UniProtKB - P43354 (NR4A2_HUMAN)
Protein
Nuclear receptor subfamily 4 group A member 2
Gene
NR4A2
Organism
Homo sapiens (Human)
Status
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 (By similarity).By similarity1 Publication
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 260 – 335 | Nuclear receptorPROSITE-ProRule annotationAdd BLAST | 76 | |
Zinc fingeri | 263 – 283 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 299 – 323 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
GO - Molecular functioni
- beta-catenin binding Source: ParkinsonsUK-UCL
- DNA binding Source: ParkinsonsUK-UCL
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- glucocorticoid receptor binding Source: GO_Central
- nuclear receptor activity Source: ParkinsonsUK-UCL
- protein heterodimerization activity Source: UniProtKB
- retinoid X receptor binding Source: ParkinsonsUK-UCL
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: GO_Central
- sequence-specific DNA binding Source: GO_Central
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- zinc ion binding Source: InterPro
GO - Biological processi
- adult locomotory behavior Source: Ensembl
- canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
- cellular response to corticotropin-releasing hormone stimulus Source: UniProtKB
- cellular response to extracellular stimulus Source: MGI
- cellular response to oxidative stress Source: Ensembl
- central nervous system neuron differentiation Source: GO_Central
- central nervous system projection neuron axonogenesis Source: Ensembl
- dopamine biosynthetic process Source: Ensembl
- dopaminergic neuron differentiation Source: UniProtKB
- fat cell differentiation Source: UniProtKB
- general adaptation syndrome Source: Ensembl
- habenula development Source: Ensembl
- midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
- negative regulation of apoptotic signaling pathway Source: ParkinsonsUK-UCL
- negative regulation of neuron apoptotic process Source: Ensembl
- negative regulation of transcription by RNA polymerase II Source: ParkinsonsUK-UCL
- neuron maturation Source: Ensembl
- neuron migration Source: ParkinsonsUK-UCL
- positive regulation of catalytic activity Source: Ensembl
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- post-embryonic development Source: Ensembl
- regulation of dopamine metabolic process Source: Ensembl
- regulation of respiratory gaseous exchange Source: Ensembl
- response to amphetamine Source: Ensembl
- response to hypoxia Source: Ensembl
- signal transduction Source: ProtInc
- transcription, DNA-templated Source: UniProtKB
- transcription initiation from RNA polymerase II promoter Source: Reactome
Keywordsi
Molecular function | DNA-binding, Receptor |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | P43354 |
Reactomei | R-HSA-383280, Nuclear Receptor transcription pathway R-HSA-4090294, SUMOylation of intracellular receptors |
SignaLinki | P43354 |
SIGNORi | P43354 |
Names & Taxonomyi
Protein namesi | Recommended name: Nuclear receptor subfamily 4 group A member 2Alternative name(s): Immediate-early response protein NOT Orphan nuclear receptor NURR1 Transcriptionally-inducible nuclear receptor |
Gene namesi | Name:NR4A2 Synonyms:NOT, NURR1, TINUR |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000153234.13 |
HGNCi | HGNC:7981, NR4A2 |
MIMi | 601828, gene |
neXtProti | NX_P43354 |
Subcellular locationi
Nucleus
- nuclear chromatin Source: NTNU_SB
- nuclear speck Source: HPA
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB-SubCell
- protein-containing complex Source: ParkinsonsUK-UCL
- transcription regulator complex Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Organism-specific databases
DisGeNETi | 4929 |
MalaCardsi | NR4A2 |
OpenTargetsi | ENSG00000153234 |
PharmGKBi | PA31762 |
Miscellaneous databases
Pharosi | P43354, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5002 |
Polymorphism and mutation databases
BioMutai | NR4A2 |
DMDMi | 1171750 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000053718 | 1 – 598 | Nuclear receptor subfamily 4 group A member 2Add BLAST | 598 |
Proteomic databases
jPOSTi | P43354 |
MassIVEi | P43354 |
MaxQBi | P43354 |
PaxDbi | P43354 |
PeptideAtlasi | P43354 |
PRIDEi | P43354 |
ProteomicsDBi | 55616 [P43354-1] 66777 |
PTM databases
iPTMneti | P43354 |
PhosphoSitePlusi | P43354 |
SwissPalmi | P43354 |
Expressioni
Tissue specificityi
Expressed in a number of cell lines of T-cell, B-cell and fibroblast origin. Strong expression in brain tissue.
