======= NR1D1 =======
== Gene Information ==
* **Official Symbol**: NR1D1
* **Official Name**: nuclear receptor subfamily 1 group D member 1
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=9572|9572]]
* **UniProt**: [[https://www.uniprot.org/uniprot/P20393|P20393]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=NR1D1&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20NR1D1|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/602408|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: 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].
* **UniProt Summary**: 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. {ECO:0000269|PubMed:12021280, ECO:0000269|PubMed:15761026, ECO:0000269|PubMed:16968709, ECO:0000269|PubMed:18006707, ECO:0000269|PubMed:19710360, ECO:0000269|PubMed:1971514, ECO:0000269|PubMed:21479263, ECO:0000269|PubMed:22184247, ECO:0000269|PubMed:23398316, ECO:0000269|PubMed:2539258}.
|Hormone recep|
|zf-C4|
|negative regulation of astrocyte activation|
|circadian temperature homeostasis|
|positive regulation of bile acid metabolic process|
|positive regulation of bile acid biosynthetic process|
|regulation of astrocyte activation|
|negative regulation of receptor biosynthetic process|
|negative regulation of microglial cell activation|
|regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter|
|negative regulation of toll-like receptor 4 signaling pathway|
|regulation of bile acid biosynthetic process|
|negative regulation of astrocyte differentiation|
|negative regulation of neuroinflammatory response|
|regulation of bile acid metabolic process|
|regulation of carbohydrate metabolic process by regulation of transcription from RNA polymerase II promoter|
|regulation of type B pancreatic cell proliferation|
|transcription corepressor binding|
|negative regulation of macrophage activation|
|regulation of microglial cell activation|
|positive regulation of steroid biosynthetic process|
|glycogen biosynthetic process|
|glucan biosynthetic process|
|regulation of circadian sleep/wake cycle|
|regulation of toll-like receptor 4 signaling pathway|
|response to leptin|
|regulation of receptor biosynthetic process|
|negative regulation of glial cell differentiation|
|positive regulation of steroid metabolic process|
|regulation of astrocyte differentiation|
|temperature homeostasis|
|regulation of neuroinflammatory response|
|negative regulation of toll-like receptor signaling pathway|
|negative regulation of gliogenesis|
|negative regulation of I-kappaB kinase/NF-kappaB signaling|
|polysaccharide biosynthetic process|
|cellular polysaccharide biosynthetic process|
|regulation of gluconeogenesis|
|protein destabilization|
|negative regulation of cold-induced thermogenesis|
|nuclear receptor activity|
|glycogen metabolic process|
|E-box binding|
|glucan metabolic process|
|cellular glucan metabolic process|
|regulation of macrophage activation|
|steroid hormone receptor activity|
|regulation of insulin secretion involved in cellular response to glucose stimulus|
|cellular carbohydrate biosynthetic process|
|circadian regulation of gene expression|
|energy reserve metabolic process|
|nuclear receptor transcription coactivator activity|
|regulation of toll-like receptor signaling pathway|
|regulation of glial cell differentiation|
|RNA polymerase II transcription factor complex|
|regulation of behavior|
|transcription regulatory region sequence-specific DNA binding|
|cellular polysaccharide metabolic process|
|positive regulation of lipid biosynthetic process|
|cholesterol homeostasis|
|sterol homeostasis|
|polysaccharide metabolic process|
|regulation of steroid biosynthetic process|
|regulation of carbohydrate biosynthetic process|
|regulation of glucose metabolic process|
|regulation of circadian rhythm|
|regulation of steroid metabolic process|
|regulation of gliogenesis|
|steroid hormone mediated signaling pathway|
|regulation of fat cell differentiation|
|carbohydrate biosynthetic process|
|lipid homeostasis|
|negative regulation of inflammatory response|
|positive regulation of small molecule metabolic process|
|regulation of cellular carbohydrate metabolic process|
|heme binding|
|positive regulation of lipid metabolic process|
|circadian rhythm|
|regulation of cold-induced thermogenesis|
|dendritic spine|
|intracellular receptor signaling pathway|
|hormone-mediated signaling pathway|
|cellular carbohydrate metabolic process|
|regulation of cellular ketone metabolic process|
|cellular response to interleukin-1|
|negative regulation of leukocyte activation|
|transcription initiation from RNA polymerase II promoter|
|regulation of insulin secretion|
|cellular response to lipopolysaccharide|
|regulation of lipid biosynthetic process|
|cellular response to steroid hormone stimulus|
|cellular response to molecule of bacterial origin|
|negative regulation of cell activation|
|response to interleukin-1|
