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P43354 (NR4A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear receptor subfamily 4 group A member 2
Alternative name(s):
Immediate-early response protein NOT
Orphan nuclear receptor NURR1
Transcriptionally-inducible nuclear receptor
Gene names
Name:NR4A2
Synonyms:NOT, NURR1, TINUR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length598 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Ref.8

Subunit structure

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

Subcellular location

Cytoplasm. Nucleus. Note: Mostly nuclear; oxidative stress promotes cytoplasmic localization. Ref.8 Ref.10

Tissue specificity

Expressed in a number of cell lines of T-cell, B-cell and fibroblast origin. Strong expression in brain tissue.

Developmental stage

Rapidly and only very transiently expressed after cell activation, during the G0-G1 transition of the cell cycle.

Domain

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 (Ref.11).

Sequence similarities

Belongs to the nuclear hormone receptor family. NR4 subfamily.

Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainZinc-finger
   LigandDNA-binding
Metal-binding
Zinc
   Molecular functionReceptor
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadult locomotory behavior

Inferred from electronic annotation. Source: Ensembl

cellular response to extracellular stimulus

Inferred from direct assay Ref.1. Source: MGI

cellular response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

central nervous system projection neuron axonogenesis

Inferred from electronic annotation. Source: Ensembl

death

Inferred from electronic annotation. Source: Ensembl

dopamine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

dopaminergic neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

gene expression

Traceable author statement. Source: Reactome

general adaptation syndrome

Inferred from electronic annotation. Source: Ensembl

habenula development

Inferred from electronic annotation. Source: Ensembl

intracellular receptor signaling pathway

Traceable author statement Ref.1. Source: GOC

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

neuron maturation

Inferred from electronic annotation. Source: Ensembl

neuron migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of catalytic activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

post-embryonic development

Inferred from electronic annotation. Source: Ensembl

regulation of dopamine metabolic process

Inferred from electronic annotation. Source: Ensembl

regulation of respiratory gaseous exchange

Inferred from electronic annotation. Source: Ensembl

response to amphetamine

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to inorganic substance

Inferred from electronic annotation. Source: Ensembl

response to insecticide

Inferred from electronic annotation. Source: Ensembl

signal transduction

Non-traceable author statement Ref.1. Source: ProtInc

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from direct assay Ref.8. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.8. Source: UniProtKB

   Molecular_functionligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction PubMed 20195357. Source: IntAct

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TCEAL5Q5H9L22EBI-2681738,EBI-2681773

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 598598Nuclear receptor subfamily 4 group A member 2
PRO_0000053718

Regions

DNA binding260 – 33576Nuclear receptor
Zinc finger263 – 28321NR C4-type
Zinc finger299 – 32325NR C4-type
Region409 – 45951Ligand-binding Potential
Motif287 – 31428Bipartite nuclear localization signal (NLS1)
Motif338 – 35013Nuclear localization signal (NLS1) Ref.10
Motif443 – 45210nuclear export sequence (NES1)
Motif568 – 57710nuclear export sequence (NES2)
Compositional bias80 – 13859Gln-rich
Compositional bias127 – 233107Pro-rich
Compositional bias346 – 39146Pro-rich

Experimental info

Sequence conflict4651C → W in AAB33999. Ref.7
Sequence conflict4681V → W in AAB33999. Ref.7

Secondary structure

.............................. 598
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P43354 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 28D8199AACE3E211

FASTA59866,591
        10         20         30         40         50         60 
MPCVQAQYGS SPQGASPASQ SYSYHSSGEY SSDFLTPEFV KFSMDLTNTE ITATTSLPSF 

        70         80         90        100        110        120 
STFMDNYSTG YDVKPPCLYQ MPLSGQQSSI KVEDIQMHNY QQHSHLPPQS EEMMPHSGSV 

       130        140        150        160        170        180 
YYKPSSPPTP TTPGFQVQHS PMWDDPGSLH NFHQNYVATT HMIEQRKTPV SRLSLFSFKQ 

       190        200        210        220        230        240 
SPPGTPVSSC QMRFDGPLHV PMNPEPAGSH HVVDGQTFAV PNPIRKPASM GFPGLQIGHA 

       250        260        270        280        290        300 
SQLLDTQVPS PPSRGSPSNE GLCAVCGDNA ACQHYGVRTC EGCKGFFKRT VQKNAKYVCL 

       310        320        330        340        350        360 
ANKNCPVDKR RRNRCQYCRF QKCLAVGMVK EVVRTDSLKG RRGRLPSKPK SPQEPSPPSP 

       370        380        390        400        410        420 
PVSLISALVR AHVDSNPAMT SLDYSRFQAN PDYQMSGDDT QHIQQFYDLL TGSMEIIRGW 

       430        440        450        460        470        480 
AEKIPGFADL PKADQDLLFE SAFLELFVLR LAYRSNPVEG KLIFCNGVVL HRLQCVRGFG 

