NR4A2_MOUSE
ID NR4A2_MOUSE Reviewed; 598 AA.
AC Q06219; O08690;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Nuclear receptor subfamily 4 group A member 2;
DE AltName: Full=NUR-related factor 1;
DE AltName: Full=Orphan nuclear receptor NURR1;
GN Name=Nr4a2; Synonyms=Nurr1;
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] (ISOFORM NURR1).
RC TISSUE=Brain;
RX PubMed=1491694; DOI=10.1210/mend.6.12.1491694;
RA Law S.W., Conneely O.M., DeMayo F.J., O'Malley B.W.;
RT "Identification of a new brain-specific transcription factor, NURR1.";
RL Mol. Endocrinol. 6:2129-2135(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=9143501; DOI=10.1006/geno.1997.4677;
RA Castillo S.O., Xiao Q., Lyu M.S., Kozak C.A., Nikodem V.M.;
RT "Organization, sequence, chromosomal localization, and promoter
RT identification of the mouse orphan nuclear receptor Nurr1 gene.";
RL Genomics 41:250-257(1997).
RN [3]
RP FUNCTION, AND INTERACTION WITH SFPQ; NCOR2; SIN3A AND HDAC1.
RX PubMed=19144721; DOI=10.1242/dev.029769;
RA Jacobs F.M., van Erp S., van der Linden A.J., von Oerthel L., Burbach J.P.,
RA Smidt M.P.;
RT "Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation
RT through release of SMRT-mediated repression.";
RL Development 136:531-540(2009).
RN [4]
RP INTERACTION WITH PER2.
RX PubMed=20159955; DOI=10.1101/gad.564110;
RA Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.;
RT "The mammalian clock component PERIOD2 coordinates circadian output by
RT interaction with nuclear receptors.";
RL Genes Dev. 24:345-357(2010).
CC -!- FUNCTION: Transcriptional regulator which is important for the
CC differentiation and maintenance of meso-diencephalic dopaminergic
CC (mdDA) neurons during development. It is crucial for expression of a
CC set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential
CC for development of mdDA neurons. {ECO:0000269|PubMed:19144721}.
CC -!- SUBUNIT: Interacts with SFPQ, NCOR2, SIN3A and HADC1. The interaction
CC with NCOR2 increases in the absence of PITX3. Interacts with PER2.
CC {ECO:0000269|PubMed:19144721, ECO:0000269|PubMed:20159955}.
CC -!- INTERACTION:
CC Q06219; Q8CFE3: Rcor1; NbExp=5; IntAct=EBI-2337255, EBI-2337309;
CC Q06219; Q04207: Rela; NbExp=2; IntAct=EBI-2337255, EBI-644400;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus. Note=Mostly
CC nuclear; oxidative stress promotes cytoplasmic localization.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=NURR1;
CC IsoId=Q06219-1; Sequence=Displayed;
CC Name=NURR1A;
CC IsoId=Q06219-2; Sequence=VSP_003710, VSP_003711;
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- DEVELOPMENTAL STAGE: Expression begins in the embryo, increases in
CC neonates and decreases in the adult.
CC -!- DOMAIN: the ligand-binding domain (LBD) contains no cavity as a result
CC of the tight packing of side chains from several bulky hydrophobic
CC residues in the region normally occupied by ligands. NR4A2 lacks a
CC 'classical' binding site for coactivators (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR4
CC subfamily. {ECO:0000305}.
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DR EMBL; S53744; AAB25138.1; -; mRNA.
DR EMBL; U86783; AAC53153.1; -; Genomic_DNA.
DR EMBL; U86783; AAC53154.1; -; Genomic_DNA.
DR CCDS; CCDS16043.1; -. [Q06219-1]
DR PIR; A46225; A46225.
DR RefSeq; NP_001132981.1; NM_001139509.1. [Q06219-1]
DR RefSeq; NP_038641.1; NM_013613.2. [Q06219-1]
DR RefSeq; XP_011237335.1; XM_011239033.2. [Q06219-1]
DR RefSeq; XP_011237336.1; XM_011239034.2. [Q06219-1]
DR AlphaFoldDB; Q06219; -.
DR BMRB; Q06219; -.
DR SMR; Q06219; -.
DR BioGRID; 201880; 4.
DR IntAct; Q06219; 5.
DR STRING; 10090.ENSMUSP00000028166; -.
DR BindingDB; Q06219; -.
DR ChEMBL; CHEMBL3879839; -.
DR iPTMnet; Q06219; -.
DR PhosphoSitePlus; Q06219; -.
DR PaxDb; Q06219; -.
DR PRIDE; Q06219; -.
DR ProteomicsDB; 293968; -. [Q06219-1]
DR ProteomicsDB; 293969; -. [Q06219-2]
DR Antibodypedia; 621; 424 antibodies from 40 providers.
DR DNASU; 18227; -.
DR Ensembl; ENSMUST00000028166; ENSMUSP00000028166; ENSMUSG00000026826. [Q06219-1]
DR Ensembl; ENSMUST00000112629; ENSMUSP00000108248; ENSMUSG00000026826. [Q06219-1]
DR GeneID; 18227; -.
DR KEGG; mmu:18227; -.
