Receptor nomenclature NR2E3
Receptor code 4.10.1:OR:2:E3
Other names RNR
Molecular information Hs: 410aa, Q9Y5X4, chr. 15q231
Mm: 395aa, Q9QXZ7, chr. 9 B2
DNA binding
   Structure Homodimer
   HRE core sequence AAGTCA n AAGTCA (DR-1)1
Partners Crx (physical): PNR and Crx interact via the DBD of each protein; the promoter/enhancer occupancy of PNR is Crx-dependent, suggesting that PNR is associated with photoreceptor gene targets by interacting with Crx3
Biologically important isoforms PNRα {Hs}: this is the longest transcript, but it encodes the shorter isoform; PNRn {Hs}: differs from PNAa in the 3′-UTR and coding region—the resulting isoform contains a longer C terminus compared with PNRα
Tissue distribution Exclusively expressed in the retina in the outer nuclear layer, which contains the nuclei of cone and rod photoreceptor cells {Hs, Mm} [Northern blot, in situ hybridization]1,2,46
Functional assays
Main target genes Activated: Rhodopsin {Hs, Mm, Rn}3; repressed: S-cone opsin {Hs, Mm, Rn},3 M-cone opsin {Hs, Mm, Rn}3
Mutant phenotype Spontaneous mutation associated with retinal degeneration: this mutation is a deletion of exons 4 and 5, resulting in the absence of 380 base pairs from the transcript; the predicted protein expressed from this allele would lack 127 amino acids, including sequences corresponding to the DNA binding domain; the deletion also introduces a frameshift and creates a premature stop codon {Mm} [spontaneous mutation]5
Human disease Enhanced S-cone syndrome: due to several mutations affecting NR2E34,7; retinitis pigmentosa: Crypto-Jews in Portugal with retinitis pigmentosa have a Arg311→Gln mutation in exon 6 of the NR2E3 gene8; Goldmann-Favre syndrome: an Arg311→Gln mutation in the NR2E3 gene was found in a family with classic Goldmann-Favre syndrome9
  • aa, amino acids; chr., chromosome; HRE, hormone response element; CRX, cone-rod homeobox

  • 1. Kobayashi M, Takezawa S, Hara K, Yu RT, Umesono Y, Agata K, Taniwaki M, Yasuda K, and Umesono K (1999) Identification of a photoreceptor cell-specific nuclear receptor. Proc Natl Acad Sci USA 96: 4814-4819

  • 2. Chen F, Figueroa DJ, Marmorstein AD, Zhang Q, Petrukhin K, Caskey CT, and Austin CP (1999) Retina-specific nuclear receptor: a potential regulator of cellular retinaldehyde-binding protein expressed in retinal pigment epithelium and Muller glial cells. Proc Natl Acad Sci USA 96: 15149-15154

  • 3. Peng GH, Ahmad O, Ahmad F, Liu J, and Chen S (2005) The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Hum Mol Genet 14: 747-764

  • 4. Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, Beck G, Hockey R, Hanna DB, Gorman S, et al. (2000) Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat Genet 24: 127-131

  • 5. Akhmedov NB, Piriev NI, Chang B, Rapoport AL, Hawes NL, Nishina PM, Nusinowitz S, Heckenlively JR, Roderick TH, Kozak CA, et al. (2000) A deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse. Proc Natl Acad Sci USA 97: 5551-5556

  • 6. Bumsted O'Brien KM, Cheng H, Jiang Y, Schulte D, Swaroop A, and Hendrickson AE (2004) Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina. Investig Ophthalmol Vis Sci 45: 2807-2812

  • 7. Hayashi T, Gekka T, Goto-Omoto S, Takeuchi T, Kubo A, and Kitahara K (2005) Novel NR2E3 mutations (R104Q, R334G) associated with a mild form of enhanced S-cone syndrome demonstrate compound heterozygosity. Ophthalmology 112: 2115

  • 8. Gerber S, Rozet JM, Takezawa SI, dos Santos LC, Lopes L, Gribouval O, Penet C, Perrault I, Ducroq D, Souied E, et al. (2000) The photoreceptor cell-specific nuclear receptor gene (PNR) accounts for retinitis pigmentosa in the Crypto-Jews from Portugal (Marranos), survivors from the Spanish Inquisition. Hum Genet 107: 276-284

  • 9. Chavala SH, Sari A, Lewis H, Pauer GJ, Simpson E, Hagstrom SA, and Traboulsi EI (2005) An Arg311Gln NR2E3 mutation in a family with classic Goldmann-Favre syndrome. Br J Ophthalmol 89: 1065-1066