Affinage

CRY2

Cryptochrome-2 · UniProt Q49AN0

Length
593 aa
Mass
66.9 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRY2 is a core component of the mammalian circadian clock that functions as a transcriptional repressor of CLOCK/BMAL1-driven gene expression, and loss of both CRY1 and CRY2 abolishes circadian rhythmicity while CRY2-specific loss lengthens circadian period (PMID:10217146, PMID:31143130). CRY2 represses CLOCK/BMAL1 through direct interaction with PER2 via a conserved Cys432 residue and a C-terminal domain (residues 493–512), and its stability is controlled by sequential DYRK1A/GSK-3β phosphorylation at Ser557/Ser553 followed by FBXL3- or FBXW7-mediated ubiquitination and proteasomal degradation (PMID:20123978, PMID:20840750, PMID:37724597, PMID:25855785). Beyond its clock function, CRY2 uniquely recruits phospho-T58 c-MYC to the SCF^FBXL3 E3 ligase for degradation, acts as a corepressor for nuclear receptors at genomic sites independent of other clock factors, and stabilizes specific mRNAs through interaction with Bclaf1 to regulate myoblast proliferation and muscle regeneration (PMID:27840026, PMID:28751364, PMID:29466738). Cancer-associated CRY2 missense mutations suppress P53 target gene expression and accelerate growth in fibroblasts with high c-MYC, linking CRY2 dysfunction to tumor-promoting phenotypes (PMID:34183418).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Whether mammalian cryptochromes were essential for circadian timekeeping was unknown; double knockout of Cry1 and Cry2 completely abolished free-running rhythmicity, while Cry2−/− alone lengthened period, establishing CRY2 as a non-redundant core clock component.

    Evidence Cry1/Cry2 single and double KO mice with wheel-running locomotor activity monitoring

    PMID:10217146

    Open questions at the time
    • Mechanism of repression by CRY2 unknown at this point
    • Whether CRY2 has non-clock functions not addressed
  2. 2001 Medium

    How CRY2 achieves transcriptional repression mechanistically was unclear; mutagenesis showed that unlike CRY1, CRY2 requires an intact flavin-binding domain and conserved tryptophan electron-transport pathway for CLOCK/BMAL1 suppression, revealing distinct cofactor requirements between the two CRYs.

    Evidence Site-directed mutagenesis of conserved tryptophans in Xenopus CRY2b with luciferase reporter assay

    PMID:11747820

    Open questions at the time
    • Performed in Xenopus CRY2b, not mouse CRY2
    • Whether FAD binding is catalytic or structural not resolved
    • No structural data at this stage
  3. 2002 Medium

    The feedback architecture connecting CRY2 to BMAL1 regulation was undefined; reporter assays showed CRY1/CRY2 negatively autoregulate their own transcription while positively regulating BMAL1 transcription, establishing an interlocked feedback loop model.

    Evidence Transfection/luciferase reporter assays with mouse Bmal1 promoter

    PMID:11798163

    Open questions at the time
    • Reporter assay in transfected cells, not validated in vivo at this time
    • Relative contributions of CRY1 vs CRY2 to BMAL1 activation unclear
  4. 2009 High

    How CRY2 protein abundance is rhythmically controlled was unknown; identification of DYRK1A-mediated Ser557 priming phosphorylation followed by GSK-3β phosphorylation at Ser553, which triggers proteasomal degradation, revealed a two-step kinase cascade governing CRY2 turnover and circadian period.

    Evidence In vitro kinase assays, S557A/S553A mutagenesis, Dyrk1a siRNA knockdown with circadian period analysis, mouse liver fractionation

    PMID:20123978

    Open questions at the time
    • Which E3 ligase acts downstream of Ser553 phosphorylation not identified here
    • Whether this pathway operates in all tissues unknown
  5. 2009 Medium

    The structural basis for CRY2-PER2 interaction and CRY2-specific repression was undefined; mutagenesis identified residues R501/K503 in the CRY2 C-terminal domain as essential for PER2 binding, and G351 as mediating a CRY2-unique repression mechanism distinct from CRY1.

    Evidence Mammalian two-hybrid, co-immunoprecipitation, random and targeted mutagenesis screens with circadian amplitude readout

    PMID:19687303 PMID:20840750

    Open questions at the time
    • No crystal structure of CRY2-PER2 complex at this point
    • Whether G351 and R501/K503 act through the same or independent pathways not resolved
  6. 2010 Medium

    Whether CRY proteins mediate photic regulation of downstream physiology beyond the SCN was untested; Cry1/Cry2 double KO mice lost circadian melatonin rhythmicity and acute light-pulse suppression of pineal melatonin, establishing CRY as an obligate link in the SCN–pineal photic pathway.

    Evidence Cry1/Cry2 double KO mice on C3H background, pineal melatonin ELISA under LD/DD and light pulse

    PMID:20825493

    Open questions at the time
    • Individual contributions of CRY1 vs CRY2 to melatonin regulation not separated
    • Mechanism downstream of SCN clock not defined
  7. 2013 High

    The relative repressive potency of CRY1 vs CRY2 in the SCN and how protein stability tunes period were unclear; genetic epistasis with the Fbxl3(Afh) stabilizing mutation showed CRY1 is more potent than CRY2 as a repressor, and CRY2 attenuates the period-lengthening effect of CRY1 in a dose-dependent manner.

    Evidence Fbxl3(Afh) mutant crossed with Cry1−/− and Cry2−/− mice, SCN bioluminescence and wheel-running behavior

    PMID:23616524

    Open questions at the time
    • Biochemical basis for differential repressive potency not defined
    • Whether FBXL3 differentially degrades CRY1 vs CRY2 in vivo not quantified
  8. 2015 Medium

    Whether E3 ligases other than FBXL3 regulate CRY2 turnover was unknown; FBXW7 was shown to bind phospho-Thr300 of CRY2 and promote its ubiquitination and degradation, revealing a second E3 ligase pathway for CRY2.

    Evidence Co-IP, ubiquitination assay, Thr300 mutagenesis, CRY2 pulse-chase analysis

    PMID:25855785

    Open questions at the time
    • Relative physiological contribution of FBXW7 vs FBXL3 to CRY2 turnover not determined
    • Kinase responsible for Thr300 phosphorylation not identified
  9. 2016 High

    Whether CRY2 has non-clock substrates was an open question; CRY2 was found to function as a substrate adaptor within an FBXL3-containing E3 ligase that recruits phospho-T58 c-MYC for ubiquitination and degradation, a role unique to CRY2 and not shared by CRY1.

    Evidence Co-IP, ubiquitination assays, CRY2 KO cells, c-MYC stability measurements

    PMID:27840026

    Open questions at the time
    • Whether CRY2 recruits other substrates to FBXL3 beyond c-MYC not explored
    • Structural basis for CRY2 specificity over CRY1 in c-MYC recruitment unknown
  10. 2017 Medium

    Whether CRY proteins regulate transcription independently of CLOCK/BMAL1 was untested genome-wide; ChIP-seq revealed CRY1 and CRY2 bind thousands of genomic sites enriched for nuclear receptor motifs independently of other clock factors, functioning as broad nuclear receptor corepressors that modulate drug metabolism genes.

    Evidence ChIP-seq, Co-IP, genomic binding analysis in mammalian cells

    PMID:28751364

    Open questions at the time
    • Specific nuclear receptor partners for CRY2 vs CRY1 not fully delineated
    • Mechanism of corepressor activity (direct DNA contact vs tethering) not resolved
  11. 2018 Medium

    A post-transcriptional role for CRY2 had not been described; CRY2 was shown to interact with Bclaf1 to stabilize cyclin D1 and Tmem176b mRNAs, controlling circadian myoblast proliferation and myogenic cell fusion, with Cry2−/− mice exhibiting impaired muscle regeneration.

    Evidence Co-IP of CRY2–Bclaf1, Cry2 KO mice, mRNA stability assays, muscle regeneration assays

    PMID:29466738

    Open questions at the time
    • Full mRNA target repertoire of CRY2–Bclaf1 not defined
    • Whether this post-transcriptional role is circadian-gated not fully established
  12. 2019 High

    Whether the distinct period phenotypes of CRY knockouts hold in human cells was unconfirmed; CRISPR-generated CRY2 KO in human U-2 OS cells produced long-period rhythms and CRY1/CRY2 double KO arrhythmicity, confirming conserved, non-redundant roles in the human clock.

