======= CRY2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CRY2
  * **<color #00a2e8>Official Name</color>**: cryptochrome circadian regulator 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1408|1408]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q49AN0|Q49AN0]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CRY2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CRY2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/603732|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. Less potent transcriptional repressor in cerebellum and liver than CRY1, though less effective in lengthening the period of the SCN oscillator. Seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY1, dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. May mediate circadian regulation of cAMP signaling and gluconeogenesis by blocking glucagon-mediated increases in intracellular cAMP concentrations and in CREB1 phosphorylation. Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. 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. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs). Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1. Represses the CLOCK-ARNTL/BMAL1 induced transcription of NAMPT (By similarity). {ECO:0000250|UniProtKB:Q9R194, ECO:0000269|PubMed:10531061, ECO:0000269|PubMed:14672706, ECO:0000269|PubMed:16790549}.

<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'>
|FAD binding 7|
|DNA photolyase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|photoreactive repair|
|response to blue light|
|cellular response to blue light|
|deoxyribodipyrimidine photo-lyase activity|
|DNA (6-4) photolyase activity|
|blue light signaling pathway|
|blue light photoreceptor activity|
|regulation of sodium-dependent phosphate transport|
|negative regulation of glucocorticoid receptor signaling pathway|
|regulation of phosphate transport|
|regulation of glucocorticoid receptor signaling pathway|
|pyrimidine dimer repair|
|protein-chromophore linkage|
|negative regulation of circadian rhythm|
|entrainment of circadian clock by photoperiod|
|photoperiodism|
|entrainment of circadian clock|
|FAD binding|
|negative regulation of intracellular steroid hormone receptor signaling pathway|
|phosphatase binding|
|damaged DNA binding|
|negative regulation of phosphoprotein phosphatase activity|
|circadian regulation of gene expression|
|response to activity|
|negative regulation of protein dephosphorylation|
|transcription regulatory region sequence-specific DNA binding|
|regulation of intracellular steroid hormone receptor signaling pathway|
|regulation of anion transport|
|negative regulation of phosphatase activity|
|single-stranded DNA binding|
|negative regulation of dephosphorylation|
|cellular response to light stimulus|
|regulation of circadian rhythm|
|regulation of phosphoprotein phosphatase activity|
|regulation of protein dephosphorylation|
|circadian rhythm|
|intracellular receptor signaling pathway|
|cellular response to radiation|
|regulation of phosphatase activity|
|glucose homeostasis|
|carbohydrate homeostasis|
|regulation of dephosphorylation|
|rhythmic process|
|response to light stimulus|
|cellular response to environmental stimulus|
|cellular response to abiotic stimulus|
|nuclear speck|
|response to radiation|
|negative regulation of hydrolase activity|
|DNA repair|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|negative regulation of protein modification process|
|regulation of ion transport|
|DNA metabolic process|
|cellular response to DNA damage stimulus|
|negative regulation of catalytic activity|
|negative regulation of transcription by RNA polymerase II|
|negative regulation of cellular protein metabolic process|
|negative regulation of protein metabolic process|
|chemical homeostasis|
|negative regulation of molecular function|
|response to abiotic stimulus|
|negative regulation of transcription, DNA-templated|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|regulation of hydrolase activity|
|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|
|negative regulation of cellular biosynthetic process|
|negative regulation of biosynthetic process|
|negative regulation of response to stimulus|
|homeostatic process|
|cellular response to stress|
|negative regulation of gene expression|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of protein modification process|
|regulation of transport|
|extracellular region|
</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:exp215|Colchicine 0.009μM R05 exp215]]|2.05|
</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>**: 7152
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.84 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CRY2 Expression in NALM6 Cells: 4.84'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>