Developmental stagei
Rapidly and only very transiently expressed after cell activation, during the G0-G1 transition of the cell cycle.
Gene expression databases
Bgeei | ENSG00000153234, Expressed in female gonad and 234 other tissues |
ExpressionAtlasi | P43354, baseline and differential |
Genevisiblei | P43354, HS |
Organism-specific databases
HPAi | ENSG00000153234, Tissue enhanced (seminal) |
Interactioni
Subunit structurei
Interacts with SFPQ, NCOR2, SIN3A and HADC1. The interaction with NCOR2 increases in the absence of PITX3.
Interacts with PER2 (By similarity).
By similarityBinary interactionsi
Hide detailsP43354
With | #Exp. | IntAct |
---|---|---|
ARMC4 [Q5T2S8] | 3 | EBI-2681738,EBI-12200605 |
CDKN2D [P55273] | 4 | EBI-2681738,EBI-745859 |
TCEAL5 [Q5H9L2] | 2 | EBI-2681738,EBI-2681773 |
GO - Molecular functioni
- beta-catenin binding Source: ParkinsonsUK-UCL
- glucocorticoid receptor binding Source: GO_Central
- protein heterodimerization activity Source: UniProtKB
- retinoid X receptor binding Source: ParkinsonsUK-UCL
Protein-protein interaction databases
BioGRIDi | 110983, 17 interactors |
IntActi | P43354, 16 interactors |
STRINGi | 9606.ENSP00000344479 |
Chemistry databases
BindingDBi | P43354 |
Miscellaneous databases
RNActi | P43354, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P43354 |
SMRi | P43354 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P43354 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 360 – 595 | NR LBDPROSITE-ProRule annotationAdd BLAST | 236 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 287 – 314 | Bipartite nuclear localization signal (NLS1)Add BLAST | 28 | |
Motifi | 338 – 350 | Nuclear localization signal (NLS1)1 PublicationAdd BLAST | 13 | |
Motifi | 443 – 452 | nuclear export sequence (NES1) | 10 | |
Motifi | 568 – 577 | nuclear export sequence (NES2) | 10 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 80 – 138 | Gln-richAdd BLAST | 59 | |
Compositional biasi | 127 – 233 | Pro-richAdd BLAST | 107 | |
Compositional biasi | 346 – 391 | Pro-richAdd BLAST | 46 |
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 (PubMed:12774125).1 Publication
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 263 – 283 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 299 – 323 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG4217, Eukaryota |
GeneTreei | ENSGT00950000183038 |
HOGENOMi | CLU_007368_14_2_1 |
InParanoidi | P43354 |
OMAi | VQMHSYH |
OrthoDBi | 454476at2759 |
PhylomeDBi | P43354 |
TreeFami | TF315430 |
Family and domain databases
Gene3Di | 1.10.565.10, 1 hit 3.30.50.10, 1 hit |
InterProi | View protein in InterPro IPR035500, NHR-like_dom_sf IPR003070, Nuc_orph_rcpt IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt IPR003073, NURR_rcpt IPR001628, Znf_hrmn_rcpt IPR013088, Znf_NHR/GATA |
Pfami | View protein in Pfam PF00104, Hormone_recep, 1 hit PF00105, zf-C4, 1 hit |
PRINTSi | PR01284, NUCLEARECPTR PR01287, NURRNUCRCPTR PR00398, STRDHORMONER PR00047, STROIDFINGER |
SMARTi | View protein in SMART SM00430, HOLI, 1 hit SM00399, ZnF_C4, 1 hit |
SUPFAMi | SSF48508, SSF48508, 1 hit |
PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit PS00031, NUCLEAR_REC_DBD_1, 1 hit PS51030, NUCLEAR_REC_DBD_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P43354-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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 TTPGFQVQHS 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
SPQEPSPPSP 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
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8W6I3 | F8W6I3_HUMAN | Nuclear receptor subfamily 4 group ... | NR4A2 | 553 | Annotation score: | ||
C9J8W4 | C9J8W4_HUMAN | Nuclear receptor subfamily 4 group ... | NR4A2 | 490 | Annotation score: | ||
E9PBQ4 | E9PBQ4_HUMAN | Nuclear receptor subfamily 4 group ... | NR4A2 | 392 | Annotation score: | ||
C9IYM5 | C9IYM5_HUMAN | Nuclear receptor subfamily 4 group ... | NR4A2 | 258 | Annotation score: | ||
H7BZ00 | H7BZ00_HUMAN | Nuclear receptor subfamily 4 group ... | NR4A2 | 150 | Annotation score: | ||
C9JWQ1 | C9JWQ1_HUMAN | Nuclear receptor subfamily 4 group ... | NR4A2 | 106 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 465 | C → W in AAB33999 (PubMed:7706727).Curated | 1 | |
Sequence conflicti | 468 | V → W in AAB33999 (PubMed:7706727).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056057 | 1 – 63 | Missing in isoform 2. 2 PublicationsAdd BLAST | 63 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X75918 mRNA Translation: CAA53518.1 AB017586 Genomic DNA Translation: BAA75666.1 AB019433 Genomic DNA Translation: BAA77328.1 AK291456 mRNA Translation: BAF84145.1 AC074099 Genomic DNA Translation: AAY24203.1 CH471058 Genomic DNA Translation: EAX11454.1 CH471058 Genomic DNA Translation: EAX11455.1 BC009288 mRNA Translation: AAH09288.1 BC066890 mRNA Translation: AAH66890.1 S77154 mRNA Translation: AAB33999.1 |
CCDSi | CCDS2201.1 [P43354-1] CCDS86887.1 [P43354-2] |
PIRi | A57040 |
RefSeqi | NP_006177.1, NM_006186.3 [P43354-1] XP_005246679.1, XM_005246622.3 XP_016859708.1, XM_017004219.1 [P43354-1] |
Genome annotation databases
Ensembli | ENST00000339562; ENSP00000344479; ENSG00000153234 [P43354-1] ENST00000409572; ENSP00000386747; ENSG00000153234 [P43354-1] ENST00000426264; ENSP00000389986; ENSG00000153234 [P43354-2] |
GeneIDi | 4929 |
KEGGi | hsa:4929 |
UCSCi | uc002tyx.5, human [P43354-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X75918 mRNA Translation: CAA53518.1 AB017586 Genomic DNA Translation: BAA75666.1 AB019433 Genomic DNA Translation: BAA77328.1 AK291456 mRNA Translation: BAF84145.1 AC074099 Genomic DNA Translation: AAY24203.1 CH471058 Genomic DNA Translation: EAX11454.1 CH471058 Genomic DNA Translation: EAX11455.1 BC009288 mRNA Translation: AAH09288.1 BC066890 mRNA Translation: AAH66890.1 S77154 mRNA Translation: AAB33999.1 |
CCDSi | CCDS2201.1 [P43354-1] CCDS86887.1 [P43354-2] |
PIRi | A57040 |
RefSeqi | NP_006177.1, NM_006186.3 [P43354-1] XP_005246679.1, XM_005246622.3 XP_016859708.1, XM_017004219.1 [P43354-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1OVL | X-ray | 2.20 | A/B/C/D/E/F | 328-598 | [»] | |
5Y41 | X-ray | 2.05 | A/B | 328-598 | [»] | |
5YD6 | X-ray | 2.34 | A/B/C/D | 328-598 | [»] | |
6DDA | X-ray | 3.20 | A/B/C | 328-598 | [»] | |
6L6L | X-ray | 2.78 | A/B | 262-346 | [»] | |
6L6Q | X-ray | 2.60 | A/B | 262-346 | [»] | |
BMRBi | P43354 | |||||
SMRi | P43354 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110983, 17 interactors |
