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Q64104 (NR2E1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear receptor subfamily 2 group E member 1
Alternative name(s):
Nuclear receptor TLX
Protein tailless homolog
Short name=Tll
Short name=mTll
Gene names
Name:Nr2e1
Synonyms:Tll, Tlx
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length385 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Orphan receptor that binds DNA as a monomer to hormone response elements (HRE) containing an extended core motif half-site sequence 5'-AAGGTCA-3' in which the 5' flanking nucleotides participate in determining receptor specificity By similarity. Regulates cell cycle progression in neural stem cells of rhe developing brain. Involved in the regulation of retinal development and essential for vision. During retinogenesis, regulates PTEN-Cyclin D expression via binding to the promoter region of PTEN and suppressing its activity. May be involved in retinoic acid receptor (RAR) regulation in retinal cells. Ref.3 Ref.5 Ref.6

Subunit structure

Monomer By similarity. Interacts with ATN1; the interaction represses the transcription. Ref.5

Subcellular location

Nucleus Ref.6.

Tissue specificity

Expressed in embryonic developing forebrain and in dorsal midbrain. Outside the neural epithelium only found in the surface ectoderm at the site of nasal placode formation, where subsequently the nasal and olfactory epithelium is formed. Also expressed in adult brain. Ref.1

Developmental stage

Expression is first detected on 8 dpc and increases until 13.5 dpc, then sharply decreases from day 13 dpc until 18 dpc. Expression is barely detected in newborn brains but increases again after birth. Highly expressed in the retinal neuroblastic layer during the early stages of retinogenesis. Down-regulated during neuronal development. At E14.5, expressed in the periventricular neural stem cells of the brain. Ref.1 Ref.6

Disruption phenotype

Mice show exhibit hyperaggressivity, decreased body fat and have ocular defects. Female mice lack maternal instincts. In developing brain, there are reduced areas of the ventricular zone and enlarged ventricles. Neuron progenitor cell divide more slowly. There is complete loss of visual acuity, with mice not being able to distinguish the cliff nor light and dark transition. There is a dramatic reduction in retina thickness and enhanced generation of S-cones with more differentiated neurons, fewer proliferation retinal progenitor cells (RPCs) and more cells undergoing apoptosis leading to progressive retinal dystrophy, optic nerve degradation and blindness. Ref.3 Ref.4 Ref.5 Ref.6

Sequence similarities

Belongs to the nuclear hormone receptor family. NR2 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionActivator
Developmental protein
Receptor
Repressor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaggressive behavior

Inferred from mutant phenotype PubMed 12527005PubMed 14994267PubMed 16000615PubMed 17953618. Source: MGI

amygdala development

Inferred from mutant phenotype PubMed 12527005. Source: MGI

anterior commissure morphogenesis

Inferred from mutant phenotype Ref.4. Source: MGI

behavioral fear response

Inferred from mutant phenotype PubMed 12527005. Source: MGI

brain development

Inferred from mutant phenotype PubMed 14994267. Source: MGI

camera-type eye development

Inferred from mutant phenotype PubMed 15371513PubMed 16000615. Source: MGI

cell fate commitment

Inferred from genetic interaction PubMed 15229646. Source: MGI

cerebral cortex development

Inferred from mutant phenotype Ref.4PubMed 12527005PubMed 15950290PubMed 16000615. Source: MGI

cerebral cortex neuron differentiation

Inferred from mutant phenotype PubMed 12902391PubMed 15950290. Source: MGI

dentate gyrus development

Inferred from mutant phenotype PubMed 12527005PubMed 17953618. Source: MGI

extracellular matrix organization

Inferred from mutant phenotype PubMed 16424942. Source: MGI

forebrain generation of neurons

Inferred from mutant phenotype PubMed 9394001. Source: MGI

glial cell migration

Inferred from mutant phenotype PubMed 15371513. Source: MGI

layer formation in cerebral cortex

Inferred from mutant phenotype PubMed 15385616. Source: MGI

long-term synaptic potentiation

Inferred from mutant phenotype PubMed 16289828. Source: MGI

negative regulation of apoptotic process

Inferred from mutant phenotype Ref.5. Source: MGI

negative regulation of astrocyte differentiation

Inferred from mutant phenotype PubMed 14702088. Source: MGI

negative regulation of neural precursor cell proliferation

Inferred from mutant phenotype PubMed 12527005PubMed 15385616. Source: MGI

negative regulation of neuron differentiation

Inferred from mutant phenotype PubMed 12527005PubMed 14702088Ref.5Ref.6. Source: MGI

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL

olfactory bulb development

Inferred from mutant phenotype Ref.4PubMed 12527005. Source: MGI

positive regulation of angiogenesis

Inferred from mutant phenotype PubMed 16424942. Source: MGI

positive regulation of cell cycle

Inferred from mutant phenotype Ref.6. Source: MGI

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 14702088Ref.5. Source: MGI

positive regulation of neural precursor cell proliferation

Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL

positive regulation of stem cell proliferation

Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 19555662. Source: GOC

regulation of cell migration involved in sprouting angiogenesis

Inferred from mutant phenotype PubMed 16424942. Source: MGI

regulation of cellular component organization

Inferred from mutant phenotype PubMed 16424942. Source: MGI

regulation of dendrite morphogenesis

Inferred from mutant phenotype PubMed 16289828. Source: MGI

regulation of timing of neuron differentiation

Inferred from mutant phenotype PubMed 15385616. Source: MGI

retina development in camera-type eye

Inferred from mutant phenotype Ref.4Ref.5. Source: MGI

social behavior

Inferred from mutant phenotype Ref.4. Source: MGI

somatic stem cell maintenance

Inferred from mutant phenotype PubMed 12527005PubMed 14702088PubMed 18794344. Source: MGI

visual perception

Inferred from mutant phenotype Ref.3Ref.5. Source: MGI

   Cellular_componentnucleus

Inferred from direct assay Ref.6. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay Ref.5. Source: MGI

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription

Inferred from direct assay PubMed 14702088. Source: MGI

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from direct assay PubMed 19555662. Source: MGI

enzyme binding

Inferred from physical interaction PubMed 20123967. Source: BHF-UCL

histone deacetylase binding

Inferred from physical interaction PubMed 20123967. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.5. Source: MGI

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 385385Nuclear receptor subfamily 2 group E member 1
PRO_0000053593

Regions

DNA binding13 – 9078Nuclear receptor
Zinc finger16 – 3621NR C4-type
Zinc finger52 – 7827NR C4-type
Region187 – 354168Ligand-binding By similarity
Region341 – 38545Required for transcriptional repression
Compositional bias343 – 3475Poly-Leu

Sequences

Sequence LengthMass (Da)Tools
Q64104 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: BCEFE4F2163691AC

FASTA38542,619
        10         20         30         40         50         60 
MSKPAGSTSR ILDIPCKVCG DRSSGKHYGV YACDGCSGFF KRSIRRNRTY VCKSGNQGGC 

        70         80         90        100        110        120 
PVDKTHRNQC RACRLKKCLE VNMNKDAVQH ERGPRTSTIR KQVALYFRGH KEDNGAAAHF 

       130        140        150        160        170        180 
PSTALPAPAF FTAVTQLEPH GLELAAVSAT PERQTLVSLA QPTPKYPHEV NGTPMYLYEV 

       190        200        210        220        230        240 
ATESVCESAA RLLFMSIKWA KSVPAFSTLS LQDQLMLLED AWRELFVLGI AQWAIPVDAN 

       250        260        270        280        290        300 
TLLAVSGMNT DNTDSQKLNK IISEIQALQE VVARFRQLRL DATEFACLKC IVTFKAVPTH 

       310        320        330        340        350        360 
SGSELRSFRN AAAIAALQDE AQLTLNSYIH TRYPTQPCRF GKLLLLLPAL RSISPSTIEE 

       370        380 
VFFKKTIGNV PITRLLSDMY KSSDI 

« Hide

References

« Hide 'large scale' references
[1]"The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain."
Monaghan A.P., Grau E., Bock D., Schuetz G.
Development 121:839-853(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Tissue: Embryo.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[3]"The orphan nuclear receptor Tlx regulates Pax2 and is essential for vision."
Yu R.T., Chiang M.-Y., Tanabe T., Kobayashi M., Yasuda K., Evans R.M., Umesono K.
Proc. Natl. Acad. Sci. U.S.A. 97:2621-2625(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[4]"Fierce: a new mouse deletion of Nr2e1; violent behaviour and ocular abnormalities are background-dependent."
Young K.A., Berry M.L., Mahaffey C.L., Saionz J.R., Hawes N.L., Chang B., Zheng Q.Y., Smith R.S., Bronson R.T., Nelson R.J., Simpson E.M.
Behav. Brain Res. 132:145-158(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[5]"Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1."
Zhang C.L., Zou Y., Yu R.T., Gage F.H., Evans R.M.
Genes Dev. 20:1308-1320(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ATN1, DISRUPTION PHENOTYPE.
[6]"Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain."
Li W., Sun G., Yang S., Qu Q., Nakashima K., Shi Y.
Mol. Endocrinol. 22:56-64(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S77482 mRNA. Translation: AAB34090.1.
BC057104 mRNA. Translation: AAH57104.1.
CCDSCCDS23813.1.
RefSeqNP_689415.1. NM_152229.2.
UniGeneMm.287100.

3D structure databases

ProteinModelPortalQ64104.
SMRQ64104. Positions 16-382.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204227. 1 interaction.
DIPDIP-46432N.
STRING10090.ENSMUSP00000019938.

PTM databases

PhosphoSiteQ64104.

Proteomic databases

PRIDEQ64104.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000019938; ENSMUSP00000019938; ENSMUSG00000019803.
GeneID21907.
KEGGmmu:21907.
UCSCuc007eyt.1. mouse.

Organism-specific databases

CTD7101.
MGIMGI:1100526. Nr2e1.

Phylogenomic databases

eggNOGNOG277339.
HOGENOMHOG000260820.
HOVERGENHBG005606.
InParanoidQ64104.
KOK08545.
OMAILLEDAW.
OrthoDBEOG7WT41C.
PhylomeDBQ64104.
TreeFamTF315716.

Gene expression databases

BgeeQ64104.
CleanExMM_NR2E1.
GenevestigatorQ64104.

Family and domain databases

Gene3D1.10.565.10. 2 hits.
3.30.50.10. 1 hit.
InterProIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
PROSITEPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio301450.
PROQ64104.
SOURCESearch...

Entry information

Entry nameNR2E1_MOUSE
AccessionPrimary (citable) accession number: Q64104
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot