PNR

Nomenclature: PNR

Systematic Nomenclature: NR2E3

Family: 2E. Tailless-like receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
Species AA Chromosomal Location Gene Symbol Gene Name Reference
Human 410 15q24 NR2E3 nuclear receptor subfamily 2, group E, member 3 8
Mouse 395 9C Nr2e3 nuclear receptor subfamily 2, group E, member 3 4
Gene and Protein Information Comments
PNR is absent from the Rat Genome Database.
Previous and Unofficial Names
rd7
RP37
Photoreceptor-specific nuclear receptor
retina-specific nuclear receptor
RNR
A930035N01Rik
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
NURSA Receptor
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniProtKB
Wikipedia
Natural/Endogenous Ligands
Comments: Orphan
DNA Binding
Structure:  Homodimer
HRE core sequence:  AAGTCA n AAGTCA
Response element:  DR1
DNA Binding Comments
The DNA binding domain of NR2E3 presents an unsual P-Box reminiscent of the DBD of the orphan NR2E1. However, NR2E3 does not bind the monomeric RE recognize by NR2E1 but a direct repeat element containing two AAGTCA half-sites separated by one spacer nucleotide [8].
Co-binding Partners
Name Interaction Effect Reference
Crx Physical NR2E3 and Crx interact via the DNA-binding domain of each protein. The promoter/enhancer occupancy of NR2E3 is Crx-dependent, suggesting that NR2E3 is associated with photoreceptor gene targets by interacting with Crx. 9
Main Target Genes
Name Species Effect Technique Comments References
RHODOPSIN Human Activated ChIP, Transient transfection, Other NR2E3 enhances the synergistic activation of the rhodopsin promoter by Crx and Nrl together. This effect is observed in other species. 9
M-cone Opsin Human Repressed ChIP, Transient transfection, Other NR2E3 inhibits the synergistic activation of the M-cone opsin promoter by Crx and Nrl together. (Also in rodents and other species) 9
S-cone Opsin Human Repressed ChIP, Transient transfection, Other NR2E3 inhibits the synergistic activation of the S-cone opsin promoter by Crx and Nrl together. 9
Tissue Distribution
Retina
Species:  Human
Technique:  Northern, in situ, other
References:  1-2,4,6,8
Tissue Distribution Comments
This gene is expressed in human as 7.5 kb, 3 kb and 2.3 kb transcripts whereas in mouse a unique 2.3 kb species was detected. These transcripts are exclusively expressed in the retina and in situ hybridization experiments reveal that the expression was restricted to the outer nuclear layer which contains the nuclei of cone and rod photoreceptor cells. These data suggest that one essential function of PNR is eye development. This has been substantiated by knock-out experiments as well as by the implication of PNR in a disorder of retinal fate in human.
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Nr2e3rd7 Nr2e3rd7/Nr2e3rd7
Not Specified
MGI:1346317  MP:0004022 abnormal cone electrophysiology PMID: 10805811 
Nr2e3rd7 Nr2e3rd7/Nr2e3rd7
B6.Cg-Nr2e3/J
MGI:1346317  MP:0006072 abnormal retinal apoptosis PMID: 19358158 
Nr2e3rd7 Nr2e3rd7/Nr2e3rd7
B6.Cg-Nr2e3/J
MGI:1346317  MP:0001006 abnormal retinal cone cell morphology PMID: 16110338 
Nr2e3rd7 Nr2e3rd7/Nr2e3rd7
B6.Cg-Nr2e3/J
MGI:1346317  MP:0003731 abnormal retinal outer nuclear layer morphology PMID: 16110338 
Nr2e3tm1Dgen Nr2e3tm1Dgen/Nr2e3tm1Dgen
involves: 129P2/OlaHsd * C57BL/6J
MGI:1346317  MP:0003731 abnormal retinal outer nuclear layer morphology PMID: 18547563 
Nr2e3rd7 Nr2e3rd7/Nr2e3rd7
B6.Cg-Nr2e3/J
MGI:1346317  MP:0001004 abnormal retinal photoreceptor morphology PMID: 16110338 
Nr2e3rd7 Nr2e3rd7/Nr2e3rd7
Not Specified
MGI:1346317  MP:0004021 abnormal rod electrophysiology PMID: 10805811 
Nr2e3rd7 Nr2e3rd7/Nr2e3rd7
B6.Cg-Nr2e3/J
MGI:1346317  MP:0008516 disorganized retinal outer nuclear layer PMID: 19358158 
Nr2e3rd7 Nr2e3rd7/Nr2e3rd7
Not Specified
MGI:1346317  MP:0001326 retinal degeneration PMID: 10805811 
Nr2e3rd7 Nr2e3rd7/Nr2e3rd7
B6.Cg-Nr2e3/J
MGI:1346317  MP:0008518 retinal outer nuclear layer degeneration PMID: 19358158 
Nr2e3rd7 Nr2e3rd7/Nr2e3rd7
B6.Cg-Nr2e3/J
MGI:1346317  MP:0008587 short photoreceptor outer segment PMID: 19358158 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Retinis pigmentosa
OMIM:  611131
Orphanet:  791
Comments: 
References:  5
Mutations not determined
Disease:  Enhanced S-cone syndrome
OMIM:  268100
Orphanet:  53540
Comments: 
References:  6-7
Mutations not determined
Disease:  Goldmann-Favre syndrome
OMIM:  268100
Orphanet:  53540
Comments: 
References:  3
Mutations not determined
Clinically-Relevant Mutations and Pathophysiology Comments
Spontaneous mutation associated with retinal degeneration. This mutation is a deletion of exons 4 and 5, resulting in the absence of 380 bp from the transcript. The predicted protein expressed from this allele would lack 127 amino acids including sequences corresponding to the DNA binding domain. The deletion also introduces a frameshift and creates a premature stop codon. The rd7 mouse is an animal model for human hereditary retinal degeneration [1].

