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NR1D1 a widely expressed member of the orphan nuclear receptor family of proteins. Expressed at relatively high levels in adipose tissue, skeletal muscle, brain and liver, and regulates cellular proliferation and differentiation. Expression increases during differentiation in adipocytes and its ectopic expression in 3T3-L1 cells potentiates adipocyte differentiation. A metabolic regulator whose expression is increased in HER2-positive breast cancer cells. Regulates malate dehydrogenase 1 (MDH1) and malic enzyme 1 (ME1), enzymes that link glycolysis and fatty acid synthesis. May contribute to the abnormal cellular energy metabolism observed in HER2-positive breast cancers. Its expression oscillates with circadian rhythm in liver cells, regulating the expression of BMAL1, ApoA1 and ApoC3, all key regulators of circadian rhythm. Represses the basal activity of the mouse Bmal1 gene promoter. Phosphorylation by GSK3b at S55/59 stabilizes NRD1 protein levels. Regulates inflammation by targeting the NF-??B responsive genes IL-6 and COX-2. NR1D1 lacks the activation function 2 domain required for ligand-dependent activation of transcription by other members of the nuclear receptor family; thus it behaves as a constitutive repressor protein, recruiting the nuclear receptor co-repressor N-CoR1/HDAC3 complex to target genes to repress transcription. Note: This description may include information from UniProtKB.
Protein type: Nuclear receptor; Transcription factor
Chromosomal Location of Human Ortholog: 17q21.1
Cellular Component: cytoplasm; dendrite; dendritic spine; nuclear body; nuclear chromatin; nucleoplasm; nucleus
Molecular Function: heme binding; ligand-dependent nuclear receptor activity; protein binding; transcription corepressor activity
Biological Process: circadian regulation of gene expression; circadian rhythm; circadian thermoregulation; glycogen biosynthetic process; negative regulation of toll-like receptor 4 signaling pathway; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; positive regulation of transcription, DNA-dependent; proteasomal protein catabolic process; regulation of circadian rhythm; regulation of fat cell differentiation; regulation of lipid metabolic process; transcription initiation from RNA polymerase II promoter
Reference #:  P20393 (UniProtKB)
Alt. Names/Synonyms: EAR-1; EAR1; HREV; NR1D1; Nuclear receptor subfamily 1 group D member 1; nuclear receptor subfamily 1, group D, member 1; Rev-erbA-alpha; Rev-ErbAalpha; THRA1; THRAL; thyroid hormone receptor, alpha-like; V-erbA-related protein 1
Gene Symbols: NR1D1
Molecular weight: 66,805 Da
Basal Isoelectric point: 8.83  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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