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Protein

Nuclear receptor subfamily 4 group A member 3

Gene

Nr4a3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner (PubMed:7811288). Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (PubMed:10523643). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (By similarity). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression (PubMed:16945922). In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (PubMed:24706823). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (By similarity). Mediates also survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (By similarity). Plays also a role in inflammation; Upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (By similarity). In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation. Plays also a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP-glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (By similarity). Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (By similarity). Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration (By similarity). Also participates in cardiac hypertrophy by activating PARP1 (PubMed:25625556).By similarity5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi291 – 366Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri294 – 314NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri330 – 354NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-383280. Nuclear Receptor transcription pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 4 group A member 3
Alternative name(s):
Neuron-derived orphan receptor 1/2
Nuclear hormone receptor NOR-1/NOR-2
Gene namesi
Name:Nr4a3
Synonyms:Nor1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 5

Organism-specific databases

RGDi61882. Nr4a3.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000537241 – 628Nuclear receptor subfamily 4 group A member 3Add BLAST628

Post-translational modificationi

Phosphorylated by PRKDC.By similarity

Proteomic databases

PaxDbiP51179.

PTM databases

PhosphoSitePlusiP51179.

Expressioni

Tissue specificityi

Expressed at high levels in cultured apoptotic neuronal cells and fetal brain, and at low level in adult brain.

Inductioni

By PDGF through a CREB-dependent transactivation of the NOR1 promoter.1 Publication

Gene expression databases

BgeeiENSRNOG00000005964.
GenevisibleiP51179. RN.

Interactioni

Subunit structurei

Interacts with SIX3 (via homeobox); differentially regulates the transcriptional activities of NR4A3. Interacts with NR3C1 (via nuclear receptor DNA-binding domain); the interactions represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE) (PubMed:15591535). Interacts with TRIM28; the interactions potentiates NR4A3 activity on NurRE promoter (PubMed:19321449). Binds DNA as a monomer and homodimer (PubMed:10523643). Interacts with PARP1; activates PARP1 by improving acetylation of PARP1 and suppressing the interaction between PARP1 and SIRT1 (PubMed:25625556). Interacts with the constituents of DNA-PK heterotrimer PRKDC, XRCC6 and XRCC5; phosphorylates and prevents NR4A3 ubiquitinylation and degradation (By similarity). Interacts with NCOA2; potentiates the activity of the NR4A3. Interacts with NCOA1, NCOA3, MED1 and KAT2B. Interacts with EP300 and NCOA2; mediates the recruitment of MED1 in the coactivator complex (By similarity).By similarity4 Publications

GO - Molecular functioni

  • glucocorticoid receptor binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

IntActiP51179. 1 interactor.
STRINGi10116.ENSRNOP00000008302.

Structurei

3D structure databases

ProteinModelPortaliP51179.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 293Interaction with NCOA1, NCOA2, NCOA3 and KAT2BBy similarityAdd BLAST293
Regioni1 – 140Required for DNA-PK heterotrimerBy similarityAdd BLAST140
Regioni1 – 112Activation function (AF)-1 domainBy similarityAdd BLAST112
Regioni381 – 628Interaction with KAT2BBy similarityAdd BLAST248
Regioni442 – 492Ligand-bindingSequence analysisAdd BLAST51

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi99 – 112Poly-HisAdd BLAST14
Compositional biasi113 – 116Poly-Gln4
Compositional biasi286 – 289Poly-Ser4

Domaini

The AF-1 domain mediates transcription activation. The N-terminal region (1-292) directly interacts with the C-terminal LBD (380-627): the interaction is potentiated by AF-1-mediated recruitment of NCOA2.By similarity

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri294 – 314NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri330 – 354NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4217. Eukaryota.
ENOG410YWNC. LUCA.
GeneTreeiENSGT00760000118887.
HOGENOMiHOG000230925.
HOVERGENiHBG052663.
InParanoidiP51179.
KOiK08559.
OMAiHPYGLPL.
OrthoDBiEOG091G0GUM.
PhylomeDBiP51179.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003072. NOR1_rcpt.
IPR003070. Nuc_orph_rcpt.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01286. NORNUCRECPTR.
PR01284. NUCLEARECPTR.
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 1 (identifier: P51179-1) [UniParc]FASTAAdd to basket
Also known as: NOR-1

