Affinage

CRY2

Cryptochrome-2 · UniProt Q49AN0

Length
593 aa
Mass
66.9 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRY2 is a core component of the mammalian circadian clockwork that acts as a transcriptional repressor of the CLOCK/BMAL1 complex, and its loss alters or, in combination with CRY1, abolishes free-running circadian rhythmicity (PMID:10217146, PMID:31143130). Repression depends on a C-terminal domain that mediates direct heterodimerization with PER2 through residues including Arg-501/Lys-503 and Cys-432, the latter disrupting PER2 association without affecting BMAL1 binding, and on additional residues such as Gly-351 that define a CRY2-specific repression activity distinct from CRY1 (PMID:20840750, PMID:37724597, PMID:19687303); an intact flavin/electron-transport pathway is also required for CLOCK/BMAL1 suppression (PMID:11747820). CRY2 abundance is set by regulated proteolysis: DYRK1A primes Ser557 phosphorylation to enable GSK-3β phosphorylation of Ser553 and proteasomal turnover, while FBXL3/FBXL21 and FBXW7 (the latter binding phospho-Thr300) target CRY2 for ubiquitin-mediated degradation, with Ser-420 required for E3 ligase engagement and a parallel lysosomal route also operating (PMID:20123978, PMID:25855785, PMID:37951306). Beyond the canonical loop, CRY2 performs non-redundant, isoform-specific output functions that CRY1 cannot substitute: it serves as an adaptor in an SCF-FBXL3 complex to recruit phospho-T58 c-MYC for ubiquitylation, links the clock to cell proliferation and P53 target regulation, and binds Bclaf1 to stabilize myogenic mRNAs controlling myoblast proliferation and muscle regeneration (PMID:27840026, PMID:34183418, PMID:29466738). CRY2 additionally acts as a corepressor for nuclear hormone receptors at NR-motif-enriched genomic sites and mediates steroid-hormone-receptor-dependent serum-induced phase resetting independently of its period-setting role (PMID:28751364, PMID:41354650). A crystal structure of CRY2 bound to the period-lengthening compound SHP656 defines a gatekeeper W417 conformation underlying isoform-selective small-molecule modulation (PMID:36161947).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Established that CRY2 is not merely a photoreceptor but an essential clock component, resolving whether cryptochromes maintain mammalian rhythmicity.

    Evidence Single and double Cry1/Cry2 knockout mice with locomotor activity monitoring

    PMID:10217146

    Open questions at the time
    • Did not define the molecular mechanism of repression
    • Behavioral phenotype does not localize CRY2 action to specific molecular partners
  2. 2001 Medium

    Addressed whether the flavin/electron-transport apparatus is functionally required for transcriptional repression, distinguishing CRY2 from CRY1.

    Evidence Site-directed mutagenesis of conserved tryptophans with transcriptional suppression assays in Xenopus CRY2

    PMID:11747820

    Open questions at the time
    • Used Xenopus ortholog, not mammalian CRY2
    • Did not establish a photochemical or redox mechanism in mammalian cells
  3. 2002 Medium

    Defined the interlocked feedback architecture by showing CRY2 activates Bmal1 transcription while CLOCK/BMAL1 represses it.

    Evidence Transcriptional reporter assays and mBmal1 promoter characterization in cell culture

    PMID:11798163

    Open questions at the time
    • Reporter-based; in vivo contribution to the loop not directly tested
    • Mechanism of CRY2-mediated activation unresolved
  4. 2009 Medium

    Distinguished clock-protein binding from a CRY2-unique repression step, showing CRY2 has a repression mechanism separable from complex assembly.

    Evidence Random mutagenesis screen (G354D, G351D), reporter assays, Co-IP and rhythm analysis in NIH 3T3 cells

    PMID:19687303

    Open questions at the time
    • Molecular nature of the CRY2-specific repression defect not defined
    • Single lab, cell-based
  5. 2010 High

    Mapped the PER2 interaction surface and the priming-phosphorylation degradation switch, defining how CRY2 abundance is timed.

    Evidence Two-hybrid/Co-IP mutagenesis (R501/K503) and in vitro DYRK1A/GSK-3β kinase assays with S557A/S553A mutants and RNAi

    PMID:20123978 PMID:20840750

    Open questions at the time
    • Did not identify the cognate E3 ligase acting on phospho-CRY2
    • Kinase priming hierarchy shown in vitro and cells but not in vivo timing
  6. 2013 High

    Quantified the functional asymmetry between CRY1 and CRY2, showing CRY2 is a weaker repressor that modulates CRY1 action.

    Evidence Fbxl3(Afh) epistasis across Cry-deficient backgrounds with SCN bioluminescence and wheel-running

    PMID:23616524

    Open questions at the time
    • Structural basis of differential repressor potency not resolved
    • Does not explain CRY2's non-redundant output roles
  7. 2015 Medium

    Identified FBXW7 as a phospho-Thr300-dependent E3 ligase for CRY2, expanding the degradation machinery beyond FBXL3/FBXL21.

