a transcriptional repressor which forms a core component of the circadian clock. The core clock components are CLOCK, NPAS2, ARNTL, ARNTL2, PER1, PER2, PER3, CRY1 and CRY2. play a critical role in rhythm generation. The transcription factors CLOCK or NPAS2, and ARNTL or ARNTL2, form heterodimers that activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes PER1/2/3 and CRY1/2 are transcriptional repressors that interact with CLOCK-ARNTL|ARNTL2 heterodimers, inhibiting their activity and thereby negatively regulating their own expression. CRY2 is s less potent transcriptional repressor in cerebellum and liver than CRY1, though less effective in lengthening the period of the SCN oscillator. Seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY1, dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. Plays a key role in glucose and lipid metabolism modulation, in part, through the transcriptional regulation of genes involved in these pathways, such as LEP or ACSL4. Represses glucocorticoid receptor GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs). Represses the CLOCK-ARNTL induced transcription of BHLHE40. Represses the CLOCK-ARNTL induced transcription of NAMPT. Represses PPARD and its target genes in the skeletal muscle and limits exercise capacity. Represses the transcriptional activity of NR1I2. Belongs to the DNA photolyase class-1 family. Expressed in all tissues examined including fetal brain, fibroblasts, heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocytes. Highest levels in heart and skeletal muscle. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: DNA-binding; Lyase; Transcription, coactivator/corepressor
Molecular Function: blue light photoreceptor activity; DNA binding; double-stranded DNA binding; E-box binding; histone deacetylase binding; nuclear hormone receptor binding; nucleotide binding; phosphatase binding; protein binding; protein kinase binding
Biological Process: blue light signaling pathway; circadian regulation of gene expression; circadian rhythm; DNA damage induced protein phosphorylation; entrainment of circadian clock by photoperiod; gluconeogenesis; glucose homeostasis; lipid storage; negative regulation of circadian rhythm; negative regulation of G protein-coupled receptor signaling pathway; negative regulation of glucocorticoid receptor signaling pathway; negative regulation of glucocorticoid secretion; negative regulation of gluconeogenesis; negative regulation of protein ubiquitination; negative regulation of transcription by RNA polymerase II; negative regulation of transcription, DNA-templated; positive regulation of protein ubiquitination; protein-chromophore linkage; regulation of circadian rhythm; regulation of DNA damage checkpoint; response to activity; response to glucagon; response to insulin; response to light stimulus