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Details on Person UniProt:O35973 Per1
| Class:Id | ReferenceGeneProduct:98035 |
|---|---|
| _chainChangeLog | chain:1-1291 added on Fri February 6 2015 |
| _displayName | UniProt:O35973 Per1 |
| _timestamp | 2023-11-03 16:08:51 |
| chain | chain:1-1291 |
| checksum | 77FB9BC71EDF31A6 |
| comment | FUNCTION Transcriptional repressor which forms 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 NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates circadian target genes expression at post-transcriptional levels, but may not be required for the repression at transcriptional level. Controls PER2 protein decay. Represses CRY2 preventing its repression on CLOCK/BMAL1 target genes such as FXYD5 and SCNN1A in kidney and PPARA in liver. Besides its involvement in the maintenance of 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 BMAL1: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 MAPK14/p38 and MAPK8/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. Can act as gene expression activator in a gene and tissue specific manner, in kidney enhances WNK1 and SLC12A3 expression in collaboration with CLOCK. Modulates hair follicle cycling. Represses the CLOCK-BMAL1 induced transcription of BHLHE40/DEC1.SUBUNIT Homodimer (PubMed:22331899). 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 (PubMed:11779462). Interacts directly with TIMELESS (PubMed:10231394, PubMed:9856465). Interacts directly with PER2, PER3, CRY1 and CRY2 (PubMed:10428031, PubMed:10848614, PubMed:11875063, PubMed:14701732, PubMed:16478995, PubMed:24154698). Interacts with BMAL1 and CLOCK (PubMed:16717091, PubMed:24154698). Interacts with GPRASP1 (By similarity). Interacts (phosphorylated) with BTRC and FBXW11; the interactions trigger proteasomal degradation (By similarity). Interacts with NONO and SFPQ (PubMed:22966205). Interacts with WDR5 (By similarity). Interacts with U2AF1L4 (Isoform 3) (PubMed:24837677). Interacts with USP2 (PubMed:23213472). Interacts with HNF4A (By similarity).INTERACTION Nucleocytoplasmic shuttling is effected by interaction with other circadian core oscillator proteins and/or by phosphorylation. Retention of PER1 in the cytoplasm occurs through PER1-PER2 heterodimer formation. Translocate to the nucleus after phosphorylation by CSNK1D or CSNK1E. Also translocated to the nucleus by CRY1 or CRY2.TISSUE SPECIFICITY In brain, highest expression is observed in the SCN. Highly expressed in the pyramidal cell layer of the piriform cortex, the periventricular part of the caudate-putamen, many thalamic nuclei, and the granular layer of the cerebellar cortex. Weaker expression is detected in most area of the brain, including cortical and non cortical structures. Expression but no oscillations occurs in the glomerular and mitral cell layers of the olfactory bulb, the internal granular layer of the cerebellum, the cornu ammonis and dentate gyrus of the hippocampus, the cerebral and piriform cortices. Expressed in the renal cortex (at protein level). Also found in heart, brain, bladder, lumbar spinal cord, spleen, lung, liver, skeletal muscle and testis.DEVELOPMENTAL STAGE Expressed in the suprachiasmatic nucleus (SCN) during late fetal and early neonatal life.INDUCTION In the suprachiasmatic nucleus (SCN), behaves like a day-type oscillator, with maximum expression during the light period. Oscillations are maintained under constant darkness and are responsive to changes of the light/dark cycles. There is a 4 hour time delay between PER1 and PER2 oscillations. The expression rhythms appear to originate from retina. In liver, peak levels at CT9. In the SCN, levels increase by light exposure during subjective night. Circadian oscillations also observed in skeletal muscle, bladder, lumbar spinal cord and liver but not in testis.PTM Phosphorylated on serine residues by CSNK1D, CSNK1E and probably also by CSNK1G2. Phosphorylation by CSNK1D or CSNK1E promotes nuclear location of PER proteins as well as ubiquitination and subsequent degradation. May be dephosphorylated by PP1.PTM Ubiquitinated; requires phosphorylation by CSNK1E and interaction with BTRC and FBXW11. Deubiquitinated by USP2.DISRUPTION PHENOTYPE Animals show disrupted circadian behavior. The prolongation of light exposure produces larger phase delay of behavioral rhythm compared to wild-types. Double knocknouts for PER2 and PER1 show an abrupt loss of rhythmicity immediately upon transfer to exprosure to constant darkness. Animals have largely affected the water intake (polydipsia) and urine volume (polyuria). |
| description | recommendedName: Period circadian protein homolog 1 shortName: mPER1 alternativeName: Circadian clock protein PERIOD 1 alternativeName: Circadian pacemaker protein Rigui |
| geneName | Per1 Per Rigui |
| identifier | O35973 |
| 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:3445779] 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:9645058] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9796772] Weiser, Joel [InstanceEdit:9829221] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 |
| name | Per1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | PER1_MOUSE B1ASX0 |
| sequenceLength | 1291 |
| species | [Species:48892] Mus musculus |
| (referenceEntity) | [EntityWithAccessionedSequence:508663] Per1 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:508664] p-Per1 [nucleoplasm] [Mus musculus] [EntityWithAccessionedSequence:508667] p-S-Per1 [cytosol] [Mus musculus] [EntityWithAccessionedSequence:517957] Ub-K,p-S-Per1 [cytosol] [Mus musculus] |
| (referenceSequence) | [ModifiedResidue:508678] O-phospho-L-serine at unknown position [GroupModifiedResidue:517954] ubiquitinylated lysine (K48polyUb [cytosol]) at unknown position |
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No pathways have been reviewed or authored by UniProt:O35973 Per1 (98035)
