Photoreceptor cell-specific nuclear receptor

NR2E3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4LOG
Identifiers
Aliases	NR2E3, Nr2e3, A930035N01Rik, PNR, RNR, rd7, ESCS, RP37, nuclear receptor subfamily 2 group E member 3
External IDs	OMIM: 604485; MGI: 1346317; HomoloGene: 84397; GeneCards: NR2E3; OMA:NR2E3 - orthologs
Gene location (Human) Chr. Chromosome 15 (human) Band 15q23 Start 71,792,638 bp End 71,818,259 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9 B|9 32.35 cM Start 59,850,054 bp End 59,867,942 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell testicle secondary oocyte gonad retinal pigment epithelium right uterine tube tendon of biceps brachii prostate fundus Descending thoracic aorta Top expressed in neural layer of retina outer nuclear layer retinal pigment epithelium epithelium of lens zygote embryo epithelium of small intestine secondary oocyte primary oocyte ileum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding DNA-binding transcription factor activity zinc ion binding metal ion binding steroid hormone receptor activity nuclear receptor activity RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific sequence-specific DNA binding Cellular component transcription regulator complex nucleoplasm nucleus Biological process phototransduction regulation of transcription, DNA-templated response to stimulus negative regulation of transcription by RNA polymerase II transcription by RNA polymerase II transcription, DNA-templated retina development in camera-type eye eye photoreceptor cell development transcription initiation from RNA polymerase II promoter negative regulation of cell population proliferation steroid hormone mediated signaling pathway signal transduction visual perception intracellular receptor signaling pathway positive regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10002 23958 Ensembl ENSG00000278570 ENSMUSG00000032292 UniProt Q9Y5X4 Q9QXZ7 RefSeq (mRNA) NM_001281446 NM_014249 NM_016346 NM_013708 RefSeq (protein) NP_055064 NP_057430 NP_038736 Location (UCSC) Chr 15: 71.79 – 71.82 Mb Chr 9: 59.85 – 59.87 Mb PubMed search
Wikidata
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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. 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.

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. 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.

Clinical significance

Mutations in the NR2E3 gene have been linked to several inherited retinal diseases, including enhanced S-cone syndrome (ESCS), a form of retinitis pigmentosa, and Goldmann-Favre syndrome.

Further reading

• Chen F, Figueroa DJ, Marmorstein AD, Zhang Q, Petrukhin K, Caskey CT, Austin CP (December 1999). "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. Bibcode:1999PNAS...9615149C. doi:10.1073/pnas.96.26.15149. PMC 24788. PMID 10611353.
• 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. PMID 10655056. S2CID 19508439.
• 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. PMID 10965145. S2CID 34825159.
• 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. PMID 11071390. S2CID 2774255.
• Haider NB, Naggert JK, Nishina PM (August 2001). "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. doi:10.1093/hmg/10.16.1619. PMID 11487564.
• Milam AH, Rose L, Cideciyan AV, Barakat MR, Tang WX, Gupta N, et al. (January 2002). "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. doi:10.1073/pnas.022533099. PMC 117584. PMID 11773633.
• 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. PMID 12963616.
• 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. PMID 15190009.
• 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. PMID 15277507.
• 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. PMID 15459973. S2CID 18561451.
• Chen J, Rattner A, Nathans J (January 2005). "The rod photoreceptor-specific nuclear receptor Nr2e3 represses transcription of multiple cone-specific genes". The Journal of Neuroscience. 25 (1): 118–29. doi:10.1523/JNEUROSCI.3571-04.2005. PMC 6725199. PMID 15634773.
• Peng GH, Ahmad O, Ahmad F, Liu J, Chen S (March 2005). "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. doi:10.1093/hmg/ddi070. PMID 15689355.
• Hayashi T, Gekka T, Goto-Omoto S, Takeuchi T, Kubo A, Kitahara K (December 2005). "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. doi:10.1016/j.ophtha.2005.07.002. PMID 16225923.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
• Coppieters F, Leroy BP, Beysen D, Hellemans J, De Bosscher K, Haegeman G, et al. (July 2007). "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. doi:10.1086/518426. PMC 1950922. PMID 17564971.

External links

• NR2E3+protein,+human at the U.S. 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.