Summary | |
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Symbol | CRY2 |
Name | cryptochrome circadian clock 2 |
Aliases | cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2 |
Chromosomal Location | 11p11.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway |
Subcellular Location | Cytoplasm Nucleus Note=Translocated to the nucleus through interaction with other Clock proteins such as PER2 or ARNTL. |
Domain |
PF00875 DNA photolyase PF03441 FAD binding domain of DNA photolyase |
Function |
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). |
Biological Process |
GO:0006470 protein dephosphorylation GO:0006817 phosphate ion transport GO:0006820 anion transport GO:0007623 circadian rhythm GO:0009314 response to radiation GO:0009416 response to light stimulus GO:0009637 response to blue light GO:0009648 photoperiodism GO:0009649 entrainment of circadian clock GO:0009755 hormone-mediated signaling pathway GO:0009785 blue light signaling pathway GO:0010921 regulation of phosphatase activity GO:0010923 negative regulation of phosphatase activity GO:0010966 regulation of phosphate transport GO:0015698 inorganic anion transport GO:0016311 dephosphorylation GO:0018298 protein-chromophore linkage GO:0030518 intracellular steroid hormone receptor signaling pathway GO:0030522 intracellular receptor signaling pathway GO:0031958 corticosteroid receptor signaling pathway GO:0032515 negative regulation of phosphoprotein phosphatase activity GO:0032922 circadian regulation of gene expression GO:0033143 regulation of intracellular steroid hormone receptor signaling pathway GO:0033144 negative regulation of intracellular steroid hormone receptor signaling pathway GO:0033500 carbohydrate homeostasis GO:0035303 regulation of dephosphorylation GO:0035304 regulation of protein dephosphorylation GO:0035305 negative regulation of dephosphorylation GO:0035308 negative regulation of protein dephosphorylation GO:0042593 glucose homeostasis GO:0042752 regulation of circadian rhythm GO:0042754 negative regulation of circadian rhythm GO:0042921 glucocorticoid receptor signaling pathway GO:0043153 entrainment of circadian clock by photoperiod GO:0043401 steroid hormone mediated signaling pathway GO:0043666 regulation of phosphoprotein phosphatase activity GO:0044070 regulation of anion transport GO:0044341 sodium-dependent phosphate transport GO:0048511 rhythmic process GO:0048545 response to steroid hormone GO:0051346 negative regulation of hydrolase activity GO:0071214 cellular response to abiotic stimulus GO:0071383 cellular response to steroid hormone stimulus GO:0071396 cellular response to lipid GO:0071407 cellular response to organic cyclic compound GO:0071478 cellular response to radiation GO:0071482 cellular response to light stimulus GO:0071483 cellular response to blue light GO:2000118 regulation of sodium-dependent phosphate transport GO:2000322 regulation of glucocorticoid receptor signaling pathway GO:2000323 negative regulation of glucocorticoid receptor signaling pathway |
Molecular Function |
GO:0003684 damaged DNA binding GO:0003697 single-stranded DNA binding GO:0009881 photoreceptor activity GO:0009882 blue light photoreceptor activity GO:0019902 phosphatase binding GO:0032182 ubiquitin-like protein binding GO:0043130 ubiquitin binding GO:0048037 cofactor binding GO:0050660 flavin adenine dinucleotide binding GO:0050662 coenzyme binding GO:0071949 FAD binding |
Cellular Component | - |
KEGG |
hsa04710 Circadian rhythm |
Reactome |
R-HSA-1368108: BMAL1 R-HSA-400253: Circadian Clock |
Summary | |
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Symbol | CRY2 |
Name | cryptochrome circadian clock 2 |
Aliases | cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2 |
Chromosomal Location | 11p11.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Literatures that report relations between CRY2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells. |
Literatures describing the relation between CRY2 and anti-tumor immunity in human cancer.
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Summary | |
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Symbol | CRY2 |
Name | cryptochrome circadian clock 2 |
Aliases | cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2 |
Chromosomal Location | 11p11.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets. |
> High-throughput Screening
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Statistical results of CRY2 in screening data sets for detecting immune reponses.
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Summary | |
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Symbol | CRY2 |
Name | cryptochrome circadian clock 2 |
Aliases | cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2 |
Chromosomal Location | 11p11.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders |
Points in the above scatter plot represent the expression difference of CRY2 in various data sets.
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Points in the above scatter plot represent the mutation difference of CRY2 in various data sets.
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Summary | |
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Symbol | CRY2 |
Name | cryptochrome circadian clock 2 |
Aliases | cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2 |
Chromosomal Location | 11p11.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CRY2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene. |
Summary | |
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Symbol | CRY2 |
Name | cryptochrome circadian clock 2 |
Aliases | cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2 |
Chromosomal Location | 11p11.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CRY2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CRY2. > Immunoinhibitor > Immunostimulator > MHC molecule |
Summary | |
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Symbol | CRY2 |
Name | cryptochrome circadian clock 2 |
Aliases | cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2 |
Chromosomal Location | 11p11.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CRY2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor |
Summary | |
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Symbol | CRY2 |
Name | cryptochrome circadian clock 2 |
Aliases | cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2 |
Chromosomal Location | 11p11.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Distribution of CRY2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype |
Summary | |
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Symbol | CRY2 |
Name | cryptochrome circadian clock 2 |
Aliases | cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2 |
Chromosomal Location | 11p11.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Associations between CRY2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade |
Summary | |
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Symbol | CRY2 |
Name | cryptochrome circadian clock 2 |
Aliases | cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2 |
Chromosomal Location | 11p11.2 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Drugs targeting CRY2 collected from DrugBank database. |
There is no record. |