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Aliases for NR1D2 Gene

Aliases for NR1D2 Gene

  • Nuclear Receptor Subfamily 1 Group D Member 2 2 3 5
  • Orphan Nuclear Hormone Receptor BD73 3 4
  • V-ErbA-Related Protein 1-Related 3 4
  • Rev-Erb Alpha-Related Receptor 3 4
  • Rev-Erb-Beta 3 4
  • EAR-1R 3 4
  • RVR 3 4
  • Nuclear Receptor Subfamily 1, Group D, Member 2 2
  • Nuclear Receptor Rev-ErbA Beta Variant 1 3
  • Nuclear Receptor Rev-ErbA Beta Variant 2 3
  • Rev-Erba-Alpha-Related Receptor 3
  • BD73 3

External Ids for NR1D2 Gene

Previous GeneCards Identifiers for NR1D2 Gene

  • GC03U990106
  • GC03P023669
  • GC03P023836

Summaries for NR1D2 Gene

Entrez Gene Summary for NR1D2 Gene

  • This gene encodes a member of the nuclear hormone receptor family, specifically the NR1 subfamily of receptors. The encoded protein functions as a transcriptional repressor and may play a role in circadian rhythms and carbohydrate and lipid metabolism. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

GeneCards Summary for NR1D2 Gene

NR1D2 (Nuclear Receptor Subfamily 1 Group D Member 2) is a Protein Coding gene. Among its related pathways are Gene Expression and Circadian rythm related genes. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and steroid hormone receptor activity. An important paralog of this gene is NR1D1.

UniProtKB/Swiss-Prot for NR1D2 Gene

  • Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARNTL/BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5-[A/G]GGTCA-3 preceded by an A/T-rich 5 sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle.

Tocris Summary for NR1D2 Gene

  • Rev-Erb receptors are orphan nuclear receptors belonging to the NR1D receptor family. There are two types, Rev-Erbalpha and Rev-Erbbeta. They are important in the regulation of circadian rhythm, as well as lipid homeostasis and lipid metabolism.

Gene Wiki entry for NR1D2 Gene

Additional gene information for NR1D2 Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NR1D2 Gene

Genomics for NR1D2 Gene

GeneHancer (GH) Regulatory Elements for NR1D2 Gene

Promoters and enhancers for NR1D2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH03I023944 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 561.4 +1.4 1403 4.6 CLOCK MLX FEZF1 DMAP1 YY1 ZNF213 E2F8 ZNF143 SP3 NFYC NR1D2 NKIRAS1 NPM1P23
GH03I023945 Enhancer 0.5 ENCODE 550.8 -1.1 -1141 0 ZNF335 L3MBTL2 FOXK2 ZNF10 PRDM10 MNT ZBTB17 NR1D2 NKIRAS1 RPL15
GH03I023915 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 13.1 -28.0 -28046 4.1 MLX ZFP64 FEZF1 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ZNF143 NKIRAS1 RPL15 NR1D2
GH03I023805 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 10.1 -136.5 -136453 6.9 PKNOX1 FOXA2 SMAD1 ARNT SIN3A DMAP1 YBX1 ZNF2 YY1 POLR2B UBE2E1-AS1 UBE2E1 RPL15 NKIRAS1 NR1D2 GC03P023841
GH03I024237 Enhancer 1.3 Ensembl ENCODE dbSUPER 12.3 +293.1 293148 1.8 PKNOX1 FEZF1 ZNF2 ZNF213 ZNF143 FOS KLF13 SP3 YY2 REST NR1D2 RPL15 LOC101927854 GC03M024338 THRB
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around NR1D2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the NR1D2 gene promoter:

Genomic Locations for NR1D2 Gene

Genomic Locations for NR1D2 Gene
chr3:23,945,260-23,980,618
(GRCh38/hg38)
Size:
35,359 bases
Orientation:
Plus strand
chr3:23,986,751-24,022,109
(GRCh37/hg19)

Genomic View for NR1D2 Gene

Genes around NR1D2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NR1D2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NR1D2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NR1D2 Gene

Proteins for NR1D2 Gene

  • Protein details for NR1D2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14995-NR1D2_HUMAN
    Recommended name:
    Nuclear receptor subfamily 1 group D member 2
    Protein Accession:
    Q14995
    Secondary Accessions:
    • B2R8Q3
    • O00402
    • Q86XD4

    Protein attributes for NR1D2 Gene

    Size:
    579 amino acids
    Molecular mass:
    64625 Da
    Quaternary structure:
    • Binds DNA as a monomer or a homodimer. Interacts with NCOA5 coactivator, leading to a strong increase of transcription of target genes. Interacts (via N-terminus) with KAT5. Interacts (via C-terminus) with HDAC1. Interacts with ZNHIT1.