    Evidence CRISPR/Cas9 knockout with bioluminescence circadian recording in human U-2 OS cells

    PMID:31143130

    Open questions at the time
    • Whether period effects are identical across human cell types not tested
    • Molecular basis for period lengthening vs shortening by CRY2 vs CRY1 not resolved
  13. 2021 Medium

    Whether cancer-associated CRY2 mutations alter its clock and tumor-suppressive functions was unknown; D325H and S510L mutations suppressed P53 target genes and accelerated growth in high-c-MYC fibroblasts, with divergent effects on circadian period and FBXL3 binding, linking specific CRY2 residues to oncogenic phenotypes.

    Evidence Stable expression of cancer-derived CRY2 mutants in primary mouse fibroblasts, P53 target gene expression, Co-IP with FBXL3, circadian period assay

    PMID:34183418

    Open questions at the time
    • Whether these mutations are cancer drivers or passengers not definitively established
    • In vivo tumorigenicity of CRY2 mutants not tested
  14. 2022 High

    The structural basis for isoform-selective pharmacological modulation of CRY2 was lacking; the crystal structure of CRY2 with SHP656 revealed that selectivity is governed by the gatekeeper residue W417, whose conformational flexibility accommodates compound binding, enabling rational design of CRY2-selective modulators.

    Evidence X-ray crystallography of CRY2–SHP656 complex, molecular dynamics, W417 mutagenesis, cellular circadian assay

    PMID:36161947

    Open questions at the time
    • In vivo pharmacokinetic and circadian effects of SHP656 not reported
    • Whether W417 conformational states are dynamically regulated by physiological signals unknown
  15. 2023 Medium

    The specific residue mediating PER2-dependent repression by CRY2 was undefined; Cys432 was identified as essential for PER2 association (but not BMAL1 binding), and its mutation abolished repression of Wnt pathway components and impaired adipocyte differentiation, linking CRY2's repressor function to developmental outputs.

    Evidence C432 site-directed mutagenesis, Co-IP, luciferase reporter, adipogenic differentiation assays

    PMID:37724597

    Open questions at the time
    • Whether C432 mediates a direct protein–protein contact or acts allosterically not resolved
    • Structural basis of C432-PER2 interaction not determined
  16. 2023 Medium

    How CRY2 loss affects satellite cell biology was unexplored; conditional Cry2 KO in satellite cells activated ERK1/2–ETS1 signaling, with ETS1 directly driving PAX7 transcription to enhance proliferation and muscle regeneration, revealing a CRY2-specific growth-suppressive pathway in stem cells.

    Evidence Satellite cell-specific Cry2 KO mice, ChIP of ETS1 at PAX7 promoter, ERK1/2 phosphorylation analysis, single-myofiber culture

