand dependent | AF-2 dependent | Comments | References |
| NCOR1 | Co-repressor | No | No | No | 6,25 | |
| NCOR2 | Co-repressor | - | No | No | 6,25 | |
| UIMC1 | Other | Yes | No | - | RAP80 interaction inhibits GCNF/NCoR interaction | 26 |
| Main Target Genes |
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| Name | Species | Effect | Technique | Comments | References |
| Gdf9 | Mouse | Repressed | Transient transfection,EMSA ,Other | Repression of GDF9 was validated in CreLox KO of GCNF in the oocyte. GCNF also represses expression of Nanog upon ES cell differentiation through binding to DR0 elements in the promoter and 3' untranslated region. | 18 |
| POU5F1 | Human | Repressed | ChIP, Transient transfection, EMSA, Other | GCNF represses Oct4 expression upon RA induced differentiation (also shown in mice and rat) | 5-7 |
| Prm1 | Mouse | Repressed | Transient transfection, EMSA | 13 | |
| Prm2 | Mouse | Repressed | Transient transfection, EMSA | 5 | |
| Bmp15 | Mouse | Repressed | Transient transfection, EMSA, Other | Repression of BMP15 was validated in CreLox KO of GCNF in the oocyte | 18 |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| This gene is also expressed in mice and rat. In the mouse two mRNA (7.5 and 2.4 kb) were observed due to the differential use of alternative polyadenylation sites [3,11,15,28]. In human the size of the smaller transcript is 2.2 kb [1,14,19-20,22]. Expression of GCNF in embryos and in developping brain was observed in the mouse. GCNF expression is induced in embryonic stem cells and embryocarcinoma cell lines by retinoic acid and subsequently repressed but its expression is repressed upon differentiation. Northern blot analysis has also demonstrated expression of GCNF during mouse gastrulation and early organogenesis. In situ hybridization revealed that the early expression is localized in ectodermal cells as well as in the primitive streak . At later developmental stages, the expression appears to be more restricted to the cells of the developing nervous system. In adult, the first expression studies carried out in the mouse has revealed a very narrow expression pattern in testis with very low levels in ovary, liver and kidney. In situ hybridization studies have shown a specific expression in both male and female germ cells, both in mouse and human. Northern blot analysis allowed precise determination of the expression stage of GCNF during male germ cell differentiation to the round spermatid stage. More recently, it has been shown both at the RNA and protein levels that in adult mouse testis GCNF is expressed in late pachytene spermatocytes and round spermatids. This suggests a role of GCNF in regulating both meoitic and post-meiotic events. | ||||||||
| 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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References
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2. Borgmeyer U. (1997) Dimeric binding of the mouse germ cell nuclear factor. Eur J Biochem, 244 (1): 120-7. [PMID:9063454]
3. Chen F, Cooney AJ, Wang Y, Law SW, O'Malley BW. (1994) Cloning of a novel orphan receptor (GCNF) expressed during germ cell development. Mol Endocrinol, 8 (10): 1434-44. [PMID:7854358]
4. Chung AC, Katz D, Pereira FA, Jackson KJ, DeMayo FJ, Cooney AJ, O'Malley BW. (2001) Loss of orphan receptor germ cell nuclear factor function results in ectopic development of the tail bud and a novel posterior truncation. Mol Cell Biol, 21 (2): 663-77. [PMID:11134352]
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18. Lan ZJ, Gu P, Xu X, Jackson KJ, DeMayo FJ, O'Malley BW, Cooney AJ. (2003) GCNF-dependent repression of BMP-15 and GDF-9 mediates gamete regulation of female fertility. EMBO J, 22 (16): 4070-81. [PMID:12912906]
19. Lei W, Hirose T, Zhang LX, Adachi H, Spinella MJ, Dmitrovsky E, Jetten AM. (1997) Cloning of the human orphan receptor germ cell nuclear factor/retinoid receptor-related testis-associated receptor and its differential regulation during embryonal carcinoma cell differentiation. J Mol Endocrinol, 18 (2): 167-76. [PMID:9134503]
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27. Yan ZH, Medvedev A, Hirose T, Gotoh H, Jetten AM. (1997) Characterization of the response element and DNA binding properties of the nuclear orphan receptor germ cell nuclear factor/retinoid receptor-related testis-associated receptor. J Biol Chem, 272 (16): 10565-72. [PMID:9099702]
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How to cite this page
6A. Germ cell nuclear factor receptors: Germ cell nuclear factor. Last modified on 22/03/2016. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=634.
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