|regulation of carbohydrate metabolic process|
|signaling receptor activity|
|negative regulation of defense response|
|regulation of peptide hormone secretion|
|cellular response to biotic stimulus|
|DNA-templated transcription, initiation|
|transcription regulatory region DNA binding|
|energy derivation by oxidation of organic compounds|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|nuclear chromatin|
|cellular response to tumor necrosis factor|
|transcription corepressor activity|
|DNA-binding transcription repressor activity, RNA polymerase II-specific|
|response to tumor necrosis factor|
|regulation of hormone secretion|
|rhythmic process|
|nuclear body|
|regulation of protein stability|
|negative regulation of neurogenesis|
|negative regulation of nervous system development|
|RNA polymerase II regulatory region sequence-specific DNA binding|
|response to lipopolysaccharide|
|multicellular organismal homeostasis|
|response to molecule of bacterial origin|
|response to steroid hormone|
|transcription factor binding|
|regulation of epithelial cell proliferation|
|negative regulation of cell development|
|regulation of inflammatory response|
|proteasomal protein catabolic process|
|negative regulation of response to external stimulus|
|regulation of lipid metabolic process|
|dendrite|
|generation of precursor metabolites and energy|
|regulation of small molecule metabolic process|
|negative regulation of immune system process|
|regulation of innate immune response|
|regulation of protein secretion|
|carbohydrate metabolic process|
|transcription by RNA polymerase II|
|regulation of peptide secretion|
|RNA polymerase II proximal promoter sequence-specific DNA binding|
|negative regulation of intracellular signal transduction|
|cellular response to lipid|
|regulation of response to biotic stimulus|
|regulation of hormone levels|
|cellular response to organic cyclic compound|
|proteolysis involved in cellular protein catabolic process|
|regulation of leukocyte activation|
|cellular response to hormone stimulus|
|cellular protein catabolic process|
|transcription, DNA-templated|
|regulation of cell activation|
|nucleic acid-templated transcription|
|RNA biosynthetic process|
|protein catabolic process|
|response to bacterium|
|regulation of protein transport|
|negative regulation of cell differentiation|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|regulation of defense response|
|regulation of multi-organism process|
|regulation of secretion|
|regulation of neurogenesis|
|zinc ion binding|
|response to lipid|
|negative regulation of transcription by RNA polymerase II|
|cellular macromolecule catabolic process|
|response to hormone|
|regulation of cellular localization|
|response to organic cyclic compound|
|regulation of nervous system development|
|regulation of cell development|
|negative regulation of developmental process|
|oxidation-reduction process|
|cellular response to cytokine stimulus|
|regulation of protein localization|
|macromolecule catabolic process|
|cellular response to oxygen-containing compound|
|organonitrogen compound catabolic process|
|regulation of response to external stimulus|
|nucleobase-containing compound biosynthetic process|
|response to cytokine|
|chemical homeostasis|
|regulation of immune response|
|heterocycle biosynthetic process|
|aromatic compound biosynthetic process|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|positive regulation of transcription by RNA polymerase II|
|cellular response to endogenous stimulus|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|proteolysis|
|response to other organism|
|organic cyclic compound biosynthetic process|
|response to external biotic stimulus|
|response to biotic stimulus|
|negative regulation of RNA metabolic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|positive regulation of transcription, DNA-templated|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|DNA-binding transcription factor activity, RNA polymerase II-specific|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|neurogenesis|
|cellular nitrogen compound biosynthetic process|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|homeostatic process|
|regulation of immune system process|
|RNA metabolic process|
|cellular macromolecule biosynthetic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|macromolecule biosynthetic process|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|regulation of intracellular signal transduction|
|regulation of transport|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|gene expression|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp124|GSK343 3μM R03 exp124]]|-1.79|
|[[:results:exp27|Pimelic-diphenylamide-106 0.5μM R00 exp27]]|1.72|
|[[:results:exp69|Deguelin 0.05μM R02 exp69]]|2.15|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 3430
* **Expression level (log2 read counts)**: 2.95
{{:chemogenomics:nalm6 dist.png?nolink |}}