    Three dimensional structures from OCA and Proteopedia for NR1D2 Gene

neXtProt entry for NR1D2 Gene

Post-translational modifications for NR1D2 Gene

  • Deacetylated by HDAC1. Acetylation and deacetylation regulate its transcriptional regulatory activity.
  • Under more reducing intracellular redox conditions, Cys-384 is in its heme-bound state, which is optimal for recruitment of the NCOR1/HDAC3 corepressor complex and repression of target genes. When subjected to oxidative stress conditions, Cys-384 undergoes oxidation to form a disulfide bridge with Cys-374, also triggering a ligand switch that results in release of bound heme and derepression of target genes.

Other Protein References for NR1D2 Gene

No data available for DME Specific Peptides for NR1D2 Gene

Domains & Families for NR1D2 Gene

Gene Families for NR1D2 Gene

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

Graphical View of Domain Structure for InterPro Entry

Q14995

UniProtKB/Swiss-Prot:

NR1D2_HUMAN :
  • Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.
Domain:
  • Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Family:
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.
genes like me logo Genes that share domains with NR1D2: view

Function for NR1D2 Gene

Molecular function for NR1D2 Gene

GENATLAS Biochemistry:
nuclear receptor subfamily 1,group D,member 2,in a duplicated region including THRB and RARB in a region paralog to a region of chromosome 17q11.12 including THRA,NR1D1,RARA
UniProtKB/Swiss-Prot EnzymeRegulation:
The heme-bound form can bind gaseous signaling molecules such as CO and nitric oxide (NO) and NO can reverse its transcriptional repressor activity.
UniProtKB/Swiss-Prot Function:
Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARNTL/BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5-[A/G]GGTCA-3 preceded by an A/T-rich 5 sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle.

Phenotypes From GWAS Catalog for NR1D2 Gene

Gene Ontology (GO) - Molecular Function for NR1D2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000980 RNA polymerase II distal enhancer sequence-specific DNA binding IEA --
GO:0001046 core promoter sequence-specific DNA binding IDA,IEA 17892483
GO:0001206 transcriptional repressor activity, RNA polymerase II distal enhancer sequence-specific binding IEA --
GO:0003677 DNA binding IEA --
GO:0003700 DNA binding transcription factor activity IEA --
genes like me logo Genes that share ontologies with NR1D2: view
genes like me logo Genes that share phenotypes with NR1D2: view

Animal Models for NR1D2 Gene

MGI Knock Outs for NR1D2:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NR1D2 Gene

Localization for NR1D2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NR1D2 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 NR1D2 gene
Compartment Confidence
nucleus 5

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for NR1D2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus TAS,IEA 7997240
GO:0005654 nucleoplasm TAS --
genes like me logo Genes that share ontologies with NR1D2: view

Pathways & Interactions for NR1D2 Gene

genes like me logo Genes that share pathways with NR1D2: view

Gene Ontology (GO) - Biological Process for NR1D2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IEA --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA,TAS 7997240
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
GO:0019216 regulation of lipid metabolic process IEA,ISS --
genes like me logo Genes that share ontologies with NR1D2: view

No data available for SIGNOR curated interactions for NR1D2 Gene

Drugs & Compounds for NR1D2 Gene

(3) Drugs for NR1D2 Gene - From: ApexBio, DGIdb, and IUPHAR

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
heme Pharma Agonist 0
GSK 4112 Pharma antagonist of the Nuclear Heme Receptor REV-ERB 0
SR 8278 Pharma 0

(1) Additional Compounds for NR1D2 Gene - From:

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(2) ApexBio Compounds for NR1D2 Gene

Compound Action Cas Number
GSK 4112 antagonist of the Nuclear Heme Receptor REV-ERB 1216744-19-2
SR 8278 1254944-66-5
genes like me logo Genes that share compounds with NR1D2: view

Drug Products

Transcripts for NR1D2 Gene

Unigene Clusters for NR1D2 Gene

Nuclear receptor subfamily 1, group D, member 2:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for NR1D2 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9a · 9b
SP1: -
SP2: - -
SP3:

Relevant External Links for NR1D2 Gene

GeneLoc Exon Structure for
NR1D2
ECgene alternative splicing isoforms for
NR1D2

Expression for NR1D2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for NR1D2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NR1D2 Gene

This gene is overexpressed in Cervix (54.9) and Heart (14.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for NR1D2 Gene



Protein tissue co-expression partners for NR1D2 Gene

NURSA nuclear receptor signaling pathways regulating expression of NR1D2 Gene:

NR1D2

SOURCE GeneReport for Unigene cluster for NR1D2 Gene:

Hs.37288

mRNA Expression by UniProt/SwissProt for NR1D2 Gene:

Q14995-NR1D2_HUMAN
Tissue specificity: Widely expressed. Expressed at high levels in the liver, adipose tissue, skeletal muscle and brain. Expression oscillates diurnally in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as in peripheral tissues.