    Evidence Co-IP, ubiquitination assays, Thr300 mutagenesis and cycloheximide chase

    PMID:25855785

    Open questions at the time
    • Kinase phosphorylating Thr300 not identified
    • Relative contribution versus FBXL3/FBXL21 unresolved
  8. 2016 High

    Revealed a non-redundant output function: CRY2 acts as an SCF-FBXL3 adaptor recruiting phospho-T58 c-MYC, linking the clock to proliferation.

    Evidence Co-IP, in-cell ubiquitylation, phospho-specific recruitment and CRY1 non-complementation

    PMID:27840026

    Open questions at the time
    • In vivo tumor-suppressive role not established here
    • Structural basis of the c-MYC recruitment specificity unknown
  9. 2017 Medium

    Showed CRY2 broadly corepresses nuclear hormone receptors independently of core clock factors, connecting the clock to drug metabolism.

    Evidence Genomic binding analysis and corepressor functional assays across multiple NRs

    PMID:28751364

    Open questions at the time
    • CRY2-versus-CRY1 specificity at NR sites not dissected
    • Direct versus indirect genomic recruitment unclear
  10. 2018 High

    Demonstrated a post-transcriptional output role: CRY2-specific binding to Bclaf1 stabilizes myogenic mRNAs and controls muscle regeneration.

    Evidence Co-IP, Cry2-/- mice, mRNA stability assays, single myofiber and regeneration assays

    PMID:29466738

    Open questions at the time
    • Mechanism of CRY2/Bclaf1 mRNA selectivity unknown
    • Relationship to CRY2's nuclear repressor role not integrated
  11. 2019 Medium

    Confirmed CRY2's period-setting role in human cells, validating cross-species conservation of the phenotype.

    Evidence CRISPR/Cas9 CRY2 and CRY1/CRY2 knockouts in U-2 OS cells with bioluminescence

    PMID:31143130

    Open questions at the time
    • No molecular dissection beyond period phenotype
    • Output functions not tested in this system
  12. 2020 Medium

    Connected CRY2 turnover to trophoblast behavior, showing FBXW7-driven degradation and CRY2 suppression of the c-Myc-BMAL1-MMP axis.

    Evidence RNA pull-down, Co-IP, stability and migration/invasion assays; ChIP of c-Myc on BMAL1 promoter in HTR-8/SVneo cells

    PMID:31536114 PMID:32776544

    Open questions at the time
    • In vivo relevance to placentation not established
    • Single cell-line systems
  13. 2021 Medium

    Linked cancer-associated CRY2 missense variants to P53 target suppression and c-MYC-dependent growth, implicating CRY2 in tumor biology.

    Evidence Stable CRY2 mutant expression in primary fibroblasts, P53 target and circadian assays, FBXL3 Co-IP

    PMID:34183418

    Open questions at the time
    • Mechanism connecting variants to P53 targets undefined
    • No in vivo tumorigenesis data
  14. 2022 High

    Provided a structural basis for isoform-selective small-molecule modulation, defining the W417 gatekeeper conformation.

    Evidence X-ray crystallography of CRY2-SHP656, MD simulations, W417 mutagenesis and CRY2-dependent period assays

    PMID:36161947

    Open questions at the time
    • Structure of full repressor complex with PER2/CLOCK/BMAL1 not resolved
    • Endogenous ligand state not addressed
  15. 2023 High

    Resolved the Cys432/Ser420 determinants of PER2 binding, repression and E3 engagement, and extended CRY2 repression to Wnt-driven adipogenesis and ERK/ETS1-PAX7 muscle programs.

    Evidence C432 and S420F mutagenesis with PER2/FBXL3/FBXL21 Co-IP, localization imaging, degradation inhibitors, adipogenesis assays, and satellite-cell Cry2 KO with ChIP

    PMID:36636367 PMID:37724597 PMID:37951306

    Open questions at the time
    • How a single residue couples binding, localization and degradation not fully mechanized
    • Tissue-specific output mechanisms not unified
  16. 2025 Medium

    Identified period-independent and signaling-coupled roles: CRY2 mediates steroid-hormone-receptor-dependent phase resetting, interacts with TRPC1 in electromagnetic-field responses, and modulates renal drug efflux.

    Evidence Single-cell phase-transition (Circa-SCOPE) with CRY2 perturbation; Co-IP/co-localization with TRPC1 and riboflavin-kinase silencing in myoblasts; CRY2 overexpression with ATP7A/MRP2 readouts in renal cells

    PMID:39937022 PMID:40254427 PMID:41354650

    Open questions at the time
    • TRPC1 interaction is single-lab without reciprocal in vivo validation
    • Renal efflux role rests on a single overexpression experiment (Low confidence)
    • Molecular link between steroid receptors and CRY2 phase resetting undefined
  17. 2026 Medium

    Showed CRY2 nuclear-cytoplasmic shuttling is mechanosensitive, coupling ROCK/actin dynamics to clock oscillations in cartilage.

    Evidence ROCK inhibition, actin polymerization assays, CRY2 localization imaging and knockdown in chondrocytes and condyle explants

    PMID:41490462

    Open questions at the time
    • Direct molecular link between actin and CRY2 transport unknown
    • In vivo cartilage relevance from explant model only

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CRY2's distinct activities — transcriptional repression, E3-adaptor function, mRNA stabilization, NR corepression, and mechano-/hormone-coupled localization — are integrated and isoform-specifically partitioned from CRY1 remains unresolved.
  • No structure of the assembled CRY2-PER2-CLOCK/BMAL1 repressor complex
  • Mechanism determining when CRY2 acts as repressor versus SCF adaptor versus RNA-stabilizing factor unknown
  • Endogenous flavin/redox cofactor function in mammalian CRY2 not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-9909396 Circadian clock 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3
Partners
BCLAF1BMAL1C-MYCCLOCKFBXL3FBXW7PER2TRPC1
Complex memberships
CRY2-PER2 repressor complexSCF-FBXL3 E3 ubiquitin ligase complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Mice lacking both CRY1 and CRY2 show instantaneous and complete loss of free-running circadian rhythmicity, demonstrating that CRY1 and CRY2 are essential for maintenance of circadian rhythms (not merely photoreceptors). CRY1-null mice show accelerated and CRY2-null mice show delayed free-running locomotor activity periodicity. Genetic knockout (Cry1-/-, Cry2-/-, Cry1-/-/Cry2-/- mice) with locomotor activity monitoring Nature High 10217146
2002 CRY2 (and CRY1, PER2) activates transcription of the mouse Bmal1 gene, while BMAL1-CLOCK dimers repress it, establishing an interlocked feedback loop within the circadian clockwork. Transcriptional reporter assays in cell culture; promoter characterization of mBmal1 Biochemical and biophysical research communications Medium 11798163
2001 An intact flavin binding domain is required for CRY2 function in suppressing CLOCK/BMAL1-mediated transcription. Mutation of any of the three conserved tryptophan residues in the putative electron transport chain inhibits xCRY2b function, indicating CRY2 requires electron transport through the conserved tryptophan pathway, unlike CRY1 which depends only on the last tryptophan. Site-directed mutagenesis of conserved tryptophan residues; transcriptional suppression assays in Xenopus CRY2 Current biology Medium 11747820
2010 CRY2 undergoes proteasomal degradation initiated by a dual-kinase mechanism: DYRK1A phosphorylates Ser557 as a priming event, enabling subsequent GSK-3β-mediated phosphorylation of Ser553, which leads to proteasomal degradation of CRY2. Knockdown of Dyrk1a causes abnormal cytosolic CRY2 accumulation and shortens circadian period. In vitro kinase assays, site-directed mutagenesis (S557A/S553A), RNAi knockdown in cells, circadian period measurement Molecular and cellular biology High 20123978
2010 Two residues in the C-terminal domain of mouse CRY2, Arg-501 and Lys-503 (within residues 493–512), are essential for direct physical interaction with PER2. Mutation of both residues abolishes CRY2-PER2 interaction. Mammalian two-hybrid assay, co-immunoprecipitation, oligonucleotide-based degenerate PCR mutagenesis BMC molecular biology Medium 20840750
2013 CRY1 and CRY2 are both transcriptional repressors within the SCN clockwork, but CRY1 is significantly more potent than CRY2. CRY1 prolongs the interval of transcriptional suppression while CRY2 does not, and CRY2 attenuates the period-lengthening effects of CRY1. Both CRYs dose-dependently lengthen the intrinsic high-frequency SCN rhythm. Genetic epistasis using Fbxl3(Afh) allele in Cry1- and Cry2-deficient mouse backgrounds; SCN bioluminescence recording; wheel-running analysis The Journal of neuroscience High 23616524