    PMID:36636367

    Open questions at the time
    • Whether this pathway is clock-dependent or clock-independent not resolved
    • Whether findings extend to non-muscle stem cells unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The full extent of CRY2-specific (non-redundant with CRY1) functions—including the scope of its substrate adaptor role for FBXL3, the structural basis of its differential potency relative to CRY1, and whether its post-transcriptional mRNA-stabilization activity is broadly deployed—remains to be defined.
  • No full-length CRY2–PER2 complex structure available
  • Complete substrate repertoire of CRY2–FBXL3 E3 ligase not cataloged
  • Whether CRY2 post-transcriptional functions extend beyond Bclaf1-mediated mRNA stabilization unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-9909396 Circadian clock 6 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-5357801 Programmed Cell Death 2
Partners
BCLAF1BMAL1CLOCKDYRK1AFBXL3FBXW7GSK3BPER2
Complex memberships
CLOCK–BMAL1–CRY2 complexCRY2–PER2 repressor complexSCF^FBXL3–CRY2 E3 ligase complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CRY1 and CRY2 are essential components of the mammalian circadian oscillator; mice lacking both proteins display instantaneous and complete loss of free-running circadian rhythmicity, while single knockouts show accelerated (Cry1-/-) or delayed (Cry2-/-) free-running periodicity of locomotor activity. Genetic knockout (Cry1-/-, Cry2-/-, Cry1-/-Cry2-/- double knockout mice), locomotor activity monitoring Nature High 10217146
2002 CRY1 and CRY2 upregulate BMAL1 transcription and negatively autoregulate their own expression via an interlocked feedback loop; BMAL1-CLOCK dimers repress BMAL1, while CRY1, CRY2, and PER2 activate BMAL1 transcription, forming a third positive forward loop. Transfection/luciferase reporter assays, characterization of mouse Bmal1 promoter genomic structure Biochemical and biophysical research communications Medium 11798163
2001 An intact flavin-binding domain is required for normal 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 depends on electron transport through the conserved tryptophan pathway, unlike CRY1. Site-directed mutagenesis of conserved tryptophan residues, luciferase reporter suppression assay in Xenopus CRY2b Current biology : CB Medium 11747820
2009 Mammalian CRY2 undergoes rhythmic phosphorylation; DYRK1A phosphorylates Ser557 as a priming event for subsequent GSK-3β-mediated phosphorylation of Ser553, which promotes proteasomal degradation of CRY2. DYRK1A kinase activity toward Ser557 shows circadian variation in mouse liver, and knockdown of Dyrk1a causes abnormal CRY2 accumulation and shortened circadian period. In vitro kinase assay, mutagenesis (S557A/S553A), siRNA knockdown, circadian period analysis in cells, mouse liver fractionation Molecular and cellular biology High 20123978
2016 CRY2 functions as a component of an FBXL3-containing E3 ubiquitin ligase that recruits T58-phosphorylated c-MYC for ubiquitylation and proteasomal degradation; CRY1 cannot substitute for CRY2 in this function. Co-immunoprecipitation, ubiquitination assays, genetic loss-of-function (CRY2 KO cells), c-MYC stability assays Molecular cell High 27840026
2015 FBXW7 is an E3 ubiquitin ligase that targets CRY2 for proteasomal degradation by binding directly to phosphorylated Thr300 of CRY2; FBXW7 enhances CRY2 ubiquitination and accelerates its turnover. Co-immunoprecipitation, ubiquitination assay, mutagenesis (Thr300 phosphorylation site), CRY2 turnover/pulse-chase analysis Molecular cancer therapeutics Medium 25855785
2013 CRY1 and CRY2 are both transcriptional repressors of clock-controlled genes in the SCN, but CRY1 is more potent; CRY2 also attenuates the period-lengthening effect of CRY1. Stabilization of either CRY protein via the Fbxl3(Afh) mutation lengthens circadian period in a dose-dependent manner. Genetic epistasis using Fbxl3(Afh) mutant combined with Cry1-/- and Cry2-/- mice; bioluminescence recordings of SCN slices, wheel-running behavior The Journal of neuroscience : the official journal of the Society for Neuroscience High 23616524
2009 Mutagenesis of mouse CRY2 identified a region (residues 493–512) in the C-terminal domain responsible for direct physical interaction with PER2; mutation of Arg-501 and Lys-503 abolishes this interaction. Mammalian two-hybrid assay, co-immunoprecipitation, oligonucleotide-based degenerate PCR mutagenesis BMC molecular biology Medium 20840750
2009 Mutagenesis screen identified CRY2 residue G354 as critical for clock protein binding (required for repression by both CRYs), and G351 as specific to a CRY2-unique repression mechanism; overexpression of CRY2G351D abolishes circadian rhythmicity in NIH 3T3 cells. Random mutagenesis, cell-based screen for CLOCK-BMAL1 repression, protein binding assays, circadian rhythm amplitude measurements Molecular and cellular biology Medium 19687303