Evidence on tissue expression from TISSUES for NR1D2 Gene

  • Nervous system(4.7)
  • Blood(4.1)
  • Muscle(2.2)
  • Liver(2.1)
genes like me logo Genes that share expression patterns with NR1D2: view

Primer Products

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for NR1D2 Gene

Orthologs for NR1D2 Gene

This gene was present in the common ancestor of animals.

Orthologs for NR1D2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NR1D2 33 34
  • 99.42 (n)
dog
(Canis familiaris)
Mammalia NR1D2 33 34
  • 95.83 (n)
mouse
(Mus musculus)
Mammalia Nr1d2 33 16 34
  • 89.06 (n)
oppossum
(Monodelphis domestica)
Mammalia NR1D2 34
  • 88 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NR1D2 34
  • 87 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NR1D2 33 34
  • 86.27 (n)
rat
(Rattus norvegicus)
Mammalia Nr1d2 33
  • 84.52 (n)
chicken
(Gallus gallus)
Aves NR1D2 33
  • 79.41 (n)
REV-ERBB 34
  • 79 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NR1D2 34
  • 75 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii nr1d2b 33 34
  • 64.66 (n)
reverbb 33
fruit fly
(Drosophila melanogaster)
Insecta Eip75B 34
  • 12 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea nhr-85 34
  • 24 (a)
ManyToMany
sex-1 34
  • 22 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 18 (a)
OneToMany
Species where no ortholog for NR1D2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • rainbow trout (Oncorhynchus mykiss)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for NR1D2 Gene

ENSEMBL:
Gene Tree for NR1D2 (if available)
TreeFam:
Gene Tree for NR1D2 (if available)

Paralogs for NR1D2 Gene

Paralogs for NR1D2 Gene

genes like me logo Genes that share paralogs with NR1D2: view

Variants for NR1D2 Gene

Sequence variations from dbSNP and Humsavar for NR1D2 Gene

SNP ID Clin Chr 03 pos Variation AA Info Type
rs1000066365 -- 23,946,154(+) G/A 5_prime_UTR_variant, intron_variant
rs1000199906 -- 23,979,157(+) A/G 3_prime_UTR_variant, non_coding_transcript_variant
rs1000220944 -- 23,950,161(+) A/T intron_variant
rs1000266795 -- 23,943,828(+) G/A upstream_transcript_variant
rs1000300175 -- 23,950,411(+) G/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for NR1D2 Gene

Variant ID Type Subtype PubMed ID
nsv834638 CNV loss 17160897
nsv1126644 CNV deletion 24896259
nsv1123633 CNV deletion 24896259
nsv1073208 CNV deletion 25765185
nsv1005186 CNV gain 25217958
esv3568648 CNV loss 25503493
esv3404389 CNV duplication 20981092

Variation tolerance for NR1D2 Gene

Residual Variation Intolerance Score: 32.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.01; 37.10% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NR1D2 Gene

Human Gene Mutation Database (HGMD)
NR1D2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NR1D2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NR1D2 Gene

Disorders for NR1D2 Gene

Additional Disease Information for NR1D2

No disorders were found for NR1D2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for NR1D2 Gene

Publications for NR1D2 Gene

  1. A new orphan member of the nuclear hormone receptor superfamily closely related to Rev-Erb. (PMID: 7997240) Dumas B … Moore DD (Molecular endocrinology (Baltimore, Md.) 1994) 2 3 4 58
  2. Thiol-disulfide redox dependence of heme binding and heme ligand switching in nuclear hormone receptor rev-erb{beta}. (PMID: 21123168) Gupta N … Ragsdale SW (The Journal of biological chemistry 2011) 3 4 58
  3. The orphan nuclear receptor Rev-erbbeta recruits Tip60 and HDAC1 to regulate apolipoprotein CIII promoter. (PMID: 17996965) Wang J … Lu H (Biochimica et biophysica acta 2008) 3 4 58
  4. Identification of heme as the ligand for the orphan nuclear receptors REV-ERBalpha and REV-ERBbeta. (PMID: 18037887) Raghuram S … Rastinejad F (Nature structural & molecular biology 2007) 3 22 58
  5. A zinc finger HIT domain-containing protein, ZNHIT-1, interacts with orphan nuclear hormone receptor Rev-erbbeta and removes Rev-erbbeta-induced inhibition of apoCIII transcription. (PMID: 17892483) Wang J … Lu H (The FEBS journal 2007) 3 4 58

Products for NR1D2 Gene

Sources for NR1D2 Gene

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