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Aliases for NR1D2 Gene

Aliases for NR1D2 Gene

  • Nuclear Receptor Subfamily 1, Group D, Member 2 2 3
  • RVR 3 4 6
  • 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
  • BD73 3 6
  • Nuclear Receptor Subfamily 1 Group D Member 2 3
  • Nuclear Receptor Rev-ErbA Beta Variant 1 3
  • Nuclear Receptor Rev-ErbA Beta Variant 2 3
  • Rev-Erba-Alpha-Related Receptor 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 Gene Expression. GO annotations related to this gene include sequence-specific DNA binding and ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity. An important paralog of this gene is NR1I2.

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.

Gene Wiki entry for NR1D2 Gene

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

Genomics for NR1D2 Gene

Regulatory Elements for NR1D2 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for NR1D2 Gene

Start:
23,945,260 bp from pter
End:
23,980,618 bp from pter
Size:
35,359 bases
Orientation:
Plus strand

Genomic View for NR1D2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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

Proteomics data for NR1D2 Gene at MOPED

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
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NR1D2 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for NR1D2 (Rev-erb beta/NR1D2)

No data available for DME Specific Peptides for NR1D2 Gene

Domains for NR1D2 Gene

Gene Families for NR1D2 Gene

HGNC:
  • NR :Nuclear hormone receptors
IUPHAR :

Graphical View of Domain Structure for InterPro Entry

Q14995

UniProtKB/Swiss-Prot:

NR1D2_HUMAN :
  • Q14995
Domain:
  • Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain
  • Contains 1 nuclear receptor DNA-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.

Gene Ontology (GO) - Molecular Function for NR1D2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001046 core promoter sequence-specific DNA binding IDA 17892483
GO:0003677 DNA binding --
GO:0003700 sequence-specific DNA binding transcription factor activity --
GO:0003707 steroid hormone receptor activity IEA --
GO:0004879 ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity TAS 7997240
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

miRNA for NR1D2 Gene

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for NR1D2

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for NR1D2 Gene

Localization for NR1D2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NR1D2 Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NR1D2 Gene COMPARTMENTS Subcellular localization image for NR1D2 gene
Compartment Confidence
nucleus 4

Gene Ontology (GO) - Cellular Components for NR1D2 Gene

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

Pathways for NR1D2 Gene

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

Pathways by source for NR1D2 Gene

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

Gene Ontology (GO) - Biological Process for NR1D2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006351 transcription, DNA-templated --
GO:0006355 regulation of transcription, DNA-templated TAS 7997240
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
GO:0010467 gene expression TAS --
GO:0019216 regulation of lipid metabolic process ISS --
genes like me logo Genes that share ontologies with NR1D2: view

Compounds for NR1D2 Gene

(1) IUPHAR Ligand for NR1D2 Gene

Ligand Type Action Affinity Pubmed IDs
heme Agonist Agonist
genes like me logo Genes that share compounds with NR1D2: view

Transcripts for NR1D2 Gene

Unigene Clusters for NR1D2 Gene

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

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for NR1D2

Primer Products

  • QuantiTect SYBR Green Assays in human,mouse,rat
  • Pre-validated RT² qPCR Primer Assay in human,mouse,rat
  • QuantiFast Probe-based Assays in human,mouse,rat

Flow Cytometry 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 for NR1D2 Gene

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for NR1D2 Gene

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

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues 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 35
  • 99.42 (n)
  • 99.48 (a)
NR1D2 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NR1D2 35
  • 86.27 (n)
  • 88.66 (a)
NR1D2 36
  • 87 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NR1D2 35
  • 95.83 (n)
  • 98.26 (a)
NR1D2 36
  • 98 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nr1d2 35
  • 89.06 (n)
  • 91.32 (a)
Nr1d2 16
Nr1d2 36
  • 91 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NR1D2 36
  • 88 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia NR1D2 36
  • 87 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nr1d2 35
  • 84.52 (n)
  • 87.58 (a)
chicken
(Gallus gallus)
Aves NR1D2 35
  • 79.41 (n)
  • 83.92 (a)
REV-ERBB 36
  • 79 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia NR1D2 36
  • 75 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii nr1d2b 35
  • 64.66 (n)
  • 66.85 (a)
nr1d2b 36
  • 60 (a)
OneToOne
reverbb 35
fruit fly
(Drosophila melanogaster)
Insecta Eip75B 36
  • 12 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea nhr-85 36
  • 24 (a)
ManyToMany
sex-1 36
  • 22 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 18 (a)
OneToMany
Species with no ortholog for NR1D2:
  • 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

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 Sequence Context AA Info Type MAF
rs1135452 -- 23,947,800(+) CTATC(A/T)GTAAG intron-variant
rs3935253 -- 23,958,265(+) TGATC(C/T)TGGAA intron-variant
rs4131403 -- 23,951,946(-) CCATT(C/T)ATTCT intron-variant
rs4131404 -- 23,951,697(-) GAATT(C/T)AAACA intron-variant
rs4131864 -- 23,944,318(-) TAGAA(G/T)GTGGG upstream-variant-2KB

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

Variant ID Type Subtype PubMed ID
nsv834638 CNV Loss 17160897

Relevant External Links for NR1D2 Gene

HapMap Linkage Disequilibrium report
NR1D2

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

Disorders for NR1D2 Gene

No disorders were found for NR1D2 Gene.

No data available for UniProtKB/Swiss-Prot 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 D.D. (Mol. Endocrinol. 1994) 2 3 4
  2. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard D.S. … Malek J. (Genome Res. 2004) 3 4
  3. Thiol-disulfide redox dependence of heme binding and heme ligand switching in nuclear hormone receptor rev-erb{beta}. (PMID: 21123168) Gupta N. … Ragsdale S.W. (J. Biol. Chem. 2011) 3 4
  4. Structural insight into the constitutive repression function of the nuclear receptor Rev-erbbeta. (PMID: 17870090) Woo E.-J. … Eon Ryu S. (J. Mol. Biol. 2007) 3 4
  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. (FEBS J. 2007) 3 4

Products for NR1D2 Gene

  • Addgene plasmids for NR1D2

Sources for NR1D2 Gene

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