======= CRY1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CRY1
  * **<color #00a2e8>Official Name</color>**: cryptochrome circadian regulator 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1407|1407]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q16526|Q16526]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CRY1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CRY1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/601933|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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. CRY1 and CRY2 have redundant functions but also differential and selective contributions at least in defining the pace of the SCN circadian clock and its circadian transcriptional outputs. More potent transcriptional repressor in cerebellum and liver than CRY2, though more effective in lengthening the period of the SCN oscillator. On its side, CRY2 seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY2, is dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. Interacts with CLOCK-ARNTL/BMAL1 independently of PER proteins and is found at CLOCK-ARNTL/BMAL1-bound sites, suggesting that CRY may act as a molecular gatekeeper to maintain CLOCK-ARNTL/BMAL1 in a poised and repressed state until the proper time for transcriptional activation. Represses the CLOCK- ARNTL/BMAL1 induced transcription of BHLHE40/DEC1. Represses the CLOCK-ARNTL/BMAL1 induced transcription of ATF4, MTA1, KLF10 and NAMPT (By similarity). May repress circadian target genes expression in collaboration with HDAC1 and HDAC2 through histone deacetylation. Mediates the clock-control activation of ATR and modulates ATR-mediated DNA damage checkpoint. In liver, mediates circadian regulation of cAMP signaling and gluconeogenesis by binding to membrane-coupled G proteins and blocking glucagon- mediated increases in intracellular cAMP concentrations and CREB1 phosphorylation. Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs). Plays a key role in glucose and lipid metabolism modulation, in part, through the transcriptional regulation of genes involved in these pathways, such as LEP or ACSL4. {ECO:0000250|UniProtKB:P97784, ECO:0000269|PubMed:10531061, ECO:0000269|PubMed:14672706, ECO:0000269|PubMed:22170608, ECO:0000269|PubMed:23133559, ECO:0000269|PubMed:28388406}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|DNA photolyase|
|FAD binding 7|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|deoxyribodipyrimidine photo-lyase activity|
|blue light photoreceptor activity|
|cellular response to blue light|
|blue light signaling pathway|
|DNA (6-4) photolyase activity|
|negative regulation of glucocorticoid secretion|
|negative regulation of steroid hormone secretion|
|negative regulation of corticosteroid hormone secretion|
|response to blue light|
|negative regulation of glucocorticoid receptor signaling pathway|
|regulation of glucocorticoid receptor signaling pathway|
|DNA damage induced protein phosphorylation|
|regulation of glucocorticoid secretion|
|protein-chromophore linkage|
|negative regulation of circadian rhythm|
|regulation of DNA damage checkpoint|
|regulation of corticosteroid hormone secretion|
|negative regulation of gluconeogenesis|
|regulation of steroid hormone secretion|
|entrainment of circadian clock by photoperiod|
|photoperiodism|
|negative regulation of lipid transport|
|nuclear hormone receptor binding|
|entrainment of circadian clock|
|lipid storage|
|regulation of cell cycle checkpoint|
|negative regulation of intracellular steroid hormone receptor signaling pathway|
|response to glucagon|
|negative regulation of lipid localization|
|negative regulation of cellular carbohydrate metabolic process|
|gluconeogenesis|
|regulation of endocrine process|
|regulation of gluconeogenesis|
|hexose biosynthetic process|
|negative regulation of G protein-coupled receptor signaling pathway|
|negative regulation of carbohydrate metabolic process|
|phosphatase binding|
|E-box binding|
|monosaccharide biosynthetic process|
|nucleotide binding|
|circadian regulation of gene expression|
|negative regulation of hormone secretion|
|response to activity|
|negative regulation of protein ubiquitination|
|regulation of intracellular steroid hormone receptor signaling pathway|
|negative regulation of protein modification by small protein conjugation or removal|
|negative regulation of small molecule metabolic process|
|regulation of carbohydrate biosynthetic process|
|double-stranded DNA binding|
|regulation of lipid transport|
|histone deacetylase binding|
|regulation of glucose metabolic process|
|glucose metabolic process|
|cellular response to light stimulus|
|regulation of circadian rhythm|
|positive regulation of protein ubiquitination|
|carbohydrate biosynthetic process|
|positive regulation of protein modification by small protein conjugation or removal|
|regulation of lipid localization|
|regulation of cellular carbohydrate metabolic process|
|circadian rhythm|
|regulation of G protein-coupled receptor signaling pathway|
|hexose metabolic process|
|intracellular receptor signaling pathway|
|maintenance of location|
|cellular response to radiation|
|glucose homeostasis|
|carbohydrate homeostasis|
|monosaccharide metabolic process|
|regulation of protein ubiquitination|
|negative regulation of secretion by cell|
|regulation of carbohydrate metabolic process|
|regulation of response to DNA damage stimulus|
|response to insulin|
|regulation of protein modification by small protein conjugation or removal|
|negative regulation of secretion|
|regulation of hormone secretion|
|rhythmic process|
|response to light stimulus|
|cellular response to abiotic stimulus|
|cellular response to environmental stimulus|
|lipid localization|
|response to peptide hormone|
|regulation of small molecule metabolic process|
|response to radiation|
|protein kinase binding|
|response to peptide|
|carbohydrate metabolic process|
|negative regulation of transport|
|regulation of hormone levels|
|small molecule biosynthetic process|
|regulation of system process|
|negative regulation of protein modification process|
|regulation of cellular response to stress|
|regulation of secretion by cell|
|cellular response to DNA damage stimulus|
|regulation of secretion|
|negative regulation of transcription by RNA polymerase II|
|response to hormone|
|protein phosphorylation|
|response to organonitrogen compound|
|negative regulation of cellular protein metabolic process|
|response to nitrogen compound|
|negative regulation of protein metabolic process|
|chemical homeostasis|
|response to abiotic stimulus|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|negative regulation of multicellular organismal process|
|positive regulation of protein modification process|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|mitochondrion|
|negative regulation of signal transduction|
|phosphorylation|
|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|
|DNA binding|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|homeostatic process|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|small molecule metabolic process|
|regulation of protein modification process|
|regulation of transport|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp448|Ammonium tetrathiomolybdate 10μM R08 exp448]]|-1.86|
|[[:results:exp27|Pimelic-diphenylamide-106 0.5μM R00 exp27]]|-1.75|
|[[:results:exp29|Rapamycin 1μM R00 exp29]]|-1.75|
|[[:results:exp493|IL-3 9ng/ml R08 exp493]]|1.82|
|[[:results:exp517|Quercetin 20μM R08 exp517]]|1.88|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 11734
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.42 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CRY1 Expression in NALM6 Cells: 5.42'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>