IntActi | P43354, 16 interactors |
STRINGi | 9606.ENSP00000344479 |
Chemistry databases
BindingDBi | P43354 |
ChEMBLi | CHEMBL5002 |
PTM databases
iPTMneti | P43354 |
PhosphoSitePlusi | P43354 |
SwissPalmi | P43354 |
Polymorphism and mutation databases
BioMutai | NR4A2 |
DMDMi | 1171750 |
Proteomic databases
jPOSTi | P43354 |
MassIVEi | P43354 |
MaxQBi | P43354 |
PaxDbi | P43354 |
PeptideAtlasi | P43354 |
PRIDEi | P43354 |
ProteomicsDBi | 55616 [P43354-1] 66777 |
Protocols and materials databases
Antibodypediai | 621, 390 antibodies |
DNASUi | 4929 |
Genome annotation databases
Ensembli | ENST00000339562; ENSP00000344479; ENSG00000153234 [P43354-1] ENST00000409572; ENSP00000386747; ENSG00000153234 [P43354-1] ENST00000426264; ENSP00000389986; ENSG00000153234 [P43354-2] |
GeneIDi | 4929 |
KEGGi | hsa:4929 |
UCSCi | uc002tyx.5, human [P43354-1] |
Organism-specific databases
CTDi | 4929 |
DisGeNETi | 4929 |
EuPathDBi | HostDB:ENSG00000153234.13 |
GeneCardsi | NR4A2 |
HGNCi | HGNC:7981, NR4A2 |
HPAi | ENSG00000153234, Tissue enhanced (seminal) |
MalaCardsi | NR4A2 |
MIMi | 601828, gene |
neXtProti | NX_P43354 |
OpenTargetsi | ENSG00000153234 |
PharmGKBi | PA31762 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4217, Eukaryota |
GeneTreei | ENSGT00950000183038 |
HOGENOMi | CLU_007368_14_2_1 |
InParanoidi | P43354 |
OMAi | VQMHSYH |
OrthoDBi | 454476at2759 |
PhylomeDBi | P43354 |
TreeFami | TF315430 |
Enzyme and pathway databases
PathwayCommonsi | P43354 |
Reactomei | R-HSA-383280, Nuclear Receptor transcription pathway R-HSA-4090294, SUMOylation of intracellular receptors |
SignaLinki | P43354 |
SIGNORi | P43354 |
Miscellaneous databases
BioGRID-ORCSi | 4929, 8 hits in 863 CRISPR screens |
ChiTaRSi | NR4A2, human |
EvolutionaryTracei | P43354 |
GeneWikii | Nuclear_receptor_related-1_protein |
GenomeRNAii | 4929 |
Pharosi | P43354, Tchem |
PROi | PR:P43354 |
RNActi | P43354, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000153234, Expressed in female gonad and 234 other tissues |
ExpressionAtlasi | P43354, baseline and differential |
Genevisiblei | P43354, HS |
Family and domain databases
Gene3Di | 1.10.565.10, 1 hit 3.30.50.10, 1 hit |
InterProi | View protein in InterPro IPR035500, NHR-like_dom_sf IPR003070, Nuc_orph_rcpt IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt IPR003073, NURR_rcpt IPR001628, Znf_hrmn_rcpt IPR013088, Znf_NHR/GATA |
Pfami | View protein in Pfam PF00104, Hormone_recep, 1 hit PF00105, zf-C4, 1 hit |
PRINTSi | PR01284, NUCLEARECPTR PR01287, NURRNUCRCPTR PR00398, STRDHORMONER PR00047, STROIDFINGER |
SMARTi | View protein in SMART SM00430, HOLI, 1 hit SM00399, ZnF_C4, 1 hit |
SUPFAMi | SSF48508, SSF48508, 1 hit |
PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit PS00031, NUCLEAR_REC_DBD_1, 1 hit PS51030, NUCLEAR_REC_DBD_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NR4A2_HUMAN | |
Accessioni | P43354Primary (citable) accession number: P43354 Secondary accession number(s): Q16311, Q53RZ2, Q6NXU0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1995 |
Last sequence update: | November 1, 1995 | |
Last modified: | December 2, 2020 | |
This is version 213 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM