PNR

Target not currently curated in GtoImmuPdb

Target id: 616

Nomenclature: PNR

Systematic Nomenclature: NR2E3

Gene and Protein Information
Species	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	410	15q23	NR2E3	nuclear receptor subfamily 2 group E member 3	8
Mouse	395	9 32.35 cM	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
nuclear receptor subfamily 2 \| nuclear receptor subfamily 2, group E, member 3 \| Photoreceptor-specific nuclear receptor \| rd7 \| retina-specific nuclear receptor \| RNR \| RP37

Previous and Unofficial Names

nuclear receptor subfamily 2 | nuclear receptor subfamily 2, group E, member 3 | Photoreceptor-specific nuclear receptor | rd7 | retina-specific nuclear receptor | RNR | RP37

Database Links
Alphafold	Q9Y5X4 (Hs), Q9QXZ7 (Mm)
CATH/Gene3D	3.30.50.10
ChEMBL Target	CHEMBL4374 (Hs)
Ensembl Gene	ENSG00000278570 (Hs), ENSMUSG00000032292 (Mm)
Entrez Gene	10002 (Hs), 23958 (Mm)
Human Protein Atlas	ENSG00000278570 (Hs)
KEGG Gene	hsa:10002 (Hs), mmu:23958 (Mm)
OMIM	604485 (Hs)
Orphanet	ORPHA123912 (Hs)
Pharos	Q9Y5X4 (Hs)
RefSeq Nucleotide	NM_016346 (Hs), NM_013708 (Mm)
RefSeq Protein	NP_055064 (Hs), NP_038736 (Mm)
UniProtKB	Q9Y5X4 (Hs), Q9QXZ7 (Mm)
Wikipedia	NR2E3 (Hs)

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
Nr2e3^rd7	Nr2e3^rd7/Nr2e3^rd7 Not Specified	MGI:1346317	MP:0004022	abnormal cone electrophysiology	PMID: 10805811
Nr2e3^rd7	Nr2e3^rd7/Nr2e3^rd7 B6.Cg-Nr2e3/J	MGI:1346317	MP:0006072	abnormal retinal apoptosis	PMID: 19358158
Nr2e3^rd7	Nr2e3^rd7/Nr2e3^rd7 B6.Cg-Nr2e3/J	MGI:1346317	MP:0001006	abnormal retinal cone cell morphology	PMID: 16110338
Nr2e3^rd7	Nr2e3^rd7/Nr2e3^rd7 B6.Cg-Nr2e3/J	MGI:1346317	MP:0003731	abnormal retinal outer nuclear layer morphology	PMID: 16110338
Nr2e3^tm1Dgen	Nr2e3^tm1Dgen/Nr2e3^tm1Dgen involves: 129P2/OlaHsd * C57BL/6J	MGI:1346317	MP:0003731	abnormal retinal outer nuclear layer morphology	PMID: 18547563
Nr2e3^rd7	Nr2e3^rd7/Nr2e3^rd7 B6.Cg-Nr2e3/J	MGI:1346317	MP:0001004	abnormal retinal photoreceptor morphology	PMID: 16110338
Nr2e3^rd7	Nr2e3^rd7/Nr2e3^rd7 Not Specified	MGI:1346317	MP:0004021	abnormal rod electrophysiology	PMID: 10805811
Nr2e3^rd7	Nr2e3^rd7/Nr2e3^rd7 B6.Cg-Nr2e3/J	MGI:1346317	MP:0008516	disorganized retinal outer nuclear layer	PMID: 19358158
Nr2e3^rd7	Nr2e3^rd7/Nr2e3^rd7 Not Specified	MGI:1346317	MP:0001326	retinal degeneration	PMID: 10805811
Nr2e3^rd7	Nr2e3^rd7/Nr2e3^rd7 B6.Cg-Nr2e3/J	MGI:1346317	MP:0008518	retinal outer nuclear layer degeneration	PMID: 19358158
Nr2e3^rd7	Nr2e3^rd7/Nr2e3^rd7 B6.Cg-Nr2e3/J	MGI:1346317	MP:0008587	short photoreceptor outer segment	PMID: 19358158

Clinically-Relevant Mutations and Pathophysiology

Disease:

Enhanced S-cone syndrome; ESCS

Synonyms:	Goldmann-Favre syndrome [Orphanet: ORPHA53540]
OMIM:	268100
Orphanet:	ORPHA53540

Comments:

Several mutation affecting NR2E3 are associated with ESCS. A splice acceptor site mutation, an A-to-C transversion in the splice acceptor site of intron 1 of the NR2E3 gene, an arg76-to-trp missense mutation in the NR2E3 gene, caused by a C-to-T transition, an arg76-to-gln mutation resulting from a G-to-A transition and a. deletion of 9 bp of the NR2E3 gene, resulting in a 3-amino acid deletion (codons 67-69) in the NR2E3 protein. Other reports include NR2E3 Mutations (R104Q, R334G) Associated with a mild form of Enhanced S-Cone Syndrome. A potential Arg311Gln mutation in the NR2E3 gene has been identified in a family with classic Goldmann-Favre syndrome.

References:

3,6-7

Disease:

Retinitis pigmentosa 37; RP37

Synonyms:	Retinitis pigmentosa [Orphanet: ORPHA791] [Disease Ontology: DOID:10584]
Disease Ontology:	DOID:10584
OMIM:	611131
Orphanet:	ORPHA791

Comments:

Gerber and collaborators demonstrated that retinitis pigmentosa in the Crypto-Jews (Marranos) in Portugal is due to an arg311-to-gln (R311Q) mutation in exon 6 of the NR2E3 gene. A G-to-A transition at nucleotide 1020 changed codon 311 from CGG to CAG.

References:

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 USA, 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 Ophthalmol, 89 (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 USA, 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. Ophthalmology, 112 (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 USA, 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 18/03/2015. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=616.

PNR

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