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 ge... See more...

Aliases for NR2C2 Gene

Aliases for NR2C2 Gene

  • Nuclear Receptor Subfamily 2 Group C Member 2 2 3 4 5
  • TAK1 2 3 4
  • Orphan Nuclear Receptor TAK1 3 4
  • Orphan Nuclear Receptor TR4 3 4
  • TR4 3 4
  • Nuclear Receptor Subfamily 2, Group C, Member 2 2
  • Testicular Nuclear Receptor 4 3
  • Nuclear Hormone Receptor TR4 3
  • Testicular Receptor 4 4
  • Orphan Receptor TR4 3
  • NR2C2 5
  • TR2R1 2
  • HTAK1 2

External Ids for NR2C2 Gene

Previous HGNC Symbols for NR2C2 Gene

  • TR4

Previous GeneCards Identifiers for NR2C2 Gene

  • GC03P014918
  • GC03P014964
  • GC03P014989

Summaries for NR2C2 Gene

Entrez Gene Summary for NR2C2 Gene

  • 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]

GeneCards Summary for NR2C2 Gene

NR2C2 (Nuclear Receptor Subfamily 2 Group C Member 2) is a Protein Coding gene. Diseases associated with NR2C2 include Premature Aging and Lateral Myocardial Infarction. Among its related pathways are Androgen receptor signaling pathway and Gene Expression. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and protein heterodimerization activity. An important paralog of this gene is NR2C1.

UniProtKB/Swiss-Prot Summary for NR2C2 Gene

  • Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor 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.

Gene Wiki entry for NR2C2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NR2C2 Gene

Genomics for NR2C2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NR2C2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NR2C2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NR2C2

Top Transcription factor binding sites by QIAGEN in the NR2C2 gene promoter:
  • Ik-1
  • LCR-F1
  • Sp1
  • SREBP-1a
  • SREBP-1b
  • SREBP-1c
  • TBP
  • Zic3

Genomic Locations for NR2C2 Gene

Genomic Locations for NR2C2 Gene
chr3:14,947,583-15,053,600
(GRCh38/hg38)
Size:
106,018 bases
Orientation:
Plus strand
chr3:14,989,091-15,095,107
(GRCh37/hg19)
Size:
106,017 bases
Orientation:
Plus strand

Genomic View for NR2C2 Gene

Genes around NR2C2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NR2C2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NR2C2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NR2C2 Gene

Proteins for NR2C2 Gene

  • Protein details for NR2C2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49116-NR2C2_HUMAN
    Recommended name:
    Nuclear receptor subfamily 2 group C member 2
    Protein Accession:
    P49116
    Secondary Accessions:
    • A8K3H5
    • B6ZGT8
    • P55092

    Protein attributes for NR2C2 Gene

    Size:
    596 amino acids
    Molecular mass:
    65414 Da
    Quaternary structure:
    • 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 (By similarity). Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2-mediated activity (PubMed:9556573). Interacts with NR2C2AP; the interaction represses selective NR2C2-mediated transcriptional activity (PubMed:12486131). Interacts with NLRP10 (PubMed:22672233). Interacts (via ligand-binding region) with transcriptional corepressor JAZF1; the interaction promotes NR2C2-mediated transcriptional repression (PubMed:15302918).

    Three dimensional structures from OCA and Proteopedia for NR2C2 Gene

    Alternative splice isoforms for NR2C2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NR2C2 Gene

Post-translational modifications for NR2C2 Gene

  • 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).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Boster Bio Antibodies for NR2C2

No data available for DME Specific Peptides for NR2C2 Gene

Domains & Families for NR2C2 Gene

Gene Families for NR2C2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Nuclear receptors
  • Plasma proteins
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for NR2C2 Gene

InterPro:
Blocks:
  • Vitamin D receptor signature
  • Steroid hormone receptor signature
ProtoNet:

Suggested Antigen Peptide Sequences for NR2C2 Gene

GenScript: Design optimal peptide antigens:
  • Testicular nuclear receptor 4 (F2YGU2_HUMAN)
  • Testicular receptor 4 (NR2C2_HUMAN)
  • NR2C2 protein (Q6PHZ7_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P49116

UniProtKB/Swiss-Prot:

NR2C2_HUMAN :
  • Belongs to the nuclear hormone receptor family. NR2 subfamily.
Family:
  • Belongs to the nuclear hormone receptor family. NR2 subfamily.
genes like me logo Genes that share domains with NR2C2: view

Function for NR2C2 Gene

Molecular function for NR2C2 Gene

UniProtKB/Swiss-Prot Function:
Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor 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.
UniProtKB/Swiss-Prot Induction:
Induced by oxidative stress via FOXO3 activation.
GENATLAS Biochemistry:
nuclear receptor subfamily 2,group C,member 2,with two isoforms short TR4ORA2,long TR4ORA1,predominantly expressed in granule cell of the hippocampus and cerebellum,steroid/thyroid hormone receptor superfamily

Phenotypes From GWAS Catalog for NR2C2 Gene

Gene Ontology (GO) - Molecular Function for NR2C2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 9556573
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 10644740
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific ISM 19274049
GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific IDA 9556573
GO:0003677 DNA binding IEA --
genes like me logo Genes that share ontologies with NR2C2: view
genes like me logo Genes that share phenotypes with NR2C2: view

Animal Models for NR2C2 Gene

MGI Knock Outs for NR2C2:

Animal Model Products

CRISPR Products

miRNA for NR2C2 Gene

miRTarBase miRNAs that target NR2C2
Targeted motifs for NR2C2 Gene
HOMER Transcription Factor Regulatory Elements motif NR2C2
  • Consensus sequence: GAGGTCAAAGGTCA Submotif: DR1 Cell Type: Hela GEO ID: GSE24685

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NR2C2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology and Transcription Factor Targets for NR2C2 Gene

Localization for NR2C2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NR2C2 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NR2C2 gene
Compartment Confidence
nucleus 5
plasma membrane 2
extracellular 2
cytosol 2
cytoskeleton 1
mitochondrion 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NR2C2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin ISA --
GO:0005634 nucleus IBA 21873635
GO:0005654 nucleoplasm TAS --
GO:0042025 host cell nucleus IEA --
genes like me logo Genes that share ontologies with NR2C2: view

Pathways & Interactions for NR2C2 Gene

genes like me logo Genes that share pathways with NR2C2: view

SIGNOR curated interactions for NR2C2 Gene

Is inactivated by:

Gene Ontology (GO) - Biological Process for NR2C2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IPI 17974920
GO:0006355 regulation of transcription, DNA-templated TAS 9006963
GO:0006357 regulation of transcription by RNA polymerase II IBA 21873635
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
GO:0007283 spermatogenesis IEA --
genes like me logo Genes that share ontologies with NR2C2: view

Drugs & Compounds for NR2C2 Gene

(5) Drugs for NR2C2 Gene - From: DGIdb, IUPHAR, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Tretinoin Approved, Investigational Nutra Agonist, Full agonist, Antagonist, binder 273
retinol Pharma Agonist, Full agonist 685

(3) Additional Compounds for NR2C2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with NR2C2: view

Transcripts for NR2C2 Gene

mRNA/cDNA for NR2C2 Gene

2 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
13 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NR2C2

Alternative Splicing Database (ASD) splice patterns (SP) for NR2C2 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15a · 15b
SP1: - - -
SP2: - - - -
SP3: -
SP4:
SP5:

Relevant External Links for NR2C2 Gene

GeneLoc Exon Structure for
NR2C2

Expression for NR2C2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NR2C2 Gene

Protein differential expression in normal tissues from HIPED for NR2C2 Gene

This gene is overexpressed in Tlymphocyte (12.1), Peripheral blood mononuclear cells (11.7), CD8 Tcells (9.2), and Plasma (8.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NR2C2 Gene



Protein tissue co-expression partners for NR2C2 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NR2C2

SOURCE GeneReport for Unigene cluster for NR2C2 Gene:

Hs.555973

Evidence on tissue expression from TISSUES for NR2C2 Gene

  • Nervous system(4.3)
  • Liver(2.6)
  • Muscle(2.4)
  • Skin(2.4)
  • Blood(2.4)
  • Kidney(2.4)
  • Heart(2.4)
  • Intestine(2.3)
  • Thyroid gland(2.2)
  • Spleen(2.2)
  • Lymph node(2.1)
  • Bone marrow(2)
genes like me logo Genes that share expression patterns with NR2C2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for NR2C2 Gene

Orthologs for NR2C2 Gene

This gene was present in the common ancestor of animals.

