CRY2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0016301 kinase activity	IDA NOT PMID:17073458 Analysis of autophosphorylating kinase activities of Arabido...	ACCEPT	Summary: Correct negated annotation: Arabidopsis CRY2 is not an autokinase. Reason: PMID:17073458 directly tested AtCry2 and found that it lacked kinase activity despite FAD binding; retaining the NOT kinase annotation prevents propagation of the older cryptochrome autokinase model to CRY2. Supporting Evidence: PMID:17073458 AtCry2 which is known to be phosphorylated upon light exposure in vivo ( 16 ) lacked kinase activity.
GO:0046777 protein autophosphorylation	IDA NOT PMID:17073458 Analysis of autophosphorylating kinase activities of Arabido...	ACCEPT	Summary: Correct negated annotation: AtCRY2 does not carry out protein autophosphorylation. Reason: The same biochemical study found AtCry2 lacks autokinase/autophosphorylating activity, so the NOT annotation is appropriate. Supporting Evidence: PMID:17073458 AtCry2, which also contains stoichiometric amounts of FAD does not.
GO:0006325 chromatin organization	IMP PMID:20935177 Photoreceptors CRYTOCHROME2 and phytochrome B control chroma...	KEEP AS NON CORE	Summary: Supported downstream chromatin phenotype, not the core molecular role of CRY2. Reason: CRY2 contributes to light-dependent chromatin compaction/decompaction, but as a photoreceptor signaling input rather than a chromatin-organizing factor. Supporting Evidence: PMID:20935177 Photoreceptors CRYTOCHROME2 and phytochrome B control chromatin compaction in Arabidopsis. file:ARATH/CRY2/CRY2-uniprot.txt Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation and photoperiodic control of floral initiation
GO:0006338 chromatin remodeling	IMP PMID:17470059 Light-regulated large-scale reorganization of chromatin duri...	KEEP AS NON CORE	Summary: Supported as a downstream flowering-transition chromatin phenotype. Reason: The annotation uses acts_upstream_of_or_within and is best treated as a non-core consequence of CRY2 signaling during floral transition, not as chromatin-remodeling activity by CRY2 itself. Supporting Evidence: PMID:17470059 Light-regulated large-scale reorganization of chromatin during the floral transition in Arabidopsis. file:ARATH/CRY2/CRY2-uniprot.txt Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation and photoperiodic control of floral initiation
GO:0009414 response to water deprivation	IGI PMID:16093319 From The Cover: A role for Arabidopsis cryptochromes and COP...	KEEP AS NON CORE	Summary: Water-deprivation phenotypes arise through CRY-dependent stomatal regulation. Reason: CRY2 contributes to water-loss and drought-related phenotypes through stomatal opening, but this is a physiological output of blue-light signaling and not the core function of the photoreceptor. Supporting Evidence: PMID:16093319 CRY functions additively with PHOT in mediating blue light-induced stomatal opening
GO:0009416 response to light stimulus	IEP PMID:20935177 Photoreceptors CRYTOCHROME2 and phytochrome B control chroma...	MODIFY	Summary: The evidence supports a blue-light photoreceptor/signaling role; this term is too broad. Reason: CRY2 senses blue light and signals through CIB, SPA/COP1, PIF, and related partners. The generic response to light stimulus term should be replaced by blue-light-specific terms. Proposed replacements: response to blue light blue light signaling pathway Supporting Evidence: PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:26724867 CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5. PMID:36508461 A role for brassinosteroid signalling in decision-making processes in the Arabidopsis seedling.
GO:0009416 response to light stimulus	IMP PMID:36508461 A role for brassinosteroid signalling in decision-making pro...	MODIFY	Summary: The evidence supports a blue-light photoreceptor/signaling role; this term is too broad. Reason: CRY2 senses blue light and signals through CIB, SPA/COP1, PIF, and related partners. The generic response to light stimulus term should be replaced by blue-light-specific terms. Proposed replacements: response to blue light blue light signaling pathway Supporting Evidence: PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:26724867 CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5. PMID:36508461 A role for brassinosteroid signalling in decision-making processes in the Arabidopsis seedling.
GO:0009637 response to blue light	IMP PMID:9565033 Cryptochrome blue-light photoreceptors of Arabidopsis implic...	ACCEPT	Summary: Core biological process: CRY2 mediates blue-light responses. Reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor controlling phototropism, flowering, clock, and growth outputs. Supporting Evidence: PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT PMID:24780222 Upon illumination, CRY2 is photoactivated to contact and associate with CIB1. PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0009785 blue light signaling pathway	IGI PMID:27846570 Photoactivation and inactivation of Arabidopsis cryptochrome...	ACCEPT	Summary: Core pathway annotation: CRY2 is a blue-light signaling photoreceptor. Reason: CRY2 photoactivation, homodimerization, photobody formation, and interaction with signaling partners such as BIC1, SPA1, and CIBs are central to blue-light signaling. Supporting Evidence: PMID:27846570 Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active. PMID:27846570 BICs also inhibit the blue light-induced formation of CRY2 photobodies PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1.
GO:0009909 regulation of flower development	IDA PMID:17259260 CRYPTOCHROME2 in vascular bundles regulates flowering in Ara...	ACCEPT	Summary: CRY2 regulates flowering through vascular-bundle FT expression. Reason: CRY2 in vascular bundles promotes FT expression and flowering, making regulation of flower development a major supported developmental output. Supporting Evidence: PMID:17259260 cry2-GFP expressed in vascular bundles increased FT expression only in vascular bundles.
GO:0009911 positive regulation of flower development	IMP PMID:17259260 CRYPTOCHROME2 in vascular bundles regulates flowering in Ara...	ACCEPT	Summary: CRY2 positively regulates flowering in appropriate light/photoperiod contexts. Reason: CRY2-GFP expression in vascular bundles rescues late flowering and increases FT expression; this supports a positive flowering role. Supporting Evidence: PMID:17259260 cry2-GFP expressed in vascular bundles increased FT expression only in vascular bundles.
GO:0010075 regulation of meristem growth	IGI PMID:18424613 Distinct light-initiated gene expression and cell cycle prog...	KEEP AS NON CORE	Summary: Supported light-dependent shoot apex/meristem phenotype, not core photoreceptor function. Reason: CRY2 affects meristem/cell-cycle programs downstream of light perception, but its core role remains blue-light photoreceptor signaling. Supporting Evidence: file:ARATH/CRY2/CRY2-uniprot.txt Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation and photoperiodic control of floral initiation
GO:0010118 stomatal movement	IGI PMID:16093319 From The Cover: A role for Arabidopsis cryptochromes and COP...	KEEP AS NON CORE	Summary: Supported stomatal output of CRY signaling. Reason: CRY2 participates with CRY1/PHOT/COP1 pathways in blue-light-induced stomatal opening, but stomatal movement is a downstream physiological response. Supporting Evidence: PMID:16093319 CRY functions additively with PHOT in mediating blue light-induced stomatal opening
GO:0010617 circadian regulation of calcium ion oscillation	IMP PMID:17982000 Distinct light and clock modulation of cytosolic free Ca2+ o...	KEEP AS NON CORE	Summary: Circadian calcium oscillation is a downstream clock/light-signaling phenotype. Reason: The evidence links cryptochrome light input to clock-regulated calcium rhythms; this is not the primary molecular function of CRY2. Supporting Evidence: PMID:11743105 Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator.
GO:0003904 deoxyribodipyrimidine photo-lyase activity	IBA GO_REF:0000033	REMOVE	Summary: Over-propagated photolyase-family annotation; CRY2 is a signaling cryptochrome, not a DNA photolyase. Reason: PANTHER PTHR11455 mixes cryptochromes and DNA photolyases, and UniProt explicitly cautions that CRY2 was originally thought to be a DNA photolyase. The Arabidopsis CRY2 literature supports FAD-dependent blue-light signaling rather than deoxyribodipyrimidine repair activity. Supporting Evidence: file:interpro/panther/PTHR11455/PTHR11455-notes.md The family contains both cryptochromes and photolyases; subfamilies separate circadian cryptochromes from repair enzymes. file:ARATH/CRY2/CRY2-uniprot.txt Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation and photoperiodic control of floral initiation
GO:0005515 protein binding	IPI PMID:11089975 Functional interaction of phytochrome B and cryptochrome 2.	REMOVE	Summary: PHYB interaction supports photoreceptor crosstalk, but GO:0005515 is too generic for CRY2. Reason: The evidence supports light-dependent CRY2-PHYB crosstalk in flowering, hypocotyl, and clock outputs. It does not define a distinct CRY2 molecular function beyond blue-light photoreceptor signaling, so generic protein binding should not be retained. Supporting Evidence: PMID:11089975 PhyB interacts directly with cry2 as observed in co-immunoprecipitation experiments with transgenic Arabidopsis plants overexpressing cry2.
GO:0005515 protein binding	IPI PMID:11509693 Direct interaction of Arabidopsis cryptochromes with COP1 in...	MODIFY	Summary: COP1 binding is real and mechanistically important, but generic protein binding should be replaced. Reason: COP1 is the E3 ubiquitin ligase repressed by photoactivated cryptochromes. Ubiquitin protein ligase binding captures the relevant molecular interaction better than GO:0005515. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:11509693 Photoactivated cryptochromes repress COP1 activity through a direct protein-protein contact.
GO:0005515 protein binding	IPI PMID:18988809 Photoexcited CRY2 interacts with CIB1 to regulate transcript...	MODIFY	Summary: CIB1 interaction should be captured as bHLH transcription factor binding, not generic protein binding. Reason: CIB1 is a CRY2-interacting basic helix-loop-helix transcription factor that promotes FT expression and floral initiation. The more specific bHLH transcription factor binding term captures this interaction. Proposed replacements: bHLH transcription factor binding Supporting Evidence: PMID:18988809 CIB1 interacts with CRY2 (cryptochrome 2) in a blue light-specific manner in yeast and Arabidopsis cells PMID:18988809 CIB1 binds to G box (CACGTG) in vitro with a higher affinity than its interaction with other E-box elements (CANNTG).
GO:0005515 protein binding	IPI PMID:20624951 Cryptochrome 2 and phototropin 2 regulate resistance protein...	MODIFY	Summary: The defense-context interaction is mediated through COP1, so generic protein binding should be replaced. Reason: The paper links CRY2/PHOT2 control of resistance protein stability to COP1, an E3 ubiquitin ligase. Ubiquitin protein ligase binding is more informative than retaining GO:0005515. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20624951 HRT does not directly associate with either CRY2 or PHOT2 but does bind the CRY2-/PHOT2-interacting E3 ubiquitin ligase, COP1.
GO:0005515 protein binding	IPI PMID:21511872 Blue-light-dependent interaction of cryptochrome 1 with SPA1...	REMOVE	Summary: This SPA1 paper is CRY1-focused and does not justify retaining generic CRY2 protein binding. Reason: The source title and evidence concern cryptochrome 1-SPA1 signaling. Even if related to the broader cryptochrome mechanism, GO:0005515 is not an informative CRY2 molecular function and should not remain as a non-core annotation. Supporting Evidence: PMID:21511872 Blue-light-dependent interaction of cryptochrome 1 with SPA1 defines a dynamic signaling mechanism.
GO:0005515 protein binding	IPI PMID:21514160 Blue light-dependent interaction of CRY2 with SPA1 regulates...	MODIFY	Summary: CRY2-SPA1/COP1 complex formation should be captured with a COP1 ligase-binding term. Reason: SPA1 acts through the COP1 E3 ubiquitin ligase, and the study shows CRY2-SPA1 interaction enhances CRY2-COP1 interaction and suppresses COP1-dependent CO degradation. Ubiquitin protein ligase binding is more informative than GO:0005515. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:21514160 The blue light-dependent CRY2-SPA1 interaction enhances the CRY2-COP1 interaction to suppress the COP1 activity.
GO:0005515 protein binding	IPI PMID:22139370 Arabidopsis cryptochrome 2 (CRY2) functions by the photoacti...	REMOVE	Summary: Photoactivation mechanism evidence does not require retaining generic protein binding. Reason: The paper supports CRY2 photoactivation biology, which is already represented by blue-light photoreceptor activity and blue-light signaling annotations. GO:0005515 is too broad to retain. Supporting Evidence: PMID:22139370 Arabidopsis cryptochrome 2 (CRY2) functions by the photoactivation mechanism distinct from the tryptophan (trp) triad-dependent photoreduction.
GO:0005515 protein binding	IPI PMID:22739826 Degradation of Arabidopsis CRY2 is regulated by SPA proteins...	REMOVE	Summary: SPA-dependent CRY2 degradation is pathway regulation, not a useful generic binding annotation. Reason: The evidence supports control of CRY2 abundance by SPA proteins and phyA. This is already captured in CRY2 signaling/degradation context, while GO:0005515 adds no informative molecular function. Supporting Evidence: PMID:22739826 Studies showed a robust physical interaction of cry2 with SPA1 in nuclei of living cells.
GO:0005515 protein binding	IPI PMID:24130508 Multiple bHLH proteins form heterodimers to mediate CRY2-dep...	MODIFY	Summary: CIB-family interactions should be represented as bHLH transcription factor binding. Reason: CIB proteins are bHLH transcription factors that act redundantly downstream of CRY2 in flowering. The specific bHLH transcription factor binding term is more informative than GO:0005515. Proposed replacements: bHLH transcription factor binding Supporting Evidence: PMID:24130508 Our study demonstrates that CIBs function redundantly in regulating CRY2-dependent flowering.
GO:0005515 protein binding	IPI PMID:24780222 Quantitative real-time kinetics of optogenetic proteins CRY2...	MODIFY	Summary: CRY2-CIB1 kinetic interaction should be replaced by bHLH transcription factor binding. Reason: CIB1 is a bHLH transcription factor and the evidence measures blue-light-driven CRY2 association with CIB1. GO:0043425 is more specific than generic protein binding. Proposed replacements: bHLH transcription factor binding Supporting Evidence: PMID:24780222 Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
GO:0005515 protein binding	IPI PMID:26724867 Cryptochromes Interact Directly with PIFs to Control Plant G...	MODIFY	Summary: PIF4/PIF5 contacts should be represented as bHLH transcription factor binding. Reason: PIF4 and PIF5 are bHLH transcription factors contacted by CRY2 during low-blue-light growth regulation. GO:0043425 is the informative replacement for generic protein binding. Proposed replacements: bHLH transcription factor binding Supporting Evidence: PMID:26724867 CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5.
GO:0005515 protein binding	IPI PMID:27846570 Photoactivation and inactivation of Arabidopsis cryptochrome...	REMOVE	Summary: BIC1 interaction explains CRY2 inactivation but does not warrant retaining GO:0005515. Reason: BIC1 is an inhibitory regulator of CRY2 homodimerization and photobody formation. The biology belongs in the blue-light signaling description, while generic protein binding remains uninformative. Supporting Evidence: PMID:27846570 BICs also inhibit the blue light-induced formation of CRY2 photobodies.
GO:0005515 protein binding	IPI PMID:28492234 Molecular basis for blue light-dependent phosphorylation of ...	MODIFY	Summary: PPK interaction should be captured as protein kinase binding. Reason: The study identifies photoregulatory protein kinases that bind photoexcited CRY2 and catalyze blue-light-dependent CRY2 phosphorylation. Protein kinase binding is more informative than GO:0005515. Proposed replacements: protein kinase binding Supporting Evidence: PMID:28492234 Photoregulatory Protein Kinases (previously referred to as MUT9-like kinases) interact with and phosphorylate photoexcited CRY2.
GO:0005515 protein binding	IPI PMID:28633330 The asparagine-rich protein NRP interacts with the Verticill...	REMOVE	Summary: NRP-dependent localization effects are not an informative CRY2 protein binding annotation. Reason: The evidence links NRP/PevD1 context to CRY2 subcellular localization. No more specific CRY2 molecular function term is supported, and generic protein binding should not be retained. Supporting Evidence: PMID:28633330 The asparagine-rich protein NRP interacts with the Verticillium effector PevD1 and regulates the subcellular localization of cryptochrome 2.
GO:0005515 protein binding	IPI PMID:32661061 Photoexcited Cryptochrome2 Interacts Directly with TOE1 and ...	MODIFY	Summary: TOE1/TOE2 interactions should be represented as DNA-binding transcription factor binding. Reason: TOE1 and TOE2 are AP2-like DNA-binding transcription factors that interact with photoexcited CRY2 in flowering regulation. GO:0140297 is more informative than generic protein binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:32661061 Photoexcited Cryptochrome2 Interacts Directly with TOE1 and TOE2 in Flowering Regulation. PMID:32661061 The AP2-like transcriptional factor TOE1 negatively regulates FT expression and flowering by indirectly inhibiting CO transcriptional activation activity and directly binding to FT.
GO:0005515 protein binding	IPI PMID:36396657 CRY2 interacts with CIS1 to regulate thermosensory flowering...	REMOVE	Summary: CIS1 interaction supports thermosensory flowering signaling, but generic protein binding should not be retained. Reason: CIS1 is a splicing/RNA-binding factor whose activity is regulated in a CRY2-dependent pathway. The evidence is important for biological process interpretation, but GO:0005515 is not an informative CRY2 molecular function. Supporting Evidence: PMID:36396657 CRY2 interacts with CIS1 to regulate thermosensory flowering via FLM alternative splicing.
GO:0005524 ATP binding	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ATP binding is supported but is an accessory biochemical property of the photoreceptor. Reason: UniProt and biochemical literature support ATP binding as influencing CRY2 conformation/photochemistry, but ATP binding is not the central GO molecular function; blue-light photoreceptor activity is the core MF. Supporting Evidence: file:ARATH/CRY2/CRY2-uniprot.txt Binding to ATP mediates conformational changes which facilitate flavin binding file:ARATH/CRY2/CRY2-deep-research-falcon.md Arabidopsis thaliana CRY2 (UniProt: Q96524) is a plant blue-light photoreceptor
GO:0005524 ATP binding	IDA PMID:17073458 Analysis of autophosphorylating kinase activities of Arabido...	KEEP AS NON CORE	Summary: ATP binding is supported but is an accessory biochemical property of the photoreceptor. Reason: UniProt and biochemical literature support ATP binding as influencing CRY2 conformation/photochemistry, but ATP binding is not the central GO molecular function; blue-light photoreceptor activity is the core MF. Supporting Evidence: file:ARATH/CRY2/CRY2-uniprot.txt Binding to ATP mediates conformational changes which facilitate flavin binding file:ARATH/CRY2/CRY2-deep-research-falcon.md Arabidopsis thaliana CRY2 (UniProt: Q96524) is a plant blue-light photoreceptor
GO:0009882 blue light photoreceptor activity	IEA GO_REF:0000002	ACCEPT	Summary: Core molecular function: CRY2 is a blue-light photoreceptor. The crystal structure of the CRY2 PHR/photolyase-homology region (CRY2N) with bound FAD (PDB 6K8I) directly visualizes the FAD-bound photosensory module underlying this activity. Reason: CRY2 is a plant cryptochrome whose FAD-dependent blue-light photoactivation drives dimerization, photobody formation, and downstream signaling. Supporting Evidence: PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:27846570 Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active. PMID:32398826 Cryptochromes (CRYs) are blue-light receptors in plants that harbor FAD as a cofactor and regulate various physiological responses. file:ARATH/CRY2/CRY2-deep-research-falcon.md Arabidopsis thaliana CRY2 (UniProt: Q96524) is a plant blue-light photoreceptor
GO:0009882 blue light photoreceptor activity	ISS PMID:11493548 Hierarchical coupling of phytochromes and cryptochromes reco...	ACCEPT	Summary: Core molecular function: CRY2 is a blue-light photoreceptor. Reason: CRY2 is a plant cryptochrome whose FAD-dependent blue-light photoactivation drives dimerization, photobody formation, and downstream signaling. Supporting Evidence: PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:27846570 Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active. PMID:32398826 Cryptochromes (CRYs) are blue-light receptors in plants that harbor FAD as a cofactor and regulate various physiological responses. file:ARATH/CRY2/CRY2-deep-research-falcon.md Arabidopsis thaliana CRY2 (UniProt: Q96524) is a plant blue-light photoreceptor
GO:0042802 identical protein binding	IPI PMID:15805487 N-terminal domain-mediated homodimerization is required for ...	KEEP AS NON CORE	Summary: Self-association is an important activation mechanism but not the primary MF term. Reason: CRY2 homodimerization/oligomerization is physiologically important for photoactivation and photobody formation, but this term should support the photoreceptor mechanism rather than replace blue-light photoreceptor activity as the core MF. Supporting Evidence: PMID:27846570 Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active. PMID:22311776 photoexcited cryptochromes form oligomers, preceding other biochemical changes of CRY2
GO:0042802 identical protein binding	IPI PMID:17438275 Derepression of the NC80 motif is critical for the photoacti...	KEEP AS NON CORE	Summary: Self-association is an important activation mechanism but not the primary MF term. Reason: CRY2 homodimerization/oligomerization is physiologically important for photoactivation and photobody formation, but this term should support the photoreceptor mechanism rather than replace blue-light photoreceptor activity as the core MF. Supporting Evidence: PMID:27846570 Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active. PMID:22311776 photoexcited cryptochromes form oligomers, preceding other biochemical changes of CRY2
GO:0042803 protein homodimerization activity	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Homodimerization is supported mechanistically but is secondary to photoreceptor activity. Reason: CRY2 becomes physiologically active through blue-light-dependent homodimerization, but the core molecular function is blue-light photoreceptor activity. Supporting Evidence: PMID:27846570 Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active.
GO:0042803 protein homodimerization activity	IPI PMID:15805487 N-terminal domain-mediated homodimerization is required for ...	KEEP AS NON CORE	Summary: Homodimerization is supported mechanistically but is secondary to photoreceptor activity. Reason: CRY2 becomes physiologically active through blue-light-dependent homodimerization, but the core molecular function is blue-light photoreceptor activity. Supporting Evidence: PMID:27846570 Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active.
GO:0071949 FAD binding	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: FAD binding is an essential chromophore-binding property of CRY2. The crystal structures of CRY2N (PDB 6K8I; and 6K8K with FAD plus Mg/AMP) resolve the bound FAD cofactor in the photolyase-homology region. Reason: CRY2 is an FAD-containing photoreceptor; FAD binding supports photochemistry but is best treated as a non-core cofactor-binding annotation relative to blue-light photoreceptor activity. Supporting Evidence: PMID:17073458 Cryptochromes are FAD-based blue-light photoreceptors that regulate growth and development in plants and the circadian clock in animals. PMID:32398826 Cryptochromes (CRYs) are blue-light receptors in plants that harbor FAD as a cofactor and regulate various physiological responses. file:ARATH/CRY2/CRY2-uniprot.txt Binds 1 FAD per subunit.
GO:0071949 FAD binding	IDA PMID:17073458 Analysis of autophosphorylating kinase activities of Arabido...	KEEP AS NON CORE	Summary: FAD binding is an essential chromophore-binding property of CRY2. The crystal structures of CRY2N (PDB 6K8I; and 6K8K with FAD plus Mg/AMP) resolve the bound FAD cofactor in the photolyase-homology region. Reason: CRY2 is an FAD-containing photoreceptor; FAD binding supports photochemistry but is best treated as a non-core cofactor-binding annotation relative to blue-light photoreceptor activity. Supporting Evidence: PMID:17073458 Cryptochromes are FAD-based blue-light photoreceptors that regulate growth and development in plants and the circadian clock in animals. PMID:32398826 Cryptochromes (CRYs) are blue-light receptors in plants that harbor FAD as a cofactor and regulate various physiological responses. file:ARATH/CRY2/CRY2-uniprot.txt Binds 1 FAD per subunit.
GO:0007623 circadian rhythm	IEP PMID:11743105 Circadian clock-regulated expression of phytochrome and cryp...	KEEP AS NON CORE	Summary: CRY2 expression and signaling are connected to the circadian system, but this is not the core CRY2 role. Reason: Cryptochromes provide light input to circadian regulation, while CRY2 core function is blue-light photoreceptor signaling. Supporting Evidence: PMID:11743105 Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator.
GO:0009414 response to water deprivation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Water-deprivation phenotypes arise through CRY-dependent stomatal regulation. Reason: CRY2 contributes to water-loss and drought-related phenotypes through stomatal opening, but this is a physiological output of blue-light signaling and not the core function of the photoreceptor. Supporting Evidence: PMID:16093319 CRY functions additively with PHOT in mediating blue light-induced stomatal opening
GO:0009416 response to light stimulus	IMP PMID:21296763 Double loss-of-function mutation in EARLY FLOWERING 3 and CR...	MODIFY	Summary: The evidence supports a blue-light photoreceptor/signaling role; this term is too broad. Reason: CRY2 senses blue light and signals through CIB, SPA/COP1, PIF, and related partners. The generic response to light stimulus term should be replaced by blue-light-specific terms. Proposed replacements: response to blue light blue light signaling pathway Supporting Evidence: PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:26724867 CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5. PMID:36508461 A role for brassinosteroid signalling in decision-making processes in the Arabidopsis seedling.
GO:0009637 response to blue light	IMP PMID:12857830 Second positive phototropism results from coordinated co-act...	ACCEPT	Summary: Core biological process: CRY2 mediates blue-light responses. Reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor controlling phototropism, flowering, clock, and growth outputs. Supporting Evidence: PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT PMID:24780222 Upon illumination, CRY2 is photoactivated to contact and associate with CIB1. PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0009637 response to blue light	IEP PMID:20624951 Cryptochrome 2 and phototropin 2 regulate resistance protein...	ACCEPT	Summary: Core biological process: CRY2 mediates blue-light responses. Reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor controlling phototropism, flowering, clock, and growth outputs. Supporting Evidence: PMID:20624951 The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are required for the stability of the R protein HRT PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT PMID:24780222 Upon illumination, CRY2 is photoactivated to contact and associate with CIB1. PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0009637 response to blue light	IDA PMID:21511872 Blue-light-dependent interaction of cryptochrome 1 with SPA1...	ACCEPT	Summary: Core biological process: CRY2 mediates blue-light responses. Reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor controlling phototropism, flowering, clock, and growth outputs. Supporting Evidence: PMID:21514160 blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear bodies PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT PMID:24780222 Upon illumination, CRY2 is photoactivated to contact and associate with CIB1. PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0009637 response to blue light	IDA PMID:21514160 Blue light-dependent interaction of CRY2 with SPA1 regulates...	ACCEPT	Summary: Core biological process: CRY2 mediates blue-light responses. Reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor controlling phototropism, flowering, clock, and growth outputs. Supporting Evidence: PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT PMID:24780222 Upon illumination, CRY2 is photoactivated to contact and associate with CIB1. PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0009637 response to blue light	IDA PMID:22739826 Degradation of Arabidopsis CRY2 is regulated by SPA proteins...	ACCEPT	Summary: Core biological process: CRY2 mediates blue-light responses. Reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor controlling phototropism, flowering, clock, and growth outputs. Supporting Evidence: PMID:22739826 Degradation of Arabidopsis CRY2 is regulated by SPA proteins and phytochrome A. PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT PMID:24780222 Upon illumination, CRY2 is photoactivated to contact and associate with CIB1. PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0009637 response to blue light	IMP PMID:23511208 Network balance via CRY signalling controls the Arabidopsis ...	ACCEPT	Summary: Core biological process: CRY2 mediates blue-light responses. Reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor controlling phototropism, flowering, clock, and growth outputs. Supporting Evidence: PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT PMID:24780222 Upon illumination, CRY2 is photoactivated to contact and associate with CIB1. PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0009637 response to blue light	IDA PMID:24130508 Multiple bHLH proteins form heterodimers to mediate CRY2-dep...	ACCEPT	Summary: Core biological process: CRY2 mediates blue-light responses. Reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor controlling phototropism, flowering, clock, and growth outputs. Supporting Evidence: PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT PMID:24780222 Upon illumination, CRY2 is photoactivated to contact and associate with CIB1. PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0009637 response to blue light	IDA PMID:24780222 Quantitative real-time kinetics of optogenetic proteins CRY2...	ACCEPT	Summary: Core biological process: CRY2 mediates blue-light responses. Reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor controlling phototropism, flowering, clock, and growth outputs. Supporting Evidence: PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT PMID:24780222 Upon illumination, CRY2 is photoactivated to contact and associate with CIB1. PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0009638 phototropism	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: CRY2 contributes to phototropism with phototropins, but this is a downstream response. Reason: Cryptochromes modulate phototropism depending on blue-light fluence; the core CRY2 role is light perception/signaling rather than tropic growth execution. Supporting Evidence: PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates
GO:0009638 phototropism	IMP PMID:12857830 Second positive phototropism results from coordinated co-act...	KEEP AS NON CORE	Summary: CRY2 contributes to phototropism with phototropins, but this is a downstream response. Reason: Cryptochromes modulate phototropism depending on blue-light fluence; the core CRY2 role is light perception/signaling rather than tropic growth execution. Supporting Evidence: PMID:9565033 cryptochrome is one of the photoreceptors mediating phototropism in plants. PMID:12857830 phototropins and cryptochromes function together to enhance phototropism under low fluence rates
GO:0009646 response to absence of light	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Darkness affects CRY2 abundance and signaling state, but this is not a core process annotation. Reason: CRY2 expression/protein stability changes in darkness and light; the underlying core function is blue-light photoreception and light-regulated signaling. Supporting Evidence: PMID:11743105 Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator. PMID:20624951 The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are required for the stability of the R protein HRT
GO:0009646 response to absence of light	IEP PMID:11743105 Circadian clock-regulated expression of phytochrome and cryp...	KEEP AS NON CORE	Summary: Darkness affects CRY2 abundance and signaling state, but this is not a core process annotation. Reason: CRY2 expression/protein stability changes in darkness and light; the underlying core function is blue-light photoreception and light-regulated signaling. Supporting Evidence: PMID:11743105 Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator. PMID:20624951 The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are required for the stability of the R protein HRT
GO:0009646 response to absence of light	IEP PMID:20624951 Cryptochrome 2 and phototropin 2 regulate resistance protein...	KEEP AS NON CORE	Summary: Darkness affects CRY2 abundance and signaling state, but this is not a core process annotation. Reason: CRY2 expression/protein stability changes in darkness and light; the underlying core function is blue-light photoreception and light-regulated signaling. Supporting Evidence: PMID:11743105 Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator. PMID:20624951 The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are required for the stability of the R protein HRT
GO:0009785 blue light signaling pathway	IEA GO_REF:0000002	ACCEPT	Summary: Core pathway annotation: CRY2 is a blue-light signaling photoreceptor. Reason: CRY2 photoactivation, homodimerization, photobody formation, and interaction with signaling partners such as BIC1, SPA1, and CIBs are central to blue-light signaling. Supporting Evidence: PMID:27846570 Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active. PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT
GO:0009785 blue light signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: Core pathway annotation: CRY2 is a blue-light signaling photoreceptor. Reason: CRY2 photoactivation, homodimerization, photobody formation, and interaction with signaling partners such as BIC1, SPA1, and CIBs are central to blue-light signaling. Supporting Evidence: PMID:27846570 Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active. PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1. PMID:24130508 CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to blue light to activate the transcription of FT
GO:0009791 post-embryonic development	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Too broad; CRY2 affects several post-embryonic traits through light signaling. Reason: Post-embryonic development is a broad phenotypic umbrella. More specific CRY2 annotations to blue-light signaling, flowering, phototropism, and low-blue-light growth are preferable. Supporting Evidence: file:ARATH/CRY2/CRY2-uniprot.txt Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation and photoperiodic control of floral initiation
GO:0010075 regulation of meristem growth	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Supported light-dependent shoot apex/meristem phenotype, not core photoreceptor function. Reason: CRY2 affects meristem/cell-cycle programs downstream of light perception, but its core role remains blue-light photoreceptor signaling. Supporting Evidence: file:ARATH/CRY2/CRY2-uniprot.txt Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation and photoperiodic control of floral initiation
GO:0010118 stomatal movement	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Supported stomatal output of CRY signaling. Reason: CRY2 participates with CRY1/PHOT/COP1 pathways in blue-light-induced stomatal opening, but stomatal movement is a downstream physiological response. Supporting Evidence: PMID:16093319 CRY functions additively with PHOT in mediating blue light-induced stomatal opening
GO:0010244 response to low fluence blue light stimulus by blue low-fluence system	IEA GO_REF:0000117	ACCEPT	Summary: CRY2 is important for limiting/low-blue-light growth responses. Reason: CRY1/CRY2 perceive reduced blue light and directly contact PIF4/PIF5 to control growth under limiting blue light. Supporting Evidence: PMID:26724867 CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5. PMID:19558423 Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal regulation.
GO:0010244 response to low fluence blue light stimulus by blue low-fluence system	IMP PMID:19558423 Differential petiole growth in Arabidopsis thaliana: photoco...	ACCEPT	Summary: CRY2 is important for limiting/low-blue-light growth responses. Reason: CRY1/CRY2 perceive reduced blue light and directly contact PIF4/PIF5 to control growth under limiting blue light. Supporting Evidence: PMID:26724867 CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5. PMID:19558423 Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal regulation.
GO:0010244 response to low fluence blue light stimulus by blue low-fluence system	IEP PMID:26724867 Cryptochromes Interact Directly with PIFs to Control Plant G...	ACCEPT	Summary: CRY2 is important for limiting/low-blue-light growth responses. Reason: CRY1/CRY2 perceive reduced blue light and directly contact PIF4/PIF5 to control growth under limiting blue light. Supporting Evidence: PMID:26724867 CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5.
GO:0010617 circadian regulation of calcium ion oscillation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Circadian calcium oscillation is a downstream clock/light-signaling phenotype. Reason: The evidence links cryptochrome light input to clock-regulated calcium rhythms; this is not the primary molecular function of CRY2. Supporting Evidence: PMID:11743105 Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator.
GO:0032922 circadian regulation of gene expression	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic circadian gene-expression annotation is plausible but not the main plant CRY2 function. Reason: Cryptochromes are light inputs to clock gene expression, but Arabidopsis CRY2 is primarily a blue-light signaling photoreceptor for flowering and growth responses. Supporting Evidence: PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0042752 regulation of circadian rhythm	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Supported CRY contribution to clock period/rhythmicity, not core CRY2 function. Reason: CRY signaling affects circadian period and temperature/light input balance, but this is a downstream regulatory output of photoreceptor signaling. Supporting Evidence: PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0042752 regulation of circadian rhythm	IMP PMID:23511208 Network balance via CRY signalling controls the Arabidopsis ...	KEEP AS NON CORE	Summary: Supported CRY contribution to clock period/rhythmicity, not core CRY2 function. Reason: CRY signaling affects circadian period and temperature/light input balance, but this is a downstream regulatory output of photoreceptor signaling. Supporting Evidence: PMID:23511208 reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period
GO:0043153 entrainment of circadian clock by photoperiod	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Photoperiodic clock entrainment is a plausible cryptochrome output, not core molecular activity. Reason: Cryptochromes are light inputs to clock entrainment, but the annotation is phylogenetically inferred and broader than the experimentally established CRY2 photoreceptor mechanism. Supporting Evidence: PMID:11743105 Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator.
GO:0048574 long-day photoperiodism, flowering	IMP PMID:21296763 Double loss-of-function mutation in EARLY FLOWERING 3 and CR...	ACCEPT	Summary: CRY2 promotes flowering under photoperiodic/continuous-light contexts. Reason: Loss and rescue experiments support CRY2 promotion of flowering through FT and photoperiodic signaling pathways. Supporting Evidence: PMID:21296763 an important role for Arabidopsis CRY2 to accelerate flowering time in continuous light. PMID:17259260 cry2-GFP expressed in vascular bundles increased FT expression only in vascular bundles.
GO:0048580 regulation of post-embryonic development	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Overly broad developmental-process annotation. Reason: CRY2 regulates specific light-responsive developmental outputs; broad regulation of post-embryonic development is less informative than blue-light signaling and flowering terms. Supporting Evidence: file:ARATH/CRY2/CRY2-uniprot.txt Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation and photoperiodic control of floral initiation
GO:0048731 system development	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Overly broad system-development annotation. Reason: System development does not capture the CRY2 mechanism and should not be used when specific light signaling and flowering annotations are available. Supporting Evidence: file:ARATH/CRY2/CRY2-uniprot.txt Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation and photoperiodic control of floral initiation
GO:0051607 defense response to virus	IMP PMID:20624951 Cryptochrome 2 and phototropin 2 regulate resistance protein...	KEEP AS NON CORE	Summary: Supported antiviral-defense output of CRY2/PHOT2 regulation of HRT stability. Reason: CRY2 contributes to R-protein-mediated viral defense via COP1/HRT stability, but this is a specialized downstream output rather than the conserved core photoreceptor function. Supporting Evidence: PMID:20624951 The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are required for the stability of the R protein HRT
GO:0072387 flavin adenine dinucleotide metabolic process	IEA GO_REF:0000117	MODIFY	Summary: FAD is the CRY2 chromophore, but CRY2 is not an FAD metabolic enzyme. Reason: The evidence concerns FAD redox photochemistry and light sensitivity, not FAD biosynthesis, catabolism, or metabolism. Replace with FAD binding and blue-light photoreceptor activity. Proposed replacements: FAD binding blue light photoreceptor activity Supporting Evidence: PMID:25428980 Cellular metabolites enhance the light sensitivity of Arabidopsis cryptochrome through alternate electron transfer pathways. file:ARATH/CRY2/CRY2-uniprot.txt Binds 1 FAD per subunit.
GO:0072387 flavin adenine dinucleotide metabolic process	IMP PMID:25428980 Cellular metabolites enhance the light sensitivity of Arabid...	MODIFY	Summary: FAD is the CRY2 chromophore, but CRY2 is not an FAD metabolic enzyme. Reason: The evidence concerns FAD redox photochemistry and light sensitivity, not FAD biosynthesis, catabolism, or metabolism. Replace with FAD binding and blue-light photoreceptor activity. Proposed replacements: FAD binding blue light photoreceptor activity Supporting Evidence: PMID:25428980 Cellular metabolites enhance the light sensitivity of Arabidopsis cryptochrome through alternate electron transfer pathways. file:ARATH/CRY2/CRY2-uniprot.txt Binds 1 FAD per subunit.
GO:1901371 regulation of leaf morphogenesis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Leaf/petiole morphogenesis is a low-blue-light growth output. Reason: CRY2 affects petiole/leaf morphogenesis through light and hormone-regulated growth responses, but this is downstream of photoreceptor signaling. Supporting Evidence: PMID:19558423 Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal regulation.
GO:1901371 regulation of leaf morphogenesis	IMP PMID:19558423 Differential petiole growth in Arabidopsis thaliana: photoco...	KEEP AS NON CORE	Summary: Leaf/petiole morphogenesis is a low-blue-light growth output. Reason: CRY2 affects petiole/leaf morphogenesis through light and hormone-regulated growth responses, but this is downstream of photoreceptor signaling. Supporting Evidence: PMID:19558423 Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal regulation.
GO:1902347 response to strigolactone	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Strigolactone response is a hormone/light crosstalk phenotype. Reason: The strigolactone annotation reflects hypocotyl-growth crosstalk with photoreceptor pathways; it is not a core CRY2 molecular function. Supporting Evidence: PMID:24126495 Strigolactone-regulated hypocotyl elongation is dependent on cryptochrome and phytochrome signaling pathways in Arabidopsis.
GO:1902347 response to strigolactone	IMP PMID:24126495 Strigolactone-regulated hypocotyl elongation is dependent on...	KEEP AS NON CORE	Summary: Strigolactone response is a hormone/light crosstalk phenotype. Reason: The strigolactone annotation reflects hypocotyl-growth crosstalk with photoreceptor pathways; it is not a core CRY2 molecular function. Supporting Evidence: PMID:24126495 Strigolactone-regulated hypocotyl elongation is dependent on cryptochrome and phytochrome signaling pathways in Arabidopsis.
GO:2000028 regulation of photoperiodism, flowering	IDA PMID:21514160 Blue light-dependent interaction of CRY2 with SPA1 regulates...	ACCEPT	Summary: CRY2 regulates photoperiodic flowering via SPA1/COP1/CO/FT signaling. Reason: Blue-light-dependent CRY2-SPA1 interaction suppresses COP1-dependent CO degradation and promotes FT expression and floral initiation. Supporting Evidence: PMID:21514160 SPA1 acts as a signaling molecule to mediate CRY2-dependent control of CO protein stability, FT transcription, and floral initiation in response to blue light. PMID:21514160 CRY2 undergoes blue light-dependent physical interaction with SPA1.
GO:2000377 regulation of reactive oxygen species metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ROS regulation is a reported CRY2 signaling output, not the central function. Reason: CRY2 may promote blue-light-dependent ROS formation, but this is downstream of photoreceptor activation and remains less central than blue-light signaling/flowering. Supporting Evidence: PMID:26179959 Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling role.
GO:2000379 positive regulation of reactive oxygen species metabolic process	IDA PMID:26179959 Blue-light dependent ROS formation by Arabidopsis cryptochro...	KEEP AS NON CORE	Summary: Positive ROS regulation is supported but non-core. Reason: Blue-light-dependent ROS formation may contribute to CRY2 signaling, but it is not the primary molecular function of CRY2. Supporting Evidence: PMID:26179959 Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling role.
GO:0000325 plant-type vacuole	HDA PMID:15539469 The vegetative vacuole proteome of Arabidopsis thaliana reve...	REMOVE	Summary: High-throughput vacuole localization conflicts with the established nuclear photoreceptor localization. Reason: CRY2 is repeatedly localized to the nucleus and nuclear bodies, with only limited/transient cytosolic evidence. A single HDA vacuole proteomics annotation is likely incidental contamination or overinterpretation. Supporting Evidence: PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005634 nucleus	ISM GO_REF:0000122	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005634 nucleus	IDA PMID:10476076 Nuclear localization of the Arabidopsis blue light receptor ...	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005634 nucleus	EXP PMID:17438275 Derepression of the NC80 motif is critical for the photoacti...	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005634 nucleus	IDA PMID:18988809 Photoexcited CRY2 interacts with CIB1 to regulate transcript...	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:18988809 CIB1 interacts with CRY2 (cryptochrome 2) in a blue light-specific manner in yeast and Arabidopsis cells PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005634 nucleus	EXP PMID:20624951 Cryptochrome 2 and phototropin 2 regulate resistance protein...	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:20624951 The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are required for the stability of the R protein HRT PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005634 nucleus	EXP PMID:22311776 A study of the blue-light-dependent phosphorylation, degrada...	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005634 nucleus	IDA PMID:22739826 Degradation of Arabidopsis CRY2 is regulated by SPA proteins...	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:22739826 Degradation of Arabidopsis CRY2 is regulated by SPA proteins and phytochrome A. PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005634 nucleus	IDA PMID:25792146 The blue light-dependent phosphorylation of the CCE domain d...	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005634 nucleus	IDA PMID:26179959 Blue-light dependent ROS formation by Arabidopsis cryptochro...	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:26179959 Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling role. PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005634 nucleus	IDA PMID:26724867 Cryptochromes Interact Directly with PIFs to Control Plant G...	ACCEPT	Summary: Correct cellular component: CRY2 acts predominantly in the nucleus. Reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional outputs. Supporting Evidence: PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2. PMID:17438275 These CRY2 fusion proteins were all found in the nucleus PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:25792146 all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as the endogenous CRY2 or the wild-type GFP-CRY2 PMID:26724867 CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other TFs
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Cytoplasmic CRY2 can be detected/translocate, but the principal signaling site is nuclear. Reason: CRY2 may be present in the cytoplasm in some contexts, yet the core photoreceptor signaling annotations are best assigned to nucleus/nuclear body. Supporting Evidence: PMID:26179959 Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling role. PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2.
GO:0005737 cytoplasm	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Cytoplasmic CRY2 can be detected/translocate, but the principal signaling site is nuclear. Reason: CRY2 may be present in the cytoplasm in some contexts, yet the core photoreceptor signaling annotations are best assigned to nucleus/nuclear body. Supporting Evidence: PMID:26179959 Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling role. PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2.
GO:0005737 cytoplasm	IDA PMID:26179959 Blue-light dependent ROS formation by Arabidopsis cryptochro...	KEEP AS NON CORE	Summary: Cytoplasmic CRY2 can be detected/translocate, but the principal signaling site is nuclear. Reason: CRY2 may be present in the cytoplasm in some contexts, yet the core photoreceptor signaling annotations are best assigned to nucleus/nuclear body. Supporting Evidence: PMID:26179959 Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling role. PMID:10476076 CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2.
GO:0016604 nuclear body	IEA GO_REF:0000117	ACCEPT	Summary: Correct cellular component: blue light induces CRY2-containing nuclear photobodies. Reason: CRY2 forms nuclear bodies/photobodies after blue-light activation, and these are linked to phosphorylation, degradation, signal amplification, and partner colocalization. Supporting Evidence: PMID:21514160 blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear bodies PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:27846570 BICs also inhibit the blue light-induced formation of CRY2 photobodies
GO:0016604 nuclear body	IDA PMID:21511872 Blue-light-dependent interaction of cryptochrome 1 with SPA1...	ACCEPT	Summary: Correct cellular component: blue light induces CRY2-containing nuclear photobodies. Reason: CRY2 forms nuclear bodies/photobodies after blue-light activation, and these are linked to phosphorylation, degradation, signal amplification, and partner colocalization. Supporting Evidence: PMID:21514160 blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear bodies PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:27846570 BICs also inhibit the blue light-induced formation of CRY2 photobodies
GO:0016604 nuclear body	IMP PMID:22311776 A study of the blue-light-dependent phosphorylation, degrada...	ACCEPT	Summary: Correct cellular component: blue light induces CRY2-containing nuclear photobodies. Reason: CRY2 forms nuclear bodies/photobodies after blue-light activation, and these are linked to phosphorylation, degradation, signal amplification, and partner colocalization. Supporting Evidence: PMID:21514160 blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear bodies PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus PMID:27846570 BICs also inhibit the blue light-induced formation of CRY2 photobodies
GO:0016605 PML body	IEA GO_REF:0000044	MODIFY	Summary: PML body is not the right plant-specific term for CRY2 photobodies. Reason: The evidence supports nuclear photobodies/nuclear bodies in Arabidopsis. PML bodies are an inappropriate or over-specific mapping for this plant photoreceptor. Proposed replacements: nuclear body Supporting Evidence: PMID:21514160 blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear bodies PMID:22311776 CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus

Core Functions

CRY2 acts as a nuclear FAD-dependent blue-light photoreceptor. Blue light promotes CRY2 photoactivation, homodimerization/oligomerization, nuclear photobody formation, and partner interactions that drive blue-light signaling, low-blue-light growth responses, and photoperiodic flowering through CO/FT and CIB-dependent mechanisms.

Molecular Function:

blue light photoreceptor activity

Directly Involved In:

blue light signaling pathway response to low fluence blue light stimulus by blue low-fluence system long-day photoperiodism, flowering regulation of photoperiodism, flowering

Cellular Locations:

nucleus nuclear body

Supporting Evidence:

PMID:22311776
CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus
PMID:27846570
Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active.
PMID:21514160
SPA1 acts as a signaling molecule to mediate CRY2-dependent control of CO protein stability, FT transcription, and floral initiation in response to blue light.
PMID:26724867
CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5.
file:ARATH/CRY2/CRY2-deep-research-falcon.md
Arabidopsis thaliana CRY2 (UniProt: Q96524) is a plant blue-light photoreceptor

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000122

AtSubP analysis

PMID:10476076

Nuclear localization of the Arabidopsis blue light receptor cryptochrome 2.

CRY2 is localized to the nucleus through its C-terminal region.

"CRY2 is localized in the nucleus and that nuclear localization is mediated by the C-terminal region of CRY2."

PMID:11089975

Functional interaction of phytochrome B and cryptochrome 2.

PMID:11493548

Hierarchical coupling of phytochromes and cryptochromes reconciles stability and light modulation of Arabidopsis development.

CRY2 is a photoreceptor coupled to developmental processes.

"coupling of the photoreceptor cryptochrome 2 to developmental processes is broader than previously appreciated."

PMID:11509693

Direct interaction of Arabidopsis cryptochromes with COP1 in light control development.

PMID:11743105

Circadian clock-regulated expression of phytochrome and cryptochrome genes in Arabidopsis.

Cryptochromes are involved in circadian light input.

"Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock by transducing the light signal to the central oscillator."

PMID:12857830

Second positive phototropism results from coordinated co-action of the phototropins and cryptochromes.

Cryptochromes and phototropins coordinate phototropism under blue light.

"phototropins and cryptochromes function together to enhance phototropism under low fluence rates"

PMID:15539469

The vegetative vacuole proteome of Arabidopsis thaliana reveals predicted and unexpected proteins.

PMID:15805487

N-terminal domain-mediated homodimerization is required for photoreceptor activity of Arabidopsis CRYPTOCHROME 1.

PMID:16093319

From The Cover: A role for Arabidopsis cryptochromes and COP1 in the regulation of stomatal opening.

CRY pathways contribute to blue-light-induced stomatal opening.

"CRY functions additively with PHOT in mediating blue light-induced stomatal opening"

PMID:17073458

Analysis of autophosphorylating kinase activities of Arabidopsis and human cryptochromes.

AtCRY2 contains FAD but lacks detectable autokinase/autophosphorylation activity.

"AtCry2 which is known to be phosphorylated upon light exposure in vivo ( 16 ) lacked kinase activity."

PMID:17259260

CRYPTOCHROME2 in vascular bundles regulates flowering in Arabidopsis.

CRY2 in vascular bundles promotes FT expression and flowering.

"cry2-GFP expressed in vascular bundles increased FT expression only in vascular bundles."

PMID:17438275

Derepression of the NC80 motif is critical for the photoactivation of Arabidopsis CRY2.

CRY2 mediates blue-light inhibition of hypocotyl elongation and photoperiodic flowering.

"Arabidopsis cryptochrome 2 (CRY2) mediates blue light inhibition of hypocotyl elongation and photoperiodic control of floral initiation."

PMID:17470059

Light-regulated large-scale reorganization of chromatin during the floral transition in Arabidopsis.

PMID:17982000

Distinct light and clock modulation of cytosolic free Ca2+ oscillations and rhythmic CHLOROPHYLL A/B BINDING PROTEIN2 promoter activity in Arabidopsis.

PMID:18424613

Distinct light-initiated gene expression and cell cycle programs in the shoot apex and cotyledons of Arabidopsis.

PMID:18988809

Photoexcited CRY2 interacts with CIB1 to regulate transcription and floral initiation in Arabidopsis.

Photoexcited CRY2 interacts with CIB1 to promote FT expression and floral initiation.

"CIB1 interacts with CRY2 (cryptochrome 2) in a blue light-specific manner in yeast and Arabidopsis cells"

PMID:19558423

Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal regulation.

PMID:20624951

Cryptochrome 2 and phototropin 2 regulate resistance protein-mediated viral defense by negatively regulating an E3 ubiquitin ligase.

CRY2 contributes to TCV defense by maintaining HRT stability through COP1 regulation.

"The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are required for the stability of the R protein HRT"

PMID:20935177

Photoreceptors CRYTOCHROME2 and phytochrome B control chromatin compaction in Arabidopsis.

PMID:21296763

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.

PMID:21511872

Blue-light-dependent interaction of cryptochrome 1 with SPA1 defines a dynamic signaling mechanism.

PMID:21514160

Blue light-dependent interaction of CRY2 with SPA1 regulates COP1 activity and floral initiation in Arabidopsis.

Blue light stimulates CRY2-SPA1 interaction and CRY2-dependent control of CO/FT and floral initiation.

"SPA1 acts as a signaling molecule to mediate CRY2-dependent control of CO protein stability, FT transcription, and floral initiation in response to blue light."

PMID:22139370

Arabidopsis cryptochrome 2 (CRY2) functions by the photoactivation mechanism distinct from the tryptophan (trp) triad-dependent photoreduction.

PMID:22311776

A study of the blue-light-dependent phosphorylation, degradation, and photobody formation of Arabidopsis CRY2.

CRY2 forms nuclear photobodies and undergoes blue-light-dependent phosphorylation, ubiquitination, and degradation.

"CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation, ubiquitination, photobody formation, and degradation in the nucleus"

PMID:22739826

Degradation of Arabidopsis CRY2 is regulated by SPA proteins and phytochrome A.

PMID:23511208

Network balance via CRY signalling controls the Arabidopsis circadian clock over ambient temperatures.

Cryptochrome light input affects circadian period over temperature.

"reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors lengthens the circadian period"

PMID:24126495

Strigolactone-regulated hypocotyl elongation is dependent on cryptochrome and phytochrome signaling pathways in Arabidopsis.

PMID:24130508

Multiple bHLH proteins form heterodimers to mediate CRY2-dependent regulation of flowering-time in Arabidopsis.

CIB bHLH proteins act redundantly in CRY2-dependent flowering.

"CIBs function redundantly in regulating CRY2-dependent flowering"

PMID:24780222

Quantitative real-time kinetics of optogenetic proteins CRY2 and CIB1/N using single-molecule tools.

CRY2 photoactivation drives association with CIB1.

"Upon illumination, CRY2 is photoactivated to contact and associate with CIB1."

PMID:25428980

Cellular metabolites enhance the light sensitivity of Arabidopsis cryptochrome through alternate electron transfer pathways.

Cellular metabolites affect Arabidopsis cryptochrome light sensitivity through electron-transfer routes.

"Cellular metabolites enhance the light sensitivity of Arabidopsis cryptochrome through alternate electron transfer pathways."

PMID:25792146

The blue light-dependent phosphorylation of the CCE domain determines the photosensitivity of Arabidopsis CRY2.

Blue-light-dependent phosphorylation of the CCE domain regulates CRY2 photosensitivity.

"CRY2 undergoes blue light-dependent phosphorylation in multiple serine residues of the CCE domain"

PMID:26179959

Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling role.

PMID:26724867

Cryptochromes Interact Directly with PIFs to Control Plant Growth in Limiting Blue Light.

CRY1/CRY2 directly contact PIF4 and PIF5 to control growth under limiting blue light.

"CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription factors, PIF4 and PIF5."

PMID:27846570

Photoactivation and inactivation of Arabidopsis cryptochrome 2.

Blue-light-dependent CRY2 homodimerization is required for physiological activation.

"Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization to become physiologically active."

PMID:28492234

Molecular basis for blue light-dependent phosphorylation of Arabidopsis cryptochrome 2.

PMID:28633330

The asparagine-rich protein NRP interacts with the Verticillium effector PevD1 and regulates the subcellular localization of cryptochrome 2.

PMID:32398826

Structural insights into BIC-mediated inactivation of Arabidopsis cryptochrome 2.

Crystal structures of the CRY2 PHR (photolyase-homology) domain with bound FAD and of the BIC2-CRY2N complex reveal how BIC inactivates the FAD-bound photoreceptor.

"Here, we report crystal structures of CRY2N (CRY2 PHR domain) and the BIC2-CRY2N complex with resolutions of 2.7 and 2.5 Å, respectively."

PMID:32661061

Photoexcited Cryptochrome2 Interacts Directly with TOE1 and TOE2 in Flowering Regulation.

PMID:36396657

CRY2 interacts with CIS1 to regulate thermosensory flowering via FLM alternative splicing.

PMID:36508461

A role for brassinosteroid signalling in decision-making processes in the Arabidopsis seedling.

PMID:9565033

Cryptochrome blue-light photoreceptors of Arabidopsis implicated in phototropism.

Cryptochromes contribute to Arabidopsis phototropism.

"cryptochrome is one of the photoreceptors mediating phototropism in plants."

file:ARATH/CRY2/CRY2-deep-research-falcon.md

Falcon deep research summary for Arabidopsis CRY2

Deep research synthesis identifies CRY2 as a nuclear plant blue-light photoreceptor with FAD-dependent photochemistry, condensate/photobody behavior, and flowering/growth outputs.

file:ARATH/CRY2/CRY2-uniprot.txt

UniProtKB record for Arabidopsis CRY2 (Q96524)

UniProt summarizes CRY2 as a photoreceptor mediating blue-light inhibition of hypocotyl elongation and photoperiodic control of floral initiation.

file:interpro/panther/PTHR11455/PTHR11455-notes.md

PANTHER PTHR11455 cryptochrome family notes

PANTHER family PTHR11455 contains both signaling cryptochromes and repair photolyases, so family-level IBA photolyase annotations require caution.

Suggested Experiments

Experiment: Compare CRY2 photobody composition, light dependence, dynamics, and partner colocalization across PMID:21514160, PMID:22311776, PMID:27846570, and recent condensate studies; define term boundaries and synonym needs.

Hypothesis: CRY2 photobodies are distinct enough from generic nuclear bodies to warrant a GO cellular-component child term.

Type: curation/ontology review

Experiment: Measure chromatin compaction and floral-transition markers in cry2, CIB/SPAs, and photobody-defective CRY2 mutants under matched blue-light conditions, paired with CRY2 chromatin-proximity or CUT&Tag assays.

Hypothesis: CRY2 affects chromatin organization indirectly through photoreceptor signaling partners rather than by direct chromatin remodeling activity.

Type: targeted genetic and imaging assay

Deep Research

Falcon

(CRY2-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 41 citations 2026-05-05T04:08:21.760874

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Arabidopsis thaliana CRY2 (UniProt: Q96524; locus At1g04400) — Functional Annotation

1) Target identity verification (CRITICAL)

The literature reviewed here corresponds to Arabidopsis thaliana cryptochrome-2 (CRY2) encoded by At1G04400, matching the UniProt-provided identity (Q96524) as a blue-light photoreceptor of the DNA photolyase/cryptochrome family. In a primary biochemical/physiological study, CRY2 is explicitly handled as the Arabidopsis gene At1G04400, and the protein is described as a plant cryptochrome composed of an N-terminal photolyase homology region (PHR; aa ~2–495) and a C-terminal cryptochrome C-terminal extension (CCE) (full length ~612 aa), consistent with UniProt’s domain architecture and family assignment. (eckel2018atpboostslit pages 8-10)

Multiple authoritative sources also distinguish plant CRY2 (light-activated signaling photoreceptor regulating development/flowering) from animal CRY2 (typically circadian clock components/transcriptional repressors), reducing risk of symbol ambiguity (CRY2 is common across taxa). (chen2021regulationofarabidopsis pages 1-2, deoliveira2025astructuraldecryption pages 1-2)

2) Key concepts and definitions (current understanding)

2.1 Cryptochromes (CRYs)

Plant cryptochromes are flavoprotein blue-light photoreceptors that regulate growth and development largely by changing gene expression. They are evolutionarily related to DNA photolyases but function primarily as sensory/signaling proteins rather than DNA-repair enzymes. (fraikin2023molecularbasesof pages 1-2, deoliveira2024dualfacetsof pages 17-21)

2.2 PHR and CCE domains

A defining architectural concept is the two-part structure:
- PHR (Photolyase Homology Region): conserved photolyase-like core that binds the FAD chromophore and executes the primary photochemistry. (fraikin2023molecularbasesof pages 1-2, fraikin2023molecularbasesof pages 4-5)
- CCE (Cryptochrome C-terminal Extension): plant CRY1/CRY2-specific extension (absent from photolyases), often described as functionally important for signaling output, protein–protein interactions, and regulatory modifications; after photoactivation, PHR–CCE association can disengage, exposing interaction surfaces. (fraikin2023molecularbasesof pages 4-5)

2.3 Photobodies and liquid–liquid phase separation (LLPS)

Recent plant cell biology increasingly frames many “nuclear bodies” as biomolecular condensates. LLPS is described as separation of macromolecules into a dense liquid-like phase and a dilute phase, forming membrane-less compartments that can accelerate reactions by locally concentrating factors. (liu2024liquid–liquidphaseseparation pages 1-2)

For CRY2 specifically, blue light triggers assembly into nuclear photobodies, and recent work connects CRY2-dependent condensates to downstream biochemical regulation (including post-transcriptional control). (jiang2023lightinducedllpsof pages 1-2, liu2024liquid–liquidphaseseparation pages 1-2)

3) Molecular function of CRY2: photochemistry → conformational change → oligomerization/condensation → signaling

3.1 Primary photochemistry (FAD-centered photocycle)

The mechanistic starting point is absorption of blue light by oxidized FAD in the PHR. A 2023 review summarizes that photoexcitation drives electron transfer through a conserved Trp-triad with ultrafast steps (~0.4 ps and 31 ps) to generate radical intermediates, followed by microsecond-scale protonation to a semiquinone signaling state. (fraikin2023molecularbasesof pages 4-5)

This photoreduction is coupled to larger-scale conformational rearrangements, including PHR–CCE disengagement and exposure of previously buried segments, facilitating binding to signaling partners and/or assembly into higher-order states. (fraikin2023molecularbasesof pages 4-5)

A key regulatory concept is spectral antagonism: the semiquinone signaling state absorbs broadly (reviewed as 500–650 nm), and green light can reduce active signaling levels by shifting the flavin to an inactive form. (fraikin2023molecularbasesof pages 4-5)

3.2 Oligomerization, photobodies, and LLPS

CRY2 photoactivation is accompanied by homooligomerization and formation of nuclear photobodies. (kong2025complexsignalingnetworks pages 2-4)

A major recent development is the demonstration that CRY2 can participate in light-induced LLPS with specific partners. In Nature Plants (Dec 2023), CRY2 is shown to undergo blue-light-dependent co-condensation with the METTL16-type m6A writer FIONA1 (FIO1), but notably this co-condensation requires the CRY2-signaling protein SPA1. (jiang2023lightinducedllpsof pages 1-2)

4) Subcellular localization

CRY2 is repeatedly described as predominantly nuclear, completing key post-translational and signaling steps in the nucleus, consistent with its role in transcriptional and post-transcriptional regulation. (fraikin2023molecularbasesof pages 1-2, kong2025complexsignalingnetworks pages 2-4)

5) Pathways and biological processes controlled by CRY2

5.1 Photoperiodic flowering: CRY2 → CIBs/FT (and CO stabilization via COP1/SPA)

A well-established CRY2-specific output is promotion of flowering via transcriptional control of FLOWERING LOCUS T (FT).

Mechanistically, CRY2 can directly engage CIB (CRY-interacting bHLH) transcription factors: the PHR domain of CRY2 binds CIB1 (and related CIBs), and this complex is linked to activation of FT transcription (via promoter-associated actions of CIBs). (spaninksUnknownyearlightsignallingpathways pages 12-16, kong2025complexsignalingnetworks pages 26-27)

In addition, CRY2 contributes to flowering by suppressing the activity of the COP1/SPA E3 ligase system that otherwise promotes degradation of flowering regulators such as CONSTANS (CO) in darkness; light-mediated inhibition of COP1/SPA thereby helps stabilize CO and enables FT induction under inductive photoperiods. (spaninksUnknownyearlightsignallingpathways pages 12-16, kong2025complexsignalingnetworks pages 15-17)

5.2 Hypocotyl elongation and early seedling development

A 2024 Annual Review frames CRY2 as the dominant cryptochrome in low blue-light conditions (with CRY1 more dominant at higher intensities), and emphasizes that cryptochromes collectively account for more than half of dark-to-blue transcriptome differences in Arabidopsis. (krahmer2024environmentalcontrolof pages 7-9)

CRY2 contributes to repression of elongation growth in blue light via inhibition of COP1/SPA and through interactions with growth-regulating transcriptional networks, including PIFs under specific conditions. (krahmer2024environmentalcontrolof pages 7-9, fraikin2023molecularbasesof pages 6-8)

5.3 Circadian-associated outputs

CRY2 has roles in circadian regulation and entrainment, including effects that depend on light intensity and on CRY2 turnover; review-level synthesis links CRY2 interactions and stability to clock timing outputs. (kong2025complexsignalingnetworks pages 24-26)

6) Regulation of CRY2 activity and abundance (phosphorylation, ubiquitination, proteasomal degradation)

A recurring theme in CRY2 biology is that the active, light-induced state is tightly coupled to regulated destruction, enabling dynamic responsiveness.

A 2023 review describes CRY2 phosphorylation by a set of four related kinases (PPK1–4), with purified CRY2 reported to contain multiple phosphorylation sites (including seven major phosphoserines). Phosphorylation increases CRY2 signaling but also promotes ubiquitination and 26S proteasome-mediated degradation; in PPK triple mutants, CRY2 phosphorylation is strongly reduced and CRY2 is neither ubiquitinated nor degraded. (fraikin2023molecularbasesof pages 6-8)

A mechanistic 2021 study (Nature Communications) demonstrates that CRY2 is targeted by two distinct E3 ubiquitin ligase systems in blue light: the known CUL4–COP1/SPA complex and a second ligase CUL3–LRBs. LRB proteins physically interact with photoexcited, phosphorylated CRY2 via the CCE domain, promoting polyubiquitination and degradation in response to blue light. (chen2021regulationofarabidopsis pages 1-2)

The 2024 Annual Review also summarizes that blue-light-dependent degradation of cryptochromes is mediated by CUL4COP1-SPA and CUL3–LRBs, and highlights that CRY2 is degraded rapidly even at relatively low light intensities. (krahmer2024environmentalcontrolof pages 7-9)

7) Quantitative data and statistics (recent studies prioritized where available)

7.1 ATP binding and modulation of CRY2 photochemistry (biochemical parameter)

A quantitative biochemical parameter for Arabidopsis CRY2 is its ATP binding affinity. Eckel et al. report that recombinant CRY2 binds ATP with KD = 1.09 ± 0.48 μM (ITC), and interpret ATP binding as a booster (not an absolute requirement) for formation of the signaling-active state and biological activity. (eckel2018atpboostslit pages 1-3, eckel2018atpboostslit pages 6-7)

The ITC binding curve and the fitted KD are directly shown in the extracted figure panel. (eckel2018atpboostslit media 1d942dcd)

7.2 Blue-light-dependent degradation kinetics (example time course)

In the same study, CRY2 degradation was quantified under 10 μmol m−2 s−1 blue light. After 10 min exposure, ~15% of WT CRY2 protein remained, whereas ~72% remained for an ATP-binding–defective mutant (cry2Y399A), supporting a role for ATP binding in promoting efficient signaling-state formation and/or turnover. (eckel2018atpboostslit pages 6-7)

This time course is displayed in the extracted degradation plot (Figure 6e panel). (eckel2018atpboostslit media 76edfc28)

7.3 Photochemistry time constants and spectral antagonism

Ultrafast photochemical transfer steps of ~0.4 ps and 31 ps are summarized for the Trp-triad electron transfer chain in plant cryptochromes, and green light is summarized to reduce active semiquinone signaling levels by shifting the flavin to an inactive state. (fraikin2023molecularbasesof pages 4-5)

7.4 Growth phenotype effect size (example)

In one quantified seedling assay context, mean hypocotyl length under blue light was reported as WT: 7 ± 1.5 mm vs cry2 mutant: 12.5 ± 1 mm, illustrating a substantial elongation phenotype when CRY2 function is absent under those specific conditions. (eckel2018atpboostslit pages 4-6)

8) Recent developments and latest research highlights (2023–2024 priority)

8.1 2023: CRY2 condensates link light perception to epitranscriptomic regulation

A key 2023 advance is the demonstration that light-triggered CRY2 condensate behavior can regulate mRNA m6A methylation and translation. Jiang et al. (Nature Plants, published Dec 2023) show that CRY2 co-condenses with FIO1 only when SPA1 is present, and that CRY2+SPA1 can stimulate FIO1 methyltransferase activity in vitro. In vivo, CRY2 and FIO1 are required for light-induced methylation and translation of mRNAs encoding chlorophyll homeostasis regulators. (jiang2023lightinducedllpsof pages 1-2, jiang2023lightinducedllpsof pages 6-7)

This reframes CRY2 output beyond classical transcription-factor stabilization/activation, extending it to post-transcriptional control mediated by light-dependent protein co-condensation. (jiang2023lightinducedllpsof pages 1-2)

8.2 2024: Integration with growth-control networks and COP1/SPA logic

The 2024 Annual Review of Plant Biology emphasizes cryptochromes as major contributors to rapid transcriptome reprogramming and discusses mechanistic crosstalk where CRY2 affects COP1/SPA-mediated degradation pathways, with CRY2 particularly important at low blue-light intensity. (krahmer2024environmentalcontrolof pages 7-9)

9) Current applications and real-world implementations

9.1 Optogenetics: CRY2/CIB as a light-inducible dimerization tool

Outside plant biology, Arabidopsis CRY2 is widely implemented as an optogenetic module (typically using CRY2 and CIB1/CIBN) to control protein localization and interactions.

A 2024 preprint demonstrates a concrete real-world implementation in bacteria: the Arabidopsis CRY2/CIBN system is used in live E. coli to rapidly recruit proteins to the nucleoid, poles, membrane, or midcell division plane, and the authors show acute inhibition of cytokinesis. Activation is reported around 468–488 nm, with kinetics tunable by green light. (mcquillen2024lightdependentmodulationof pages 1-6)

10) Expert synthesis and interpretation (authoritative perspectives)

Signal transduction is inseparable from controlled turnover: A consistent conclusion across mechanistic and review sources is that blue-light activation, phosphorylation, ubiquitination, and proteasomal degradation form a coupled cycle that shapes CRY2 signal amplitude and duration in planta. (fraikin2023molecularbasesof pages 6-8, chen2021regulationofarabidopsis pages 1-2, krahmer2024environmentalcontrolof pages 7-9)
Condensates provide a mechanistic bridge between photochemistry and biochemical output: Recent work positions CRY2 photobodies/LLPS not merely as microscopy-visible puncta but as functional reaction compartments, including for RNA-modification machinery affecting chlorophyll homeostasis. (jiang2023lightinducedllpsof pages 1-2, liu2024liquid–liquidphaseseparation pages 1-2)
CRY2’s pathway specificity differs from CRY1: Review-level synthesis emphasizes CRY2’s prominence in low blue light and its more direct linkage to flowering via CIBs/FT, while CRY1 dominates many high-intensity blue-light seedling growth outputs. (krahmer2024environmentalcontrolof pages 7-9)

Evidence summary table

The following table provides a compact mapping of CRY2 concepts, mechanisms, and evidence to primary sources.

Topic	Key points	Key citations	Primary sources with URL + publication date
identity/domains	• Target verified as Arabidopsis thaliana CRY2 / At1g04400, a plant blue-light photoreceptor, distinct from animal CRY2 proteins. • Domain architecture matches UniProt: N-terminal PHR (photolyase homology region; ~aa 2–495) plus C-terminal extension (CCE). • CRY2 is photolyase-related but functions in signaling rather than DNA repair.	(eckel2018atpboostslit pages 8-10, fraikin2023molecularbasesof pages 1-2, deoliveira2025astructuraldecryption pages 1-2)	Eckel et al., Plant Journal (2018-08), https://doi.org/10.1111/tpj.14039; Fraikin et al., Biochemistry (Moscow) (2023-06), https://doi.org/10.1134/s0006297923060056; DeOliveira & Crane, Frontiers in Chemistry (2025-08), https://doi.org/10.3389/fchem.2024.1436322
photochemistry	• Blue light excites FAD in the PHR, driving electron transfer via the Trp triad and formation of a long-lived semiquinone signaling state. • Reported ultrafast photochemical steps are ~0.4 ps and 31 ps before microsecond-scale protonation/conformational change. • Photoactivation promotes PHR–CCE disengagement and oligomerization.	(fraikin2023molecularbasesof pages 4-5, deoliveira2025astructuraldecryption pages 10-11)	Fraikin et al., Biochemistry (Moscow) (2023-06), https://doi.org/10.1134/s0006297923060056; DeOliveira & Crane, Frontiers in Chemistry (2025-08), https://doi.org/10.3389/fchem.2024.1436322
localization/photobodies/LLPS	• CRY2 is described as a predominantly nuclear photoreceptor. • Blue light induces homooligomerization, formation of nuclear photobodies, and LLPS-like condensates. • CRY2/SPA1/FIO1 co-condensation links photobody formation to post-transcriptional regulation (m6A/chlorophyll homeostasis).	(fraikin2023molecularbasesof pages 1-2, jiang2023lightinducedllpsof pages 1-2, liu2024liquid–liquidphaseseparation pages 1-2)	Fraikin et al., Biochemistry (Moscow) (2023-06), https://doi.org/10.1134/s0006297923060056; Jiang et al., Nature Plants (2023-12), https://doi.org/10.1038/s41477-023-01580-0; Liu et al., Plant Communications (2024-01), https://doi.org/10.1016/j.xplc.2023.100663
key partners	• SPA1 is a major CRY2 signaling partner and helps mediate CRY2-dependent co-condensation with FIO1. • CIB bHLH transcription factors bind photoactivated CRY2 to activate flowering genes. • CRY2 also interfaces with COP1/SPA, PIFs, PPK1–4, LRB1/2/3, and antagonists BIC1/BIC2.	(jiang2023lightinducedllpsof pages 6-7, spaninksUnknownyearlightsignallingpathways pages 12-16, chen2021regulationofarabidopsis pages 1-2)	Jiang et al., Nature Plants (2023-12), https://doi.org/10.1038/s41477-023-01580-0; Chen et al., Nature Communications (2021-12), https://doi.org/10.1038/s41467-021-22410-x; Spaninks & Offringa, source/year not specified in retrieved context
downstream processes	• Major annotated outputs are photoperiodic flowering, photomorphogenesis, hypocotyl growth control, and circadian regulation. • CRY2 activates CIBs and promotes FT transcription; it also stabilizes CO indirectly by suppressing COP1/SPA activity. • Recent work links CRY2 to mRNA methylation/translation and chlorophyll homeostasis under blue light.	(kong2025complexsignalingnetworks pages 26-27, kong2025complexsignalingnetworks pages 15-17, jiang2023lightinducedllpsof pages 1-2)	Kong & Zheng, Plants (2025-05), https://doi.org/10.3390/plants14101533; Jiang et al., Nature Plants (2023-12), https://doi.org/10.1038/s41477-023-01580-0
regulation/degradation	• Activated CRY2 is phosphorylated mainly in the nucleus by PPK1–4; phosphorylation promotes signaling but also turnover. • CRY2 is polyubiquitinated by CUL4-COP1/SPA and also by CUL3-LRBs, then degraded by the 26S proteasome. • BIC1/BIC2 inhibit CRY2 oligomerization/activation, while blue light drives degradation in an intensity-dependent manner.	(fraikin2023molecularbasesof pages 6-8, chen2021regulationofarabidopsis pages 1-2, krahmer2024environmentalcontrolof pages 7-9)	Fraikin et al., Biochemistry (Moscow) (2023-06), https://doi.org/10.1134/s0006297923060056; Chen et al., Nature Communications (2021-12), https://doi.org/10.1038/s41467-021-22410-x; Krahmer & Fankhauser, Annual Review of Plant Biology (2024-07), https://doi.org/10.1146/annurev-arplant-062923-023852
quantitative data	• ATP binding affinity for CRY2 PHR: KD = 1.09 ± 0.48 µM; previously reported full-length value ~0.9 µM. • Under 10 µmol m−2 s−1 blue light, after 10 min, ~15% of WT CRY2 remained vs 72% of ATP-binding mutant cry2Y399A. • Blue-light hypocotyl assay example: WT 7 ± 1.5 mm vs cry2 mutant 12.5 ± 1 mm; cryptochromes account for >50% of dark-to-blue transcriptome differences in one review summary.	(eckel2018atpboostslit pages 6-7, eckel2018atpboostslit pages 4-6, krahmer2024environmentalcontrolof pages 7-9)	Eckel et al., Plant Journal (2018-08), https://doi.org/10.1111/tpj.14039; Krahmer & Fankhauser, Annual Review of Plant Biology (2024-07), https://doi.org/10.1146/annurev-arplant-062923-023852
applications	• Arabidopsis CRY2/CIBN is widely used as an optogenetic dimerization module outside plants. • A 2024 study used CRY2/CIBN in live E. coli to relocalize proteins to nucleoid, pole, membrane, or midcell and to inhibit cytokinesis. • Activation used blue light around 468–488 nm, with kinetics additionally tunable by green light.	(mcquillen2024lightdependentmodulationof pages 1-6)	McQuillen et al., bioRxiv (2024-05), https://doi.org/10.1101/2022.05.01.490209

Table: This table summarizes the main functional annotation evidence for Arabidopsis thaliana CRY2, including identity, mechanism, localization, partners, pathways, regulation, quantitative findings, and applications. It is useful as a compact evidence map tied directly to the gathered citation context.

Source notes, URLs, and publication dates

Fraikin et al. “Molecular Bases of Signaling Processes Regulated by Cryptochrome Sensory Photoreceptors in Plants.” Biochemistry (Moscow). Jun 2023. https://doi.org/10.1134/s0006297923060056 (fraikin2023molecularbasesof pages 1-2)
Jiang et al. “Light-induced LLPS of the CRY2/SPA1/FIO1 complex…” Nature Plants. Dec 2023. https://doi.org/10.1038/s41477-023-01580-0 (jiang2023lightinducedllpsof pages 1-2)
Krahmer & Fankhauser. “Environmental Control of Hypocotyl Elongation.” Annual Review of Plant Biology. Jul 2024. https://doi.org/10.1146/annurev-arplant-062923-023852 (krahmer2024environmentalcontrolof pages 7-9)
Chen et al. “Regulation of Arabidopsis photoreceptor CRY2 by two distinct E3 ubiquitin ligases.” Nature Communications. Dec 2021. https://doi.org/10.1038/s41467-021-22410-x (chen2021regulationofarabidopsis pages 1-2)
Eckel et al. “ATP boosts lit state formation and activity of Arabidopsis cryptochrome 2.” The Plant Journal. Aug 2018. https://doi.org/10.1111/tpj.14039 (eckel2018atpboostslit pages 1-3)
McQuillen et al. “Light-dependent modulation of protein localization and function in living bacteria cells.” bioRxiv. May 2024. https://doi.org/10.1101/2022.05.01.490209 (mcquillen2024lightdependentmodulationof pages 1-6)

Limitations of the retrieved evidence set

This report emphasizes 2023–2024 where available, but some quantitative biophysical parameters (e.g., LLPS partition coefficients, saturation concentrations for CRY2 condensates) were not present in the retrieved text excerpts; additional targeted retrieval of figures/tables from the 2023 Nature Plants LLPS paper and related LLPS/photobody biophysics literature would be needed for a fuller quantitative phase-separation parameterization. (jiang2023lightinducedllpsof pages 1-2)

References

(eckel2018atpboostslit pages 8-10): Maike Eckel, Wieland Steinchen, and Alfred Batschauer. Atp boosts lit state formation and activity of arabidopsis cryptochrome 2. The Plant journal : for cell and molecular biology, 96 2:389-403, Aug 2018. URL: https://doi.org/10.1111/tpj.14039, doi:10.1111/tpj.14039. This article has 15 citations.
(chen2021regulationofarabidopsis pages 1-2): Yadi Chen, Xiaohuan Hu, Siyuan Liu, Tiantian Su, Hsiaochi Huang, Huibo Ren, Zhensheng Gao, Xu Wang, Deshu Lin, J. Wohlschlegel, Qin Wang, and Chentao Lin. Regulation of arabidopsis photoreceptor cry2 by two distinct e3 ubiquitin ligases. Nature Communications, Dec 2021. URL: https://doi.org/10.1038/s41467-021-22410-x, doi:10.1038/s41467-021-22410-x. This article has 59 citations and is from a highest quality peer-reviewed journal.
(deoliveira2025astructuraldecryption pages 1-2): Cristina C. DeOliveira and Brian R. Crane. A structural decryption of cryptochromes. Frontiers in Chemistry, Aug 2025. URL: https://doi.org/10.3389/fchem.2024.1436322, doi:10.3389/fchem.2024.1436322. This article has 18 citations.
(fraikin2023molecularbasesof pages 1-2): Grigori Ya. Fraikin, Natalia S. Belenikina, and Andrey B. Rubin. Molecular bases of signaling processes regulated by cryptochrome sensory photoreceptors in plants. Biochemistry (Moscow), 88:770-782, Jun 2023. URL: https://doi.org/10.1134/s0006297923060056, doi:10.1134/s0006297923060056. This article has 5 citations.
(deoliveira2024dualfacetsof pages 17-21): C DeOliveira. Dual facets of drosophila melanogaster cryptochrome: unveiling interactions with jetlag for timeless degradation and …. Unknown journal, 2024.
(fraikin2023molecularbasesof pages 4-5): Grigori Ya. Fraikin, Natalia S. Belenikina, and Andrey B. Rubin. Molecular bases of signaling processes regulated by cryptochrome sensory photoreceptors in plants. Biochemistry (Moscow), 88:770-782, Jun 2023. URL: https://doi.org/10.1134/s0006297923060056, doi:10.1134/s0006297923060056. This article has 5 citations.
(liu2024liquid–liquidphaseseparation pages 1-2): Qianwen Liu, Wenxuan Liu, Yiding Niu, Tao Wang, and Jiangli Dong. Liquid–liquid phase separation in plants: advances and perspectives from model species to crops. Plant Communications, 5:100663, Jan 2024. URL: https://doi.org/10.1016/j.xplc.2023.100663, doi:10.1016/j.xplc.2023.100663. This article has 59 citations and is from a peer-reviewed journal.
(jiang2023lightinducedllpsof pages 1-2): Bochen Jiang, Zhenhui Zhong, Lianfeng Gu, Xueyang Zhang, Jiangbo Wei, Chang Ye, Guifang Lin, Gaoping Qu, Xian Xiang, Chenjin Wen, Maureen Hummel, Julia Bailey-Serres, Qin Wang, Chuan He, Xu Wang, and Chentao Lin. Light-induced llps of the cry2/spa1/fio1 complex regulating mrna methylation and chlorophyll homeostasis in arabidopsis. Nature Plants, 9:2042-2058, Dec 2023. URL: https://doi.org/10.1038/s41477-023-01580-0, doi:10.1038/s41477-023-01580-0. This article has 79 citations and is from a highest quality peer-reviewed journal.
(kong2025complexsignalingnetworks pages 2-4): Yun Kong and Youbin Zheng. Complex signaling networks underlying blue-light-mediated floral transition in plants. Plants, 14:1533, May 2025. URL: https://doi.org/10.3390/plants14101533, doi:10.3390/plants14101533. This article has 12 citations.
(spaninksUnknownyearlightsignallingpathways pages 12-16): K Spaninks and R Offringa. Light signalling pathways during early plant development.(general introduction). Unknown journal, Unknown year.
(kong2025complexsignalingnetworks pages 26-27): Yun Kong and Youbin Zheng. Complex signaling networks underlying blue-light-mediated floral transition in plants. Plants, 14:1533, May 2025. URL: https://doi.org/10.3390/plants14101533, doi:10.3390/plants14101533. This article has 12 citations.
(kong2025complexsignalingnetworks pages 15-17): Yun Kong and Youbin Zheng. Complex signaling networks underlying blue-light-mediated floral transition in plants. Plants, 14:1533, May 2025. URL: https://doi.org/10.3390/plants14101533, doi:10.3390/plants14101533. This article has 12 citations.
(krahmer2024environmentalcontrolof pages 7-9): Johanna Krahmer and Christian Fankhauser. Environmental control of hypocotyl elongation. Annual Review of Plant Biology, 75:489-519, Jul 2024. URL: https://doi.org/10.1146/annurev-arplant-062923-023852, doi:10.1146/annurev-arplant-062923-023852. This article has 48 citations and is from a domain leading peer-reviewed journal.
(fraikin2023molecularbasesof pages 6-8): Grigori Ya. Fraikin, Natalia S. Belenikina, and Andrey B. Rubin. Molecular bases of signaling processes regulated by cryptochrome sensory photoreceptors in plants. Biochemistry (Moscow), 88:770-782, Jun 2023. URL: https://doi.org/10.1134/s0006297923060056, doi:10.1134/s0006297923060056. This article has 5 citations.
(kong2025complexsignalingnetworks pages 24-26): Yun Kong and Youbin Zheng. Complex signaling networks underlying blue-light-mediated floral transition in plants. Plants, 14:1533, May 2025. URL: https://doi.org/10.3390/plants14101533, doi:10.3390/plants14101533. This article has 12 citations.
(eckel2018atpboostslit pages 1-3): Maike Eckel, Wieland Steinchen, and Alfred Batschauer. Atp boosts lit state formation and activity of arabidopsis cryptochrome 2. The Plant journal : for cell and molecular biology, 96 2:389-403, Aug 2018. URL: https://doi.org/10.1111/tpj.14039, doi:10.1111/tpj.14039. This article has 15 citations.
(eckel2018atpboostslit pages 6-7): Maike Eckel, Wieland Steinchen, and Alfred Batschauer. Atp boosts lit state formation and activity of arabidopsis cryptochrome 2. The Plant journal : for cell and molecular biology, 96 2:389-403, Aug 2018. URL: https://doi.org/10.1111/tpj.14039, doi:10.1111/tpj.14039. This article has 15 citations.
(eckel2018atpboostslit media 1d942dcd): Maike Eckel, Wieland Steinchen, and Alfred Batschauer. Atp boosts lit state formation and activity of arabidopsis cryptochrome 2. The Plant journal : for cell and molecular biology, 96 2:389-403, Aug 2018. URL: https://doi.org/10.1111/tpj.14039, doi:10.1111/tpj.14039. This article has 15 citations.
(eckel2018atpboostslit media 76edfc28): Maike Eckel, Wieland Steinchen, and Alfred Batschauer. Atp boosts lit state formation and activity of arabidopsis cryptochrome 2. The Plant journal : for cell and molecular biology, 96 2:389-403, Aug 2018. URL: https://doi.org/10.1111/tpj.14039, doi:10.1111/tpj.14039. This article has 15 citations.
(eckel2018atpboostslit pages 4-6): Maike Eckel, Wieland Steinchen, and Alfred Batschauer. Atp boosts lit state formation and activity of arabidopsis cryptochrome 2. The Plant journal : for cell and molecular biology, 96 2:389-403, Aug 2018. URL: https://doi.org/10.1111/tpj.14039, doi:10.1111/tpj.14039. This article has 15 citations.
(jiang2023lightinducedllpsof pages 6-7): Bochen Jiang, Zhenhui Zhong, Lianfeng Gu, Xueyang Zhang, Jiangbo Wei, Chang Ye, Guifang Lin, Gaoping Qu, Xian Xiang, Chenjin Wen, Maureen Hummel, Julia Bailey-Serres, Qin Wang, Chuan He, Xu Wang, and Chentao Lin. Light-induced llps of the cry2/spa1/fio1 complex regulating mrna methylation and chlorophyll homeostasis in arabidopsis. Nature Plants, 9:2042-2058, Dec 2023. URL: https://doi.org/10.1038/s41477-023-01580-0, doi:10.1038/s41477-023-01580-0. This article has 79 citations and is from a highest quality peer-reviewed journal.
(mcquillen2024lightdependentmodulationof pages 1-6): Ryan McQuillen, Xinxing Yang, Christopher H. Bohrer, Joshua W. McCausland, and Jie Xiao. Light-dependent modulation of protein localization and function in living bacteria cells. bioRxiv, May 2024. URL: https://doi.org/10.1101/2022.05.01.490209, doi:10.1101/2022.05.01.490209. This article has 9 citations.
(deoliveira2025astructuraldecryption pages 10-11): Cristina C. DeOliveira and Brian R. Crane. A structural decryption of cryptochromes. Frontiers in Chemistry, Aug 2025. URL: https://doi.org/10.3389/fchem.2024.1436322, doi:10.3389/fchem.2024.1436322. This article has 18 citations.

Citations

eckel2018atpboostslit pages 8-10
fraikin2023molecularbasesof pages 4-5
kong2025complexsignalingnetworks pages 2-4
jiang2023lightinducedllpsof pages 1-2
krahmer2024environmentalcontrolof pages 7-9
kong2025complexsignalingnetworks pages 24-26
fraikin2023molecularbasesof pages 6-8
chen2021regulationofarabidopsis pages 1-2
eckel2018atpboostslit pages 6-7
eckel2018atpboostslit pages 4-6
mcquillen2024lightdependentmodulationof pages 1-6
fraikin2023molecularbasesof pages 1-2
eckel2018atpboostslit pages 1-3
deoliveira2025astructuraldecryption pages 1-2
deoliveira2024dualfacetsof pages 17-21
kong2025complexsignalingnetworks pages 26-27
kong2025complexsignalingnetworks pages 15-17
jiang2023lightinducedllpsof pages 6-7
deoliveira2025astructuraldecryption pages 10-11
https://doi.org/10.1111/tpj.14039;
https://doi.org/10.1134/s0006297923060056;
https://doi.org/10.3389/fchem.2024.1436322
https://doi.org/10.1038/s41477-023-01580-0;
https://doi.org/10.1016/j.xplc.2023.100663
https://doi.org/10.1038/s41467-021-22410-x;
https://doi.org/10.3390/plants14101533;
https://doi.org/10.1038/s41477-023-01580-0
https://doi.org/10.1146/annurev-arplant-062923-023852
https://doi.org/10.1101/2022.05.01.490209
https://doi.org/10.1134/s0006297923060056
https://doi.org/10.1038/s41467-021-22410-x
https://doi.org/10.1111/tpj.14039
https://doi.org/10.1111/tpj.14039,
https://doi.org/10.1038/s41467-021-22410-x,
https://doi.org/10.3389/fchem.2024.1436322,
https://doi.org/10.1134/s0006297923060056,
https://doi.org/10.1016/j.xplc.2023.100663,
https://doi.org/10.1038/s41477-023-01580-0,
https://doi.org/10.3390/plants14101533,
https://doi.org/10.1146/annurev-arplant-062923-023852,
https://doi.org/10.1101/2022.05.01.490209,

📄 View Raw YAML

id: Q96524
gene_symbol: CRY2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:3702
  label: Arabidopsis thaliana
description: Arabidopsis thaliana CRY2 (cryptochrome 2; At1g04400) is a nuclear, FAD-binding plant cryptochrome
  that functions as a blue-light photoreceptor. Blue-light excitation promotes CRY2 phosphorylation, homodimerization/oligomerization,
  nuclear photobody formation, and interactions with signaling partners including SPA/COP1, CIB transcription
  factors, PIF4/PIF5, BIC proteins, and flowering regulators. Its principal biological outputs are blue-light
  signaling, low-blue-light growth responses, and photoperiodic promotion of flowering through CO/FT and
  CIB-dependent pathways; broader effects on chromatin state, stomata, circadian rhythms, ROS, pathogen
  defense, and hormone responses are treated as downstream or context-specific outputs rather than the
  core molecular function.
existing_annotations:
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IDA
  original_reference_id: PMID:17073458
  negated: true
  review:
    action: ACCEPT
    summary: 'Correct negated annotation: Arabidopsis CRY2 is not an autokinase.'
    reason: PMID:17073458 directly tested AtCry2 and found that it lacked kinase activity despite FAD
      binding; retaining the NOT kinase annotation prevents propagation of the older cryptochrome autokinase
      model to CRY2.
    supported_by:
    - reference_id: PMID:17073458
      supporting_text: AtCry2 which is known to be phosphorylated upon light exposure in vivo ( 16 ) lacked
        kinase activity.
- term:
    id: GO:0046777
    label: protein autophosphorylation
  evidence_type: IDA
  original_reference_id: PMID:17073458
  negated: true
  review:
    action: ACCEPT
    summary: 'Correct negated annotation: AtCRY2 does not carry out protein autophosphorylation.'
    reason: The same biochemical study found AtCry2 lacks autokinase/autophosphorylating activity, so
      the NOT annotation is appropriate.
    supported_by:
    - reference_id: PMID:17073458
      supporting_text: AtCry2, which also contains stoichiometric amounts of FAD does not.
- term:
    id: GO:0006325
    label: chromatin organization
  evidence_type: IMP
  original_reference_id: PMID:20935177
  review:
    action: KEEP_AS_NON_CORE
    summary: Supported downstream chromatin phenotype, not the core molecular role of CRY2.
    reason: CRY2 contributes to light-dependent chromatin compaction/decompaction, but as a photoreceptor
      signaling input rather than a chromatin-organizing factor.
    supported_by:
    - reference_id: PMID:20935177
      supporting_text: Photoreceptors CRYTOCHROME2 and phytochrome B control chromatin compaction in Arabidopsis.
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation
        and photoperiodic control of floral initiation
- term:
    id: GO:0006338
    label: chromatin remodeling
  evidence_type: IMP
  original_reference_id: PMID:17470059
  review:
    action: KEEP_AS_NON_CORE
    summary: Supported as a downstream flowering-transition chromatin phenotype.
    reason: The annotation uses acts_upstream_of_or_within and is best treated as a non-core consequence
      of CRY2 signaling during floral transition, not as chromatin-remodeling activity by CRY2 itself.
    supported_by:
    - reference_id: PMID:17470059
      supporting_text: Light-regulated large-scale reorganization of chromatin during the floral transition
        in Arabidopsis.
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation
        and photoperiodic control of floral initiation
- term:
    id: GO:0009414
    label: response to water deprivation
  evidence_type: IGI
  original_reference_id: PMID:16093319
  review:
    action: KEEP_AS_NON_CORE
    summary: Water-deprivation phenotypes arise through CRY-dependent stomatal regulation.
    reason: CRY2 contributes to water-loss and drought-related phenotypes through stomatal opening, but
      this is a physiological output of blue-light signaling and not the core function of the photoreceptor.
    supported_by:
    - reference_id: PMID:16093319
      supporting_text: CRY functions additively with PHOT in mediating blue light-induced stomatal opening
- term:
    id: GO:0009416
    label: response to light stimulus
  evidence_type: IEP
  original_reference_id: PMID:20935177
  review:
    action: MODIFY
    summary: The evidence supports a blue-light photoreceptor/signaling role; this term is too broad.
    reason: CRY2 senses blue light and signals through CIB, SPA/COP1, PIF, and related partners. The generic
      response to light stimulus term should be replaced by blue-light-specific terms.
    proposed_replacement_terms:
    - id: GO:0009637
      label: response to blue light
    - id: GO:0009785
      label: blue light signaling pathway
    supported_by:
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:26724867
      supporting_text: CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH
        transcription factors, PIF4 and PIF5.
    - reference_id: PMID:36508461
      supporting_text: A role for brassinosteroid signalling in decision-making processes in the Arabidopsis
        seedling.
- term:
    id: GO:0009416
    label: response to light stimulus
  evidence_type: IMP
  original_reference_id: PMID:36508461
  review:
    action: MODIFY
    summary: The evidence supports a blue-light photoreceptor/signaling role; this term is too broad.
    reason: CRY2 senses blue light and signals through CIB, SPA/COP1, PIF, and related partners. The generic
      response to light stimulus term should be replaced by blue-light-specific terms.
    proposed_replacement_terms:
    - id: GO:0009637
      label: response to blue light
    - id: GO:0009785
      label: blue light signaling pathway
    supported_by:
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:26724867
      supporting_text: CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH
        transcription factors, PIF4 and PIF5.
    - reference_id: PMID:36508461
      supporting_text: A role for brassinosteroid signalling in decision-making processes in the Arabidopsis
        seedling.
- term:
    id: GO:0009637
    label: response to blue light
  evidence_type: IMP
  original_reference_id: PMID:9565033
  review:
    action: ACCEPT
    summary: 'Core biological process: CRY2 mediates blue-light responses.'
    reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor
      controlling phototropism, flowering, clock, and growth outputs.
    supported_by:
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
    - reference_id: PMID:24780222
      supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0009785
    label: blue light signaling pathway
  evidence_type: IGI
  original_reference_id: PMID:27846570
  review:
    action: ACCEPT
    summary: 'Core pathway annotation: CRY2 is a blue-light signaling photoreceptor.'
    reason: CRY2 photoactivation, homodimerization, photobody formation, and interaction with signaling
      partners such as BIC1, SPA1, and CIBs are central to blue-light signaling.
    supported_by:
    - reference_id: PMID:27846570
      supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
        to become physiologically active.
    - reference_id: PMID:27846570
      supporting_text: BICs also inhibit the blue light-induced formation of CRY2 photobodies
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
- term:
    id: GO:0009909
    label: regulation of flower development
  evidence_type: IDA
  original_reference_id: PMID:17259260
  review:
    action: ACCEPT
    summary: CRY2 regulates flowering through vascular-bundle FT expression.
    reason: CRY2 in vascular bundles promotes FT expression and flowering, making regulation of flower
      development a major supported developmental output.
    supported_by:
    - reference_id: PMID:17259260
      supporting_text: cry2-GFP expressed in vascular bundles increased FT expression only in vascular
        bundles.
- term:
    id: GO:0009911
    label: positive regulation of flower development
  evidence_type: IMP
  original_reference_id: PMID:17259260
  review:
    action: ACCEPT
    summary: CRY2 positively regulates flowering in appropriate light/photoperiod contexts.
    reason: CRY2-GFP expression in vascular bundles rescues late flowering and increases FT expression;
      this supports a positive flowering role.
    supported_by:
    - reference_id: PMID:17259260
      supporting_text: cry2-GFP expressed in vascular bundles increased FT expression only in vascular
        bundles.
- term:
    id: GO:0010075
    label: regulation of meristem growth
  evidence_type: IGI
  original_reference_id: PMID:18424613
  review:
    action: KEEP_AS_NON_CORE
    summary: Supported light-dependent shoot apex/meristem phenotype, not core photoreceptor function.
    reason: CRY2 affects meristem/cell-cycle programs downstream of light perception, but its core role
      remains blue-light photoreceptor signaling.
    supported_by:
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation
        and photoperiodic control of floral initiation
- term:
    id: GO:0010118
    label: stomatal movement
  evidence_type: IGI
  original_reference_id: PMID:16093319
  review:
    action: KEEP_AS_NON_CORE
    summary: Supported stomatal output of CRY signaling.
    reason: CRY2 participates with CRY1/PHOT/COP1 pathways in blue-light-induced stomatal opening, but
      stomatal movement is a downstream physiological response.
    supported_by:
    - reference_id: PMID:16093319
      supporting_text: CRY functions additively with PHOT in mediating blue light-induced stomatal opening
- term:
    id: GO:0010617
    label: circadian regulation of calcium ion oscillation
  evidence_type: IMP
  original_reference_id: PMID:17982000
  review:
    action: KEEP_AS_NON_CORE
    summary: Circadian calcium oscillation is a downstream clock/light-signaling phenotype.
    reason: The evidence links cryptochrome light input to clock-regulated calcium rhythms; this is not
      the primary molecular function of CRY2.
    supported_by:
    - reference_id: PMID:11743105
      supporting_text: Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock
        by transducing the light signal to the central oscillator.
- term:
    id: GO:0003904
    label: deoxyribodipyrimidine photo-lyase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    action: REMOVE
    summary: Over-propagated photolyase-family annotation; CRY2 is a signaling cryptochrome, not a DNA
      photolyase.
    reason: PANTHER PTHR11455 mixes cryptochromes and DNA photolyases, and UniProt explicitly cautions
      that CRY2 was originally thought to be a DNA photolyase. The Arabidopsis CRY2 literature supports
      FAD-dependent blue-light signaling rather than deoxyribodipyrimidine repair activity.
    supported_by:
    - reference_id: file:interpro/panther/PTHR11455/PTHR11455-notes.md
      supporting_text: The family contains both cryptochromes and photolyases; subfamilies separate circadian
        cryptochromes from repair enzymes.
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation
        and photoperiodic control of floral initiation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11089975
  review:
    action: REMOVE
    summary: PHYB interaction supports photoreceptor crosstalk, but GO:0005515 is too generic for CRY2.
    reason: The evidence supports light-dependent CRY2-PHYB crosstalk in flowering, hypocotyl, and clock
      outputs. It does not define a distinct CRY2 molecular function beyond blue-light photoreceptor
      signaling, so generic protein binding should not be retained.
    supported_by:
    - reference_id: PMID:11089975
      supporting_text: PhyB interacts directly with cry2 as observed in co-immunoprecipitation experiments
        with transgenic Arabidopsis plants overexpressing cry2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11509693
  review:
    action: MODIFY
    summary: COP1 binding is real and mechanistically important, but generic protein binding should be
      replaced.
    reason: COP1 is the E3 ubiquitin ligase repressed by photoactivated cryptochromes. Ubiquitin protein
      ligase binding captures the relevant molecular interaction better than GO:0005515.
    proposed_replacement_terms:
    - id: GO:0031625
      label: ubiquitin protein ligase binding
    supported_by:
    - reference_id: PMID:11509693
      supporting_text: Photoactivated cryptochromes repress COP1 activity through a direct protein-protein
        contact.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18988809
  review:
    action: MODIFY
    summary: CIB1 interaction should be captured as bHLH transcription factor binding, not generic protein
      binding.
    reason: CIB1 is a CRY2-interacting basic helix-loop-helix transcription factor that promotes FT expression
      and floral initiation. The more specific bHLH transcription factor binding term captures this interaction.
    proposed_replacement_terms:
    - id: GO:0043425
      label: bHLH transcription factor binding
    supported_by:
    - reference_id: PMID:18988809
      supporting_text: CIB1 interacts with CRY2 (cryptochrome 2) in a blue light-specific manner in yeast
        and Arabidopsis cells
    - reference_id: PMID:18988809
      supporting_text: CIB1 binds to G box (CACGTG) in vitro with a higher affinity than its interaction
        with other E-box elements (CANNTG).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20624951
  review:
    action: MODIFY
    summary: The defense-context interaction is mediated through COP1, so generic protein binding should
      be replaced.
    reason: The paper links CRY2/PHOT2 control of resistance protein stability to COP1, an E3 ubiquitin
      ligase. Ubiquitin protein ligase binding is more informative than retaining GO:0005515.
    proposed_replacement_terms:
    - id: GO:0031625
      label: ubiquitin protein ligase binding
    supported_by:
    - reference_id: PMID:20624951
      supporting_text: HRT does not directly associate with either CRY2 or PHOT2 but does bind the CRY2-/PHOT2-interacting
        E3 ubiquitin ligase, COP1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21511872
  review:
    action: REMOVE
    summary: This SPA1 paper is CRY1-focused and does not justify retaining generic CRY2 protein binding.
    reason: The source title and evidence concern cryptochrome 1-SPA1 signaling. Even if related to the
      broader cryptochrome mechanism, GO:0005515 is not an informative CRY2 molecular function and should
      not remain as a non-core annotation.
    supported_by:
    - reference_id: PMID:21511872
      supporting_text: Blue-light-dependent interaction of cryptochrome 1 with SPA1 defines a dynamic signaling
        mechanism.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21514160
  review:
    action: MODIFY
    summary: CRY2-SPA1/COP1 complex formation should be captured with a COP1 ligase-binding term.
    reason: SPA1 acts through the COP1 E3 ubiquitin ligase, and the study shows CRY2-SPA1 interaction
      enhances CRY2-COP1 interaction and suppresses COP1-dependent CO degradation. Ubiquitin protein
      ligase binding is more informative than GO:0005515.
    proposed_replacement_terms:
    - id: GO:0031625
      label: ubiquitin protein ligase binding
    supported_by:
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:21514160
      supporting_text: The blue light-dependent CRY2-SPA1 interaction enhances the CRY2-COP1 interaction
        to suppress the COP1 activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22139370
  review:
    action: REMOVE
    summary: Photoactivation mechanism evidence does not require retaining generic protein binding.
    reason: The paper supports CRY2 photoactivation biology, which is already represented by blue-light
      photoreceptor activity and blue-light signaling annotations. GO:0005515 is too broad to retain.
    supported_by:
    - reference_id: PMID:22139370
      supporting_text: Arabidopsis cryptochrome 2 (CRY2) functions by the photoactivation mechanism distinct
        from the tryptophan (trp) triad-dependent photoreduction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22739826
  review:
    action: REMOVE
    summary: SPA-dependent CRY2 degradation is pathway regulation, not a useful generic binding annotation.
    reason: The evidence supports control of CRY2 abundance by SPA proteins and phyA. This is already
      captured in CRY2 signaling/degradation context, while GO:0005515 adds no informative molecular
      function.
    supported_by:
    - reference_id: PMID:22739826
      supporting_text: Studies showed a robust physical interaction of cry2 with SPA1 in nuclei of living
        cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24130508
  review:
    action: MODIFY
    summary: CIB-family interactions should be represented as bHLH transcription factor binding.
    reason: CIB proteins are bHLH transcription factors that act redundantly downstream of CRY2 in flowering.
      The specific bHLH transcription factor binding term is more informative than GO:0005515.
    proposed_replacement_terms:
    - id: GO:0043425
      label: bHLH transcription factor binding
    supported_by:
    - reference_id: PMID:24130508
      supporting_text: Our study demonstrates that CIBs function redundantly in regulating CRY2-dependent
        flowering.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24780222
  review:
    action: MODIFY
    summary: CRY2-CIB1 kinetic interaction should be replaced by bHLH transcription factor binding.
    reason: CIB1 is a bHLH transcription factor and the evidence measures blue-light-driven CRY2 association
      with CIB1. GO:0043425 is more specific than generic protein binding.
    proposed_replacement_terms:
    - id: GO:0043425
      label: bHLH transcription factor binding
    supported_by:
    - reference_id: PMID:24780222
      supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26724867
  review:
    action: MODIFY
    summary: PIF4/PIF5 contacts should be represented as bHLH transcription factor binding.
    reason: PIF4 and PIF5 are bHLH transcription factors contacted by CRY2 during low-blue-light growth
      regulation. GO:0043425 is the informative replacement for generic protein binding.
    proposed_replacement_terms:
    - id: GO:0043425
      label: bHLH transcription factor binding
    supported_by:
    - reference_id: PMID:26724867
      supporting_text: CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH
        transcription factors, PIF4 and PIF5.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27846570
  review:
    action: REMOVE
    summary: BIC1 interaction explains CRY2 inactivation but does not warrant retaining GO:0005515.
    reason: BIC1 is an inhibitory regulator of CRY2 homodimerization and photobody formation. The biology
      belongs in the blue-light signaling description, while generic protein binding remains uninformative.
    supported_by:
    - reference_id: PMID:27846570
      supporting_text: BICs also inhibit the blue light-induced formation of CRY2 photobodies.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28492234
  review:
    action: MODIFY
    summary: PPK interaction should be captured as protein kinase binding.
    reason: The study identifies photoregulatory protein kinases that bind photoexcited CRY2 and catalyze
      blue-light-dependent CRY2 phosphorylation. Protein kinase binding is more informative than GO:0005515.
    proposed_replacement_terms:
    - id: GO:0019901
      label: protein kinase binding
    supported_by:
    - reference_id: PMID:28492234
      supporting_text: Photoregulatory Protein Kinases (previously referred to as MUT9-like kinases) interact
        with and phosphorylate photoexcited CRY2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28633330
  review:
    action: REMOVE
    summary: NRP-dependent localization effects are not an informative CRY2 protein binding annotation.
    reason: The evidence links NRP/PevD1 context to CRY2 subcellular localization. No more specific CRY2
      molecular function term is supported, and generic protein binding should not be retained.
    supported_by:
    - reference_id: PMID:28633330
      supporting_text: The asparagine-rich protein NRP interacts with the Verticillium effector PevD1 and
        regulates the subcellular localization of cryptochrome 2.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32661061
  review:
    action: MODIFY
    summary: TOE1/TOE2 interactions should be represented as DNA-binding transcription factor binding.
    reason: TOE1 and TOE2 are AP2-like DNA-binding transcription factors that interact with photoexcited
      CRY2 in flowering regulation. GO:0140297 is more informative than generic protein binding.
    proposed_replacement_terms:
    - id: GO:0140297
      label: DNA-binding transcription factor binding
    supported_by:
    - reference_id: PMID:32661061
      supporting_text: Photoexcited Cryptochrome2 Interacts Directly with TOE1 and TOE2 in Flowering Regulation.
    - reference_id: PMID:32661061
      supporting_text: The AP2-like transcriptional factor TOE1 negatively regulates FT expression and
        flowering by indirectly inhibiting CO transcriptional activation activity and directly binding
        to FT.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36396657
  review:
    action: REMOVE
    summary: CIS1 interaction supports thermosensory flowering signaling, but generic protein binding
      should not be retained.
    reason: CIS1 is a splicing/RNA-binding factor whose activity is regulated in a CRY2-dependent pathway.
      The evidence is important for biological process interpretation, but GO:0005515 is not an informative
      CRY2 molecular function.
    supported_by:
    - reference_id: PMID:36396657
      supporting_text: CRY2 interacts with CIS1 to regulate thermosensory flowering via FLM alternative
        splicing.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: ATP binding is supported but is an accessory biochemical property of the photoreceptor.
    reason: UniProt and biochemical literature support ATP binding as influencing CRY2 conformation/photochemistry,
      but ATP binding is not the central GO molecular function; blue-light photoreceptor activity is the
      core MF.
    supported_by:
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Binding to ATP mediates conformational changes which facilitate flavin binding
    - reference_id: file:ARATH/CRY2/CRY2-deep-research-falcon.md
      supporting_text: 'Arabidopsis thaliana CRY2 (UniProt: Q96524) is a plant blue-light photoreceptor'
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:17073458
  review:
    action: KEEP_AS_NON_CORE
    summary: ATP binding is supported but is an accessory biochemical property of the photoreceptor.
    reason: UniProt and biochemical literature support ATP binding as influencing CRY2 conformation/photochemistry,
      but ATP binding is not the central GO molecular function; blue-light photoreceptor activity is the
      core MF.
    supported_by:
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Binding to ATP mediates conformational changes which facilitate flavin binding
    - reference_id: file:ARATH/CRY2/CRY2-deep-research-falcon.md
      supporting_text: 'Arabidopsis thaliana CRY2 (UniProt: Q96524) is a plant blue-light photoreceptor'
- term:
    id: GO:0009882
    label: blue light photoreceptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    action: ACCEPT
    summary: 'Core molecular function: CRY2 is a blue-light photoreceptor. The crystal structure of the
      CRY2 PHR/photolyase-homology region (CRY2N) with bound FAD (PDB 6K8I) directly visualizes the FAD-bound
      photosensory module underlying this activity.'
    reason: CRY2 is a plant cryptochrome whose FAD-dependent blue-light photoactivation drives dimerization,
      photobody formation, and downstream signaling.
    supported_by:
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:27846570
      supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
        to become physiologically active.
    - reference_id: PMID:32398826
      supporting_text: Cryptochromes (CRYs) are blue-light receptors in plants that harbor FAD as a cofactor
        and regulate various physiological responses.
    - reference_id: file:ARATH/CRY2/CRY2-deep-research-falcon.md
      supporting_text: 'Arabidopsis thaliana CRY2 (UniProt: Q96524) is a plant blue-light photoreceptor'
- term:
    id: GO:0009882
    label: blue light photoreceptor activity
  evidence_type: ISS
  original_reference_id: PMID:11493548
  review:
    action: ACCEPT
    summary: 'Core molecular function: CRY2 is a blue-light photoreceptor.'
    reason: CRY2 is a plant cryptochrome whose FAD-dependent blue-light photoactivation drives dimerization,
      photobody formation, and downstream signaling.
    supported_by:
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:27846570
      supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
        to become physiologically active.
    - reference_id: PMID:32398826
      supporting_text: Cryptochromes (CRYs) are blue-light receptors in plants that harbor FAD as a cofactor
        and regulate various physiological responses.
    - reference_id: file:ARATH/CRY2/CRY2-deep-research-falcon.md
      supporting_text: 'Arabidopsis thaliana CRY2 (UniProt: Q96524) is a plant blue-light photoreceptor'
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:15805487
  review:
    action: KEEP_AS_NON_CORE
    summary: Self-association is an important activation mechanism but not the primary MF term.
    reason: CRY2 homodimerization/oligomerization is physiologically important for photoactivation and
      photobody formation, but this term should support the photoreceptor mechanism rather than replace
      blue-light photoreceptor activity as the core MF.
    supported_by:
    - reference_id: PMID:27846570
      supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
        to become physiologically active.
    - reference_id: PMID:22311776
      supporting_text: photoexcited cryptochromes form oligomers, preceding other biochemical changes
        of CRY2
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:17438275
  review:
    action: KEEP_AS_NON_CORE
    summary: Self-association is an important activation mechanism but not the primary MF term.
    reason: CRY2 homodimerization/oligomerization is physiologically important for photoactivation and
      photobody formation, but this term should support the photoreceptor mechanism rather than replace
      blue-light photoreceptor activity as the core MF.
    supported_by:
    - reference_id: PMID:27846570
      supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
        to become physiologically active.
    - reference_id: PMID:22311776
      supporting_text: photoexcited cryptochromes form oligomers, preceding other biochemical changes
        of CRY2
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: Homodimerization is supported mechanistically but is secondary to photoreceptor activity.
    reason: CRY2 becomes physiologically active through blue-light-dependent homodimerization, but the
      core molecular function is blue-light photoreceptor activity.
    supported_by:
    - reference_id: PMID:27846570
      supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
        to become physiologically active.
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IPI
  original_reference_id: PMID:15805487
  review:
    action: KEEP_AS_NON_CORE
    summary: Homodimerization is supported mechanistically but is secondary to photoreceptor activity.
    reason: CRY2 becomes physiologically active through blue-light-dependent homodimerization, but the
      core molecular function is blue-light photoreceptor activity.
    supported_by:
    - reference_id: PMID:27846570
      supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
        to become physiologically active.
- term:
    id: GO:0071949
    label: FAD binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: FAD binding is an essential chromophore-binding property of CRY2. The crystal structures of
      CRY2N (PDB 6K8I; and 6K8K with FAD plus Mg/AMP) resolve the bound FAD cofactor in the photolyase-homology
      region.
    reason: CRY2 is an FAD-containing photoreceptor; FAD binding supports photochemistry but is best treated
      as a non-core cofactor-binding annotation relative to blue-light photoreceptor activity.
    supported_by:
    - reference_id: PMID:17073458
      supporting_text: Cryptochromes are FAD-based blue-light photoreceptors that regulate growth and
        development in plants and the circadian clock in animals.
    - reference_id: PMID:32398826
      supporting_text: Cryptochromes (CRYs) are blue-light receptors in plants that harbor FAD as a cofactor
        and regulate various physiological responses.
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Binds 1 FAD per subunit.
- term:
    id: GO:0071949
    label: FAD binding
  evidence_type: IDA
  original_reference_id: PMID:17073458
  review:
    action: KEEP_AS_NON_CORE
    summary: FAD binding is an essential chromophore-binding property of CRY2. The crystal structures of
      CRY2N (PDB 6K8I; and 6K8K with FAD plus Mg/AMP) resolve the bound FAD cofactor in the photolyase-homology
      region.
    reason: CRY2 is an FAD-containing photoreceptor; FAD binding supports photochemistry but is best treated
      as a non-core cofactor-binding annotation relative to blue-light photoreceptor activity.
    supported_by:
    - reference_id: PMID:17073458
      supporting_text: Cryptochromes are FAD-based blue-light photoreceptors that regulate growth and
        development in plants and the circadian clock in animals.
    - reference_id: PMID:32398826
      supporting_text: Cryptochromes (CRYs) are blue-light receptors in plants that harbor FAD as a cofactor
        and regulate various physiological responses.
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Binds 1 FAD per subunit.
- term:
    id: GO:0007623
    label: circadian rhythm
  evidence_type: IEP
  original_reference_id: PMID:11743105
  review:
    action: KEEP_AS_NON_CORE
    summary: CRY2 expression and signaling are connected to the circadian system, but this is not the
      core CRY2 role.
    reason: Cryptochromes provide light input to circadian regulation, while CRY2 core function is blue-light
      photoreceptor signaling.
    supported_by:
    - reference_id: PMID:11743105
      supporting_text: Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock
        by transducing the light signal to the central oscillator.
- term:
    id: GO:0009414
    label: response to water deprivation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: Water-deprivation phenotypes arise through CRY-dependent stomatal regulation.
    reason: CRY2 contributes to water-loss and drought-related phenotypes through stomatal opening, but
      this is a physiological output of blue-light signaling and not the core function of the photoreceptor.
    supported_by:
    - reference_id: PMID:16093319
      supporting_text: CRY functions additively with PHOT in mediating blue light-induced stomatal opening
- term:
    id: GO:0009416
    label: response to light stimulus
  evidence_type: IMP
  original_reference_id: PMID:21296763
  review:
    action: MODIFY
    summary: The evidence supports a blue-light photoreceptor/signaling role; this term is too broad.
    reason: CRY2 senses blue light and signals through CIB, SPA/COP1, PIF, and related partners. The generic
      response to light stimulus term should be replaced by blue-light-specific terms.
    proposed_replacement_terms:
    - id: GO:0009637
      label: response to blue light
    - id: GO:0009785
      label: blue light signaling pathway
    supported_by:
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:26724867
      supporting_text: CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH
        transcription factors, PIF4 and PIF5.
    - reference_id: PMID:36508461
      supporting_text: A role for brassinosteroid signalling in decision-making processes in the Arabidopsis
        seedling.
- term:
    id: GO:0009637
    label: response to blue light
  evidence_type: IMP
  original_reference_id: PMID:12857830
  review:
    action: ACCEPT
    summary: 'Core biological process: CRY2 mediates blue-light responses.'
    reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor
      controlling phototropism, flowering, clock, and growth outputs.
    supported_by:
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
    - reference_id: PMID:24780222
      supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0009637
    label: response to blue light
  evidence_type: IEP
  original_reference_id: PMID:20624951
  review:
    action: ACCEPT
    summary: 'Core biological process: CRY2 mediates blue-light responses.'
    reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor
      controlling phototropism, flowering, clock, and growth outputs.
    supported_by:
    - reference_id: PMID:20624951
      supporting_text: The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are
        required for the stability of the R protein HRT
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
    - reference_id: PMID:24780222
      supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0009637
    label: response to blue light
  evidence_type: IDA
  original_reference_id: PMID:21511872
  review:
    action: ACCEPT
    summary: 'Core biological process: CRY2 mediates blue-light responses.'
    reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor
      controlling phototropism, flowering, clock, and growth outputs.
    supported_by:
    - reference_id: PMID:21514160
      supporting_text: blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear
        bodies
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
    - reference_id: PMID:24780222
      supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0009637
    label: response to blue light
  evidence_type: IDA
  original_reference_id: PMID:21514160
  review:
    action: ACCEPT
    summary: 'Core biological process: CRY2 mediates blue-light responses.'
    reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor
      controlling phototropism, flowering, clock, and growth outputs.
    supported_by:
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
    - reference_id: PMID:24780222
      supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0009637
    label: response to blue light
  evidence_type: IDA
  original_reference_id: PMID:22739826
  review:
    action: ACCEPT
    summary: 'Core biological process: CRY2 mediates blue-light responses.'
    reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor
      controlling phototropism, flowering, clock, and growth outputs.
    supported_by:
    - reference_id: PMID:22739826
      supporting_text: Degradation of Arabidopsis CRY2 is regulated by SPA proteins and phytochrome A.
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
    - reference_id: PMID:24780222
      supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0009637
    label: response to blue light
  evidence_type: IMP
  original_reference_id: PMID:23511208
  review:
    action: ACCEPT
    summary: 'Core biological process: CRY2 mediates blue-light responses.'
    reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor
      controlling phototropism, flowering, clock, and growth outputs.
    supported_by:
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
    - reference_id: PMID:24780222
      supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0009637
    label: response to blue light
  evidence_type: IDA
  original_reference_id: PMID:24130508
  review:
    action: ACCEPT
    summary: 'Core biological process: CRY2 mediates blue-light responses.'
    reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor
      controlling phototropism, flowering, clock, and growth outputs.
    supported_by:
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
    - reference_id: PMID:24780222
      supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0009637
    label: response to blue light
  evidence_type: IDA
  original_reference_id: PMID:24780222
  review:
    action: ACCEPT
    summary: 'Core biological process: CRY2 mediates blue-light responses.'
    reason: Multiple genetic, biochemical, and cell biological studies support CRY2 as a blue-light photoreceptor
      controlling phototropism, flowering, clock, and growth outputs.
    supported_by:
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
    - reference_id: PMID:24780222
      supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0009638
    label: phototropism
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: CRY2 contributes to phototropism with phototropins, but this is a downstream response.
    reason: Cryptochromes modulate phototropism depending on blue-light fluence; the core CRY2 role is
      light perception/signaling rather than tropic growth execution.
    supported_by:
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
- term:
    id: GO:0009638
    label: phototropism
  evidence_type: IMP
  original_reference_id: PMID:12857830
  review:
    action: KEEP_AS_NON_CORE
    summary: CRY2 contributes to phototropism with phototropins, but this is a downstream response.
    reason: Cryptochromes modulate phototropism depending on blue-light fluence; the core CRY2 role is
      light perception/signaling rather than tropic growth execution.
    supported_by:
    - reference_id: PMID:9565033
      supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
    - reference_id: PMID:12857830
      supporting_text: phototropins and cryptochromes function together to enhance phototropism under
        low fluence rates
- term:
    id: GO:0009646
    label: response to absence of light
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: Darkness affects CRY2 abundance and signaling state, but this is not a core process annotation.
    reason: CRY2 expression/protein stability changes in darkness and light; the underlying core function
      is blue-light photoreception and light-regulated signaling.
    supported_by:
    - reference_id: PMID:11743105
      supporting_text: Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock
        by transducing the light signal to the central oscillator.
    - reference_id: PMID:20624951
      supporting_text: The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are
        required for the stability of the R protein HRT
- term:
    id: GO:0009646
    label: response to absence of light
  evidence_type: IEP
  original_reference_id: PMID:11743105
  review:
    action: KEEP_AS_NON_CORE
    summary: Darkness affects CRY2 abundance and signaling state, but this is not a core process annotation.
    reason: CRY2 expression/protein stability changes in darkness and light; the underlying core function
      is blue-light photoreception and light-regulated signaling.
    supported_by:
    - reference_id: PMID:11743105
      supporting_text: Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock
        by transducing the light signal to the central oscillator.
    - reference_id: PMID:20624951
      supporting_text: The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are
        required for the stability of the R protein HRT
- term:
    id: GO:0009646
    label: response to absence of light
  evidence_type: IEP
  original_reference_id: PMID:20624951
  review:
    action: KEEP_AS_NON_CORE
    summary: Darkness affects CRY2 abundance and signaling state, but this is not a core process annotation.
    reason: CRY2 expression/protein stability changes in darkness and light; the underlying core function
      is blue-light photoreception and light-regulated signaling.
    supported_by:
    - reference_id: PMID:11743105
      supporting_text: Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock
        by transducing the light signal to the central oscillator.
    - reference_id: PMID:20624951
      supporting_text: The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are
        required for the stability of the R protein HRT
- term:
    id: GO:0009785
    label: blue light signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    action: ACCEPT
    summary: 'Core pathway annotation: CRY2 is a blue-light signaling photoreceptor.'
    reason: CRY2 photoactivation, homodimerization, photobody formation, and interaction with signaling
      partners such as BIC1, SPA1, and CIBs are central to blue-light signaling.
    supported_by:
    - reference_id: PMID:27846570
      supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
        to become physiologically active.
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
- term:
    id: GO:0009785
    label: blue light signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: ACCEPT
    summary: 'Core pathway annotation: CRY2 is a blue-light signaling photoreceptor.'
    reason: CRY2 photoactivation, homodimerization, photobody formation, and interaction with signaling
      partners such as BIC1, SPA1, and CIBs are central to blue-light signaling.
    supported_by:
    - reference_id: PMID:27846570
      supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
        to become physiologically active.
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
    - reference_id: PMID:24130508
      supporting_text: CIB1 (CRY2-interacting bHLH 1) specifically interacts with CRY2 in response to
        blue light to activate the transcription of FT
- term:
    id: GO:0009791
    label: post-embryonic development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: MARK_AS_OVER_ANNOTATED
    summary: Too broad; CRY2 affects several post-embryonic traits through light signaling.
    reason: Post-embryonic development is a broad phenotypic umbrella. More specific CRY2 annotations
      to blue-light signaling, flowering, phototropism, and low-blue-light growth are preferable.
    supported_by:
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation
        and photoperiodic control of floral initiation
- term:
    id: GO:0010075
    label: regulation of meristem growth
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: Supported light-dependent shoot apex/meristem phenotype, not core photoreceptor function.
    reason: CRY2 affects meristem/cell-cycle programs downstream of light perception, but its core role
      remains blue-light photoreceptor signaling.
    supported_by:
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation
        and photoperiodic control of floral initiation
- term:
    id: GO:0010118
    label: stomatal movement
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: Supported stomatal output of CRY signaling.
    reason: CRY2 participates with CRY1/PHOT/COP1 pathways in blue-light-induced stomatal opening, but
      stomatal movement is a downstream physiological response.
    supported_by:
    - reference_id: PMID:16093319
      supporting_text: CRY functions additively with PHOT in mediating blue light-induced stomatal opening
- term:
    id: GO:0010244
    label: response to low fluence blue light stimulus by blue low-fluence system
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: ACCEPT
    summary: CRY2 is important for limiting/low-blue-light growth responses.
    reason: CRY1/CRY2 perceive reduced blue light and directly contact PIF4/PIF5 to control growth under
      limiting blue light.
    supported_by:
    - reference_id: PMID:26724867
      supporting_text: CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH
        transcription factors, PIF4 and PIF5.
    - reference_id: PMID:19558423
      supporting_text: 'Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal
        regulation.'
- term:
    id: GO:0010244
    label: response to low fluence blue light stimulus by blue low-fluence system
  evidence_type: IMP
  original_reference_id: PMID:19558423
  review:
    action: ACCEPT
    summary: CRY2 is important for limiting/low-blue-light growth responses.
    reason: CRY1/CRY2 perceive reduced blue light and directly contact PIF4/PIF5 to control growth under
      limiting blue light.
    supported_by:
    - reference_id: PMID:26724867
      supporting_text: CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH
        transcription factors, PIF4 and PIF5.
    - reference_id: PMID:19558423
      supporting_text: 'Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal
        regulation.'
- term:
    id: GO:0010244
    label: response to low fluence blue light stimulus by blue low-fluence system
  evidence_type: IEP
  original_reference_id: PMID:26724867
  review:
    action: ACCEPT
    summary: CRY2 is important for limiting/low-blue-light growth responses.
    reason: CRY1/CRY2 perceive reduced blue light and directly contact PIF4/PIF5 to control growth under
      limiting blue light.
    supported_by:
    - reference_id: PMID:26724867
      supporting_text: CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH
        transcription factors, PIF4 and PIF5.
- term:
    id: GO:0010617
    label: circadian regulation of calcium ion oscillation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: Circadian calcium oscillation is a downstream clock/light-signaling phenotype.
    reason: The evidence links cryptochrome light input to clock-regulated calcium rhythms; this is not
      the primary molecular function of CRY2.
    supported_by:
    - reference_id: PMID:11743105
      supporting_text: Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock
        by transducing the light signal to the central oscillator.
- term:
    id: GO:0032922
    label: circadian regulation of gene expression
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    action: KEEP_AS_NON_CORE
    summary: Phylogenetic circadian gene-expression annotation is plausible but not the main plant CRY2
      function.
    reason: Cryptochromes are light inputs to clock gene expression, but Arabidopsis CRY2 is primarily
      a blue-light signaling photoreceptor for flowering and growth responses.
    supported_by:
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0042752
    label: regulation of circadian rhythm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: Supported CRY contribution to clock period/rhythmicity, not core CRY2 function.
    reason: CRY signaling affects circadian period and temperature/light input balance, but this is a
      downstream regulatory output of photoreceptor signaling.
    supported_by:
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0042752
    label: regulation of circadian rhythm
  evidence_type: IMP
  original_reference_id: PMID:23511208
  review:
    action: KEEP_AS_NON_CORE
    summary: Supported CRY contribution to clock period/rhythmicity, not core CRY2 function.
    reason: CRY signaling affects circadian period and temperature/light input balance, but this is a
      downstream regulatory output of photoreceptor signaling.
    supported_by:
    - reference_id: PMID:23511208
      supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
        lengthens the circadian period
- term:
    id: GO:0043153