2017 CRY1 and CRY2 broadly interact with nuclear receptors and serve as corepressors, binding independently of other core clock factors to many genomic sites enriched for nuclear receptor recognition motifs, contributing to diurnal modulation of drug metabolism. ChIP-seq, Co-IP, genomic binding analysis in mammalian cells 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-/- mice show impaired muscle regeneration. Co-immunoprecipitation (Cry2-Bclaf1), Cry2 KO mice, muscle regeneration assays, mRNA stability assays Cell reports Medium 29466738
2010 Cry1/Cry2 double-deficient mice lose circadian rhythmicity of pineal melatonin concentration and fail to suppress melatonin in response to an acute light pulse, demonstrating CRY proteins mediate photic signals from the SCN to the pineal gland. Cry1/Cry2 double KO mice (C3H background), pineal melatonin measurement by ELISA under LD and DD conditions, acute light-pulse suppression test Genes to cells : devoted to molecular & cellular mechanisms Medium 20825493
2021 CRY2 missense mutations D325H and S510L (found in human cancers) suppress P53 target gene expression and accelerate growth of primary mouse fibroblasts expressing high c-MYC; the mutants have divergent effects on circadian rhythms and CRY2–SCFFBXL3 interaction. Cancer genome atlas mutation analysis, stable expression of CRY2 mutants in primary mouse fibroblasts, P53 target gene expression, circadian period assay, Co-IP with FBXL3 Proceedings of the National Academy of Sciences of the United States of America Medium 34183418
2022 CRY2 isoform selectivity of the small-molecule modulator SHP656 is determined by the gatekeeper residue W417 in CRY2; X-ray crystal structure of CRY2 complexed with SHP656 shows compound binding is compatible with the intrinsic 'in' and 'further in' orientations of W417, and perturbation of this residue reduces SHP656 efficacy. X-ray crystallography (CRY2–SHP656 complex), molecular dynamics simulations, cellular circadian period assay, CRY1/CRY2 KO cell selectivity testing Proceedings of the National Academy of Sciences of the United States of America High 36161947
2023 CRY2 represses CLOCK/BMAL1 transcriptional activation via a conserved Cys432-mediated interaction with PER2; mutagenesis of C432 disrupts PER2 association but not BMAL1 binding, abolishing repression of Wnt pathway components and impairing adipocyte differentiation. Site-directed mutagenesis (C432), co-immunoprecipitation, luciferase reporter assay, adipogenic differentiation assays, CRY2 stabilization with KL001 Molecular and cellular biology Medium 37724597
2019 CRY2 inhibits the CLOCK/BMAL1 complex to suppress transcription of P300; silencing CRY2 releases CLOCK/BMAL1 to bind the P300 E-box and drive P300 expression, which then acetylates histone 3 and forms a transcriptional complex with Runx2 to promote osteoblast differentiation. CRY2 knockdown/overexpression, ChIP assay (CLOCK/BMAL1 at P300 promoter), Co-IP (CRY2-CLOCK/BMAL1), osteoblast differentiation markers Molecular therapy. Nucleic acids Medium 31982773
2020 CRY2 suppresses trophoblast migration and invasion by inhibiting the c-Myc–BMAL1 pathway; CRY2 overexpression impairs migration/invasion, while CRY2 knockdown restores it. Mechanistically, c-Myc binds the BMAL1 promoter to drive BMAL1 transcription and activate MMP2/9, and CRY2 inhibits this pathway. CRY2 overexpression/knockdown in HTR-8/SVneo cells, wound healing/transwell assays, luciferase reporter and ChIP assay (c-Myc at BMAL1 promoter), western blot for MMP2/9 Journal of biochemistry Medium 31536114
2019 CRISPR/Cas9-generated human CRY2 knockout cells display long-period circadian rhythms, whereas CRY1 KO cells show short-period rhythms, and CRY1/CRY2 double KO cells are arrhythmic, confirming distinct and essential roles for each CRY in human circadian timekeeping. CRISPR/Cas9 knockout (duplex, exon deletion), bioluminescence circadian rhythm recording in human U-2 OS cells Frontiers in physiology High 31143130
2020 MALAT1 long non-coding RNA recruits the E3 ubiquitin ligase FBXW7 to promote CRY2 ubiquitin-mediated proteasomal degradation in trophoblasts; MALAT1 downregulation stabilizes CRY2 and impairs trophoblast migration/invasion. RNA pull-down, Co-IP (FBXW7-CRY2 interaction), CRY2 ubiquitination assay, MALAT1 KD with functional migration/invasion assays Journal of cellular physiology Medium 32776544
2009 Cry1 and Cry2 double-deficient mice (C3H strain) lose circadian rhythmicity of pineal melatonin and fail to suppress melatonin after an acute light pulse, indicating CRY genes mediate both circadian and photic regulation of the SCN-pineal axis. Double KO mice, pineal melatonin ELISA under LD and DD, light-pulse experiment Genes to cells Medium 20825493
2023 Loss of CRY2 in satellite cells activates the ERK1/2 signaling pathway and the transcription factor ETS1, which binds the PAX7 promoter to drive its transcription, enhancing satellite cell proliferation and muscle regeneration. Satellite cell-specific Cry2 KO mice, ChIP (ETS1 at PAX7 promoter), immunostaining, ERK1/2 phosphorylation western blot, single-myofiber analysis MedComm Medium 36636367

