The photoreceptor cell-specific nuclear receptor (PNR), also known as NR2E3 (nuclear receptor subfamily 2, group E, member 3), is a protein that in humans is encoded by the NR2E3gene.[5] PNR is a member of the nuclear receptor super family of intracellulartranscription 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 as allosteric 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 the NR2E3 gene have been linked to several inherited retinal diseases, including enhanced S-cone syndrome (ESCS),[9] a form of retinitis 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.