2009 Random mutagenesis identified CRY2-specific residues required for repression of CLOCK-BMAL1. CRY2(G354D) is deficient in clock protein binding required for repression by both CRYs, while CRY2(G351D) shows normal binding but a CRY2-specific repression defect. Overexpression of CRY2(G351D) abolishes circadian rhythmicity, implicating a CRY2-unique repression mechanism. Random mutagenesis screen, cell-based CLOCK-BMAL1 reporter assay, co-immunoprecipitation, circadian rhythm analysis in NIH 3T3 cells Molecular and cellular biology Medium 19687303
2015 FBXW7 is an E3 ubiquitin ligase that targets CRY2 for proteasomal degradation by binding directly to phosphorylated Thr300 of CRY2, enhancing CRY2 ubiquitination and accelerating CRY2 turnover. Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (Thr300), cycloheximide chase; biochemical and cell biology analyses Molecular cancer therapeutics Medium 25855785
2016 CRY2 functions as a component of an FBXL3-containing SCF E3 ubiquitin ligase complex that recruits T58-phosphorylated c-MYC for ubiquitylation and degradation. CRY1 cannot substitute for CRY2 in this function. This represents a circadian mechanism for control of cell proliferation via c-MYC turnover. Co-immunoprecipitation, ubiquitylation assays, phospho-specific recruitment assays; genetic complementation showing CRY1 cannot substitute Molecular cell High 27840026
2017 CRY1 and CRY2 broadly interact with nuclear hormone receptors and serve as corepressors for many NRs, binding independently of other core clock factors to genomic sites enriched for NR recognition motifs, contributing to circadian regulation of drug metabolism. Genomic binding analysis (ChIP-related), co-repressor functional assays; interaction studies with multiple NRs Proceedings of the National Academy of Sciences of the United States of America Medium 28751364
2018 CRY2, but not CRY1, specifically interacts with Bclaf1 to stabilize mRNAs encoding cyclin D1 and Tmem176b, regulating circadian patterns of myoblast proliferation and myogenic cell fusion. Cry2-/- myoblasts show premature cell cycle exit and form short myotubes, and muscle regeneration is impaired in Cry2-/- mice. Co-immunoprecipitation of CRY2-Bclaf1 complex, Cry2-/- mouse model, mRNA stability assays, single myofiber analysis, muscle regeneration assays Cell reports High 29466738
2021 Two cancer-associated CRY2 missense mutations (D325H and S510L in mouse) suppress P53 target-gene expression and accelerate growth of primary fibroblasts expressing high c-MYC. The mutations have divergent impacts on circadian rhythms and on CRY2's ability to interact with SCF-FBXL3, and neither affects steady-state levels of overexpressed c-MYC. Stable expression of CRY2 mutants in primary mouse fibroblasts, P53 target gene expression analysis, circadian rhythm assays, co-immunoprecipitation with FBXL3 Proceedings of the National Academy of Sciences of the United States of America Medium 34183418
2022 X-ray crystal structure of mammalian CRY2 in complex with the small molecule SHP656 reveals that compound binding is compatible with the intrinsic CRY2 gatekeeper W417 'in' orientation. The gatekeeper residue W417 and lid loop interactions are important for CRY2 isoform selectivity of this compound. SHP656 lengthened cellular circadian period in a CRY2-dependent manner. X-ray crystallography, molecular dynamics simulations, circadian period assays in CRY2-dependent manner, mutagenesis of W417 Proceedings of the National Academy of Sciences of the United States of America High 36161947
2019 Human CRY2 knockout cells generated by CRISPR/Cas9 show long-period circadian rhythms, while CRY1/CRY2 double knockout cells are arrhythmic, consistent with mouse knockout models and confirming CRY2's period-setting role in human cells. CRISPR/Cas9 knockout of CRY2 in human U-2 OS cells; circadian bioluminescence recording Frontiers in physiology Medium 31143130
2023 CRY2 variant p.Ser420Phe has reduced affinity for PER2 and defective nuclear translocation, resulting in reduced repression of CLOCK:BMAL1-driven transcription. This variant is unexpectedly resistant to degradation via FBXL3 and FBXL21 (canonical proteasomal pathway), indicating Ser-420 is required for E3 ligase interaction. Wild-type CRY2 (and this variant) can also be degraded via a lysosomal pathway. The variant causes a ~7 h shorter circadian period in Cry1-/-Cry2-/- MEFs. Site-directed mutagenesis, co-immunoprecipitation with PER2/FBXL3/FBXL21, nuclear localization imaging, proteasomal/lysosomal inhibitor experiments, complementation in Cry1-/-Cry2-/- double KO MEFs The Journal of biological chemistry High 37951306