References

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1. Akhmedov NB, Piriev NI, Chang B, Rapoport AL, Hawes NL, Nishina PM, Nusinowitz S, Heckenlively JR, Roderick TH, Kozak CA, Danciger M, Davisson MT, Farber DB. (2000) A deletion in a photoreceptor-specific nuclear receptor mRNA causes retinal degeneration in the rd7 mouse. Proc. Natl. Acad. Sci. U.S.A.97 (10): 5551-6. [PMID:10805811]

2. Bumsted O'Brien KM, Cheng H, Jiang Y, Schulte D, Swaroop A, Hendrickson AE. (2004) Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina. Invest. Ophthalmol. Vis. Sci.45 (8): 2807-12. [PMID:15277507]

3. Chavala SH, Sari A, Lewis H, Pauer GJ, Simpson E, Hagstrom SA, Traboulsi EI. (2005) An Arg311Gln NR2E3 mutation in a family with classic Goldmann-Favre syndrome. Br J Ophthalmol89 (8): 1065-6. [PMID:16024868]

4. Chen F, Figueroa DJ, Marmorstein AD, Zhang Q, Petrukhin K, Caskey CT, Austin CP. (1999) Retina-specific nuclear receptor: A potential regulator of cellular retinaldehyde-binding protein expressed in retinal pigment epithelium and Müller glial cells. Proc. Natl. Acad. Sci. U.S.A.96 (26): 15149-54. [PMID:10611353]

5. Gerber S, Rozet JM, Takezawa SI, dos Santos LC, Lopes L, Gribouval O, Penet C, Perrault I, Ducroq D, Souied E, Jeanpierre M, Romana S, Frézal J, Ferraz F, Yu-Umesono R, Munnich A, Kaplan J. (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. Hum. Genet.107 (3): 276-84. [PMID:11071390]

6. Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, Beck G, Hockey R, Hanna DB, Gorman S, Duhl D, Carmi R, Bennett J, Weleber RG, Fishman GA, Wright AF, Stone EM, Sheffield VC. (2000) Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat. Genet.24 (2): 127-31. [PMID:10655056]

7. Hayashi T, Gekka T, Goto-Omoto S, Takeuchi T, Kubo A, Kitahara K. (2005) Novel NR2E3 mutations (R104Q, R334G) associated with a mild form of enhanced S-cone syndrome demonstrate compound heterozygosity. Ophthalmology112 (12): 2115. [PMID:16225923]

8. Kobayashi M, Takezawa S, Hara K, Yu RT, Umesono Y, Agata K, Taniwaki M, Yasuda K, Umesono K. (1999) Identification of a photoreceptor cell-specific nuclear receptor. Proc. Natl. Acad. Sci. U.S.A.96 (9): 4814-9. [PMID:10220376]

9. Peng GH, Ahmad O, Ahmad F, Liu J, Chen S. (2005) The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Hum. Mol. Genet.14 (6): 747-64. [PMID:15689355]

How to cite this page

2E. Tailless-like receptors: PNR. Last modified on 13/12/2013. Accessed on 21/09/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=616.