Photoreceptor cell-specific nuclear receptor

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NR2E3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesNR2E3, Nr2e3, A930035N01Rik, PNR, RNR, rd7, ESCS, RP37, nuclear receptor subfamily 2 group E member 3
External IDsMGI: 1346317 HomoloGene: 84397 GeneCards: NR2E3
Gene location (Human)
Chromosome 15 (human)
Chr.Chromosome 15 (human)[1]
Chromosome 15 (human)
Genomic location for NR2E3
Genomic location for NR2E3
Band15q23Start71,792,638 bp[1]
End71,818,259 bp[1]
RNA expression pattern
PBB GE NR2E3 208388 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 MbChr 9: 59.94 – 59.96 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5] PNR is a member of the nuclear receptor super family of intracellular transcription factors.

Function[edit]

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[edit]

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[edit]

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]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000278570 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032292 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Kobayashi M, Takezawa S, Hara K, Yu RT, Umesono Y, Agata K, et al. (April 1999). "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. doi:10.1073/pnas.96.9.4814. PMC 21774. PMID 10220376.
  6. ^ 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.
  7. ^ Tan MH, Zhou XE, Soon FF, Li X, Li J, Yong EL, et al. (2013). "The crystal structure of the orphan nuclear receptor NR2E3/PNR ligand binding domain reveals a dimeric auto-repressed conformation". PloS One. 8 (9): e74359. doi:10.1371/journal.pone.0074359. PMID 24069298.
  8. ^ Nakamura PA, Tang S, Shimchuk AA, Ding S, Reh TA (November 2016). "Potential of Small Molecule-Mediated Reprogramming of Rod Photoreceptors to Treat Retinitis Pigmentosa". Investigative Ophthalmology & Visual Science. 57 (14): 6407–6415. doi:10.1167/iovs.16-20177. PMC 5134355. PMID 27893103.
  9. ^ 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.
  10. ^ 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. PMID 11071390.
  11. ^ Chavala SH, Sari A, Lewis H, Pauer GJ, Simpson E, Hagstrom SA, Traboulsi EI (August 2005). "An Arg311Gln NR2E3 mutation in a family with classic Goldmann-Favre syndrome". The British Journal of Ophthalmology. 89 (8): 1065–6. doi:10.1136/bjo.2005.068130. PMC 1772771. PMID 16024868.

Further reading[edit]

External links[edit]