NR1D1 report

I. Expression across cell types

II. Expression across tissues

III. Associated gene sets

GO_0061469Biological processregulation of type B pancreatic cell proliferation
GO_0005978Biological processglycogen biosynthetic process
GO_0044321Biological processresponse to leptin
GO_0061889Biological processnegative regulation of astrocyte activation
GO_0010498Biological processproteasomal protein catabolic process
GO_0070859Biological processpositive regulation of bile acid biosynthetic process
GO_0034144Biological processnegative regulation of toll-like receptor 4 signaling pathway
GO_0030522Biological processintracellular receptor signaling pathway
GO_0019216Biological processregulation of lipid metabolic process
GO_1903979Biological processnegative regulation of microglial cell activation
GO_0071347Biological processcellular response to interleukin-1
GO_0000122Biological processnegative regulation of transcription by RNA polymerase II
GO_0031648Biological processprotein destabilization
GO_0001678Biological processintracellular glucose homeostasis
GO_0032922Biological processcircadian regulation of gene expression
GO_0042752Biological processregulation of circadian rhythm
GO_0150079Biological processnegative regulation of neuroinflammatory response
GO_0042632Biological processcholesterol homeostasis
GO_0071356Biological processcellular response to tumor necrosis factor
GO_0050728Biological processnegative regulation of inflammatory response
GO_0045893Biological processpositive regulation of DNA-templated transcription
GO_0061178Biological processregulation of insulin secretion involved in cellular response to glucose stimulus
GO_0030154Biological processcell differentiation
GO_0042749Biological processregulation of circadian sleep/wake cycle
GO_0009755Biological processhormone-mediated signaling pathway
GO_0043401Biological processsteroid hormone receptor signaling pathway
GO_0071222Biological processcellular response to lipopolysaccharide
GO_0045598Biological processregulation of fat cell differentiation
GO_0060086Biological processcircadian temperature homeostasis
GO_0045892Biological processnegative regulation of DNA-templated transcription
GO_0043124Biological processnegative regulation of canonical NF-kappaB signal transduction
GO_0045944Biological processpositive regulation of transcription by RNA polymerase II
GO_0120163Biological processnegative regulation of cold-induced thermogenesis
GO_0043197Cellular componentdendritic spine
GO_0005654Cellular componentnucleoplasm
GO_0030425Cellular componentdendrite
GO_0016604Cellular componentnuclear body
GO_0005737Cellular componentcytoplasm
GO_0000785Cellular componentchromatin
GO_0005634Cellular componentnucleus
GO_0000978Molecular functionRNA polymerase II cis-regulatory region sequence-specific DNA binding
GO_0000977Molecular functionRNA polymerase II transcription regulatory region sequence-specific DNA binding
GO_0001227Molecular functionDNA-binding transcription repressor activity, RNA polymerase II-specific
GO_0000981Molecular functionDNA-binding transcription factor activity, RNA polymerase II-specific
GO_0003707Molecular functionnuclear steroid receptor activity
GO_0000976Molecular functiontranscription cis-regulatory region binding
GO_0004879Molecular functionnuclear receptor activity
GO_1990837Molecular functionsequence-specific double-stranded DNA binding
GO_0001222Molecular functiontranscription corepressor binding
GO_0020037Molecular functionheme binding
GO_0008270Molecular functionzinc ion binding
GO_0070888Molecular functionE-box binding
GO_0005515Molecular functionprotein binding

IV. Literature review

[source]
Gene nameNR1D1
Protein nameNuclear receptor subfamily 1 group D member 1 (Rev-erbA-alpha) (V-erbA-related protein 1) (EAR-1)
Nuclear receptor subfamily 1 group D member 1 (Rev-erbA-alpha) (V-erbA-related protein 1)
SynonymsTHRAL
HREV
hCG_93862
EAR1
DescriptionFUNCTION: 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 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 G6PC1 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. Represses the transcription of CYP2B10, CYP4A10 and CYP4A14 (By similarity). Represses the transcription of CES2 (By similarity). Represses and regulates the circadian expression of TSHB in a NCOR1-dependent manner (By similarity). Negatively regulates the protein stability of NR3C1 and influences the time-dependent subcellular distribution of NR3C1, thereby affecting its transcriptional regulatory activity (By similarity). Plays a critical role in the circadian control of neutrophilic inflammation in the lung; under resting, non-stress conditions, acts as a rhythmic repressor to limit inflammatory activity whereas in the presence of inflammatory triggers undergoes ubiquitin-mediated degradation thereby relieving inhibition of the inflammatory response (By similarity). Plays a key role in the circadian regulation of microglial activation and neuroinflammation; suppresses microglial activation through the NF-kappaB pathway in the central nervous system (By similarity). Plays a role in the regulation of the diurnal rhythms of lipid and protein metabolism in the skeletal muscle via transcriptional repression of genes controlling lipid and amino acid metabolism in the muscle (By similarity). .

AccessionsENST00000246672.4
P20393
F1D8S3