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.
Function
PNR is exclusively expressed in the retina. The main target genes of PNR are rhodopsin and several opsins which are essential for sight.[6]
Structure and ligands
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]
Clinical significance
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.
