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   24-JAN-2024, entry version 191.
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 (PubMed:19144721). It is crucial for
CC       expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which
CC       are essential for development of mdDA neurons (PubMed:19144721).
CC       {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|UniProtKB:P43354}. Nucleus
CC       {ECO:0000250|UniProtKB:P43354}. Note=Mostly nuclear; oxidative stress
CC       promotes cytoplasmic localization. {ECO:0000250|UniProtKB:P43354}.
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.
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; 10090-ENSMUSP00000028166; -.
DR   ProteomicsDB; 293968; -. [Q06219-1]
DR   ProteomicsDB; 293969; -. [Q06219-2]
DR   Antibodypedia; 621; 527 antibodies from 40 providers.
DR   DNASU; 18227; -.
DR   Ensembl; ENSMUST00000028166.9; ENSMUSP00000028166.3; ENSMUSG00000026826.14. [Q06219-1]
DR   Ensembl; ENSMUST00000112629.8; ENSMUSP00000108248.2; ENSMUSG00000026826.14. [Q06219-1]
DR   GeneID; 18227; -.
DR   KEGG; mmu:18227; -.
DR   UCSC; uc008jrw.2; mouse. [Q06219-1]
DR   UCSC; uc012bvn.1; mouse. [Q06219-2]
DR   AGR; MGI:1352456; -.
DR   CTD; 4929; -.
DR   MGI; MGI:1352456; Nr4a2.
DR   VEuPathDB; HostDB:ENSMUSG00000026826; -.
DR   eggNOG; KOG4217; Eukaryota.
DR   GeneTree; ENSGT00950000183038; -.
DR   InParanoid; Q06219; -.
DR   OMA; GSCQMRF; -.
DR   OrthoDB; 5395768at2759; -.
DR   PhylomeDB; Q06219; -.
DR   TreeFam; TF315430; -.
DR   Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR   BioGRID-ORCS; 18227; 3 hits in 80 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 244 other cell types or tissues.
DR   ExpressionAtlas; Q06219; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
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:0006351; P:DNA-templated transcription; IDA:UniProtKB.
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:0045893; P:positive regulation of DNA-templated transcription; IDA:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR   GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; 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: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   CDD; cd06969; NR_DBD_NGFI-B; 1.
DR   CDD; cd07071; NR_LBD_Nurr1; 1.
DR   Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1.
DR   Gene3D; 1.10.565.10; Retinoid X Receptor; 1.
DR   InterPro; IPR035500; NHR-like_dom_sf.
DR   InterPro; IPR003070; NR4A1-3.
DR   InterPro; IPR003073; NR4A2.
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   PANTHER; PTHR24085; NUCLEAR HORMONE RECEPTOR; 1.
DR   PANTHER; PTHR24085:SF0; NUCLEAR RECEPTOR SUBFAMILY 4 GROUP A MEMBER 2; 1.
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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR   SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1.
DR   PROSITE; PS51843; NR_LBD; 1.
DR   PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR   PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
DR   Genevisible; Q06219; MM.
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
//