PER3
Description
The PER3 (period circadian regulator 3) is a protein-coding gene located on chromosome 1.
The PER3 gene encodes the period circadian protein homolog 3 protein in humans. PER3 is a paralog to the PER1 and PER2 genes. It is a circadian gene associated with delayed sleep phase syndrome in humans. The Per3 gene was independently cloned by two research groups (Kobe University School of Medicine and Harvard Medical School) who both published their discovery in June 1998. The mammalian Per3 was discovered by searching for homologous cDNA sequences to Per2. The amino acid sequence of the mouse PERIOD3 protein (mPER3) is between 37-56% similar to the other two PER proteins. This gene is a member of the Period family of genes. It is expressed in a circadian pattern in the suprachiasmatic nucleus (SCN), the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian rhythms of locomotor activity, metabolism, and behavior. Circadian expression in the SCN continues in constant darkness, and a shift in the light/dark cycle evokes a proportional shift of gene expression in the SCN. PER1 and PER2 are necessary for molecular timekeeping and light responsiveness in the master circadian clock in the SCN, but little data is shown on the concrete function for PER3.
PER3 is involved in the regulation of sleep-wake timing and sleep homeostasis, likely through the control of genes related to these processes. It is not essential for the maintenance of circadian rhythms. PER3 has been described as a core component of the circadian clock, an internal timekeeping system that regulates physiological processes like metabolism and behavior. It contributes to the generation of approximately 24-hour rhythms in gene expression and influences a wide array of functions including metabolism, sleep, body temperature, blood pressure, and endocrine, immune, cardiovascular, and renal function. The clock consists of a central clock in the suprachiasmatic nucleus (SCN) of the brain and peripheral clocks in most tissues and organs. These clocks can be reset by environmental cues, known as Zeitgebers, primarily light for the central clock, which is sensed by the retina and signals to the SCN. The central clock aligns the peripheral clocks through various signals like neuronal and hormonal signals, body temperature, and feeding-related cues. Circadian rhythms ensure temporal homeostasis with the environment by regulating gene expression, leading to peaks of protein expression every 24 hours to control the timing of physiological processes. PER3 is part of a complex feedback loop involving various proteins (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, CRY1, CRY2) that generate rhythms, and its interaction with other proteins plays a role in this process. PER3 can bind heme and form homodimers. It interacts directly with PER1, PER2, CRY1, CRY2, and TIMELESS. Its interaction with CRY1 and CRY2 is weak and not rhythmic. It interacts with FBXW11 and BTRC.
PER3 is also known as FASPS3, GIG13.
