NR2E1_HUMAN
ID NR2E1_HUMAN Reviewed; 385 AA.
AC Q9Y466; Q6ZMP8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 193.
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=hTll;
GN Name=NR2E1; Synonyms=TLX;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=9628820; DOI=10.1006/geno.1998.5270;
RA Jackson A., Panayiotidis P., Foroni L.;
RT "The human homologue of the Drosophila tailless gene (TLX):
RT characterization and mapping to a region of common deletion in human
RT lymphoid leukemia on chromosome 6q21.";
RL Genomics 50:34-43(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND POSSIBLE FUNCTION.
RC TISSUE=Brain;
RX PubMed=11073974; DOI=10.1128/mcb.20.23.8731-8739.2000;
RA Kobayashi M., Yu R.T., Yasuda K., Umesono K.;
RT "Cell-type-specific regulation of the retinoic acid receptor mediated by
RT the orphan nuclear receptor TLX.";
RL Mol. Cell. Biol. 20:8731-8739(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Hua F., Wu J., Zhang B., Peng X., Yuan J., Qiang B.;
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC 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).
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). May be required to
CC pattern anterior brain differentiation. Involved in the regulation of
CC retinal development and essential for vision. During retinogenesis,
CC regulates PTEN-Cyclin D expression via binding to the promoter region
CC of PTEN and suppressing its activity (By similarity). May be involved
CC in retinoic acid receptor (RAR) regulation in retinal cells.
CC {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Interacts with ATN1; the interaction represses the
CC transcription. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y466-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y466-2; Sequence=VSP_054639;
CC -!- TISSUE SPECIFICITY: Brain specific. Present in all brain sections
CC tested, highest levels in the caudate nucleus and hippocampus, weakest
CC levels in the thalamus. {ECO:0000269|PubMed:9628820}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
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DR EMBL; Y13276; CAA73725.1; -; mRNA.
DR EMBL; AF220532; AAG31945.1; -; mRNA.
DR EMBL; AF411525; AAL05871.1; -; mRNA.
DR EMBL; AK131541; BAD18677.1; -; mRNA.
DR EMBL; AL078596; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48386.1; -; Genomic_DNA.
DR EMBL; BC028031; AAH28031.1; -; mRNA.
DR CCDS; CCDS5063.1; -. [Q9Y466-1]
DR CCDS; CCDS69165.1; -. [Q9Y466-2]
DR RefSeq; NP_001273031.1; NM_001286102.1. [Q9Y466-2]
DR RefSeq; NP_003260.1; NM_003269.4. [Q9Y466-1]
DR PDB; 4XAJ; X-ray; 3.55 A; A/B/C/D=180-383.
DR PDBsum; 4XAJ; -.
DR AlphaFoldDB; Q9Y466; -.
DR SMR; Q9Y466; -.
DR BioGRID; 112956; 37.
DR IntAct; Q9Y466; 14.
DR MINT; Q9Y466; -.
DR STRING; 9606.ENSP00000357979; -.
DR ChEMBL; CHEMBL1961788; -.
DR DrugCentral; Q9Y466; -.
DR GuidetoPHARMACOLOGY; 615; -.
DR iPTMnet; Q9Y466; -.
DR PhosphoSitePlus; Q9Y466; -.
DR BioMuta; NR2E1; -.
DR DMDM; 9910804; -.
DR PaxDb; Q9Y466; -.
DR PeptideAtlas; Q9Y466; -.
DR PRIDE; Q9Y466; -.
DR ProteomicsDB; 67899; -.
DR ProteomicsDB; 86113; -. [Q9Y466-1]
DR Antibodypedia; 19108; 312 antibodies from 33 providers.
DR DNASU; 7101; -.
DR Ensembl; ENST00000368983.3; ENSP00000357979.3; ENSG00000112333.12. [Q9Y466-2]
DR Ensembl; ENST00000368986.9; ENSP00000357982.5; ENSG00000112333.12. [Q9Y466-1]
DR GeneID; 7101; -.
DR KEGG; hsa:7101; -.
DR MANE-Select; ENST00000368986.9; ENSP00000357982.5; NM_003269.5; NP_003260.1.
DR UCSC; uc003psg.4; human. [Q9Y466-1]
DR CTD; 7101; -.
