NR2E3_MOUSE
ID NR2E3_MOUSE Reviewed; 395 AA.
AC Q9QXZ7;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Photoreceptor-specific nuclear receptor;
DE AltName: Full=Nuclear receptor subfamily 2 group E member 3;
DE AltName: Full=Retina-specific nuclear receptor;
GN Name=Nr2e3; Synonyms=Pnr, Rnr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=10611353; DOI=10.1073/pnas.96.26.15149;
RA Chen F., Figueroa D.J., Marmorstein A.D., Zhang Q., Petrukhin K.,
RA Caskey C.T., Austin C.P.;
RT "Retina-specific nuclear receptor: a potential regulator of cellular
RT retinaldehyde-binding protein expressed in retinal pigment epithelium and
RT Muller glial cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:15149-15154(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=10805811; DOI=10.1073/pnas.97.10.5551;
RA Akhmedov N.B., Piriev N.I., Chang B., Rapoport A.L., Hawes N.L.,
RA Nishina P.M., Nusinowitz S., Heckenlively J.R., Roderick T.H., Kozak C.A.,
RA Danciger M., Davisson M.T., Farber D.B.;
RT "A deletion in a photoreceptor-specific nuclear receptor mRNA causes
RT retinal degeneration in the rd7 mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5551-5556(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15190009; DOI=10.1093/hmg/ddh173;
RA Cheng H., Khanna H., Oh E.C., Hicks D., Mitton K.P., Swaroop A.;
RT "Photoreceptor-specific nuclear receptor NR2E3 functions as a
RT transcriptional activator in rod photoreceptors.";
RL Hum. Mol. Genet. 13:1563-1575(2004).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15634773; DOI=10.1523/jneurosci.3571-04.2005;
RA Chen J., Rattner A., Nathans J.;
RT "The rod photoreceptor-specific nuclear receptor Nr2e3 represses
RT transcription of multiple cone-specific genes.";
RL J. Neurosci. 25:118-129(2005).
RN [6]
RP SUMOYLATION AT LYS-178, INTERACTION WITH CRX AND PIAS3, FUNCTION,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-178; LYS-315 AND LYS-322.
RX PubMed=19186166; DOI=10.1016/j.neuron.2008.12.006;
RA Onishi A., Peng G.-H., Hsu C., Alexis U., Chen S., Blackshaw S.;
RT "Pias3-dependent SUMOylation directs rod photoreceptor development.";
RL Neuron 61:234-246(2009).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21408158; DOI=10.1371/journal.pone.0017494;
RA Mollema N.J., Yuan Y., Jelcick A.S., Sachs A.J., von Alpen D.,
RA Schorderet D., Escher P., Haider N.B.;
RT "Nuclear receptor Rev-erb alpha (Nr1d1) functions in concert with Nr2e3 to
RT regulate transcriptional networks in the retina.";
RL PLoS ONE 6:E17494-E17494(2011).
CC -!- FUNCTION: Orphan nuclear receptor of retinal photoreceptor cells.
CC Transcriptional factor that is an activator of rod development and
CC repressor of cone development. Binds the promoter region of a number of
CC rod- and cone-specific genes, including rhodopsin, M- and S-opsin and
CC rod-specific phosphodiesterase beta subunit. Enhances rhodopsin
CC expression. Represses M- and S-cone opsin expression.
CC {ECO:0000269|PubMed:15190009, ECO:0000269|PubMed:15634773,
CC ECO:0000269|PubMed:19186166, ECO:0000269|PubMed:21408158}.
CC -!- SUBUNIT: Homodimer. Interacts with PIAS3; the interaction sumoylates
CC NR2E3 and promotes repression of cone-specific gene transcription and
CC activation of rod-specific genes. Component of a rod photoreceptor
CC complex that includes NR2E3, PIAS3, NRL, CRX and/or NR1D1. Binds
CC directly in the complex with CRX, PIAS3 and NR1D1 (By similarity).
CC Interacts (via the DNA-binding domain) with CRX (via its DNA binding
CC domain); the interaction represses S- and M-cone opsin expression.
CC {ECO:0000250, ECO:0000269|PubMed:19186166}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:15190009, ECO:0000269|PubMed:19186166}.
CC -!- TISSUE SPECIFICITY: Retina. Rod-specific. Expressed in the outer
CC nuclear lyer of the mature retina. {ECO:0000269|PubMed:10611353,
CC ECO:0000269|PubMed:10805811, ECO:0000269|PubMed:15190009,
CC ECO:0000269|PubMed:15634773, ECO:0000269|PubMed:21408158}.
CC -!- DEVELOPMENTAL STAGE: Expression found as early as 18 dpc in developing
CC retina. From P3 to P6, expression increases in developing rods.
CC Expression, thereafter, in the future inner nuclear layer migrating to
CC the final destination of the outer nuclear layer. In the mature retina,
CC exclusively expressed in rods. {ECO:0000269|PubMed:15634773}.