       490        500        510        520        530        540 
EWIDSIVEFS SNLQNMNIDI SAFSCIAALA MVTERHGLKE PKRVEELQNK IVNCLKDHVT 

       550        560        570        580        590 
FNNGGLNRPN YLSKLLGKLP ELRTLCTQGL QRIFYLKLED LVPPPAIIDK LFLDTLPF 

« Hide

References

« Hide 'large scale' references
[1]"NOT, a human immediate-early response gene closely related to the steroid/thyroid hormone receptor NAK1/TR3."
Mages H.W., Rilke O., Bravo R., Senger G., Kroczek R.A.
Mol. Endocrinol. 8:1583-1591(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Blood.
[2]"Molecular cloning of the human Nurr1 gene: characterization of the human gene and cDNAs."
Ichinose H., Ohye T., Suzuki T., Sumi-Ichinose C., Nomura T., Hagino Y., Nagatsu T.
Gene 230:233-239(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Fibroblast.
[3]"Organization of the human orphan nuclear receptor Nurr1 gene."
Torii T., Kawarai T., Nakamura S., Kawakami H.
Gene 230:225-232(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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].
Tissue: Skin.
[7]"cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line."
Okabe T., Takayanagi R., Imasaki K., Haji M., Nawata H., Watanabe T.
J. Immunol. 154:3871-3879(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 59-598.
[8]"Induction of tyrosine hydroxylase expression by the transcription factor Pitx3."
Messmer K., Remington M.P., Skidmore F., Fishman P.S.
Int. J. Dev. Neurosci. 25:29-37(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Nuclear import and export signals control the subcellular localization of Nurr1 protein in response to oxidative stress."
Garcia-Yague A.J., Rada P., Rojo A.I., Lastres-Becker I., Cuadrado A.
J. Biol. Chem. 288:5506-5517(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNALS, NUCLEAR EXPORT SEQUENCES.
[11]"Structure and function of Nurr1 identifies a class of ligand-independent nuclear receptors."
Wang Z., Benoit G., Liu J., Prasad S., Aarnisalo P., Liu X., Xu H., Walker N.P., Perlmann T.
Nature 423:555-560(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 328-598.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X75918 mRNA. Translation: CAA53518.1.
AB017586 Genomic DNA. Translation: BAA75666.1.
AB019433 Genomic DNA. Translation: BAA77328.1.
AC074099 Genomic DNA. Translation: AAY24203.1.
CH471058 Genomic DNA. Translation: EAX11454.1.
CH471058 Genomic DNA. Translation: EAX11455.1.
BC009288 mRNA. Translation: AAH09288.1.
S77154 mRNA. Translation: AAB33999.1.
CCDSCCDS2201.1.
PIRA57040.
RefSeqNP_006177.1. NM_006186.3.
UniGeneHs.563344.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1OVLX-ray2.20A/B/C/D/E/F328-598[»]
ProteinModelPortalP43354.
SMRP43354. Positions 261-598.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110983. 14 interactions.
IntActP43354. 14 interactions.
STRING9606.ENSP00000344479.

Chemistry

ChEMBLCHEMBL5002.

PTM databases

PhosphoSiteP43354.

Polymorphism databases

DMDM1171750.

Proteomic databases

MaxQBP43354.
PaxDbP43354.
PRIDEP43354.

Protocols and materials databases

DNASU4929.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000339562; ENSP00000344479; ENSG00000153234.
ENST00000409572; ENSP00000386747; ENSG00000153234.
GeneID4929.
KEGGhsa:4929.
UCSCuc002tyx.4. human.

Organism-specific databases

CTD4929.
GeneCardsGC02M157180.
GeneReviewsNR4A2.
HGNCHGNC:7981. NR4A2.
HPACAB010481.
HPA000543.
MIM601828. gene.
neXtProtNX_P43354.
Orphanet2828. Young adult-onset Parkinsonism.
PharmGKBPA31762.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG245120.
HOVERGENHBG052663.
InParanoidP43354.
KOK08558.
OrthoDBEOG75XGKJ.
PhylomeDBP43354.
TreeFamTF315430.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.
SignaLinkP43354.

Gene expression databases

ArrayExpressP43354.
BgeeP43354.
CleanExHS_NR4A2.
GenevestigatorP43354.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProIPR003070. 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]
PfamPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSPR01284. NUCLEARECPTR.
PR01287. NURRNUCRCPTR.
PR00398. 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

ChiTaRSNR4A2. human.
EvolutionaryTraceP43354.
GeneWikiNuclear_receptor_related-1_protein.
GenomeRNAi4929.
NextBio18989.
PROP43354.
SOURCESearch...

Entry information

Entry nameNR4A2_HUMAN
AccessionPrimary (citable) accession number: P43354
Secondary accession number(s): Q16311, Q53RZ2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM