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Aliases for NR1D1 Gene

Aliases for NR1D1 Gene

  • Nuclear Receptor Subfamily 1, Group D, Member 1 2 3
  • THRAL 3 4 6
  • EAR1 3 4 6
  • V-ErbA-Related Protein 1 3 4
  • Rev-ErbA-Alpha 3 4
  • Ear-1 3 4
  • HRev 3 4
  • Nuclear Receptor Subfamily 1 Group D Member 1 3
  • Nuclear Receptor Rev-ErbA-Alpha 3
  • Rev-ErbAalpha 3
  • THRA1 3

External Ids for NR1D1 Gene

Previous Symbols for NR1D1 Gene

  • THRAL

Summaries for NR1D1 Gene

Entrez Gene Summary for NR1D1 Gene

  • This gene encodes a transcription factor that is a member of the nuclear receptor subfamily 1. The encoded protein is a ligand-sensitive transcription factor that negatively regulates the expression of core clock proteins. In particular this protein represses the circadian clock transcription factor aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL). This protein may also be involved in regulating genes that function in metabolic, inflammatory and cardiovascular processes. [provided by RefSeq, Jan 2013]

GeneCards Summary for NR1D1 Gene

NR1D1 (Nuclear Receptor Subfamily 1, Group D, Member 1) is a Protein Coding gene. Among its related pathways are Metabolism and Metabolism. GO annotations related to this gene include sequence-specific DNA binding and transcription regulatory region DNA binding. An important paralog of this gene is NR1I2.

UniProtKB/Swiss-Prot for NR1D1 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 ARTNL/BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage 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 nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner.

Gene Wiki entry for NR1D1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NR1D1 Gene

Genomics for NR1D1 Gene

Genomic Location for NR1D1 Gene

Start:
40,092,784 bp from pter
End:
40,100,725 bp from pter
Size:
7,942 bases
Orientation:
Minus strand

Genomic View for NR1D1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NR1D1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NR1D1 Gene

Regulatory Elements for NR1D1 Gene

Proteins for NR1D1 Gene

  • Protein details for NR1D1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P20393-NR1D1_HUMAN
    Recommended name:
    Nuclear receptor subfamily 1 group D member 1
    Protein Accession:
    P20393
    Secondary Accessions:
    • Q0P5Z4
    • Q15304

    Protein attributes for NR1D1 Gene

    Size:
    614 amino acids
    Molecular mass:
    66805 Da
    Quaternary structure:
    • Binds DNA as a monomer or a homodimer. Interacts with C1D, NR2E3 and SP1. Interacts with OPHN1 (via C-terminus). Interacts with ZNHIT1. Interacts with PER2; the interaction associates PER2 to ARNTL promoter region. Interacts with CRY1. Interacts with CCAR2.

    Three dimensional structures from OCA and Proteopedia for NR1D1 Gene

neXtProt entry for NR1D1 Gene

Proteomics data for NR1D1 Gene at MOPED

Post-translational modifications for NR1D1 Gene

Other Protein References for NR1D1 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for NR1D1 Gene

Domains for NR1D1 Gene

Gene Families for NR1D1 Gene

HGNC:
  • NR :Nuclear hormone receptors
IUPHAR :

UniProtKB/Swiss-Prot:

NR1D1_HUMAN
Domain:
  • Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain:
    • P20393
  • Contains 1 nuclear receptor DNA-binding domain.:
    • P20393
Family:
  • Belongs to the nuclear hormone receptor family. NR1 subfamily.:
    • P20393
genes like me logo Genes that share domains with NR1D1: view

Function for NR1D1 Gene

Molecular function for NR1D1 Gene

GENATLAS Biochemistry: nuclear receptor subfamily 1,group D,member 1,partially overlapping THRA (exon for THRA2) on the opposite strand
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 ARTNL/BMAL1, CLOCK and CRY1. Also regulates genes involved in metabolic functions, including lipid and bile acid metabolism, adipogenesis, gluconeogenesis and the macrophage 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 nucleotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and regulates the levels of its ligand heme by repressing the expression of PPARGC1A, a potent inducer of heme synthesis. Regulates lipid metabolism by repressing the expression of APOC3 and by influencing the activity of sterol response element binding proteins (SREBPs); represses INSIG2 which interferes with the proteolytic activation of SREBPs which in turn govern the rhythmic expression of enzymes with key functions in sterol and fatty acid synthesis. Regulates gluconeogenesis via repression of G6PC and PEPCK and adipocyte differentiation via repression of PPARG. Regulates glucagon release in pancreatic alpha-cells via the AMPK-NAMPT-SIRT1 pathway and the proliferation, glucose-induced insulin secretion and expression of key lipogenic genes in pancreatic-beta cells. Positively regulates bile acid synthesis by increasing hepatic expression of CYP7A1 via repression of NR0B2 and NFIL3 which are negative regulators of CYP7A1. Modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy; controls mitochondrial biogenesis and respiration by interfering with the STK11-PRKAA1/2-SIRT1-PPARGC1A signaling pathway. Represses the expression of SERPINE1/PAI1, an important modulator of cardiovascular disease and the expression of inflammatory cytokines and chemokines in macrophages. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). Plays a role in the circadian regulation of body temperature and negatively regulates thermogenic transcriptional programs in brown adipose tissue (BAT); imposes a circadian oscillation in BAT activity, increasing body temperature when awake and depressing thermogenesis during sleep. In concert with NR2E3, regulates transcriptional networks critical for photoreceptor development and function. In addition to its activity as a repressor, can also act as a transcriptional activator. In the ovarian granulosa cells acts as a transcriptional activator of STAR which plays a role in steroid biosynthesis. In collaboration with SP1, activates GJA1 transcription in a heme-independent manner.

Gene Ontology (GO) - Molecular Function for NR1D1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 19955433
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding IMP 8622974
GO:0001046 core promoter sequence-specific DNA binding IDA 15761026
GO:0001078 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription IDA 8622974
GO:0001222 transcription corepressor binding IMP 18006707
genes like me logo Genes that share ontologies with NR1D1: view
genes like me logo Genes that share phenotypes with NR1D1: view

miRNA for NR1D1 Gene

miRTarBase miRNAs that target NR1D1
Targeting motifs for NR1D1 Gene
HOMER Transcription Factor Regulatory Elements motif NR1D1
  • Consensus sequence: GTAGGTCACTGGGTCA Submotif: DR2 Cell Type: RAW GeoId: GSE45914

No data available for Enzyme Numbers (IUBMB) , Animal Models and Transcription Factor Targeting for NR1D1 Gene

Localization for NR1D1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NR1D1 Gene

Nucleus. Cytoplasm. Cell projection, dendrite. Cell projection, dendritic spine. Note=Localizes to the cytoplasm, dendrites and dendritic spine in the presence of OPHN1. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NR1D1 Gene COMPARTMENTS Subcellular localization image for NR1D1 gene
Compartment Confidence
nucleus 4

Gene Ontology (GO) - Cellular Components for NR1D1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000790 nuclear chromatin IDA 18511497
GO:0005634 nucleus ISS --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm ISS --
GO:0030425 dendrite ISS --
genes like me logo Genes that share ontologies with NR1D1: view

Pathways for NR1D1 Gene

genes like me logo Genes that share pathways with NR1D1: view

Pathways by source for NR1D1 Gene

1 Qiagen pathway for NR1D1 Gene
2 Cell Signaling Technology pathways for NR1D1 Gene
1 BioSystems pathway for NR1D1 Gene

Gene Ontology (GO) - Biological Process for NR1D1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IMP 18511497
GO:0005978 glycogen biosynthetic process ISS --
GO:0006355 regulation of transcription, DNA-templated --
GO:0006367 transcription initiation from RNA polymerase II promoter TAS --
GO:0007623 circadian rhythm TAS --
genes like me logo Genes that share ontologies with NR1D1: view

Compounds for NR1D1 Gene

(3) IUPHAR Ligand for NR1D1 Gene

Ligand Type Action Affinity Pubmed IDs
SR8278 Antagonist Antagonist 6.5
GSK4112 Agonist Agonist 6.4
heme Agonist Agonist

(1) PharmGKB related drug/compound annotations for NR1D1 Gene

Drug/compound Annotation
lithium CA
genes like me logo Genes that share compounds with NR1D1: view

Transcripts for NR1D1 Gene

mRNA/cDNA for NR1D1 Gene

Unigene Clusters for NR1D1 Gene

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

Alternative Splicing Database (ASD) splice patterns (SP) for NR1D1 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b ^ 6a · 6b ^ 7 ^ 8 ^ 9
SP1:
SP2: -
SP3:
SP4: - - -
SP5:
SP6:

Relevant External Links for NR1D1 Gene

GeneLoc Exon Structure for
NR1D1
ECgene alternative splicing isoforms for
NR1D1

Expression for NR1D1 Gene

mRNA expression in normal human tissues for NR1D1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NR1D1 Gene

This gene is overexpressed in Skin - Sun Exposed (Lower leg) (6.2) and Skin - Not Sun Exposed (Suprapubic) (6.1).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for NR1D1 Gene

SOURCE GeneReport for Unigene cluster for NR1D1 Gene Hs.592130

mRNA Expression by UniProt/SwissProt for NR1D1 Gene

P20393-NR1D1_HUMAN
Tissue specificity: Widely expressed. Expressed at high levels in the liver, adipose tissue, skeletal muscle and brain. Also expressed in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and macrophages. Expression oscillates diurnally in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as in peripheral tissues. Expression increases during the differentiation of pre-adipocytes into mature adipocytes. Expressed at high levels in some squamous carcinoma cell lines.
genes like me logo Genes that share expressions with NR1D1: view

Orthologs for NR1D1 Gene

This gene was present in the common ancestor of animals.

Orthologs for NR1D1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NR1D1 36
  • 99.84 (n)
  • 100 (a)
NR1D1 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia NR1D1 36
  • 92.59 (n)
  • 95.59 (a)
NR1D1 37
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia NR1D1 36
  • 91.72 (n)
  • 95.75 (a)
NR1D1 37
  • 96 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Nr1d1 36
  • 90.01 (n)
  • 95.44 (a)
Nr1d1 16
Nr1d1 37
  • 95 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia NR1D1 37
  • 85 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Nr1d1 36
  • 90.07 (n)
  • 94.79 (a)
chicken
(Gallus gallus)
Aves -- 37
  • 30 (a)
ManyToMany
lizard
(Anolis carolinensis)
Reptilia NR1D1 37
  • 71 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.9778 36
tropical clawed frog
(Silurana tropicalis)
Amphibia nr1d1 36
  • 69.79 (n)
  • 71.69 (a)
Str.16697 36
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.8023 36
zebrafish
(Danio rerio)
Actinopterygii Dr.27124 36
nr1d1 36
  • 62.27 (n)
  • 62.94 (a)
nr1d1 37
  • 57 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta Eip75B 37
  • 14 (a)
OneToMany
Eip78C 38
  • 71 (a)
Eip75B 38
  • 62 (a)
worm
(Caenorhabditis elegans)
Secernentea nhr-85 37
  • 24 (a)
ManyToMany
sex-1 37
  • 24 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 19 (a)
OneToMany
Species with no ortholog for NR1D1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • platypus (Ornithorhynchus anatinus)
  • 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 NR1D1 Gene

ENSEMBL:
Gene Tree for NR1D1 (if available)
TreeFam:
Gene Tree for NR1D1 (if available)

Paralogs for NR1D1 Gene

Selected SIMAP similar genes for NR1D1 Gene using alignment to 2 proteins:

Pseudogenes.org Pseudogenes for NR1D1 Gene

genes like me logo Genes that share paralogs with NR1D1: view

Variants for NR1D1 Gene

Sequence variations from dbSNP and Humsavar for NR1D1 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type MAF
rs883871 -- 40,096,407(+) TGGGC(A/G)GAAGA intron-variant
rs939346 -- 40,096,414(+) AAGAA(A/G)GGGGG intron-variant
rs939347 -- 40,100,440(+) GGGGT(A/G)GCGAA utr-variant-5-prime
rs2071427 -- 40,098,239(-) TTGCC(A/G)GAGGT intron-variant
rs2071570 -- 40,100,837(-) AAGGG(G/T)AAAGG upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for NR1D1 Gene

Variant ID Type Subtype PubMed ID
nsv908221 CNV Loss 21882294
nsv833444 CNV Loss 17160897
nsv520636 CNV Loss 19592680
nsv528369 CNV Loss 19592680

Relevant External Links for NR1D1 Gene

HapMap Linkage Disequilibrium report
NR1D1

Disorders for NR1D1 Gene

Relevant External Links for NR1D1

Genetic Association Database (GAD)
NR1D1
Human Genome Epidemiology (HuGE) Navigator
NR1D1
genes like me logo Genes that share disorders with NR1D1: view

No data available for UniProtKB/Swiss-Prot for NR1D1 Gene

Publications for NR1D1 Gene

  1. Association analysis of nuclear receptor Rev-erb alpha gene (NR1D1) with mood disorders in the Japanese population. (PMID: 18804497) Kishi T. … Iwata N. (Neurosci. Res. 2008) 3 23 49
  2. Association study in a Sardinian sample between bipolar disorder and the nuclear receptor REV-ERBalpha gene, a critical component of the circadian clock system. (PMID: 19267705) Severino G. … Del Zompo M. (Bipolar Disord 2009) 3 23 49
  3. Isolation of a cDNA encoding human Rev-ErbA alpha: transcription from the noncoding DNA strand of a thyroid hormone receptor gene results in a related protein that does not bind thyroid hormone. (PMID: 1971514) Lazar M.A. … Chin W.W. (DNA Cell Biol. 1990) 2 3 4
  4. Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus. (PMID: 2539258) Miyajima N. … Yamamoto T. (Cell 1989) 3 4
  5. Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism. (PMID: 20414452) Yin L. … Lazar M.A. (Nucl Recept Signal 2010) 4 23

Products for NR1D1 Gene

  • Addgene plasmids for NR1D1

Sources for NR1D1 Gene

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