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
MPCVQAQYSP SPPGSTYATQ TYGSEYTTEI MNPDYAKLTM DLGSTGIMAT
60 70 80 90 100
ATTSLPSFST FMEGYPSSCE LKPSCLYQMP PSGPRPLIKM EEGREHGYHH
110 120 130 140 150
HHHHHHHHHH HHQQQQPSIP PPSGPEDEVL PSTSMYFKQS PPSTPTTPGF
160 170 180 190 200
PPQAGALWDD ELPSAPGCIA PGPLLDPQMK AVPPMAAAAR FPIFFKPSPP
210 220 230 240 250
HPPAPSPAGG HHLGYDPTAA AALSLPLGAA AAAGSQAAAL EGHPYGLPLA
260 270 280 290 300
KRTATLTFPP LGLTASPTAS SLLGESPSLP SPPNRSSSSG EGTCAVCGDN
310 320 330 340 350
AACQHYGVRT CEGCKGFFKR TVQKNAKYVC LANKNCPVDK RRRNRCQYCR
360 370 380 390 400
FQKCLSVGMV KEVVRTDSLK GRRGRLPSKP KSPLQQEPSQ PSPPSPPICM
410 420 430 440 450
MNALVRALTD ATPRDLDYSR YCPTDQATAG TDAEHVQQFY NLLTASIDVS
460 470 480 490 500
RSWAEKIPGF TDLPKEDQTL LIESAFLELF VLRLSIRSNT AEDKFVFCNG
510 520 530 540 550
LVLHRLQCLR GFGEWLDSIK DFSLNLQSLN LDIQALACLS ALSMITERHG
560 570 580 590 600
LKEPKRVEEL CNKITSSLKD HQRKGQALEP SEPKVLRALV ELRKICTQGL
610 620
QRIFYLKLED LVSPPSVIDK LFLDTLPF
Length:628
Mass (Da):68,564
Last modified:October 1, 1996 - v1
Checksum:i9AC285D9A65226D9
GO
Isoform 2 (identifier: P51179-2) [UniParc]FASTAAdd to basket
Also known as: NOR-2

The sequence of this isoform differs from the canonical sequence as follows:
     421-430: YCPTDQATAG → VSSVNRFEWF
     431-628: Missing.

Show »
Length:430
Mass (Da):46,240
Checksum:i7290C789A7D3756F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13P → Q in CAA59993 (PubMed:7556683).Curated1
Sequence conflicti18A → P in CAA59993 (PubMed:7556683).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010085421 – 430YCPTDQATAG → VSSVNRFEWF in isoform 2. 1 Publication10
Alternative sequenceiVSP_010086431 – 628Missing in isoform 2. 1 PublicationAdd BLAST198

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38530 mRNA. Translation: BAA07535.1.
X86003 mRNA. Translation: CAA59993.1.
DQ268830 mRNA. Translation: ABB72200.1.
L19343 mRNA. Translation: AAB46395.1.
PIRiJC2493.
S66671.
RefSeqiNP_113816.1. NM_031628.1. [P51179-1]
XP_017449093.1. XM_017593604.1. [P51179-1]
UniGeneiRn.62694.
Rn.88129.

Genome annotation databases

EnsembliENSRNOT00000008302; ENSRNOP00000008302; ENSRNOG00000005964. [P51179-1]
GeneIDi58853.
KEGGirno:58853.
UCSCiRGD:61882. rat. [P51179-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D38530 mRNA. Translation: BAA07535.1.
X86003 mRNA. Translation: CAA59993.1.
DQ268830 mRNA. Translation: ABB72200.1.
L19343 mRNA. Translation: AAB46395.1.
PIRiJC2493.
S66671.
RefSeqiNP_113816.1. NM_031628.1. [P51179-1]
XP_017449093.1. XM_017593604.1. [P51179-1]
UniGeneiRn.62694.
Rn.88129.

3D structure databases

ProteinModelPortaliP51179.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP51179. 1 interactor.
STRINGi10116.ENSRNOP00000008302.

PTM databases

PhosphoSitePlusiP51179.

Proteomic databases

PaxDbiP51179.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000008302; ENSRNOP00000008302; ENSRNOG00000005964. [P51179-1]
GeneIDi58853.
KEGGirno:58853.
UCSCiRGD:61882. rat. [P51179-1]

Organism-specific databases

CTDi8013.
RGDi61882. Nr4a3.

Phylogenomic databases

eggNOGiKOG4217. Eukaryota.
ENOG410YWNC. LUCA.
GeneTreeiENSGT00760000118887.
HOGENOMiHOG000230925.
HOVERGENiHBG052663.
InParanoidiP51179.
KOiK08559.
OMAiHPYGLPL.
OrthoDBiEOG091G0GUM.
PhylomeDBiP51179.

Enzyme and pathway databases

ReactomeiR-RNO-383280. Nuclear Receptor transcription pathway.

Miscellaneous databases

PROiP51179.

Gene expression databases

BgeeiENSRNOG00000005964.
GenevisibleiP51179. RN.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR003072. NOR1_rcpt.
IPR003070. Nuc_orph_rcpt.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR01286. NORNUCRECPTR.
PR01284. NUCLEARECPTR.
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...

Entry informationi

Entry nameiNR4A3_RAT
AccessioniPrimary (citable) accession number: P51179
Secondary accession number(s): Q2XPY2, Q63516, Q9QWQ3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 136 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. SIMILARITY comments
    Index of protein domains and families

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 one 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.