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Protein

Nuclear receptor subfamily 4 group A member 2

Gene

Nr4a2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi260 – 33576Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri263 – 28321NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri299 – 32325NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. DNA binding Source: MGI
  2. ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Source: MGI
  3. protein heterodimerization activity Source: MGI
  4. RNA polymerase II core promoter sequence-specific DNA binding Source: MGI
  5. RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  6. RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
  7. sequence-specific DNA binding Source: MGI
  8. steroid hormone receptor activity Source: InterPro
  9. zinc ion binding Source: InterPro

GO - Biological processi

  1. adult locomotory behavior Source: MGI
  2. cellular response to extracellular stimulus Source: MGI
  3. cellular response to oxidative stress Source: MGI
  4. central nervous system neuron differentiation Source: MGI
  5. central nervous system projection neuron axonogenesis Source: MGI
  6. death Source: MGI
  7. dopamine biosynthetic process Source: MGI
  8. dopamine metabolic process Source: MGI
  9. dopaminergic neuron differentiation Source: UniProtKB
  10. gene expression Source: MGI
  11. general adaptation syndrome Source: MGI
  12. habenula development Source: MGI
  13. intracellular receptor signaling pathway Source: GOC
  14. negative regulation of neuron apoptotic process Source: MGI
  15. nervous system development Source: MGI
  16. neuron differentiation Source: MGI
  17. neuron maturation Source: MGI
  18. neuron migration Source: MGI
  19. positive regulation of catalytic activity Source: MGI
  20. positive regulation of transcription, DNA-templated Source: MGI
  21. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  22. post-embryonic development Source: MGI
  23. regulation of dopamine metabolic process Source: MGI
  24. regulation of gene expression Source: MGI
  25. regulation of respiratory gaseous exchange Source: MGI
  26. regulation of transcription, DNA-templated Source: MGI
  27. response to amphetamine Source: MGI
  28. response to hypoxia Source: MGI
  29. response to inorganic substance Source: MGI
  30. response to insecticide Source: MGI
  31. transcription, DNA-templated Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_276696. Nuclear Receptor transcription pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 4 group A member 2
Alternative name(s):
NUR-related factor 1
Orphan nuclear receptor NURR1
Gene namesi
Name:Nr4a2
Synonyms:Nurr1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1352456. Nr4a2.

Subcellular locationi

  1. Cytoplasm By similarity
  2. Nucleus

  3. Note: Mostly nuclear; oxidative stress promotes cytoplasmic localization.By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. nucleoplasm Source: MGI
  3. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 598598Nuclear receptor subfamily 4 group A member 2PRO_0000053719Add
BLAST

Proteomic databases

PRIDEiQ06219.

PTM databases

PhosphoSiteiQ06219.

Expressioni

Tissue specificityi

Brain.

Developmental stagei

Expression begins in the embryo, increases in neonates and decreases in the adult.

Gene expression databases

BgeeiQ06219.
CleanExiMM_NR4A2.
ExpressionAtlasiQ06219. baseline and differential.
GenevestigatoriQ06219.

Interactioni

Subunit structurei

Interacts with SFPQ, NCOR2, SIN3A and HADC1. The interaction with NCOR2 increases in the absence of PITX3. Interacts with PER2.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Rcor1Q8CFE35EBI-2337255,EBI-2337309
RelaQ042072EBI-2337255,EBI-644400

Protein-protein interaction databases

BioGridi201880. 1 interaction.
IntActiQ06219. 3 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ06219.
SMRiQ06219. Positions 261-598.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni409 – 45951Ligand-bindingSequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi287 – 31428Bipartite nuclear localization signal (NLS1)By similarityAdd
BLAST
Motifi338 – 35013Nuclear localization signal (NLS1)By similarityAdd
BLAST
Motifi443 – 45210nuclear export sequence (NES1)By similarity
Motifi568 – 57710nuclear export sequence (NES2)By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi80 – 13859Gln-richAdd
BLAST
Compositional biasi127 – 233107Pro-richAdd
BLAST
Compositional biasi346 – 39146Pro-richAdd
BLAST

Domaini

the ligand-binding domain (LBD) contains no cavity as a result of the tight packing of side chains from several bulky hydrophobic residues in the region normally occupied by ligands. NR4A2 lacks a 'classical' binding site for coactivators (By similarity).By similarity

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri263 – 28321NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri299 – 32325NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiNOG245120.
HOGENOMiHOG000230925.
HOVERGENiHBG052663.
InParanoidiQ06219.
KOiK08558.
OMAiVNCLKDQ.
OrthoDBiEOG75XGKJ.
PhylomeDBiQ06219.
TreeFamiTF315430.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003070. Nuc_orph_rcpt.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR003073. NURR_rcpt.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01284. NUCLEARECPTR.
PR01287. NURRNUCRCPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform NURR1 (identifier: Q06219-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPCVQAQYGS SPQGASPASQ SYSYHSSGEY SSDFLTPEFV KFSMDLTNTE
60 70 80 90 100
ITATTSLPSF STFMDNYSTG YDVKPPCLYQ MPLSGQQSSI KVEDIQMHNY
110 120 130 140 150
QQHSHLPPQS EEMMPHSGSV YYKPSSPPTP STPSFQVQHS PMWDDPGSLH
160 170 180 190 200
NFHQNYVATT HMIEQRKTPV SRLSLFSFKQ SPPGTPVSSC QMRFDGPLHV
210 220 230 240 250
PMNPEPAGSH HVVDGQTFAV PNPIRKPASM GFPGLQIGHA SQLLDTQVPS
260 270 280 290 300
PPSRGSPSNE GLCAVCGDNA ACQHYGVRTC EGCKGFFKRT VQKNAKYVCL
310 320 330 340 350
ANKNCPVDKR RRNRCQYCRF QKCLAVGMVK EVVRTDSLKG RRGRLPSKPK
360 370 380 390 400
SPQDPSPPSP PVSLISALVR AHVDSNPAMT SLDYSRFQAN PDYQMSGDDT
410 420 430 440 450
QHIQQFYDLL TGSMEIIRGW AEKIPGFADL PKADQDLLFE SAFLELFVLR
460 470 480 490 500
LAYRSNPVEG KLIFCNGVVL HRLQCVRGFG EWIDSIVEFS SNLQNMNIDI
510 520 530 540 550
SAFSCIAALA MVTERHGLKE PKRVEELQNK IVNCLKDHVT FNNGGLNRPN
560 570 580 590
YLSKLLGKLP ELRTLCTQGL QRIFYLKLED LVPPPAIIDK LFLDTLPF
Length:598
Mass (Da):66,593
Last modified:June 1, 1994 - v1
Checksum:iD1AC5EB2FFB8D366
GO
Isoform NURR1A (identifier: Q06219-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     455-455: S → I
     456-598: Missing.

