NR2E1_MOUSE
ID NR2E1_MOUSE Reviewed; 385 AA.
AC Q64104;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Nuclear receptor subfamily 2 group E member 1;
DE AltName: Full=Nuclear receptor TLX;
DE AltName: Full=Protein tailless homolog;
DE Short=Tll;
DE Short=mTll;
GN Name=Nr2e1; Synonyms=Tll, Tlx;
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], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Embryo;
RX PubMed=7720587; DOI=10.1242/dev.121.3.839;
RA Monaghan A.P., Grau E., Bock D., Schuetz G.;
RT "The mouse homolog of the orphan nuclear receptor tailless is expressed in
RT the developing forebrain.";
RL Development 121:839-853(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10706625; DOI=10.1073/pnas.050566897;
RA Yu R.T., Chiang M.-Y., Tanabe T., Kobayashi M., Yasuda K., Evans R.M.,
RA Umesono K.;
RT "The orphan nuclear receptor Tlx regulates Pax2 and is essential for
RT vision.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:2621-2625(2000).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=11997145; DOI=10.1016/s0166-4328(01)00413-2;
RA Young K.A., Berry M.L., Mahaffey C.L., Saionz J.R., Hawes N.L., Chang B.,
RA Zheng Q.Y., Smith R.S., Bronson R.T., Nelson R.J., Simpson E.M.;
RT "Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular
RT abnormalities are background-dependent.";
RL Behav. Brain Res. 132:145-158(2002).
RN [5]
RP FUNCTION, INTERACTION WITH ATN1, AND DISRUPTION PHENOTYPE.
RX PubMed=16702404; DOI=10.1101/gad.1413606;
RA Zhang C.L., Zou Y., Yu R.T., Gage F.H., Evans R.M.;
RT "Nuclear receptor TLX prevents retinal dystrophy and recruits the
RT corepressor atrophin1.";
RL Genes Dev. 20:1308-1320(2006).
RN [6]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND
RP FUNCTION.
RX PubMed=17901127; DOI=10.1210/me.2007-0290;
RA Li W., Sun G., Yang S., Qu Q., Nakashima K., Shi Y.;
RT "Nuclear receptor TLX regulates cell cycle progression in neural stem cells
RT of the developing brain.";
RL Mol. Endocrinol. 22:56-64(2008).
CC -!- FUNCTION: Orphan receptor that binds DNA as a monomer to hormone
CC response elements (HRE) containing an extended core motif half-site
CC sequence 5'-AAGGTCA-3' in which the 5' flanking nucleotides participate
CC in determining receptor specificity (By similarity). Regulates cell
CC cycle progression in neural stem cells of rhe developing brain.
CC Involved in the regulation of retinal development and essential for
CC vision. During retinogenesis, regulates PTEN-Cyclin D expression via
CC binding to the promoter region of PTEN and suppressing its activity.
CC May be involved in retinoic acid receptor (RAR) regulation in retinal
CC cells. {ECO:0000250, ECO:0000269|PubMed:10706625,
CC ECO:0000269|PubMed:16702404, ECO:0000269|PubMed:17901127}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with ATN1; the interaction
CC represses the transcription. {ECO:0000250,
CC ECO:0000269|PubMed:16702404}.
CC -!- INTERACTION:
CC Q64104; O88895: Hdac3; NbExp=2; IntAct=EBI-15658561, EBI-302263;
CC Q64104; Q9Z2V6: Hdac5; NbExp=3; IntAct=EBI-15658561, EBI-645339;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407,
CC ECO:0000269|PubMed:17901127}.
CC -!- TISSUE SPECIFICITY: Expressed in embryonic developing forebrain and in
CC dorsal midbrain. Outside the neural epithelium only found in the
CC surface ectoderm at the site of nasal placode formation, where
CC subsequently the nasal and olfactory epithelium is formed. Also
CC expressed in adult brain. {ECO:0000269|PubMed:7720587}.
CC -!- DEVELOPMENTAL STAGE: Expression is first detected on 8 dpc and
CC increases until 13.5 dpc, then sharply decreases from day 13 dpc until
CC 18 dpc. Expression is barely detected in newborn brains but increases
CC again after birth. Highly expressed in the retinal neuroblastic layer
CC during the early stages of retinogenesis. Down-regulated during
CC neuronal development. At 14.5 dpc, expressed in the periventricular
CC neural stem cells of the brain. {ECO:0000269|PubMed:17901127,
CC ECO:0000269|PubMed:7720587}.
CC -!- DISRUPTION PHENOTYPE: Mice show exhibit hyperaggressivity, decreased
CC body fat and have ocular defects. Female mice lack maternal instincts.
CC In developing brain, there are reduced areas of the ventricular zone
CC and enlarged ventricles. Neuron progenitor cell divide more slowly.
CC There is complete loss of visual acuity, with mice not being able to
CC distinguish the cliff nor light and dark transition. There is a
CC dramatic reduction in retina thickness and enhanced generation of S-
CC cones with more differentiated neurons, fewer proliferation retinal
CC progenitor cells (RPCs) and more cells undergoing apoptosis leading to
CC progressive retinal dystrophy, optic nerve degradation and blindness.
