======= PER1 =======
== Gene Information ==
* **Official Symbol**: PER1
* **Official Name**: period circadian regulator 1
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5187|5187]]
* **UniProt**: [[https://www.uniprot.org/uniprot/O15534|O15534]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=PER1&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PER1|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/602260|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: N/A
* **UniProt Summary**: 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 syndromes 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. 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/ARNTL 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 ARNTL: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- ARNTL/BMAL1 induced transcription of BHLHE40/DEC1. {ECO:0000269|PubMed:24005054}.
|PAS 3|
|Period C|
|circadian regulation of translation|
|negative regulation of glucocorticoid receptor signaling pathway|
|regulation of glucocorticoid receptor signaling pathway|
|transcription corepressor binding|
|histone H3 deacetylation|
|entrainment of circadian clock by photoperiod|
|photoperiodism|
|entrainment of circadian clock|
|regulation of hair cycle|
|negative regulation of JNK cascade|
|negative regulation of intracellular steroid hormone receptor signaling pathway|
|regulation of cytokine production involved in inflammatory response|
|regulation of p38MAPK cascade|
|negative regulation of I-kappaB kinase/NF-kappaB signaling|
|negative regulation of stress-activated MAPK cascade|
|negative regulation of stress-activated protein kinase signaling cascade|
|histone H3 acetylation|
|histone deacetylation|
|E-box binding|
|protein deacetylation|
|histone H4 acetylation|
|protein deacylation|
|circadian regulation of gene expression|
|macromolecule deacylation|
|chromatin DNA binding|
|transcription regulatory region sequence-specific DNA binding|
|regulation of intracellular steroid hormone receptor signaling pathway|
|regulation of sodium ion transport|
|kinase binding|
|response to cAMP|
|histone acetylation|
|regulation of circadian rhythm|
|internal peptidyl-lysine acetylation|
|peptidyl-lysine acetylation|
|internal protein amino acid acetylation|
|response to organophosphorus|
|circadian rhythm|
|protein acetylation|
|response to purine-containing compound|
|negative regulation of MAPK cascade|
|regulation of JNK cascade|
|protein acylation|
|regulation of stress-activated MAPK cascade|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|regulation of stress-activated protein kinase signaling cascade|
|rhythmic process|
|ubiquitin protein ligase binding|
|response to light stimulus|
|peptidyl-lysine modification|
|transcription factor binding|
|regulation of inflammatory response|
|regulation of translation|
|histone modification|
|covalent chromatin modification|
|regulation of metal ion transport|
|regulation of cellular amide metabolic process|
|negative regulation of protein phosphorylation|
|response to radiation|
|negative regulation of phosphorylation|
|RNA polymerase II proximal promoter sequence-specific DNA binding|
|negative regulation of intracellular signal transduction|
|posttranscriptional regulation of gene expression|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|negative regulation of protein modification process|
|regulation of cytokine production|
|regulation of ion transport|
|chromatin organization|
|regulation of cellular response to stress|
|regulation of MAPK cascade|
|regulation of defense response|
|negative regulation of transcription by RNA polymerase II|
|peptidyl-amino acid modification|
|response to organic cyclic compound|
|response to organonitrogen compound|
|negative regulation of cellular protein metabolic process|
|chromosome organization|
|response to nitrogen compound|
|regulation of response to external stimulus|
|negative regulation of protein metabolic process|
|response to abiotic stimulus|
|negative regulation of transcription, DNA-templated|
|positive regulation of transcription by RNA polymerase II|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|negative regulation of RNA metabolic process|
|negative regulation of cell communication|
|negative regulation of signaling|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|regulation of protein phosphorylation|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|positive regulation of transcription, DNA-templated|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|regulation of phosphorylation|
|negative regulation of response to stimulus|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|positive regulation of biosynthetic process|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp400|Senexin-A 25μM R07 exp400]]|-1.8|
|[[:results:exp326|CCT251545 20μM R07 exp326]]|-1.75|
|[[:results:exp406|Thalidomide 20μM R07 exp406]]|-1.7|
|[[:results:exp476|Dihydrosphingosine 8μM R08 exp476]]|1.78|
|[[:results:exp449|Arsenic trioxide 60μM R08 exp449]]|1.82|
|[[:results:exp243|S-trityl-L-cysteine 0.5μM R05 exp243]]|1.85|
|[[:results:exp494|Isoniazid 100μM R08 exp494]]|1.92|
|[[:results:exp489|Hippuristanol 0.12μM R08 exp489 no dilution day6]]|1.97|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 14793
* **Expression level (log2 read counts)**: 5.01
{{:chemogenomics:nalm6 dist.png?nolink |}}