Thephotoreceptor cell-specific nuclear receptor (PNR), also known asNR2E3 (nuclear receptor subfamily 2, group E, member 3), is aprotein that in humans is encoded by theNR2E3gene.[5] PNR is a member of thenuclear receptor super family ofintracellulartranscription factors.
The crystal structure of PNR's ligand-binding domain is known. It self-dimerizes into, by default, a repressor state. Computer simulations based on this model shows that a ligand could possibly fit into PNR and switch it into a transcription activator.13-cis retinoic acid is a known weak agonist that fits into such a pocket, but no physiologic ligand is known. Two synthetic compounds, 11A and 11B, appear to be agonists but do not go into the pocket and instead work asallosteric modulators.[7] A more recent screening identifies another compound called photoregulin-1 (PR1) that functions as a reverse agonist, an activity possibly useful in the management of retinitis pigmentosa.[8]
Mutations in theNR2E3 gene have been linked to several inherited retinal diseases, including enhanced S-cone syndrome (ESCS),[9] a form ofretinitis pigmentosa,[10] and Goldmann-Favre syndrome.[11]
^Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, et al. (February 2000). "Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate".Nature Genetics.24 (2):127–31.doi:10.1038/72777.PMID10655056.S2CID19508439.
^Gerber S, Rozet JM, Takezawa SI, dos Santos LC, Lopes L, Gribouval O, et al. (September 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".Human Genetics.107 (3):276–84.doi:10.1007/s004390000350.hdl:10400.17/1708.PMID11071390.S2CID2774255.
Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, et al. (February 2000). "Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate".Nature Genetics.24 (2):127–31.doi:10.1038/72777.PMID10655056.S2CID19508439.
Rendtorff ND, Vissing H, Tümer Z, Silahtaroglu A, Tommerup N (2000). "Assignment of the NR2E3 gene to mouse chromosome 9 and to human chromosome 15q22.33-->q23".Cytogenetics and Cell Genetics.89 (3–4):279–80.doi:10.1159/000015635.PMID10965145.S2CID34825159.
Gerber S, Rozet JM, Takezawa SI, dos Santos LC, Lopes L, Gribouval O, et al. (September 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".Human Genetics.107 (3):276–84.doi:10.1007/s004390000350.hdl:10400.17/1708.PMID11071390.S2CID2774255.
Sharon D, Sandberg MA, Caruso RC, Berson EL, Dryja TP (September 2003). "Shared mutations in NR2E3 in enhanced S-cone syndrome, Goldmann-Favre syndrome, and many cases of clumped pigmentary retinal degeneration".Archives of Ophthalmology.121 (9):1316–23.doi:10.1001/archopht.121.9.1316.PMID12963616.
Cheng H, Khanna H, Oh EC, Hicks D, Mitton KP, Swaroop A (August 2004). "Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors".Human Molecular Genetics.13 (15):1563–75.doi:10.1093/hmg/ddh173.PMID15190009.
Bumsted O'Brien KM, Cheng H, Jiang Y, Schulte D, Swaroop A, Hendrickson AE (August 2004). "Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina".Investigative Ophthalmology & Visual Science.45 (8):2807–12.doi:10.1167/iovs.03-1317.PMID15277507.
Wright AF, Reddick AC, Schwartz SB, Ferguson JS, Aleman TS, Kellner U, et al. (November 2004). "Mutation analysis of NR2E3 and NRL genes in Enhanced S Cone Syndrome".Human Mutation.24 (5): 439.doi:10.1002/humu.9285.PMID15459973.S2CID18561451.
