Human Gene NR4A1 (ENST00000550082.5) Description and Page Index
  Description: Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'- AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2. (from UniProt P22736)
RefSeq Summary (NM_001202233): This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. The encoded protein acts as a nuclear transcription factor. Translocation of the protein from the nucleus to mitochondria induces apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011].
Gencode Transcript: ENST00000550082.5
Gencode Gene: ENSG00000123358.20
Transcript (Including UTRs)
   Position: hg38 chr12:52,041,805-52,059,049 Size: 17,245 Total Exon Count: 7 Strand: +
Coding Region
   Position: hg38 chr12:52,041,893-52,058,944 Size: 17,052 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:52,041,805-52,059,049)mRNA (may differ from genome)Protein (611 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblExonPrimerGeneCardsHGNCLynx
MGIneXtProtPubMedReactomeStanford SOURCEUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: NR4A1_HUMAN
DESCRIPTION: RecName: Full=Nuclear receptor subfamily 4 group A member 1; AltName: Full=Early response protein NAK1; AltName: Full=Nuclear hormone receptor NUR/77; Short=Nur77; AltName: Full=Orphan nuclear receptor HMR; AltName: Full=Orphan nuclear receptor TR3; AltName: Full=ST-59; AltName: Full=Testicular receptor 3;
FUNCTION: Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'- AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2.
SUBUNIT: Binds DNA as a monomer (By similarity). Interacts with GADD45GIP1.
INTERACTION: Q9P2G1:ANKIB1; NbExp=2; IntAct=EBI-721550, EBI-2687890; P10415:BCL2; NbExp=7; IntAct=EBI-721550, EBI-77694; O60888:CUTA; NbExp=2; IntAct=EBI-721550, EBI-1051556; P32189:GK; NbExp=3; IntAct=EBI-721550, EBI-3926629; P43243:MATR3; NbExp=2; IntAct=EBI-721550, EBI-352602; P40763:STAT3; NbExp=3; IntAct=EBI-721550, EBI-518675; P04350:TUBB4A; NbExp=2; IntAct=EBI-721550, EBI-355007; P50552:VASP; NbExp=2; IntAct=EBI-721550, EBI-748201;
SUBCELLULAR LOCATION: Nucleus.
TISSUE SPECIFICITY: Fetal muscle and adult liver, brain and thyroid.
INDUCTION: By growth-stimulating agents.
PTM: Phosphorylated at Ser-351 by RPS6KA1 and RPS6KA3 in response to mitogenic or stress stimuli.
SIMILARITY: Belongs to the nuclear hormone receptor family. NR4 subfamily.
SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.

-  MalaCards Disease Associations
  MalaCards Gene Search: NR4A1
Diseases sorted by gene-association score: fetal adenoma (3), tracheal cancer (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 271.86 RPKM in Ovary
Total median expression: 2518.24 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -35.5088-0.403 Picture PostScript Text
3' UTR -31.50105-0.300 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003071 - Nuc_orp_HMR_rcpt
IPR003070 - Nuc_orph_rcpt
IPR008946 - Nucl_hormone_rcpt_ligand-bd
IPR000536 - Nucl_hrmn_rcpt_lig-bd_core
IPR001723 - Str_hrmn_rcpt
IPR001628 - Znf_hrmn_rcpt
IPR013088 - Znf_NHR/GATA

Pfam Domains:
PF00104 - Ligand-binding domain of nuclear hormone receptor
PF00105 - Zinc finger, C4 type (two domains)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

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ModBase Predicted Comparative 3D Structure on P22736
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
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MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003707 steroid hormone receptor activity
GO:0004879 RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0001938 positive regulation of endothelial cell proliferation
GO:0002042 cell migration involved in sprouting angiogenesis
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0007165 signal transduction
GO:0030522 intracellular receptor signaling pathway
GO:0035767 endothelial cell chemotaxis
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0043401 steroid hormone mediated signaling pathway
GO:0044344 cellular response to fibroblast growth factor stimulus
GO:0045444 fat cell differentiation
GO:0045786 negative regulation of cell cycle
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0061469 regulation of type B pancreatic cell proliferation
GO:0071376 cellular response to corticotropin-releasing hormone stimulus

