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
MGIneXtProtPubMedReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
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;
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

- X-ray MuPIT

- X-ray MuPIT

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P22736
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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     
Gene Sorter     
Protein SequenceProtein Sequence    

-  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.