UniProtKB - P51179 (NR4A3_RAT)
Nuclear receptor subfamily 4 group A member 3
Nr4a3
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 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 291 – 366 | Nuclear receptorPROSITE-ProRule annotationAdd BLAST | 76 | |
Zinc fingeri | 294 – 314 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 330 – 354 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
GO - Molecular functioni
- cAMP response element binding Source: UniProtKB
- DNA binding Source: RGD
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: GO_Central
- glucocorticoid receptor binding Source: UniProtKB
- histone acetyltransferase binding Source: RGD
- nuclear receptor activity Source: InterPro
- protein homodimerization activity Source: UniProtKB
- protein kinase binding Source: RGD
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: RGD
- sequence-specific DNA binding Source: RGD
- transcription coactivator binding Source: RGD
- zinc ion binding Source: InterPro
GO - Biological processi
- adult behavior Source: RGD
- animal organ regeneration Source: RGD
- axon guidance Source: RGD
- cellular respiration Source: UniProtKB
- cellular response to catecholamine stimulus Source: UniProtKB
- cellular response to corticotropin-releasing hormone stimulus Source: UniProtKB
- cellular response to leptin stimulus Source: UniProtKB
- common myeloid progenitor cell proliferation Source: UniProtKB
- energy homeostasis Source: UniProtKB
- fat cell differentiation Source: UniProtKB
- gastrulation Source: UniProtKB
- hippocampus development Source: RGD
- inner ear morphogenesis Source: RGD
- mast cell degranulation Source: UniProtKB
- mesoderm formation Source: RGD
- negative regulation of apoptotic process Source: RGD
- negative regulation of hydrogen peroxide-induced neuron death Source: UniProtKB
- negative regulation of neuron apoptotic process Source: RGD
- negative regulation of oxidative stress-induced neuron death Source: RGD
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- neuromuscular process controlling balance Source: RGD
- platelet-derived growth factor receptor signaling pathway Source: RGD
- positive regulation of cardiac muscle hypertrophy Source: UniProtKB
- positive regulation of cell cycle Source: RGD
- positive regulation of epithelial cell proliferation Source: UniProtKB
- positive regulation of fatty acid oxidation Source: UniProtKB
- positive regulation of feeding behavior Source: UniProtKB
- positive regulation of glucose transmembrane transport Source: UniProtKB
- positive regulation of leukocyte apoptotic process Source: RGD
- positive regulation of mast cell activation by Fc-epsilon receptor signaling pathway Source: UniProtKB
- positive regulation of mast cell cytokine production Source: UniProtKB
- positive regulation of monocyte aggregation Source: UniProtKB
- positive regulation of smooth muscle cell proliferation Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: RGD
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of vascular associated smooth muscle cell migration Source: RGD
- positive regulation of vascular associated smooth muscle cell proliferation Source: RGD
- pyruvate oxidation Source: UniProtKB
- regulation of smooth muscle cell proliferation Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- regulation of type B pancreatic cell proliferation Source: UniProtKB
- response to hydrogen peroxide Source: RGD
- response to peptide hormone Source: RGD
- semicircular canal morphogenesis Source: RGD
- vestibular reflex Source: RGD
Keywordsi
Molecular function | DNA-binding, Receptor |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-RNO-383280, Nuclear Receptor transcription pathway |
Names & Taxonomyi
Protein namesi | Recommended name: Nuclear receptor subfamily 4 group A member 3Alternative name(s): Neuron-derived orphan receptor 1/2 Nuclear hormone receptor NOR-1/NOR-2 |
Gene namesi | Name:Nr4a3 Synonyms:Nor1 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 61882, Nr4a3 |
Subcellular locationi
Nucleus
- Nucleus PROSITE-ProRule annotation
Nucleus
- nucleus Source: GO_Central
Other locations
- transcription regulator complex Source: RGD
Keywords - Cellular componenti
NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000053724 | 1 – 628 | Nuclear receptor subfamily 4 group A member 3Add BLAST | 628 |
Post-translational modificationi
Proteomic databases
PaxDbi | P51179 |
PRIDEi | P51179 |
PTM databases
PhosphoSitePlusi | P51179 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSRNOG00000005964, Expressed in Ammon's horn and 20 other tissues |
