Human Gene NR2C2 (ENST00000393102.7) Description and Page Index
  Description: Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear recptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation. (from UniProt P49116)
RefSeq Summary (NM_001291694): This gene encodes a protein that belongs to the nuclear hormone receptor family. Members of this family act as ligand-activated transcription factors and function in many biological processes such as development, cellular differentiation and homeostasis. The activated receptor/ligand complex is translocated to the nucleus where it binds to hormone response elements of target genes. The protein encoded by this gene plays a role in protecting cells from oxidative stress and damage induced by ionizing radiation. The lack of a similar gene in mouse results in growth retardation, severe spinal curvature, subfertility, premature aging, and prostatic intraepithelial neoplasia (PIN) development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014].
Gencode Transcript: ENST00000393102.7
Gencode Gene: ENSG00000177463.15
Transcript (Including UTRs)
   Position: hg38 chr3:14,962,407-15,043,029 Size: 80,623 Total Exon Count: 14 Strand: +
Coding Region
   Position: hg38 chr3:15,003,915-15,043,008 Size: 39,094 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsCTDRNA-Seq ExpressionMicroarray Expression
RNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathways
Other NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr3:14,962,407-15,043,029)mRNA (may differ from genome)Protein (596 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblExonPrimerGeneCardsHGNC
LynxMGIneXtProtPubMedReactomeStanford SOURCE
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: NR2C2_HUMAN
DESCRIPTION: RecName: Full=Nuclear receptor subfamily 2 group C member 2; AltName: Full=Orphan nuclear receptor TAK1; AltName: Full=Orphan nuclear receptor TR4; AltName: Full=Testicular receptor 4;
FUNCTION: Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear recptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation.
SUBUNIT: Homodimer; can bind DNA as homodimer (By similarity). Heterodimer; binds DNA as a heterodimer with NR2C1 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with PCAF; the interaction preferentially occurs on the non-phosphorylated form and induces NR2C2-mediated transactivation activity and does not require the ligand-binding domain. Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2- mediated activity (By similarity). Interacts with NR2C2AP; the interaction represses selective NR2C2-mediated transcriptional activity.
SUBCELLULAR LOCATION: Nucleus.
DEVELOPMENTAL STAGE: Transiently repressed during the meiotic phase of spermatogenesis.
INDUCTION: Induced by oxidative stress via FOXO3 activation.
PTM: Phosphorylation on Ser-19 and Ser-68 is an important regulator of NR2C2-mediated transcriptional activity. Phosphorylation on these residues recruits the corepressor, NRIP1, leading to transcripional repression, whereas the non- phosphorylated form preferentially recruits the coactivator, PCAF (By similarity).
SIMILARITY: Belongs to the nuclear hormone receptor family. NR2 subfamily.
SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.

-  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: 6.33 RPKM in Testis
Total median expression: 99.06 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 -35.10125-0.281 Picture PostScript Text
3' UTR -0.5021-0.024 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
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

3P0U
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P49116
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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     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
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:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003707 steroid hormone receptor activity
GO:0003713 transcription coactivator activity
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0038023 signaling receptor activity
GO:0043565 sequence-specific DNA binding
GO:0046872 metal ion binding
GO:0046982 protein heterodimerization activity

Biological Process:
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:0007283 spermatogenesis
GO:0007399 nervous system development
GO:0030154 cell differentiation
GO:0043401 steroid hormone mediated signaling pathway
GO:0045944 positive regulation of transcription from RNA polymerase II promoter

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm


-  Descriptions from all associated GenBank mRNAs
  AK290590 - Homo sapiens cDNA FLJ77492 complete cds, highly similar to Human nuclear receptor hTAK1 (hTAK1) mRNA.
L27586 - Human TR4 orphan receptor mRNA, complete cds.
LF384158 - JP 2014500723-A/191661: Polycomb-Associated Non-Coding RNAs.
MA619735 - JP 2018138019-A/191661: Polycomb-Associated Non-Coding RNAs.
BC051670 - Homo sapiens nuclear receptor subfamily 2, group C, member 2, mRNA (cDNA clone MGC:48324 IMAGE:5272493), complete cds.
U10990 - Human nuclear receptor hTAK1 (hTAK1) mRNA, complete cds.
KJ901807 - Synthetic construct Homo sapiens clone ccsbBroadEn_11201 NR2C2 gene, encodes complete protein.
HQ257979 - Synthetic construct Homo sapiens clone IMAGE:100072288 Unknown protein gene, encodes complete protein.
AB385125 - Synthetic construct DNA, clone: pF1KB5580, Homo sapiens NR2C2 gene for orphan nuclear receptor TR4, complete cds, without stop codon, in Flexi system.
AB307708 - Homo sapiens NR2C2 mRNA for nuclear receptor subfamily 2, group C, member 2, complete cds.
HQ995528 - Homo sapiens testicular nuclear receptor 4 (NR2C2) mRNA, complete cds.
LF364331 - JP 2014500723-A/171834: Polycomb-Associated Non-Coding RNAs.
MA599908 - JP 2018138019-A/171834: Polycomb-Associated Non-Coding RNAs.
LF364333 - JP 2014500723-A/171836: Polycomb-Associated Non-Coding RNAs.
MA599910 - JP 2018138019-A/171836: Polycomb-Associated Non-Coding RNAs.
LF207299 - JP 2014500723-A/14802: Polycomb-Associated Non-Coding RNAs.
MA442876 - JP 2018138019-A/14802: Polycomb-Associated Non-Coding RNAs.
DQ596067 - Homo sapiens piRNA piR-34133, complete sequence.
AK094590 - Homo sapiens cDNA FLJ37271 fis, clone BRAMY2011961, highly similar to ORPHAN NUCLEAR RECEPTOR TR4.
LF364340 - JP 2014500723-A/171843: Polycomb-Associated Non-Coding RNAs.
MA599917 - JP 2018138019-A/171843: Polycomb-Associated Non-Coding RNAs.
LF364345 - JP 2014500723-A/171848: Polycomb-Associated Non-Coding RNAs.
MA599922 - JP 2018138019-A/171848: Polycomb-Associated Non-Coding RNAs.
LF364346 - JP 2014500723-A/171849: Polycomb-Associated Non-Coding RNAs.
MA599923 - JP 2018138019-A/171849: Polycomb-Associated Non-Coding RNAs.
JD228099 - Sequence 209123 from Patent EP1572962.
JD524079 - Sequence 505103 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P49116 (Reactome details) participates in the following event(s):

R-HSA-376419 Formation of NR-MED1 Coactivator Complex
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: A8K3H5, B6ZGT8, L27586, NR2C2_HUMAN, P49116, P55092, TAK1, TR4, uc062hat.1
UCSC ID: uc062hat.1
RefSeq Accession: NM_001291694
Protein: P49116 (aka NR2C2_HUMAN)
CCDS: CCDS2621.1, CCDS74905.1

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