Receptor nomenclature | NR6A1 |
Receptor code | 4.1:OR:6:A1 |
Other names | RTR, NCNF, TRIF |
Molecular information | Hs: 480aa, Q15406, chr. 9q331–5 |
Rn: 453aa, chr. 3q116 | |
Mm: 495aa, Q64249, chr. 2 B7–11 | |
DNA binding | |
Structure | Homodimer |
HRE core sequence | TCA AGGTCA (DR-0, half-site)7,11–19 |
Partners | SF-1 (functional): DNA binding7,17,1 9; CREMτ (functional): DNA binding20; ERRα, ERRβ, ERRγ (functional): DNA binding21; COUP-TFI, COUP-TFII (functional): DNA binding19; LRH-1 (functional): DNA binding22 |
Agonists | |
Antagonists | |
Coactivators | RAP8023 |
Corepressors | NCOR1, NCOR219,24 |
Biologically important isoforms | GCNF2 {Hs}: uses two alternate in-frame splice sites resulting in an isoform that has the same N and C termini but is shorter than GCNF5; GCNF3 {Hs}: this variant lacks an alternate in-frame segment and uses an alternate in-frame splice site, resulting in an isoform that has the same N and C termini but is shorter than GCNF5 |
Tissue distribution | Developmental: brain, ectodermal cells, primitive streak, nervous system; adult: testis, ovary, liver, kidney, germ cells {Hs, Mm, Rn} [Northern blot, in situ hybridization, Western blot, immunohistology]1,2,6–9,17,19,25–29 |
Functional assays | |
Main target genes | Repressed: Oct4 {Hs, Mm, Rn},17,19 PRM1 {Mm},20 PRM2 {Mm},20 BMP15 {Mm},30 GDF-9 {Mm}30 |
Mutant phenotype | Homozygote GCNF-null mice have cardiovascular abnormalities, defective trunk development, impaired somite formation, failure to turn, open neural tube, hindgut, protrusion of the tailbud outside the yolk sac, and die by embryonic day 10.5 {Mm} [knockout]17,19,28,31; hypofertility because of prolonged diestrus phase of the estrous cycle and aberrant steroidogenesis {Mm} [tissue-specific Cre/Lox knockout in the oocyte]30 |
Human disease |
aa, amino acids; chr., chromosome; HRE, hormone response element; CREM, cAMP-response element modulator
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↵22. Gu P, Goodwin B, Chung AC, Xu X, Wheeler DA, Price RR, Galardi C, Peng L, Latour AM, Koller BH, et al. (2005) Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development. Mol Cell Biol 25: 3492-3505
↵23. Yan Z, Kim YS, and Jetten AM (2002) RAP80, a novel nuclear protein that interacts with the retinoid-related testis-associated receptor. J Biol Chem 277: 32379-32388
↵24. Yan Z and Jetten AM (2000) Characterization of the repressor function of the nuclear orphan receptor retinoid receptor-related testis-associated receptor/germ cell nuclear factor. J Biol Chem 275: 35077-35085
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↵28. Chung AC, Katz D, Pereira FA, Jackson KJ, DeMayo FJ, Cooney AJ, and 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: 663-677
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↵31. Lan ZJ, Chung AC, Xu X, DeMayo FJ, and Cooney AJ (2002) The embryonic function of germ cell nuclear factor is dependent on the DNA binding domain. J Biol Chem 277: 50660-50667