Biology:Photoreceptor cell-specific nuclear receptor
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
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 NR2E3 gene.[1] PNR is a member of the nuclear receptor super family of intracellular transcription 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.[2]
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.[3] 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.[4]
Clinical significance
Mutations in the NR2E3 gene have been linked to several inherited retinal diseases, including enhanced S-cone syndrome (ESCS),[5] a form of retinitis pigmentosa,[6] and Goldmann-Favre syndrome.[7]
References
- ↑ "Identification of a photoreceptor cell-specific nuclear receptor". Proceedings of the National Academy of Sciences of the United States of America 96 (9): 4814–9. April 1999. doi:10.1073/pnas.96.9.4814. PMID 10220376. Bibcode: 1999PNAS...96.4814K.
- ↑ "The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degeneration". Proceedings of the National Academy of Sciences of the United States of America 99 (1): 473–8. January 2002. doi:10.1073/pnas.022533099. PMID 11773633.
- ↑ "The crystal structure of the orphan nuclear receptor NR2E3/PNR ligand binding domain reveals a dimeric auto-repressed conformation". PLOS ONE 8 (9): e74359. 2013. doi:10.1371/journal.pone.0074359. PMID 24069298. Bibcode: 2013PLoSO...874359T.
- ↑ "Potential of Small Molecule-Mediated Reprogramming of Rod Photoreceptors to Treat Retinitis Pigmentosa". Investigative Ophthalmology & Visual Science 57 (14): 6407–6415. November 2016. doi:10.1167/iovs.16-20177. PMID 27893103.
- ↑ "Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate". Nature Genetics 24 (2): 127–31. February 2000. doi:10.1038/72777. PMID 10655056.
- ↑ "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. September 2000. doi:10.1007/s004390000350. PMID 11071390.
- ↑ "An Arg311Gln NR2E3 mutation in a family with classic Goldmann-Favre syndrome". The British Journal of Ophthalmology 89 (8): 1065–6. August 2005. doi:10.1136/bjo.2005.068130. PMID 16024868.
Further reading
- "Retina-specific nuclear receptor: A potential regulator of cellular retinaldehyde-binding protein expressed in retinal pigment epithelium and Müller glial cells". Proceedings of the National Academy of Sciences of the United States of America 96 (26): 15149–54. December 1999. doi:10.1073/pnas.96.26.15149. PMID 10611353. Bibcode: 1999PNAS...9615149C.
- "Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate". Nature Genetics 24 (2): 127–31. February 2000. doi:10.1038/72777. PMID 10655056.
- "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. 2000. doi:10.1159/000015635. PMID 10965145.
- "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. September 2000. doi:10.1007/s004390000350. PMID 11071390.
- "Excess cone cell proliferation due to lack of a functional NR2E3 causes retinal dysplasia and degeneration in rd7/rd7 mice". Human Molecular Genetics 10 (16): 1619–26. August 2001. doi:10.1093/hmg/10.16.1619. PMID 11487564.
- "The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degeneration". Proceedings of the National Academy of Sciences of the United States of America 99 (1): 473–8. January 2002. doi:10.1073/pnas.022533099. PMID 11773633.
- "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. September 2003. doi:10.1001/archopht.121.9.1316. PMID 12963616.
- "Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors". Human Molecular Genetics 13 (15): 1563–75. August 2004. doi:10.1093/hmg/ddh173. PMID 15190009.
- "Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina". Investigative Ophthalmology & Visual Science 45 (8): 2807–12. August 2004. doi:10.1167/iovs.03-1317. PMID 15277507.
- "Mutation analysis of NR2E3 and NRL genes in Enhanced S Cone Syndrome". Human Mutation 24 (5): 439. November 2004. doi:10.1002/humu.9285. PMID 15459973.
- "The rod photoreceptor-specific nuclear receptor Nr2e3 represses transcription of multiple cone-specific genes". The Journal of Neuroscience 25 (1): 118–29. January 2005. doi:10.1523/JNEUROSCI.3571-04.2005. PMID 15634773.
- "The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes". Human Molecular Genetics 14 (6): 747–64. March 2005. doi:10.1093/hmg/ddi070. PMID 15689355.
- "Novel NR2E3 mutations (R104Q, R334G) associated with a mild form of enhanced S-cone syndrome demonstrate compound heterozygosity". Ophthalmology 112 (12): 21152115.e1–2115.e10. December 2005. doi:10.1016/j.ophtha.2005.07.002. PMID 16225923.
- "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. November 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
- "Recurrent mutation in the first zinc finger of the orphan nuclear receptor NR2E3 causes autosomal dominant retinitis pigmentosa". American Journal of Human Genetics 81 (1): 147–57. July 2007. doi:10.1086/518426. PMID 17564971.
External links
- NR2E3+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
- NR2E3 human gene location in the UCSC Genome Browser.
- NR2E3 human gene details in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: Q9Y5X4 (Photoreceptor-specific nuclear receptor) at the PDBe-KB.
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