2023 CRY2 represses CLOCK/BMAL1-induced transcription via a critical Cys432 residue that mediates PER2 heterodimer formation. The C432 mutation disrupts PER2 association without affecting BMAL1 binding. This CRY2-PER2 repression complex is required for transcriptional repression of Wnt pathway components to promote adipogenesis. Site-directed mutagenesis (C432), co-immunoprecipitation, transcriptional reporter assays, adipogenic differentiation assays, CRY2 KD/OE in preadipocytes, KL001 stabilization Molecular and cellular biology High 37724597
2020 FBXW7 promotes CRY2 ubiquitin-mediated degradation and thereby promotes trophoblast migration and invasion. The lncRNA MALAT1 recruits FBXW7 to impair CRY2 protein stability; reduced MALAT1 leads to CRY2 accumulation and suppressed migration/invasion. RNA pull-down, co-immunoprecipitation of FBXW7-CRY2, CRY2 protein stability assays, trophoblast migration/invasion assays Journal of cellular physiology Medium 32776544
2020 CRY2 overexpression impairs trophoblast migration and invasion by inhibiting the c-Myc-BMAL1 pathway. c-Myc binds the BMAL1 promoter to induce BMAL1 transcription, which activates MMP2/9. CRY2 suppresses this c-Myc-BMAL1-MMP2/9 axis. Luciferase reporter assay, chromatin immunoprecipitation (c-Myc on BMAL1 promoter), wound healing and Transwell invasion assays, CRY2 overexpression/knockdown in HTR-8/SVneo cells Journal of biochemistry Medium 31536114
2023 Loss of CRY2 in satellite cells enhances muscle regeneration by activating ERK1/2 signaling and ETS1, which binds the PAX7 promoter to induce PAX7 transcription and increase satellite cell proliferation. Satellite cell/skeletal muscle lineage-specific Cry2 knockout mice (CRY2scko), immunostaining, single myofiber analysis, ERK1/2 activation assays, ChIP (ETS1 on PAX7 promoter) MedComm Medium 36636367
2025 CRY2 physically interacts with TRPC1, and this interaction is detected by co-immunoprecipitation. Both proteins co-translocate to the nucleus following pulsed electromagnetic field (PEMF) exposure. CRY2 overexpression enhances PEMF-induced myogenic responses, while CRY2 silencing reduces them. Reducing FAD content by silencing riboflavin kinase attenuates PEMF responsiveness. Co-immunoprecipitation, immunofluorescence co-localization, CRY2 overexpression/knockdown, riboflavin kinase silencing, PEMF exposure assays in myoblasts Cells Medium 39937022
2025 CRY2 plays a central role in serum-induced circadian clock phase resetting. Steroid hormone receptors (including sex-hormone receptors) are key mediators of serum-induced phase resetting, and CRY2 mediates their effect on clock phase independently of its role in period-length determination. Circa-SCOPE high-throughput single-cell phase transition curve analysis; CRY2 perturbation experiments; steroid hormone receptor pathway analysis Nature communications Medium 41354650
2025 CRY2 overexpression in mouse renal tubular cells alleviates cisplatin-induced cytotoxicity by reducing platinum accumulation through upregulation of efflux transporters ATP7A and MRP2. CRY2 overexpression in MuRTE61 cells, cell viability assays, platinum content measurement, western blot of ATP7A and MRP2 Biological & pharmaceutical bulletin Low 40254427
2026 CRY2 nuclear-cytoplasmic shuttling in chondrocytes depends on ROCK activation and actin polymerization under mechanical loading. Inhibition of ROCK causes actin depolymerization and partially blocks CRY2 nuclear-cytoplasmic trafficking. Knockdown of CRY2 attenuates mechanical loading-sustained circadian oscillations and cartilage homeostasis. ROCK inhibitor treatment, actin polymerization assays, CRY2 localization imaging (nuclear-cytoplasmic shuttling), CRY2 knockdown in chondrocytes and condyle explants Bone & joint research Medium 41490462

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature 1087 10217146
2016 Optimized second-generation CRY2-CIB dimerizers and photoactivatable Cre recombinase. Nature chemical biology 202 27065233
2016 CRY2 and FBXL3 Cooperatively Degrade c-MYC. Molecular cell 172 27840026
2017 Optogenetic protein clustering through fluorescent protein tagging and extension of CRY2. Nature communications 135 28646204
2010 CRY2 is associated with depression. PloS one 130 20195522
2002 Interactivating feedback loops within the mammalian clock: BMAL1 is negatively autoregulated and upregulated by CRY1, CRY2, and PER2. Biochemical and biophysical research communications 117 11798163
2010 DYRK1A and glycogen synthase kinase 3beta, a dual-kinase mechanism directing proteasomal degradation of CRY2 for circadian timekeeping. Molecular and cellular biology 112 20123978
2017 Understanding CRY2 interactions for optical control of intracellular signaling. Nature communications 100 28916751
2009 Circadian expression of clock genes in two mosquito disease vectors: cry2 is different. Journal of biological rhythms 83 19926804
2015 Regulation of endogenous transmembrane receptors through optogenetic Cry2 clustering. Nature communications 82 25902152
2017 Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors and modulate transcriptional activity. Proceedings of the National Academy of Sciences of the United States of America 81 28751364
2009 The circadian clock components CRY1 and CRY2 are necessary to sustain sex dimorphism in mouse liver metabolism. The Journal of biological chemistry 80 19211562
2002 Chickens' Cry2: molecular analysis of an avian cryptochrome in retinal and pineal photoreceptors. FEBS letters 79 11904144
2015 Circadian Clock Gene CRY2 Degradation Is Involved in Chemoresistance of Colorectal Cancer. Molecular cancer therapeutics 73 25855785
2017 miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in colorectal cancer. Cell death & disease 65 28749470
2010 CRY2 is associated with rapid cycling in bipolar disorder patients. PloS one 65 20856823
2019 Inhibition of CRY2 by STAT3/miRNA-7-5p Promotes Osteoblast Differentiation through Upregulation of CLOCK/BMAL1/P300 Expression. Molecular therapy. Nucleic acids 62 31982773
2018 CIB1 and CO interact to mediate CRY2-dependent regulation of flowering. EMBO reports 58 30126927
2018 Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b. Cell reports 55 29466738
2011 Variants in GLIS3 and CRY2 are associated with type 2 diabetes and impaired fasting glucose in Chinese Hans. PloS one 52 21747906
2013 Distinct and separable roles for endogenous CRY1 and CRY2 within the circadian molecular clockwork of the suprachiasmatic nucleus, as revealed by the Fbxl3(Afh) mutation. The Journal of neuroscience : the official journal of the Society for Neuroscience 51 23616524
2001 Effect of estrogen on the expression of Cry1 and Cry2 mRNAs in the suprachiasmatic nucleus of female rats. Neuroscience research 42 11672838
2021 CRY2 missense mutations suppress P53 and enhance cell growth. Proceedings of the National Academy of Sciences of the United States of America 40 34183418
2003 Characterization of cry1, cry2, and cry9 genes in Bacillus thuringiensis isolates from China. Journal of invertebrate pathology 40 12581721
1995 Feedback inhibition of the yeast ribosomal protein gene CRY2 is mediated by the nucleotide sequence and secondary structure of CRY2 pre-mRNA. Molecular and cellular biology 40 7565797
2022 CRY2 interacts with CIS1 to regulate thermosensory flowering via FLM alternative splicing. Nature communications 39 36396657
2022 CRY2 isoform selectivity of a circadian clock modulator with antiglioblastoma efficacy. Proceedings of the National Academy of Sciences of the United States of America 38 36161947
2013 CRY2 genetic variants associate with dysthymia. PloS one 36 23951166
2021 MiR-27a-3p promotes the osteogenic differentiation by activating CRY2/ERK1/2 axis. Molecular medicine (Cambridge, Mass.) 32 33902432
2014 CRY1, CRY2 and PRKCDBP genetic variants in metabolic syndrome. Hypertension research : official journal of the Japanese Society of Hypertension 32 25391456
2010 Identification of two amino acids in the C-terminal domain of mouse CRY2 essential for PER2 interaction. BMC molecular biology 32 20840750
2019 Synergism of the Bacillus thuringiensis Cry1, Cry2, and Vip3 Proteins in Spodoptera frugiperda Control. Applied biochemistry and biotechnology 31 30706415
2022 Resistance of Spodoptera frugiperda to Cry1, Cry2, and Vip3Aa Proteins in Bt Corn and Cotton in the Americas: Implications for the Rest of the World. Journal of economic entomology 30 36515105
2016 Glucose-Raising Polymorphisms in the Human Clock Gene Cryptochrome 2 (CRY2) Affect Hepatic Lipid Content. PloS one 29 26726810
2015 The circadian gene CRY2 is associated with breast cancer aggressiveness possibly via epigenomic modifications. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 29 25740058
2012 Deregulated expression of cry1 and cry2 in human gliomas. Asian Pacific journal of cancer prevention : APJCP 29 23317246
2005 The cryptochrome gene family in pea includes two differentially expressed CRY2 genes. Plant molecular biology 28 16244915
2020 CRY2 suppresses trophoblast migration and invasion in recurrent spontaneous abortion. Journal of biochemistry 26 31536114
2018 Cryptochrome 2 (CRY2) Suppresses Proliferation and Migration and Regulates Clock Gene Network in Osteosarcoma Cells. Medical science monitor : international medical journal of experimental and clinical research 26 29879092
2022 Aschoff's rule on circadian rhythms orchestrated by blue light sensor CRY2 and clock component PRR9. Nature communications 25 36198686
2019 Generation of Human CRY1 and CRY2 Knockout Cells Using Duplex CRISPR/Cas9 Technology. Frontiers in physiology 25 31143130
2010 Loss of circadian rhythm and light-induced suppression of pineal melatonin levels in Cry1 and Cry2 double-deficient mice. Genes to cells : devoted to molecular & cellular mechanisms 24 20825493
2009 Generation of a novel allelic series of cryptochrome mutants via mutagenesis reveals residues involved in protein-protein interaction and CRY2-specific repression. Molecular and cellular biology 24 19687303
2016 PRKCDBP (CAVIN3) and CRY2 associate with major depressive disorder. Journal of affective disorders 22 27721187
2008 Identification of coding polymorphisms in human circadian rhythm genes PER1, PER2, PER3, CLOCK, ARNTL, CRY1, CRY2 and TIMELESS in a multi-ethnic screening panel. DNA sequence : the journal of DNA sequencing and mapping 20 17852344
2021 Novel InDel variations of the Cry2 gene are associated with litter size in Australian White sheep. Theriogenology 19 34875538
2012 Molecular cloning, tissue distribution and daily expression of cry1 and cry2 clock genes in European seabass (Dicentrarchus labrax). Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 19 22841604
2011 Characterization of cry2-type genes of bacillus thuringiensis strains from soilisolated of sichuan basin, china. Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] 19 24031615
2020 A structural view of plant CRY2 photoactivation and inactivation. Nature structural & molecular biology 18 32398828
2020 MALAT1 recruited the E3 ubiquitin ligase FBXW7 to induce CRY2 ubiquitin-mediated degradation and participated in trophoblast migration and invasion. Journal of cellular physiology 18 32776544
2012 Sequence and expression of per, tim1, and cry2 genes in the Madeira cockroach Rhyparobia maderae. Journal of biological rhythms 18 23223371
2001 A putative flavin electron transport pathway is differentially utilized in Xenopus CRY1 and CRY2. Current biology : CB 18 11747820
2013 Altered phase-relationship between peripheral oscillators and environmental time in Cry1 or Cry2 deficient mouse models for early and late chronotypes. PloS one 17 24386234
2011 Hypertension due to loss of clock: novel insight from the molecular analysis of Cry1/Cry2-deleted mice. Current hypertension reports 17 21286865
1994 The sequence of a 36 kb segment on the left arm of yeast chromosome X identifies 24 open reading frames including NUC1, PRP21 (SPP91), CDC6, CRY2, the gene for S24, a homologue to the aconitase gene ACO1 and two homologues to chromosome III genes. Yeast (Chichester, England) 16 7754713
2025 Advancing clinical response against glioblastoma: Evaluating SHP1705 CRY2 activator efficacy in preclinical models and safety in phase I trials. Neuro-oncology 15 40168112
2017 CRY2 is suppressed by FOXM1 mediated promoter hypermethylation in breast cancer. Biochemical and biophysical research communications 15 28579430
2024 Bao Yuan decoction alleviates fatigue by restraining inflammation and oxidative stress via the AMPK/CRY2/PER1 signaling pathway. Journal of ethnopharmacology 14 38513778
2018 Root-expressed phytochromes B1 and B2, but not PhyA and Cry2, regulate shoot growth in nature. Plant, cell & environment 14 29766532
2020 Activation of Cdc42 GTPase upon CRY2-Induced Cortical Recruitment Is Antagonized by GAPs in Fission Yeast. Cells 13 32932721
2018 The expression of clock genes cry1 and cry2 in human colorectal cancer and tumor adjacent tissues correlates differently dependent on tumor location. Neoplasma 13 29940771
2017 Light-Regulated Protein Kinases Based on the CRY2-CIB1 System. Methods in molecular biology (Clifton, N.J.) 13 28293892
2014 Investigation into the promoter DNA methylation of three genes (CAMK1D, CRY2 and CALM2) in the peripheral blood of patients with type 2 diabetes. Experimental and therapeutic medicine 13 25009623
2022 Characterization of Cry2 genes (CRY2a and CRY2b) of B. napus and comparative analysis of BnCRY1 and BnCRY2a in regulating seedling photomorphogenesis. Plant molecular biology 12 35831732
2021 CHRONO and DEC1/DEC2 compensate for lack of CRY1/CRY2 in expression of coherent circadian rhythm but not in generation of circadian oscillation in the neonatal mouse SCN. Scientific reports 12 34584158
2023 Loss of CRY2 promotes regenerative myogenesis by enhancing PAX7 expression and satellite cell proliferation. MedComm 11 36636367
2023 CircZNF367 promotes osteoclast differentiation and osteoporosis by interacting with FUS to maintain CRY2 mRNA stability. Journal of orthopaedic surgery and research 10 37434265
2014 Quantitative real-time kinetics of optogenetic proteins CRY2 and CIB1/N using single-molecule tools. Analytical biochemistry 10 24780222