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 1083 10217146
2008 Photoexcited CRY2 interacts with CIB1 to regulate transcription and floral initiation in Arabidopsis. Science (New York, N.Y.) 578 18988809
2011 Blue light-dependent interaction of CRY2 with SPA1 regulates COP1 activity and floral initiation in Arabidopsis. Current biology : CB 330 21514160
2016 Optimized second-generation CRY2-CIB dimerizers and photoactivatable Cre recombinase. Nature chemical biology 198 27065233
2016 CRY2 and FBXL3 Cooperatively Degrade c-MYC. Molecular cell 168 27840026
2004 Functional analysis of each blue light receptor, cry1, cry2, phot1, and phot2, by using combinatorial multiple mutants in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America 164 14982991
2013 Multiple bHLH proteins form heterodimers to mediate CRY2-dependent regulation of flowering-time in Arabidopsis. PLoS genetics 162 24130508
2017 Optogenetic protein clustering through fluorescent protein tagging and extension of CRY2. Nature communications 130 28646204
1998 Chimeric proteins between cry1 and cry2 Arabidopsis blue light photoreceptors indicate overlapping functions and varying protein stability. The Plant cell 128 9490743
2010 CRY2 is associated with depression. PloS one 127 20195522
2009 Formation of nuclear bodies of Arabidopsis CRY2 in response to blue light is associated with its blue light-dependent degradation. The Plant cell 122 19141709
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 110 20123978
2021 The CRY2-COP1-HY5-BBX7/8 module regulates blue light-dependent cold acclimation in Arabidopsis. The Plant cell 106 34427646
2017 Understanding CRY2 interactions for optical control of intracellular signaling. Nature communications 95 28916751
2007 Derepression of the NC80 motif is critical for the photoactivation of Arabidopsis CRY2. Proceedings of the National Academy of Sciences of the United States of America 91 17438275
2006 Cryptochrome photoreceptors cry1 and cry2 antagonistically regulate primary root elongation in Arabidopsis thaliana. Planta 82 16703358
2015 Regulation of endogenous transmembrane receptors through optogenetic Cry2 clustering. Nature communications 81 25902152
2009 Circadian expression of clock genes in two mosquito disease vectors: cry2 is different. Journal of biological rhythms 81 19926804
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 80 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
2004 Linkage disequilibrium mapping of Arabidopsis CRY2 flowering time alleles. Genetics 73 15280248
2013 Arabidopsis CRY2 and ZTL mediate blue-light regulation of the transcription factor CIB1 by distinct mechanisms. Proceedings of the National Academy of Sciences of the United States of America 72 24101505
2015 Circadian Clock Gene CRY2 Degradation Is Involved in Chemoresistance of Colorectal Cancer. Molecular cancer therapeutics 71 25855785
2017 miR-181d and c-myc-mediated inhibition of CRY2 and FBXL3 reprograms metabolism in colorectal cancer. Cell death & disease 63 28749470
2010 CRY2 is associated with rapid cycling in bipolar disorder patients. PloS one 63 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 55 30126927
2018 Cry2 Is Critical for Circadian Regulation of Myogenic Differentiation by Bclaf1-Mediated mRNA Stabilization of Cyclin D1 and Tmem176b. Cell reports 53 29466738
2011 Variants in GLIS3 and CRY2 are associated with type 2 diabetes and impaired fasting glucose in Chinese Hans. PloS one 52 21747906
2020 Structural insights into the photoactivation of Arabidopsis CRY2. Nature plants 51 33199893
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
2023 Light-induced LLPS of the CRY2/SPA1/FIO1 complex regulating mRNA methylation and chlorophyll homeostasis in Arabidopsis. Nature plants 48 38066290
2012 A study of the blue-light-dependent phosphorylation, degradation, and photobody formation of Arabidopsis CRY2. Molecular plant 48 22311776
2012 Degradation of Arabidopsis CRY2 is regulated by SPA proteins and phytochrome A. The Plant cell 47 22739826
2015 The blue light-dependent phosphorylation of the CCE domain determines the photosensitivity of Arabidopsis CRY2. Molecular plant 44 25792146
2001 Effect of estrogen on the expression of Cry1 and Cry2 mRNAs in the suprachiasmatic nucleus of female rats. Neuroscience research 42 11672838
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
2021 CRY2 missense mutations suppress P53 and enhance cell growth. Proceedings of the National Academy of Sciences of the United States of America 38 34183418