CC {ECO:0000269|PubMed:10706625, ECO:0000269|PubMed:11997145,
CC ECO:0000269|PubMed:16702404, ECO:0000269|PubMed:17901127}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
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DR EMBL; S77482; AAB34090.1; -; mRNA.
DR EMBL; BC057104; AAH57104.1; -; mRNA.
DR CCDS; CCDS23813.1; -.
DR RefSeq; NP_689415.1; NM_152229.2.
DR AlphaFoldDB; Q64104; -.
DR SMR; Q64104; -.
DR BioGRID; 204227; 3.
DR DIP; DIP-46432N; -.
DR IntAct; Q64104; 3.
DR STRING; 10090.ENSMUSP00000019938; -.
DR iPTMnet; Q64104; -.
DR PhosphoSitePlus; Q64104; -.
DR PaxDb; Q64104; -.
DR PRIDE; Q64104; -.
DR ProteomicsDB; 293967; -.
DR Antibodypedia; 19108; 312 antibodies from 33 providers.
DR DNASU; 21907; -.
DR Ensembl; ENSMUST00000019938; ENSMUSP00000019938; ENSMUSG00000019803.
DR GeneID; 21907; -.
DR KEGG; mmu:21907; -.
DR UCSC; uc007eyt.1; mouse.
DR CTD; 7101; -.
DR MGI; MGI:1100526; Nr2e1.
DR VEuPathDB; HostDB:ENSMUSG00000019803; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000156693; -.
DR HOGENOM; CLU_007368_20_3_1; -.
DR InParanoid; Q64104; -.
DR OMA; VVSLMHK; -.
DR OrthoDB; 870262at2759; -.
DR PhylomeDB; Q64104; -.
DR TreeFam; TF315716; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 21907; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Nr2e1; mouse.
DR PRO; PR:Q64104; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q64104; protein.
DR Bgee; ENSMUSG00000019803; Expressed in animal zygote and 70 other tissues.
DR ExpressionAtlas; Q64104; baseline and differential.
DR Genevisible; Q64104; MM.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL.
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; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002118; P:aggressive behavior; IMP:MGI.
DR GO; GO:0021764; P:amygdala development; IMP:MGI.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0021960; P:anterior commissure morphogenesis; IMP:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0043615; P:astrocyte cell migration; IMP:MGI.
DR GO; GO:0048708; P:astrocyte differentiation; IMP:MGI.
DR GO; GO:0001662; P:behavioral fear response; IMP:MGI.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0043010; P:camera-type eye development; IMP:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; IGI:MGI.
DR GO; GO:0008283; P:cell population proliferation; IMP:MGI.
DR GO; GO:0021987; P:cerebral cortex development; IMP:MGI.
DR GO; GO:0021895; P:cerebral cortex neuron differentiation; IMP:MGI.
DR GO; GO:0021542; P:dentate gyrus development; IMP:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IMP:MGI.
DR GO; GO:0021872; P:forebrain generation of neurons; IMP:MGI.
DR GO; GO:0021819; P:layer formation in cerebral cortex; IMP:MGI.
DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; IMP:MGI.
DR GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; IMP:MGI.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IMP:MGI.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0061351; P:neural precursor cell proliferation; IMP:MGI.
DR GO; GO:0007405; P:neuroblast proliferation; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR GO; GO:0021772; P:olfactory bulb development; IMP:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:MGI.
DR GO; GO:0045787; P:positive regulation of cell cycle; IMP:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IMP:BHF-UCL.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IMP:MGI.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IMP:BHF-UCL.
DR GO; GO:0090049; P:regulation of cell migration involved in sprouting angiogenesis; IMP:MGI.
DR GO; GO:0051128; P:regulation of cellular component organization; IMP:MGI.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IMP:MGI.
DR GO; GO:0060164; P:regulation of timing of neuron differentiation; IMP: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 GO; GO:0035176; P:social behavior; IMP:MGI.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
DR GO; GO:0072089; P:stem cell proliferation; IMP:MGI.
DR GO; GO:0007601; P:visual perception; 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 Activator; Developmental protein; DNA-binding; Metal-binding; Nucleus;
KW Receptor; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..385
FT /note="Nuclear receptor subfamily 2 group E member 1"
FT /id="PRO_0000053593"
FT DOMAIN 155..383
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 13..90
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 16..36
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 52..78
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 341..385
FT /note="Required for transcriptional repression"
SQ SEQUENCE 385 AA; 42619 MW; BCEFE4F2163691AC CRC64;
MSKPAGSTSR ILDIPCKVCG DRSSGKHYGV YACDGCSGFF KRSIRRNRTY VCKSGNQGGC
PVDKTHRNQC RACRLKKCLE VNMNKDAVQH ERGPRTSTIR KQVALYFRGH KEDNGAAAHF
PSTALPAPAF FTAVTQLEPH GLELAAVSAT PERQTLVSLA QPTPKYPHEV NGTPMYLYEV
ATESVCESAA RLLFMSIKWA KSVPAFSTLS LQDQLMLLED AWRELFVLGI AQWAIPVDAN
TLLAVSGMNT DNTDSQKLNK IISEIQALQE VVARFRQLRL DATEFACLKC IVTFKAVPTH
SGSELRSFRN AAAIAALQDE AQLTLNSYIH TRYPTQPCRF GKLLLLLPAL RSISPSTIEE
VFFKKTIGNV PITRLLSDMY KSSDI