2023 Establishment of novel receptor-antibody sandwich assays to broadly detect Bacillus thuringiensis Cry1 and Cry2 toxins. International journal of biological macromolecules 9 37972832
2023 Copper-induced diurnal hepatic toxicity is associated with Cry2 and Per1 in mice. Environmental health and preventive medicine 9 38092388
2022 Knockdown of UCHL3 inhibits esophageal squamous cell carcinoma progression by reducing CRY2 methylation. Human cell 9 35088238
2021 No positive cross-resistance to Cry1 and Cry2 proteins favors pyramiding strategy for management of Vip3Aa resistance in Spodoptera frugiperda. Pest management science 9 33314557
2022 Genetic Variations within the Bovine CRY2 Gene Are Significantly Associated with Carcass Traits. Animals : an open access journal from MDPI 7 35804515
2021 Low CLOCK and CRY2 in 2nd trimester human maternal blood and risk of preterm birth: a nested case-control study†. Biology of reproduction 6 34142702
2020 Neither per, nor tim1, nor cry2 alone are essential components of the molecular circadian clockwork in the Madeira cockroach. PloS one 6 32750054
2025 The impact of circadian rhythm disruption on oxaliplatin tolerability and pharmacokinetics in Cry1-/-Cry2-/- mice under constant darkness. Archives of toxicology 5 39903276
2025 Magnetically Stimulated Myogenesis Recruits a CRY2-TRPC1 Photosensitive Signaling Axis. Cells 5 39937022
2024 Analysis of how melatonin-upregulated clock genes PER2 and CRY2 alleviate rheumatoid arthritis-associated interstitial lung disease. European journal of pharmacology 5 39551335
2005 Cloning and expression analysis of CRY2 gene in Sorghum bicolor. Zhi wu sheng li yu fen zi sheng wu xue xue bao = Journal of plant physiology and molecular biology 5 15961900
2023 Functional characterization of the CRY2 circadian clock component variant p.Ser420Phe revealed a new degradation pathway for CRY2. The Journal of biological chemistry 4 37951306
2017 Characterization of lepidopteran-specific cry1 and cry2 gene harbouring native Bacillus thuringiensis isolates toxic against Helicoverpa armigera. Biotechnology reports (Amsterdam, Netherlands) 4 28649558
2012 RFLP analysis of cry1 and cry2 genes of Bacillus thuringiensis isolates from India. Journal of microbiology and biotechnology 4 22573148
2002 Heterologous expression of cry2 gene from a local strain of Bacillus thuringiensis isolated in Nigeria. Biotechnology and applied biochemistry 4 12452809
2025 Circadian rhythm gene cryptochrome 2 (Cry2) interacts with lipid metabolism to promote vascular aging. Archives of gerontology and geriatrics 3 39879691
2024 Comparative analysis of locomotor behavior and head diurnal transcriptome regulation by PERIOD and CRY2 in the diamondback moth. Insect science 3 38414323
2023 Transcription Repression of CRY2 via PER2 Interaction Promotes Adipogenesis. Molecular and cellular biology 3 37724597
2022 Assessing fitness costs of the resistance of Spodoptera frugiperda (Lepidoptera: Noctuidae) to pyramided Cry1 and Cry2 insecticidal proteins on different host plants. Bulletin of entomological research 3 35016737
2016 Prevalence of cry2-type genes in Bacillus thuringiensis isolates recovered from diverse habitats in India and isolation of a novel cry2Af2 gene toxic to Helicoverpa armigera (cotton boll worm). Canadian journal of microbiology 3 27805417
2025 Sex-specific associations between insomnia symptoms and mental health among Chinese young adults and the modified effect of CRY2 gene DNA methylation. Clinical epigenetics 2 41053898
2024 CRY2 mediates the cognitive decline induced by sleep deprivation in 5xFAD mice. PloS one 2 39012854
2024 Advancing Clinical Response Against Glioblastoma: Evaluating SHP1705 CRY2 Activator Efficacy in Preclinical Models and Safety in Phase I Trials. bioRxiv : the preprint server for biology 2 39345648
2024 TH301 Emerges as a Novel Anti-Oncogenic Agent for Human Pancreatic Cancer Cells: The Dispensable Roles of p53, CRY2 and BMAL1 in TH301-Induced CDKN1A/p21CIP1/WAF1 Upregulation. International journal of molecular sciences 2 39796036
2021 Expression of CRY2 Gene in the Brain Is Related to Human Navigation. Frontiers in radiology 2 37492180
2009 Expression of Cry2 in the chicken pineal gland: effects of changes in light-dark conditions. Annals of the New York Academy of Sciences 2 19456395
2026 Cry2 prompts clock oscillation and temporomandibular joint homeostasis under mechanical loading. Bone & joint research 1 41490462
2023 Transcription repression of Cry2 via Per2 interaction promotes adipogenesis. bioRxiv : the preprint server for biology 1 36993226
2022 Meta-Analysis of Mechanism of Influence of CRY2 on the Differentiation of Mouse Osteoblast through the Regulation of Wnt/Β-Catenin Signaling Pathway. BioMed research international 1 36046448
2025 Cry2 Alleviates Cisplatin-Induced Cytotoxicity in Mouse Renal Cortex Tubular Cell Lines. Biological & pharmaceutical bulletin 0 40254427
2025 Steroid hormone receptors through Cry2 are key players in the circadian clock response to serum. Nature communications 0 41354650
2021 SPRR2C, DEFB4A, WIF1, CRY2, and KRT19 are correlated with the development of atopic eczema. European review for medical and pharmacological sciences 0 33629313

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