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 IDsOMIM: 604485 MGI: 1346317 HomoloGene: 84397 GeneCards: NR2E3
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: 59.85 – 59.87 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

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]

References

  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:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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. Bibcode:1999PNAS...96.4814K. 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. Bibcode:2013PLoSO...874359T. doi:10.1371/journal.pone.0074359. PMC 3771917. 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. S2CID 19508439.
  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. hdl:10400.17/1708. PMID 11071390. S2CID 2774255.
  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

External links