PER1
a transcriptional repressor and core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the circadian feedback loop, and form heterodimers that activate the transcription of core clock genes and clock-controlled genes. The core clock genes PER1/2/3 and CRY1/2 are transcriptional repressors forming the negative limb of this feedback loop. They interact with and inhibit the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimers, negatively regulating their own expression. Besides its involvement in regulating the circadian clock, has an important function in the regulation of several processes. Participates in the repression of glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) by ARNTL:CLOCK. Plays a role in the modulation of the neuroinflammatory state via the regulation of inflammatory mediators release, such as CCL2 and IL6. In spinal astrocytes, negatively regulates the p38 and JNK MAPK cascades as well as the subsequent activation of NFkappaB. Coordinately regulates the expression of multiple genes that are involved in the regulation of renal sodium reabsorption. Widely expressed. Found in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, kidney, spleen, thymus, prostate, testis, ovary and small intestine. Highest level in skeletal muscle. 4 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Molecular Function: chromatin DNA binding; DNA-binding transcription factor binding; E-box binding; kinase binding; protein binding; RNA polymerase II cis-regulatory region sequence-specific DNA binding; transcription cis-regulatory region binding; transcription corepressor binding; ubiquitin protein ligase binding
Biological Process: chromatin remodeling; circadian regulation of gene expression; circadian regulation of translation; circadian rhythm; entrainment of circadian clock; entrainment of circadian clock by photoperiod; negative regulation of DNA-templated transcription; negative regulation of glucocorticoid receptor signaling pathway; negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of JNK cascade; negative regulation of transcription by RNA polymerase II; positive regulation of transcription by RNA polymerase II; post-transcriptional regulation of gene expression; regulation of circadian rhythm; regulation of cytokine production involved in inflammatory response; regulation of hair cycle; regulation of p38MAPK cascade; regulation of sodium ion transport; response to cAMP
Alt. Names/Synonyms: Circadian clock protein PERIOD 1; Circadian pacemaker protein Rigui; hPER; hPER1; KIAA0482; MGC88021; PER; PER1; period circadian clock 1; Period circadian protein homolog 1; period circadian regulator 1; period homolog 1; period homolog 1 (Drosophila); Period, drosophila, homolog of; RIGUI