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0031965 nuclear membrane


-  Descriptions from all associated GenBank mRNAs
  AK297526 - Homo sapiens cDNA FLJ55987 complete cds, highly similar to Orphan nuclear receptor NR4A1.
LF210460 - JP 2014500723-A/17963: Polycomb-Associated Non-Coding RNAs.
MA446037 - JP 2018138019-A/17963: Polycomb-Associated Non-Coding RNAs.
AK131566 - Homo sapiens cDNA FLJ16818 fis, clone TRACH1000193, highly similar to Orphan nuclear receptor HMR.
D85245 - Homo sapiens mRNA for TR3beta, complete cds.
AK075491 - Homo sapiens cDNA PSEC0186 fis, clone OVARC1002093, highly similar to RPHAN NUCLEAR RECEPTOR HMR.
AK075054 - Homo sapiens cDNA FLJ90573 fis, clone OVARC1001807, highly similar to Human TR3 orphan receptor mRNA.
AK314437 - Homo sapiens cDNA, FLJ95235, Homo sapiens nuclear receptor subfamily 4, group A, member 1(NR4A1), transcript variant 3, mRNA.
LF214029 - JP 2014500723-A/21532: Polycomb-Associated Non-Coding RNAs.
MA449606 - JP 2018138019-A/21532: Polycomb-Associated Non-Coding RNAs.
BC016147 - Homo sapiens nuclear receptor subfamily 4, group A, member 1, mRNA (cDNA clone MGC:9485 IMAGE:3921259), complete cds.
L13740 - Human TR3 orphan receptor mRNA, complete cds.
D49728 - Homo sapiens NAK1 mRNA for DNA binding protein, complete cds.
AL831844 - Homo sapiens mRNA; cDNA DKFZp451G125 (from clone DKFZp451G125).
AB464647 - Synthetic construct DNA, clone: pF1KB9634, Homo sapiens NR4A1 gene for nuclear receptor subfamily 4, group A, member 1, without stop codon, in Flexi system.
CU677577 - Synthetic construct Homo sapiens gateway clone IMAGE:100020770 5' read NR4A1 mRNA.
CR456704 - Homo sapiens full open reading frame cDNA clone RZPDo834C1214D for gene NR4A1, nuclear receptor subfamily 4, group A, member 1; complete cds, incl. stopcodon.
AB590255 - Synthetic construct DNA, clone: pFN21AE1384, Homo sapiens NR4A1 gene for nuclear receptor subfamily 4, group A, member 1, without stop codon, in Flexi system.
BT007144 - Homo sapiens nuclear receptor subfamily 4, group A, member 1 mRNA, complete cds.
DQ891134 - Synthetic construct clone IMAGE:100003764; FLH169624.01X; RZPDo839E0596D nuclear receptor subfamily 4, group A, member 1 (NR4A1) gene, encodes complete protein.
DQ894313 - Synthetic construct Homo sapiens clone IMAGE:100008773; FLH169620.01L; RZPDo839E0595D nuclear receptor subfamily 4, group A, member 1 (NR4A1) gene, encodes complete protein.
KJ891366 - Synthetic construct Homo sapiens clone ccsbBroadEn_00760 NR4A1 gene, encodes complete protein.
AB307717 - Homo sapiens NR4A1 mRNA for nuclear receptor subfamily 4, complete cds.
HQ692855 - Homo sapiens nerve growth factor IB nuclear receptor variant 1 (NR4A1) mRNA, complete cds.
AK096816 - Homo sapiens cDNA FLJ39497 fis, clone PROST2016582.
JD023758 - Sequence 4782 from Patent EP1572962.
JD036310 - Sequence 17334 from Patent EP1572962.
LF338057 - JP 2014500723-A/145560: Polycomb-Associated Non-Coding RNAs.
MA573634 - JP 2018138019-A/145560: Polycomb-Associated Non-Coding RNAs.
JD422903 - Sequence 403927 from Patent EP1572962.
JD052782 - Sequence 33806 from Patent EP1572962.
JD524942 - Sequence 505966 from Patent EP1572962.
JD365622 - Sequence 346646 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein P22736 (Reactome details) participates in the following event(s):

R-HSA-199863 AKT can phosphorylate NR4A1 (NUR77)
R-HSA-2399988 AKT1 E17K mutant phosphorylates NR4A1 (NUR77)
R-HSA-376419 Formation of NR-MED1 Coactivator Complex
R-HSA-198693 AKT phosphorylates targets in the nucleus
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-2219528 PI3K/AKT Signaling in Cancer
R-HSA-212436 Generic Transcription Pathway
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-5663202 Diseases of signal transduction
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-162582 Signal Transduction
R-HSA-1643685 Disease
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: AK297526, B4DML7, GFRP1, HMR, NAK1, NR4A1_HUMAN, P22736, uc058ofh.1
UCSC ID: uc058ofh.1
RefSeq Accession: NM_001202233
Protein: P22736 (aka NR4A1_HUMAN or NR41_HUMAN)
CCDS: CCDS8818.1, CCDS55828.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.