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Details on Person UniProt:O70361 Per3
| Class:Id | ReferenceGeneProduct:98037 |
|---|---|
| _chainChangeLog | chain:1-1113 added on Fri February 6 2015 |
| _displayName | UniProt:O70361 Per3 |
| _timestamp | 2023-11-03 18:03:43 |
| chain | chain:1-1113 |
| checksum | 99B06113BAB743C7 |
| comment | FUNCTION Originally described as a 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. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. 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, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and 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 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1, NR1D2, RORA, RORB and RORG, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Has a redundant role with the other PER proteins PER1 and PER2 and is not essential for the circadian rhythms maintenance. In contrast, plays an important role in sleep-wake timing and sleep homeostasis probably through the transcriptional regulation of sleep homeostasis-related genes, without influencing circadian parameters. Can bind heme.SUBUNIT Homodimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with PER1, PER2, CRY1, CRY2, and TIMELESS; interaction with CRY1 and CRY2 is weak and not rhythmic. Interacts with FBXW11 and BTRC.SUBCELLULAR LOCATION Mainly cytoplasmic. Translocates to the nucleus through binding PER1, PER2, CRY1 or CRY2, but not TIMELESS.TISSUE SPECIFICITY Widely expressed. Expressed in heart, brain, lung, liver, skeletal muscle, testis, and at low level in the spleen and kidney. In brain, mainly found in the SCN, hippocampus, piriform cortex, and cerebellum. Lower level of expression in the neocortex. Expression exhibits synchronous oscillations in liver, skeletal muscle and testis.INDUCTION Exhibits circadian oscillation expression in SCN, liver, skeletal muscle, testis and eyes. In the SCN, highest levels during subjective day at CT6 and CT9, lowest levels at night, CT15, CT18 and CT 21. In the liver, skeletal muscle, testis and eyes highest levels at CT15, CT15-CT18, CT9 and CT15, and CT9-CT15, respectively. During subjective night, unresponsive to light exposure.PTM Phosphorylation by CSNK1E is weak and appears to require association with PER1 and translocation to the nucleus.PTM Ubiquitinated.DISRUPTION PHENOTYPE Animals show altered sleep and behavioral activity whitout changes in total activity or vigilance states. They have increased wheel-running activity and reduced REM (rapid eye movement) sleep and NREM (non-REM) sleep in the middle of the dark phase. At the beginning of the baseline light period, they have less wakefulness and more REM and NREM sleep. Mice spend less time in wakefulness and more time in NREM sleep on the light period immediately after sleep deprivation and REM sleep accumulates more slowly during the recovery dark phase. They also display a depression-like phenotype. Double knocknouts for PER2 and PER3 show the same phenotype as PER2 knockouts with severely disrupted circadian behavior. |
| description | recommendedName: Period circadian protein homolog 3 shortName: mPER3 alternativeName: Circadian clock protein PERIOD 3 |
| geneName | Per3 |
| identifier | O70361 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Biological rhythms Cytoplasm Nucleus Phosphoprotein Reference proteome Repeat Transcription Transcription regulation Ubl conjugation |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9829221] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 |
| name | Per3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | PER3_MOUSE A2A894 |
| sequenceLength | 1113 |
| species | [Species:48892] Mus musculus |
| (referenceEntity) | [EntityWithAccessionedSequence:508712] p-S-Per3 [nucleoplasm] [Mus musculus] [EntityWithAccessionedSequence:9909383] Per3 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:9909384] p-S-Per3 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:9932528] Ub-K,p-S-Per3 [cytosol] [Mus musculus] |
| (referenceSequence) | [ModifiedResidue:9909358] O-phospho-L-serine at unknown position [GroupModifiedResidue:9932522] ubiquitinylated lysine (K48polyUb [cytosol]) at unknown position |
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No pathways have been reviewed or authored by UniProt:O70361 Per3 (98037)