DR DisGeNET; 7101; -.
DR GeneCards; NR2E1; -.
DR HGNC; HGNC:7973; NR2E1.
DR HPA; ENSG00000112333; Group enriched (brain, choroid plexus, retina).
DR MIM; 603849; gene.
DR neXtProt; NX_Q9Y466; -.
DR OpenTargets; ENSG00000112333; -.
DR PharmGKB; PA31756; -.
DR VEuPathDB; HostDB:ENSG00000112333; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000156693; -.
DR HOGENOM; CLU_007368_20_3_1; -.
DR InParanoid; Q9Y466; -.
DR OMA; VVSLMHK; -.
DR OrthoDB; 870262at2759; -.
DR PhylomeDB; Q9Y466; -.
DR TreeFam; TF315716; -.
DR PathwayCommons; Q9Y466; -.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR SignaLink; Q9Y466; -.
DR SIGNOR; Q9Y466; -.
DR BioGRID-ORCS; 7101; 11 hits in 1090 CRISPR screens.
DR ChiTaRS; NR2E1; human.
DR GeneWiki; TLX; -.
DR GenomeRNAi; 7101; -.
DR Pharos; Q9Y466; Tbio.
DR PRO; PR:Q9Y466; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9Y466; protein.
DR Bgee; ENSG00000112333; Expressed in ventricular zone and 59 other tissues.
DR ExpressionAtlas; Q9Y466; baseline and differential.
DR Genevisible; Q9Y466; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0042826; F:histone deacetylase binding; IEA:Ensembl.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0003707; F:nuclear steroid receptor activity; TAS:ProtInc.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0002118; P:aggressive behavior; IEA:Ensembl.
DR GO; GO:0021764; P:amygdala development; IEA:Ensembl.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0021960; P:anterior commissure morphogenesis; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0043615; P:astrocyte cell migration; IEA:Ensembl.
DR GO; GO:0048708; P:astrocyte differentiation; IEA:Ensembl.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl.
DR GO; GO:0021895; P:cerebral cortex neuron differentiation; IEA:Ensembl.
DR GO; GO:0021542; P:dentate gyrus development; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0021872; P:forebrain generation of neurons; IEA:Ensembl.
DR GO; GO:0021819; P:layer formation in cerebral cortex; IEA:Ensembl.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; IEA:Ensembl.
DR GO; GO:2000178; P:negative regulation of neural precursor cell proliferation; IEA:Ensembl.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0021772; P:olfactory bulb development; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0045787; P:positive regulation of cell cycle; IEA:Ensembl.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IEA:Ensembl.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0090049; P:regulation of cell migration involved in sprouting angiogenesis; IEA:Ensembl.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IEA:Ensembl.
DR GO; GO:0060164; P:regulation of timing of neuron differentiation; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; IEA:Ensembl.
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 3D-structure; Activator; Alternative splicing; Developmental protein;
KW DNA-binding; Metal-binding; Nucleus; Receptor; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..385
FT /note="Nuclear receptor subfamily 2 group E member 1"
FT /id="PRO_0000053592"
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"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..9
FT /note="MSKPAGSTS -> MFRAGAEGAEKEPSPRPECRADPGPGLGFPLGSGLPWPS
FT LLESPGG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054639"
SQ SEQUENCE 385 AA; 42589 MW; 39181A42A2FB79C2 CRC64;
MSKPAGSTSR ILDIPCKVCG DRSSGKHYGV YACDGCSGFF KRSIRRNRTY VCKSGNQGGC
PVDKTHRNQC RACRLKKCLE VNMNKDAVQH ERGPRTSTIR KQVALYFRGH KEENGAAAHF
PSAALPAPAF FTAVTQLEPH GLELAAVSTT PERQTLVSLA QPTPKYPHEV NGTPMYLYEV
ATESVCESAA RLLFMSIKWA KSVPAFSTLS LQDQLMLLED AWRELFVLGI AQWAIPVDAN
TLLAVSGMNG DNTDSQKLNK IISEIQALQE VVARFRQLRL DATEFACLKC IVTFKAVPTH
SGSELRSFRN AAAIAALQDE AQLTLNSYIH TRYPTQPCRF GKLLLLLPAL RSISPSTIEE
VFFKKTIGNV PITRLLSDMY KSSDI