CC -!- PTM: Di- and tri-sumoylated in developing retina. PIAS3-mediated
CC sumoylation promotes repression of cone-specific gene expression and
CC activation of rod-specific genes. Sumoylation on Lys-178 appears to be
CC the main site. {ECO:0000269|PubMed:19186166}.
CC -!- DISRUPTION PHENOTYPE: Defects in Nr2e3 are the cause of the retinal
CC degeneration type 7 (Rd7) phenotype characterized by excessive blue
CC cones and loss of rods. {ECO:0000269|PubMed:10805811,
CC ECO:0000269|PubMed:15634773}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
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DR EMBL; AF148129; AAF22228.1; -; mRNA.
DR EMBL; AF204053; AAF69682.1; -; mRNA.
DR EMBL; BC017521; AAH17521.1; -; mRNA.
DR CCDS; CCDS23255.1; -.
DR RefSeq; NP_038736.1; NM_013708.4.
DR AlphaFoldDB; Q9QXZ7; -.
DR SMR; Q9QXZ7; -.
DR BioGRID; 204819; 1.
DR STRING; 10090.ENSMUSP00000034831; -.
DR iPTMnet; Q9QXZ7; -.
DR PhosphoSitePlus; Q9QXZ7; -.
DR PaxDb; Q9QXZ7; -.
DR PRIDE; Q9QXZ7; -.
DR ProteomicsDB; 253011; -.
DR Antibodypedia; 72976; 431 antibodies from 30 providers.
DR DNASU; 23958; -.
DR Ensembl; ENSMUST00000034831; ENSMUSP00000034831; ENSMUSG00000032292.
DR GeneID; 23958; -.
DR KEGG; mmu:23958; -.
DR UCSC; uc009pyu.1; mouse.
DR CTD; 10002; -.
DR MGI; MGI:1346317; Nr2e3.
DR VEuPathDB; HostDB:ENSMUSG00000032292; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000156926; -.
DR HOGENOM; CLU_007368_20_3_1; -.
DR InParanoid; Q9QXZ7; -.
DR OMA; NEEPHTV; -.
DR OrthoDB; 870262at2759; -.
DR PhylomeDB; Q9QXZ7; -.
DR TreeFam; TF315716; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 23958; 1 hit in 70 CRISPR screens.
DR ChiTaRS; Ren1; mouse.
DR PRO; PR:Q9QXZ7; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9QXZ7; protein.
DR Bgee; ENSMUSG00000032292; Expressed in retinal neural layer and 25 other tissues.
DR ExpressionAtlas; Q9QXZ7; baseline and differential.
DR Genevisible; Q9QXZ7; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0042462; P:eye photoreceptor cell development; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060041; P:retina development in camera-type eye; IMP:MGI.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Receptor;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..395
FT /note="Photoreceptor-specific nuclear receptor"
FT /id="PRO_0000053600"
FT DOMAIN 162..395
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 37..113
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 40..60
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 76..101
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 127..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 178
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT CROSSLNK 315
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT CROSSLNK 322
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT MUTAGEN 178
FT /note="K->R: Greatly reduced levels of PIAS3-mediated
FT sumoylation. Completely abolishes sumoylation; when
FT associated with R-315 and R-322."
FT /evidence="ECO:0000269|PubMed:19186166"
FT MUTAGEN 315
FT /note="K->R: Little change in sumoylation. Completely
FT abolishes sumoylation; when associated with R-178 and R-
FT 322."
FT /evidence="ECO:0000269|PubMed:19186166"
FT MUTAGEN 322
FT /note="K->R: Little change in sumoylation. Completely
FT abolishes sumoylation; when associated with R-178 and R-
FT 315."
FT /evidence="ECO:0000269|PubMed:19186166"
SQ SEQUENCE 395 AA; 43177 MW; D8E391CF24919A68 CRC64;
MSSTVAASTM PVSVAASKKE SPGRWGLGED PTGVGPSLQC RVCGDSSSGK HYGIYACNGC
SGFFKRSVRR RLIYRCQVGA GMCPVDKAHR NQCQACRLKK CLQAGMNQDA VQNERQPRSM
AQVHLDAMET GSDPRSEPVV ASPALAGPSP RGPTSVSATR AMGHHFMASL ITAETCAKLE
PEDAEENIDV TSNDPEFPAS PCSLDGIHET SARLLFMAVK WAKNLPVFSN LPFRDQVILL
EEAWNELFLL GAIQWSLPLD SCPLLAPPEA SGSSQGRLAL ASAETRFLQE TISRFRALAV
DPTEFACLKA LVLFKPETRG LKDPEHVEAL QDQSQVMLSQ HSKAHHPSQP VRFGKLLLLL
PSLRFLTAER IELLFFRKTI GNTPMEKLLC DMFKN