Genevisiblei | P51179, 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 PublicationsGO - Molecular functioni
- glucocorticoid receptor binding Source: UniProtKB
- histone acetyltransferase binding Source: RGD
- protein homodimerization activity Source: UniProtKB
- protein kinase binding Source: RGD
- transcription coactivator binding Source: RGD
Protein-protein interaction databases
IntActi | P51179, 1 interactor |
STRINGi | 10116.ENSRNOP00000008302 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 396 – 625 | NR LBDPROSITE-ProRule annotationAdd BLAST | 230 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 293 | Interaction with NCOA1, NCOA2, NCOA3 and KAT2BBy similarityAdd BLAST | 293 | |
Regioni | 1 – 140 | Required for DNA-PK heterotrimerBy similarityAdd BLAST | 140 | |
Regioni | 1 – 112 | Activation function (AF)-1 domainBy similarityAdd BLAST | 112 | |
Regioni | 96 – 163 | DisorderedSequence analysisAdd BLAST | 68 | |
Regioni | 269 – 290 | DisorderedSequence analysisAdd BLAST | 22 | |
Regioni | 366 – 396 | DisorderedSequence analysisAdd BLAST | 31 | |
Regioni | 381 – 628 | Interaction with KAT2BBy similarityAdd BLAST | 248 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 98 – 114 | Basic residuesSequence analysisAdd BLAST | 17 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 294 – 314 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
Zinc fingeri | 330 – 354 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 25 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG4217, Eukaryota |
GeneTreei | ENSGT00950000183038 |
HOGENOMi | CLU_007368_14_2_1 |
InParanoidi | P51179 |
OMAi | SYAVQTY |
OrthoDBi | 454476at2759 |
PhylomeDBi | P51179 |
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 IPR003072, NOR1_rcpt IPR003070, Nuc_orph_rcpt IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_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 | PR01286, NORNUCRECPTR PR01284, NUCLEARECPTR 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 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
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 13 | P → Q in CAA59993 (PubMed:7556683).Curated | 1 | |
Sequence conflicti | 18 | A → P in CAA59993 (PubMed:7556683).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010085 | 421 – 430 | YCPTDQATAG → VSSVNRFEWF in isoform 2. 1 Publication | 10 | |
Alternative sequenceiVSP_010086 | 431 – 628 | Missing in isoform 2. 1 PublicationAdd BLAST | 198 |
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 |
PIRi | JC2493 S66671 |
RefSeqi | NP_113816.1, NM_031628.1 [P51179-1] XP_017449093.1, XM_017593604.1 [P51179-1] |
Genome annotation databases
Ensembli | ENSRNOT00000008302; ENSRNOP00000008302; ENSRNOG00000005964 [P51179-1] |
GeneIDi | 58853 |
KEGGi | rno:58853 |
UCSCi | RGD:61882, rat [P51179-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
PIRi | JC2493 S66671 |
RefSeqi | NP_113816.1, NM_031628.1 [P51179-1] XP_017449093.1, XM_017593604.1 [P51179-1] |
3D structure databases
SMRi | P51179 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | P51179, 1 interactor |
STRINGi | 10116.ENSRNOP00000008302 |
PTM databases
PhosphoSitePlusi | P51179 |
Proteomic databases
PaxDbi | P51179 |
PRIDEi | P51179 |
Genome annotation databases
Ensembli | ENSRNOT00000008302; ENSRNOP00000008302; ENSRNOG00000005964 [P51179-1] |
GeneIDi | 58853 |
KEGGi | rno:58853 |
UCSCi | RGD:61882, rat [P51179-1] |
Organism-specific databases
CTDi | 8013 |
RGDi | 61882, Nr4a3 |
Phylogenomic databases
eggNOGi | KOG4217, Eukaryota |
GeneTreei | ENSGT00950000183038 |
HOGENOMi | CLU_007368_14_2_1 |
InParanoidi | P51179 |
OMAi | SYAVQTY |
OrthoDBi | 454476at2759 |
PhylomeDBi | P51179 |
Enzyme and pathway databases
Reactomei | R-RNO-383280, Nuclear Receptor transcription pathway |
Miscellaneous databases
PROi | PR:P51179 |
Gene expression databases
Bgeei | ENSRNOG00000005964, Expressed in Ammon's horn and 20 other tissues |
Genevisiblei | P51179, RN |
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 IPR003072, NOR1_rcpt IPR003070, Nuc_orph_rcpt IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_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 | PR01286, NORNUCRECPTR PR01284, NUCLEARECPTR 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | NR4A3_RAT | |
Accessioni | P51179Primary (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: | September 29, 2021 | |
This is version 166 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families