Browse CRY2

Summary
SymbolCRY2
Namecryptochrome circadian clock 2
Aliases cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2
Chromosomal Location11p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
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).

> Gene Ontology
 
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 and Reactome Pathway
 
KEGG hsa04710 Circadian rhythm
Reactome R-HSA-1368108: BMAL1
R-HSA-400253: Circadian Clock
Summary
SymbolCRY2
Namecryptochrome circadian clock 2
Aliases cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2
Chromosomal Location11p11.2
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.
> Text Mining
 
  Literatures describing the relation between CRY2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
19318546Non-Hodgkin's lymphomaInhibit immunityThe current study examined Cryptochrome 2 (CRY2), a core circadian gene and transcriptional repressor, as a potential circadian biomarker for NHL. In conclusion, both genetic association and functional analyses suggest that the circadian gene CRY2 may play an important role in NHL development.
Summary
SymbolCRY2
Namecryptochrome circadian clock 2
Aliases cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2
Chromosomal Location11p11.2
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
  Statistical results of CRY2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolCRY2
Namecryptochrome circadian clock 2
Aliases cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2
Chromosomal Location11p11.2
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
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of CRY2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.2110.292
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.4240.714
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0580.944
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.2960.355
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.3450.863
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.2370.923
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1370.643
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3540.779
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1550.916
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.4130.768
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.8150.679
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0890.205
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CRY2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211714.35.98.40.613
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86250250.473
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.79.1-1.41
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolCRY2
Namecryptochrome circadian clock 2
Aliases cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2
Chromosomal Location11p11.2
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.
> Lymphocyte
 
Summary
SymbolCRY2
Namecryptochrome circadian clock 2
Aliases cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2
Chromosomal Location11p11.2
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
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCRY2
Namecryptochrome circadian clock 2
Aliases cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2
Chromosomal Location11p11.2
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
> Chemokine
 
> Receptor
 
Summary
SymbolCRY2
Namecryptochrome circadian clock 2
Aliases cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2
Chromosomal Location11p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CRY2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCRY2
Namecryptochrome circadian clock 2
Aliases cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2
Chromosomal Location11p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CRY2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCRY2
Namecryptochrome circadian clock 2
Aliases cryptochrome 2 (photolyase-like); HCRY2; PHLL2; growth-inhibiting protein 37; Cryptochrome-2
Chromosomal Location11p11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CRY2 collected from DrugBank database.
> Drugs from DrugBank database
 

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