DR UCSC; uc008jrw.2; mouse. [Q06219-1]
DR UCSC; uc012bvn.1; mouse. [Q06219-2]
DR CTD; 4929; -.
DR MGI; MGI:1352456; Nr4a2.
DR VEuPathDB; HostDB:ENSMUSG00000026826; -.
DR eggNOG; KOG4217; Eukaryota.
DR GeneTree; ENSGT00950000183038; -.
DR InParanoid; Q06219; -.
DR OMA; HAAGEYS; -.
DR PhylomeDB; Q06219; -.
DR TreeFam; TF315430; -.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 18227; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Nr4a2; mouse.
DR PRO; PR:Q06219; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q06219; protein.
DR Bgee; ENSMUSG00000026826; Expressed in habenula and 242 other tissues.
DR ExpressionAtlas; Q06219; baseline and differential.
DR Genevisible; Q06219; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; IPI:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; TAS:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IMP:NTNU_SB.
DR GO; GO:0043565; F: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:0008344; P:adult locomotory behavior; IMP:MGI.
DR GO; GO:0071376; P:cellular response to corticotropin-releasing hormone stimulus; IDA:UniProtKB.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IDA:MGI.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:MGI.
DR GO; GO:0021953; P:central nervous system neuron differentiation; IMP:MGI.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; IMP:MGI.
DR GO; GO:0042416; P:dopamine biosynthetic process; IMP:MGI.
DR GO; GO:0042417; P:dopamine metabolic process; IMP:MGI.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IDA:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0051866; P:general adaptation syndrome; IMP:MGI.
DR GO; GO:0021986; P:habenula development; IMP:MGI.
DR GO; GO:0007611; P:learning or memory; ISO:MGI.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; IMP:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR GO; GO:0042551; P:neuron maturation; IMP:MGI.
DR GO; GO:0001764; P:neuron migration; IMP:MGI.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0042053; P:regulation of dopamine metabolic process; IDA:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0043576; P:regulation of respiratory gaseous exchange; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:0001975; P:response to amphetamine; IMP:MGI.
DR GO; GO:0001666; P:response to hypoxia; IMP:MGI.
DR GO; GO:0010035; P:response to inorganic substance; ISO:MGI.
DR GO; GO:0017085; P:response to insecticide; ISO:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:UniProtKB.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR003070; Nuc_orph_rcpt.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR003073; NURR_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; PR01284; NUCLEARECPTR.
DR PRINTS; PR01287; NURRNUCRCPTR.
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 Alternative splicing; Cytoplasm; DNA-binding; Metal-binding; Nucleus;
KW Receptor; Reference proteome; Transcription; Transcription regulation;
KW Zinc; Zinc-finger.
FT CHAIN 1..598
FT /note="Nuclear receptor subfamily 4 group A member 2"
FT /id="PRO_0000053719"
FT DOMAIN 360..595
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 260..335
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 263..283
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 299..323
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 337..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 287..314
FT /note="Bipartite nuclear localization signal (NLS1)"
FT /evidence="ECO:0000250"
FT MOTIF 338..350
FT /note="Nuclear localization signal (NLS1)"
FT /evidence="ECO:0000250"
FT MOTIF 443..452
FT /note="nuclear export sequence (NES1)"
FT /evidence="ECO:0000250"
FT MOTIF 568..577
FT /note="nuclear export sequence (NES2)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 455
FT /note="S -> I (in isoform NURR1A)"
FT /evidence="ECO:0000305"
FT /id="VSP_003710"
FT VAR_SEQ 456..598
FT /note="Missing (in isoform NURR1A)"
FT /evidence="ECO:0000305"
FT /id="VSP_003711"
SQ SEQUENCE 598 AA; 66593 MW; D1AC5EB2FFB8D366 CRC64;
MPCVQAQYGS SPQGASPASQ SYSYHSSGEY SSDFLTPEFV KFSMDLTNTE ITATTSLPSF
STFMDNYSTG YDVKPPCLYQ MPLSGQQSSI KVEDIQMHNY QQHSHLPPQS EEMMPHSGSV
YYKPSSPPTP STPSFQVQHS PMWDDPGSLH NFHQNYVATT HMIEQRKTPV SRLSLFSFKQ
SPPGTPVSSC QMRFDGPLHV PMNPEPAGSH HVVDGQTFAV PNPIRKPASM GFPGLQIGHA
SQLLDTQVPS PPSRGSPSNE GLCAVCGDNA ACQHYGVRTC EGCKGFFKRT VQKNAKYVCL
ANKNCPVDKR RRNRCQYCRF QKCLAVGMVK EVVRTDSLKG RRGRLPSKPK SPQDPSPPSP
PVSLISALVR AHVDSNPAMT SLDYSRFQAN PDYQMSGDDT QHIQQFYDLL TGSMEIIRGW
AEKIPGFADL PKADQDLLFE SAFLELFVLR LAYRSNPVEG KLIFCNGVVL HRLQCVRGFG
EWIDSIVEFS SNLQNMNIDI SAFSCIAALA MVTERHGLKE PKRVEELQNK IVNCLKDHVT
FNNGGLNRPN YLSKLLGKLP ELRTLCTQGL QRIFYLKLED LVPPPAIIDK LFLDTLPF