2022 CRY2 interacts with CIS1 to regulate thermosensory flowering via FLM alternative splicing. Nature communications 37 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 36 36161947
2013 CRY2 genetic variants associate with dysthymia. PloS one 35 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
2018 Reconstituting Arabidopsis CRY2 Signaling Pathway in Mammalian Cells Reveals Regulation of Transcription by Direct Binding of CRY2 to DNA. Cell reports 30 30021157
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
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 28 36515105
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
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
2022 Aschoff's rule on circadian rhythms orchestrated by blue light sensor CRY2 and clock component PRR9. Nature communications 23 36198686
2019 Generation of Human CRY1 and CRY2 Knockout Cells Using Duplex CRISPR/Cas9 Technology. Frontiers in physiology 23 31143130
2024 The Arabidopsis blue-light photoreceptor CRY2 is active in darkness to inhibit root growth. Cell 21 39549699
2016 PRKCDBP (CAVIN3) and CRY2 associate with major depressive disorder. Journal of affective disorders 21 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
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
2022 UBP12 and UBP13 deubiquitinases destabilize the CRY2 blue light receptor to regulate Arabidopsis growth. Current biology : CB 17 35700731
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 17 32776544
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
2011 Double loss-of-function mutation in EARLY FLOWERING 3 and CRYPTOCHROME 2 genes delays flowering under continuous light but accelerates it under long days and short days: an important role for Arabidopsis CRY2 to accelerate flowering time in continuous light. Journal of experimental botany 16 21296763
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
2018 Root-expressed phytochromes B1 and B2, but not PhyA and Cry2, regulate shoot growth in nature. Plant, cell & environment 14 29766532
2017 CRY2 is suppressed by FOXM1 mediated promoter hypermethylation in breast cancer. Biochemical and biophysical research communications 14 28579430
2020 Activation of Cdc42 GTPase upon CRY2-Induced Cortical Recruitment Is Antagonized by GAPs in Fission Yeast. Cells 13 32932721
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
2025 Advancing clinical response against glioblastoma: Evaluating SHP1705 CRY2 activator efficacy in preclinical models and safety in phase I trials. Neuro-oncology 12 40168112
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
2018 The expression of clock genes cry1 and cry2 in human colorectal cancer and tumor adjacent tissues correlates differently dependent on tumor location. Neoplasma 12 29940771
2023 Loss of CRY2 promotes regenerative myogenesis by enhancing PAX7 expression and satellite cell proliferation. MedComm 11 36636367
2024 Bao Yuan decoction alleviates fatigue by restraining inflammation and oxidative stress via the AMPK/CRY2/PER1 signaling pathway. Journal of ethnopharmacology 10 38513778
2023 CircZNF367 promotes osteoclast differentiation and osteoporosis by interacting with FUS to maintain CRY2 mRNA stability. Journal of orthopaedic surgery and research 10 37434265
2022 CRY2 gene of rice (Oryza sativa subsp. indica) encodes a blue light sensory receptor involved in regulating flowering, plant height and partial photomorphogenesis in dark. Plant cell reports 10 36251035
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 10 34584158
2023 Copper-induced diurnal hepatic toxicity is associated with Cry2 and Per1 in mice. Environmental health and preventive medicine 9 38092388
2014 Quantitative real-time kinetics of optogenetic proteins CRY2 and CIB1/N using single-molecule tools. Analytical biochemistry 9 24780222
2023 Establishment of novel receptor-antibody sandwich assays to broadly detect Bacillus thuringiensis Cry1 and Cry2 toxins. International journal of biological macromolecules 8 37972832
2022 Knockdown of UCHL3 inhibits esophageal squamous cell carcinoma progression by reducing CRY2 methylation. Human cell 8 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 8 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 The expression, localisation and interactome of pigeon CRY2. Scientific reports 7 34645873
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
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 Transcription Repression of CRY2 via PER2 Interaction Promotes Adipogenesis. Molecular and cellular biology 4 37724597