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IID50265
UniprotO54943
ProteinPeriod circadian protein homolog 2
GenePer2
OrganismMus musculus
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
1257
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 170-473 Homo dimer :
 Evidence X-RAY 3gdi B Reference
       Region 3gdi B 170-178 disorder
       Region 3gdi B 179-185 order
       Region 3gdi B 186-187 disorder
       Region 3gdi B 188-212 order
       Region 3gdi B 213-221 disorder
       Region 3gdi B 222-247 order
       Region 3gdi B 248-262 disorder
       Region 3gdi B 263-275 order
       Region 3gdi B 276-282 disorder
       Region 3gdi B 283-295 order
       Region 3gdi B 296-302 disorder
       Region 3gdi B 303-449 order
       Region 3gdi B 450-454 disorder
       Region 3gdi B 455-473 order
 Evidence X-RAY 3gdi A Reference
       Region 3gdi A 170-182 order
       Region 3gdi A 183-186 disorder
       Region 3gdi A 187-213 order
       Region 3gdi A 214-220 disorder
       Region 3gdi A 221-250 order
       Region 3gdi A 251-264 disorder
       Region 3gdi A 265-276 order
       Region 3gdi A 277-280 disorder
       Region 3gdi A 281-296 order
       Region 3gdi A 297-304 disorder
       Region 3gdi A 305-473 order
Seq 1095-1215 Hetero dimer : Q9R194
 Evidence X-RAY 4u8h D Reference
       Region 4u8h D 1095-1130 disorder
       Region 4u8h D 1131-1195 order
       Region 4u8h D 1196-1200 disorder
       Region 4u8h D 1201-1214 order
       Region 4u8h D 1215-1215 disorder
 Evidence X-RAY 4u8h B Reference
       Region 4u8h B 1095-1130 disorder
       Region 4u8h B 1131-1195 order
       Region 4u8h B 1196-1200 disorder
       Region 4u8h B 1201-1214 order
       Region 4u8h B 1215-1215 disorder
Seq 1132-1252 Hetero dimer : IID50287Complex
 Evidence X-RAY 4ct0 B Reference
       Region 4ct0 B 1132-1214 order
       Region 4ct0 B 1215-1252 disorder
Seqphosphorylation
    528-528 Phosphoserine
    758-758 Phosphoserine
    706-706 Phosphoserine
    697-697 Phosphoserine
    693-693 Phosphoserine
    659-659 Phosphoserine
    554-554 Phosphothreonine
    544-544 Phosphoserine
    538-538 Phosphoserine
    531-531 Phosphoserine
    525-525 Phosphoserine
    858-858 Phosphothreonine
    939-939 Phosphoserine
    964-964 Phosphothreonine
    971-971 Phosphoserine
    1126-1126 Phosphoserine
    763-763 Phosphoserine
 
Prediction
NeProc
Disorder 1-178,257-274,472-1131,1218-1257
Order 179-256,275-471,1132-1217
ProS 1-7,30-50,104-145,151-156,162-178,257-274,511-531,550-555,579-602,607-615,664-677,710-755,763-770,779-788,833-837,904-910,922-927,986-990,1040-1059,1083-1117,1127-1131,1218-1234
AlphaFold
Disorder 1-100,123-130,151-153,155-167,251-265,275-281,299-302,446-454,473-582,584-585,589-589,600-717,741-1157,1178-1178,1199-1257
Order 101-122,131-150,154-154,168-250,266-274,282-298,303-445,455-472,583-583,586-588,590-599,718-740,1158-1177,1179-1198
Pfam Hmmer
PF08447 341-436 2.5e-10
SEG 475-488 ,821-834 ,996-1014 ,1045-1061 ,1070-1092 ,1164-1175
Function
Function in SwissProt
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, ARNTL/BMAL1, ARNTL2/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 syndrome and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/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-ARNTL/BMAL1|ARNTL2/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 ARNTL/BMAL1 transcription, respectively. PER1 and PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate circadian timing, but also contribute directly to repression of clock-controlled target genes through interaction with several classes of RNA-binding proteins, helicases and others transcriptional repressors. PER appears to regulate circadian control of transcription by at least three different modes. First, interacts directly with the CLOCK-ARTNL/BMAL1 at the tail end of the nascent transcript peak to recruit complexes containing the SIN3-HDAC that remodel chromatin to repress transcription. Second, brings H3K9 methyltransferases such as SUV39H1 and SUV39H2 to the E-box elements of the circadian target genes, like PER2 itself or PER1. The recruitment of each repressive modifier to the DNA seems to be very precisely temporally orchestrated by the large PER complex, the deacetylases acting before than the methyltransferases. Additionally, large PER complexes are also recruited to the target genes 3' termination site through interactions with RNA-binding proteins and helicases that may play a role in transcription termination to regulate transcription independently of CLOCK-ARTNL/BMAL1 interactions. Recruitment of large PER complexes to the elongating polymerase at PER and CRY termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation. May propagate clock information to metabolic pathways via the interaction with nuclear receptors. Coactivator of PPARA and corepressor of NR1D1, binds rhythmically at the promoter of nuclear receptors target genes like ARNTL or G6PC1. Directly and specifically represses PPARG proadipogenic activity by blocking PPARG recruitment to target promoters and thereby transcriptional activation. Required for fatty acid and lipid metabolism, is involved as well in the regulation of circulating insulin levels. Plays an important role in the maintenance of cardiovascular functions through the regulation of NO and vasodilatatory prostaglandins production in aortas. Controls circadian glutamate uptake in synaptic vesicles through the regulation of VGLUT1 expression. May also be involved in the regulation of inflammatory processes. Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1 and ATF4. Negatively regulates the formation of the TIMELESS-CRY1 complex by competing with TIMELESS for binding to CRY1.