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Details on Person UniProt:P56645 PER3
| Class:Id | ReferenceGeneProduct:61514 |
|---|---|
| _chainChangeLog | chain:1-1201 added on Fri February 6 2015 |
| _displayName | UniProt:P56645 PER3 |
| _timestamp | 2024-11-03 20:15:55 |
| chain | chain:1-1201 |
| checksum | 8129C4246EDD1816 |
| 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.INTERACTION Mainly cytoplasmic. Translocates to the nucleus through binding PER1, PER2, CRY1 or CRY2, but not TIMELESS.ALTERNATIVE PRODUCTS Phosphorylation by CSNK1E is weak and appears to require association with PER1 and translocation to the nucleus.PTM Ubiquitinated.POLYMORPHISM The number of repeats of 18 amino acids in positions 966 to 1055 is polymorphic and varies among at least 2 different alleles. Alleles corresponding in size to a 4 (PER3.4) and 5 (PER3.5) repeats have been described. The sequence shown is that of allele PER3.5. In most populations around 10% of individuals are homozygous for the 5-repeat (PER3.5), whereas approximately 50% are homozygous for the 4-repeat (PER3.4). In some populations in Papua New Guinea the prevalence of the various genotypes appears to be reversed. These repeats and polymorphism are not present in non-primate mammals. Homozygosity for PER3.5 is more likely to show morning preference, whereas homozygosity for the PER3.4 associates with evening preferences. PER3.5 homozygous show vulnerability to sleep loss with a greater cognitive decline in response to total sleep deprivation (PubMed:11306557, PubMed:17346965, PubMed:19716732, PubMed:24439663, PubMed:24577121).DISEASE The disease is caused by variants affecting the gene represented in this entry.SEQUENCE CAUTION Extended N-terminus. |
| description | recommendedName: Period circadian protein homolog 3 shortName: hPER3 alternativeName: Cell growth-inhibiting gene 13 protein alternativeName: Circadian clock protein PERIOD 3 |
| geneName | PER3 GIG13 |
| identifier | P56645 |
| isSequenceChanged | FALSE |
| keyword | Alternative splicing Biological rhythms Cytoplasm Disease variant Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Transcription Transcription regulation Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 |
| name | PER3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8995040] ENSEMBL:ENSG00000049246 PER3 [Homo sapiens] |
| secondaryIdentifier | PER3_HUMAN Q5H8X4 Q5H8X5 Q969K6 Q96S77 Q96S78 Q9C0J3 Q9NSP9 Q9UGU8 |
| sequenceLength | 1201 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8971613] UniProt:P56645-1 PER3 [Homo sapiens] [ReferenceIsoform:8971614] UniProt:P56645-2 PER3 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:400263] PER3 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:400323] PER3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9909362] p-S-PER3 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9909370] p-S-PER3 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9932508] K48polyUb-K,p-S-PER3 [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:9909373] O-phospho-L-serine at unknown position [GroupModifiedResidue:9932518] ubiquitinylated lysine (K48polyUb [cytosol]) at unknown position |
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No pathways have been reviewed or authored by UniProt:P56645 PER3 (61514)