Show »
Length:455
Mass (Da):50,458
Checksum:iA3B91CFBAAD62D13
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei455 – 4551S → I in isoform NURR1A. CuratedVSP_003710
Alternative sequencei456 – 598143Missing in isoform NURR1A. CuratedVSP_003711Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S53744 mRNA. Translation: AAB25138.1.
U86783 Genomic DNA. Translation: AAC53153.1.
U86783 Genomic DNA. Translation: AAC53154.1.
CCDSiCCDS16043.1. [Q06219-1]
PIRiA46225.
RefSeqiNP_001132981.1. NM_001139509.1. [Q06219-1]
NP_038641.1. NM_013613.2. [Q06219-1]
UniGeneiMm.3507.

Genome annotation databases

EnsembliENSMUST00000028166; ENSMUSP00000028166; ENSMUSG00000026826. [Q06219-1]
ENSMUST00000112629; ENSMUSP00000108248; ENSMUSG00000026826. [Q06219-1]
GeneIDi18227.
KEGGimmu:18227.
UCSCiuc008jrw.2. mouse. [Q06219-1]
uc012bvn.1. mouse. [Q06219-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S53744 mRNA. Translation: AAB25138.1.
U86783 Genomic DNA. Translation: AAC53153.1.
U86783 Genomic DNA. Translation: AAC53154.1.
CCDSiCCDS16043.1. [Q06219-1]
PIRiA46225.
RefSeqiNP_001132981.1. NM_001139509.1. [Q06219-1]
NP_038641.1. NM_013613.2. [Q06219-1]
UniGeneiMm.3507.

3D structure databases

ProteinModelPortaliQ06219.
SMRiQ06219. Positions 261-598.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201880. 1 interaction.
IntActiQ06219. 3 interactions.

PTM databases

PhosphoSiteiQ06219.

Proteomic databases

PRIDEiQ06219.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028166; ENSMUSP00000028166; ENSMUSG00000026826. [Q06219-1]
ENSMUST00000112629; ENSMUSP00000108248; ENSMUSG00000026826. [Q06219-1]
GeneIDi18227.
KEGGimmu:18227.
UCSCiuc008jrw.2. mouse. [Q06219-1]
uc012bvn.1. mouse. [Q06219-2]

Organism-specific databases

CTDi4929.
MGIiMGI:1352456. Nr4a2.

Phylogenomic databases

eggNOGiNOG245120.
HOGENOMiHOG000230925.
HOVERGENiHBG052663.
InParanoidiQ06219.
KOiK08558.
OMAiVNCLKDQ.
OrthoDBiEOG75XGKJ.
PhylomeDBiQ06219.
TreeFamiTF315430.

Enzyme and pathway databases

ReactomeiREACT_276696. Nuclear Receptor transcription pathway.

Miscellaneous databases

ChiTaRSiNr4a2. mouse.
NextBioi293656.
PROiQ06219.
SOURCEiSearch...

Gene expression databases

BgeeiQ06219.
CleanExiMM_NR4A2.
ExpressionAtlasiQ06219. baseline and differential.
GenevestigatoriQ06219.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003070. Nuc_orph_rcpt.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR003073. NURR_rcpt.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01284. NUCLEARECPTR.
PR01287. NURRNUCRCPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Identification of a new brain-specific transcription factor, NURR1."
    Law S.W., Conneely O.M., DeMayo F.J., O'Malley B.W.
    Mol. Endocrinol. 6:2129-2135(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM NURR1).
    Tissue: Brain.
  2. "Organization, sequence, chromosomal localization, and promoter identification of the mouse orphan nuclear receptor Nurr1 gene."
    Castillo S.O., Xiao Q., Lyu M.S., Kozak C.A., Nikodem V.M.
    Genomics 41:250-257(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129/SvJ.
  3. "Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression."
    Jacobs F.M., van Erp S., van der Linden A.J., von Oerthel L., Burbach J.P., Smidt M.P.
    Development 136:531-540(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SFPQ; NCOR2; SIN3A AND HDAC1.
  4. "The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors."
    Schmutz I., Ripperger J.A., Baeriswyl-Aebischer S., Albrecht U.
    Genes Dev. 24:345-357(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PER2.

Entry informationi

Entry nameiNR4A2_MOUSE
AccessioniPrimary (citable) accession number: Q06219
Secondary accession number(s): O08690
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: April 1, 2015
This is version 137 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.