Orthologs for NR2C2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NR2C2 30 31
  • 99.62 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NR2C2 30 31
  • 94.52 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NR2C2 31
  • 94 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Nr2c2 30 17 31
  • 92.56 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nr2c2 30
  • 91.89 (n)
Cow
(Bos Taurus)
Mammalia NR2C2 30 31
  • 90.64 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia NR2C2 31
  • 90 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NR2C2 30 31
  • 81.18 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NR2C2 31
  • 87 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia nr2c2 30
  • 78.26 (n)
Zebrafish
(Danio rerio)
Actinopterygii nr2c2 30 31
  • 72.81 (n)
OneToOne
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.5700 30
Fruit Fly
(Drosophila melanogaster)
Insecta Hr78 31 32
  • 26 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea nhr-41 31
  • 25 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.9698 31
  • 34 (a)
OneToMany
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.4782 30
Species where no ortholog for NR2C2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NR2C2 Gene

ENSEMBL:
Gene Tree for NR2C2 (if available)
TreeFam:
Gene Tree for NR2C2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NR2C2: view image

Paralogs for NR2C2 Gene

Paralogs for NR2C2 Gene

(26) SIMAP similar genes for NR2C2 Gene using alignment to 8 proteins:

  • NR2C2_HUMAN
  • C9J2Y1_HUMAN
  • C9JKS0_HUMAN
  • C9JMI6_HUMAN
  • F2YGU2_HUMAN
  • H7C3L1_HUMAN
  • H7C3R1_HUMAN
  • Q6PHZ7_HUMAN
genes like me logo Genes that share paralogs with NR2C2: view

Variants for NR2C2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NR2C2 Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
791909 Benign: not provided 15,023,315(+) T/A SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for NR2C2 Gene

Structural Variations from Database of Genomic Variants (DGV) for NR2C2 Gene

Variant ID Type Subtype PubMed ID
esv2663121 CNV deletion 23128226
esv2759130 CNV gain 17122850
esv3595377 CNV gain 21293372
esv3595378 CNV loss 21293372
nsv1074573 CNV deletion 25765185
nsv834620 CNV gain 17160897
nsv955319 CNV duplication 24416366

Variation tolerance for NR2C2 Gene

Residual Variation Intolerance Score: 12.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.78; 16.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NR2C2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NR2C2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NR2C2 Gene

Disorders for NR2C2 Gene

MalaCards: The human disease database

(5) MalaCards diseases for NR2C2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
premature aging
  • syndrome with premature-aging
lateral myocardial infarction
anterior cerebral artery infarction
  • infarction, anterior cerebral artery
epilepsy, familial temporal lobe, 8
  • etl8
cortical thymoma
  • polygonal cell thymoma
- elite association - COSMIC cancer census association via MalaCards
Search NR2C2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for NR2C2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with NR2C2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NR2C2 Gene

Publications for NR2C2 Gene

  1. The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription. (PMID: 17974920) Tanabe O … Engel JD (Genes & development 2007) 3 4 23
  2. Identification of a novel testicular orphan receptor-4 (TR4)-associated protein as repressor for the selective suppression of TR4-mediated transactivation. (PMID: 12486131) Yang Y … Chang C (The Journal of biological chemistry 2003) 3 4 23
  3. Nuclear orphan receptors regulate transcription of the gene for the human luteinizing hormone receptor. (PMID: 10644740) Zhang Y … Dufau ML (The Journal of biological chemistry 2000) 3 4 23
  4. New variants of the human and rat nuclear hormone receptor, TR4: expression and chromosomal localization of the human gene. (PMID: 8661150) Yoshikawa T … Detera-Wadleigh SD (Genomics 1996) 2 3 23
  5. TAK1: molecular cloning and characterization of a new member of the nuclear receptor superfamily. (PMID: 7708055) Hirose T … Jetten AM (Molecular endocrinology (Baltimore, Md.) 1994) 3 4 23

Products for NR2C2 Gene

  • Signalway Proteins for NR2C2

Sources for NR2C2 Gene