    label: entrainment of circadian clock by photoperiod
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    action: KEEP_AS_NON_CORE
    summary: Photoperiodic clock entrainment is a plausible cryptochrome output, not core molecular activity.
    reason: Cryptochromes are light inputs to clock entrainment, but the annotation is phylogenetically
      inferred and broader than the experimentally established CRY2 photoreceptor mechanism.
    supported_by:
    - reference_id: PMID:11743105
      supporting_text: Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock
        by transducing the light signal to the central oscillator.
- term:
    id: GO:0048574
    label: long-day photoperiodism, flowering
  evidence_type: IMP
  original_reference_id: PMID:21296763
  review:
    action: ACCEPT
    summary: CRY2 promotes flowering under photoperiodic/continuous-light contexts.
    reason: Loss and rescue experiments support CRY2 promotion of flowering through FT and photoperiodic
      signaling pathways.
    supported_by:
    - reference_id: PMID:21296763
      supporting_text: an important role for Arabidopsis CRY2 to accelerate flowering time in continuous
        light.
    - reference_id: PMID:17259260
      supporting_text: cry2-GFP expressed in vascular bundles increased FT expression only in vascular
        bundles.
- term:
    id: GO:0048580
    label: regulation of post-embryonic development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: MARK_AS_OVER_ANNOTATED
    summary: Overly broad developmental-process annotation.
    reason: CRY2 regulates specific light-responsive developmental outputs; broad regulation of post-embryonic
      development is less informative than blue-light signaling and flowering terms.
    supported_by:
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation
        and photoperiodic control of floral initiation
- term:
    id: GO:0048731
    label: system development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: MARK_AS_OVER_ANNOTATED
    summary: Overly broad system-development annotation.
    reason: System development does not capture the CRY2 mechanism and should not be used when specific
      light signaling and flowering annotations are available.
    supported_by:
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Photoreceptor that mediates primarily blue light inhibition of hypocotyl elongation
        and photoperiodic control of floral initiation
- term:
    id: GO:0051607
    label: defense response to virus
  evidence_type: IMP
  original_reference_id: PMID:20624951
  review:
    action: KEEP_AS_NON_CORE
    summary: Supported antiviral-defense output of CRY2/PHOT2 regulation of HRT stability.
    reason: CRY2 contributes to R-protein-mediated viral defense via COP1/HRT stability, but this is a
      specialized downstream output rather than the conserved core photoreceptor function.
    supported_by:
    - reference_id: PMID:20624951
      supporting_text: The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are
        required for the stability of the R protein HRT
- term:
    id: GO:0072387
    label: flavin adenine dinucleotide metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: MODIFY
    summary: FAD is the CRY2 chromophore, but CRY2 is not an FAD metabolic enzyme.
    reason: The evidence concerns FAD redox photochemistry and light sensitivity, not FAD biosynthesis,
      catabolism, or metabolism. Replace with FAD binding and blue-light photoreceptor activity.
    proposed_replacement_terms:
    - id: GO:0071949
      label: FAD binding
    - id: GO:0009882
      label: blue light photoreceptor activity
    supported_by:
    - reference_id: PMID:25428980
      supporting_text: Cellular metabolites enhance the light sensitivity of Arabidopsis cryptochrome
        through alternate electron transfer pathways.
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Binds 1 FAD per subunit.
- term:
    id: GO:0072387
    label: flavin adenine dinucleotide metabolic process
  evidence_type: IMP
  original_reference_id: PMID:25428980
  review:
    action: MODIFY
    summary: FAD is the CRY2 chromophore, but CRY2 is not an FAD metabolic enzyme.
    reason: The evidence concerns FAD redox photochemistry and light sensitivity, not FAD biosynthesis,
      catabolism, or metabolism. Replace with FAD binding and blue-light photoreceptor activity.
    proposed_replacement_terms:
    - id: GO:0071949
      label: FAD binding
    - id: GO:0009882
      label: blue light photoreceptor activity
    supported_by:
    - reference_id: PMID:25428980
      supporting_text: Cellular metabolites enhance the light sensitivity of Arabidopsis cryptochrome
        through alternate electron transfer pathways.
    - reference_id: file:ARATH/CRY2/CRY2-uniprot.txt
      supporting_text: Binds 1 FAD per subunit.
- term:
    id: GO:1901371
    label: regulation of leaf morphogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: Leaf/petiole morphogenesis is a low-blue-light growth output.
    reason: CRY2 affects petiole/leaf morphogenesis through light and hormone-regulated growth responses,
      but this is downstream of photoreceptor signaling.
    supported_by:
    - reference_id: PMID:19558423
      supporting_text: 'Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal
        regulation.'
- term:
    id: GO:1901371
    label: regulation of leaf morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:19558423
  review:
    action: KEEP_AS_NON_CORE
    summary: Leaf/petiole morphogenesis is a low-blue-light growth output.
    reason: CRY2 affects petiole/leaf morphogenesis through light and hormone-regulated growth responses,
      but this is downstream of photoreceptor signaling.
    supported_by:
    - reference_id: PMID:19558423
      supporting_text: 'Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal
        regulation.'
- term:
    id: GO:1902347
    label: response to strigolactone
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: Strigolactone response is a hormone/light crosstalk phenotype.
    reason: The strigolactone annotation reflects hypocotyl-growth crosstalk with photoreceptor pathways;
      it is not a core CRY2 molecular function.
    supported_by:
    - reference_id: PMID:24126495
      supporting_text: Strigolactone-regulated hypocotyl elongation is dependent on cryptochrome and phytochrome
        signaling pathways in Arabidopsis.
- term:
    id: GO:1902347
    label: response to strigolactone
  evidence_type: IMP
  original_reference_id: PMID:24126495
  review:
    action: KEEP_AS_NON_CORE
    summary: Strigolactone response is a hormone/light crosstalk phenotype.
    reason: The strigolactone annotation reflects hypocotyl-growth crosstalk with photoreceptor pathways;
      it is not a core CRY2 molecular function.
    supported_by:
    - reference_id: PMID:24126495
      supporting_text: Strigolactone-regulated hypocotyl elongation is dependent on cryptochrome and phytochrome
        signaling pathways in Arabidopsis.
- term:
    id: GO:2000028
    label: regulation of photoperiodism, flowering
  evidence_type: IDA
  original_reference_id: PMID:21514160
  review:
    action: ACCEPT
    summary: CRY2 regulates photoperiodic flowering via SPA1/COP1/CO/FT signaling.
    reason: Blue-light-dependent CRY2-SPA1 interaction suppresses COP1-dependent CO degradation and promotes
      FT expression and floral initiation.
    supported_by:
    - reference_id: PMID:21514160
      supporting_text: SPA1 acts as a signaling molecule to mediate CRY2-dependent control of CO protein
        stability, FT transcription, and floral initiation in response to blue light.
    - reference_id: PMID:21514160
      supporting_text: CRY2 undergoes blue light-dependent physical interaction with SPA1.
- term:
    id: GO:2000377
    label: regulation of reactive oxygen species metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: ROS regulation is a reported CRY2 signaling output, not the central function.
    reason: CRY2 may promote blue-light-dependent ROS formation, but this is downstream of photoreceptor
      activation and remains less central than blue-light signaling/flowering.
    supported_by:
    - reference_id: PMID:26179959
      supporting_text: Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute
        toward its signaling role.
- term:
    id: GO:2000379
    label: positive regulation of reactive oxygen species metabolic process
  evidence_type: IDA
  original_reference_id: PMID:26179959
  review:
    action: KEEP_AS_NON_CORE
    summary: Positive ROS regulation is supported but non-core.
    reason: Blue-light-dependent ROS formation may contribute to CRY2 signaling, but it is not the primary
      molecular function of CRY2.
    supported_by:
    - reference_id: PMID:26179959
      supporting_text: Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute
        toward its signaling role.
- term:
    id: GO:0000325
    label: plant-type vacuole
  evidence_type: HDA
  original_reference_id: PMID:15539469
  review:
    action: REMOVE
    summary: High-throughput vacuole localization conflicts with the established nuclear photoreceptor
      localization.
    reason: CRY2 is repeatedly localized to the nucleus and nuclear bodies, with only limited/transient
      cytosolic evidence. A single HDA vacuole proteomics annotation is likely incidental contamination
      or overinterpretation.
    supported_by:
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISM
  original_reference_id: GO_REF:0000122
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:10476076
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:17438275
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18988809
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:18988809
      supporting_text: CIB1 interacts with CRY2 (cryptochrome 2) in a blue light-specific manner in yeast
        and Arabidopsis cells
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:20624951
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:20624951
      supporting_text: The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are
        required for the stability of the R protein HRT
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:22311776
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:22739826
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:22739826
      supporting_text: Degradation of Arabidopsis CRY2 is regulated by SPA proteins and phytochrome A.
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:25792146
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:26179959
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:26179959
      supporting_text: Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute
        toward its signaling role.
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:26724867
  review:
    action: ACCEPT
    summary: 'Correct cellular component: CRY2 acts predominantly in the nucleus.'
    reason: CRY2 nuclear localization is supported by direct localization experiments and by multiple
      studies of nuclear partner interactions, phosphorylation, photobody formation, and transcriptional
      outputs.
    supported_by:
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
    - reference_id: PMID:17438275
      supporting_text: These CRY2 fusion proteins were all found in the nucleus
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:25792146
      supporting_text: all CRY2 mutant proteins examined located in the nucleus of Arabidopsis cells as
        the endogenous CRY2 or the wild-type GFP-CRY2
    - reference_id: PMID:26724867
      supporting_text: CRY2 likely localizes to chromatin indirectly, via associations with PIFs or other
        TFs
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    action: KEEP_AS_NON_CORE
    summary: Cytoplasmic CRY2 can be detected/translocate, but the principal signaling site is nuclear.
    reason: CRY2 may be present in the cytoplasm in some contexts, yet the core photoreceptor signaling
      annotations are best assigned to nucleus/nuclear body.
    supported_by:
    - reference_id: PMID:26179959
      supporting_text: Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute
        toward its signaling role.
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: KEEP_AS_NON_CORE
    summary: Cytoplasmic CRY2 can be detected/translocate, but the principal signaling site is nuclear.
    reason: CRY2 may be present in the cytoplasm in some contexts, yet the core photoreceptor signaling
      annotations are best assigned to nucleus/nuclear body.
    supported_by:
    - reference_id: PMID:26179959
      supporting_text: Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute
        toward its signaling role.
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:26179959
  review:
    action: KEEP_AS_NON_CORE
    summary: Cytoplasmic CRY2 can be detected/translocate, but the principal signaling site is nuclear.
    reason: CRY2 may be present in the cytoplasm in some contexts, yet the core photoreceptor signaling
      annotations are best assigned to nucleus/nuclear body.
    supported_by:
    - reference_id: PMID:26179959
      supporting_text: Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute
        toward its signaling role.
    - reference_id: PMID:10476076
      supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
        C-terminal region of CRY2.
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    action: ACCEPT
    summary: 'Correct cellular component: blue light induces CRY2-containing nuclear photobodies.'
    reason: CRY2 forms nuclear bodies/photobodies after blue-light activation, and these are linked to
      phosphorylation, degradation, signal amplification, and partner colocalization.
    supported_by:
    - reference_id: PMID:21514160
      supporting_text: blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear
        bodies
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:27846570
      supporting_text: BICs also inhibit the blue light-induced formation of CRY2 photobodies
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: IDA
  original_reference_id: PMID:21511872
  review:
    action: ACCEPT
    summary: 'Correct cellular component: blue light induces CRY2-containing nuclear photobodies.'
    reason: CRY2 forms nuclear bodies/photobodies after blue-light activation, and these are linked to
      phosphorylation, degradation, signal amplification, and partner colocalization.
    supported_by:
    - reference_id: PMID:21514160
      supporting_text: blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear
        bodies
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:27846570
      supporting_text: BICs also inhibit the blue light-induced formation of CRY2 photobodies
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: IMP
  original_reference_id: PMID:22311776
  review:
    action: ACCEPT
    summary: 'Correct cellular component: blue light induces CRY2-containing nuclear photobodies.'
    reason: CRY2 forms nuclear bodies/photobodies after blue-light activation, and these are linked to
      phosphorylation, degradation, signal amplification, and partner colocalization.
    supported_by:
    - reference_id: PMID:21514160
      supporting_text: blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear
        bodies
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
    - reference_id: PMID:27846570
      supporting_text: BICs also inhibit the blue light-induced formation of CRY2 photobodies
- term:
    id: GO:0016605
    label: PML body
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    action: MODIFY
    summary: PML body is not the right plant-specific term for CRY2 photobodies.
    reason: The evidence supports nuclear photobodies/nuclear bodies in Arabidopsis. PML bodies are an
      inappropriate or over-specific mapping for this plant photoreceptor.
    proposed_replacement_terms:
    - id: GO:0016604
      label: nuclear body
    supported_by:
    - reference_id: PMID:21514160
      supporting_text: blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear
        bodies
    - reference_id: PMID:22311776
      supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
        ubiquitination, photobody formation, and degradation in the nucleus
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping,
    accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000122
  title: AtSubP analysis
  findings: []
- id: PMID:10476076
  title: Nuclear localization of the Arabidopsis blue light receptor cryptochrome 2.
  findings:
  - statement: CRY2 is localized to the nucleus through its C-terminal region.
    supporting_text: CRY2 is localized in the nucleus and that nuclear localization is mediated by the
      C-terminal region of CRY2.
- id: PMID:11089975
  title: Functional interaction of phytochrome B and cryptochrome 2.
  findings: []
- id: PMID:11493548
  title: Hierarchical coupling of phytochromes and cryptochromes reconciles stability and light modulation
    of Arabidopsis development.
  findings:
  - statement: CRY2 is a photoreceptor coupled to developmental processes.
    supporting_text: coupling of the photoreceptor cryptochrome 2 to developmental processes is broader
      than previously appreciated.
- id: PMID:11509693
  title: Direct interaction of Arabidopsis cryptochromes with COP1 in light control development.
  findings: []
- id: PMID:11743105
  title: Circadian clock-regulated expression of phytochrome and cryptochrome genes in Arabidopsis.
  findings:
  - statement: Cryptochromes are involved in circadian light input.
    supporting_text: Photoreceptors, phytochromes, and cryptochromes are involved in setting the clock
      by transducing the light signal to the central oscillator.
- id: PMID:12857830
  title: Second positive phototropism results from coordinated co-action of the phototropins and cryptochromes.
  findings:
  - statement: Cryptochromes and phototropins coordinate phototropism under blue light.
    supporting_text: phototropins and cryptochromes function together to enhance phototropism under low
      fluence rates
- id: PMID:15539469
  title: The vegetative vacuole proteome of Arabidopsis thaliana reveals predicted and unexpected proteins.
  findings: []
- id: PMID:15805487
  title: N-terminal domain-mediated homodimerization is required for photoreceptor activity of Arabidopsis
    CRYPTOCHROME 1.
  findings: []
- id: PMID:16093319
  title: 'From The Cover: A role for Arabidopsis cryptochromes and COP1 in the regulation of stomatal
    opening.'
  findings:
  - statement: CRY pathways contribute to blue-light-induced stomatal opening.
    supporting_text: CRY functions additively with PHOT in mediating blue light-induced stomatal opening
- id: PMID:17073458
  title: Analysis of autophosphorylating kinase activities of Arabidopsis and human cryptochromes.
  findings:
  - statement: AtCRY2 contains FAD but lacks detectable autokinase/autophosphorylation activity.
    supporting_text: AtCry2 which is known to be phosphorylated upon light exposure in vivo ( 16 ) lacked
      kinase activity.
- id: PMID:17259260
  title: CRYPTOCHROME2 in vascular bundles regulates flowering in Arabidopsis.
  findings:
  - statement: CRY2 in vascular bundles promotes FT expression and flowering.
    supporting_text: cry2-GFP expressed in vascular bundles increased FT expression only in vascular bundles.
- id: PMID:17438275
  title: Derepression of the NC80 motif is critical for the photoactivation of Arabidopsis CRY2.
  findings:
  - statement: CRY2 mediates blue-light inhibition of hypocotyl elongation and photoperiodic flowering.
    supporting_text: Arabidopsis cryptochrome 2 (CRY2) mediates blue light inhibition of hypocotyl elongation
      and photoperiodic control of floral initiation.
- id: PMID:17470059
  title: Light-regulated large-scale reorganization of chromatin during the floral transition in Arabidopsis.
  findings: []
- id: PMID:17982000
  title: Distinct light and clock modulation of cytosolic free Ca2+ oscillations and rhythmic CHLOROPHYLL
    A/B BINDING PROTEIN2 promoter activity in Arabidopsis.
  findings: []
- id: PMID:18424613
  title: Distinct light-initiated gene expression and cell cycle programs in the shoot apex and cotyledons
    of Arabidopsis.
  findings: []
- id: PMID:18988809
  title: Photoexcited CRY2 interacts with CIB1 to regulate transcription and floral initiation in Arabidopsis.
  findings:
  - statement: Photoexcited CRY2 interacts with CIB1 to promote FT expression and floral initiation.
    supporting_text: CIB1 interacts with CRY2 (cryptochrome 2) in a blue light-specific manner in yeast
      and Arabidopsis cells
- id: PMID:19558423
  title: 'Differential petiole growth in Arabidopsis thaliana: photocontrol and hormonal regulation.'
  findings: []
- id: PMID:20624951
  title: Cryptochrome 2 and phototropin 2 regulate resistance protein-mediated viral defense by negatively
    regulating an E3 ubiquitin ligase.
  findings:
  - statement: CRY2 contributes to TCV defense by maintaining HRT stability through COP1 regulation.
    supporting_text: The blue-light photoreceptors, cryptochrome (CRY) 2 and phototropin (PHOT) 2, are
      required for the stability of the R protein HRT
- id: PMID:20935177
  title: Photoreceptors CRYTOCHROME2 and phytochrome B control chromatin compaction in Arabidopsis.
  findings: []
- id: PMID:21296763
  title: '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.'
  findings: []
- id: PMID:21511872
  title: Blue-light-dependent interaction of cryptochrome 1 with SPA1 defines a dynamic signaling mechanism.
  findings: []
- id: PMID:21514160
  title: Blue light-dependent interaction of CRY2 with SPA1 regulates COP1 activity and floral initiation
    in Arabidopsis.
  findings:
  - statement: Blue light stimulates CRY2-SPA1 interaction and CRY2-dependent control of CO/FT and floral
      initiation.
    supporting_text: SPA1 acts as a signaling molecule to mediate CRY2-dependent control of CO protein
      stability, FT transcription, and floral initiation in response to blue light.
- id: PMID:22139370
  title: Arabidopsis cryptochrome 2 (CRY2) functions by the photoactivation mechanism distinct from the
    tryptophan (trp) triad-dependent photoreduction.
  findings: []
- id: PMID:22311776
  title: A study of the blue-light-dependent phosphorylation, degradation, and photobody formation of
    Arabidopsis CRY2.
  findings:
  - statement: CRY2 forms nuclear photobodies and undergoes blue-light-dependent phosphorylation, ubiquitination,
      and degradation.
    supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
      ubiquitination, photobody formation, and degradation in the nucleus
- id: PMID:22739826
  title: Degradation of Arabidopsis CRY2 is regulated by SPA proteins and phytochrome A.
  findings: []
- id: PMID:23511208
  title: Network balance via CRY signalling controls the Arabidopsis circadian clock over ambient temperatures.
  findings:
  - statement: Cryptochrome light input affects circadian period over temperature.
    supporting_text: reducing the fluence rate of either light quality or mutating the phy or cry photoreceptors
      lengthens the circadian period
- id: PMID:24126495
  title: Strigolactone-regulated hypocotyl elongation is dependent on cryptochrome and phytochrome signaling
    pathways in Arabidopsis.
  findings: []
- id: PMID:24130508
  title: Multiple bHLH proteins form heterodimers to mediate CRY2-dependent regulation of flowering-time
    in Arabidopsis.
  findings:
  - statement: CIB bHLH proteins act redundantly in CRY2-dependent flowering.
    supporting_text: CIBs function redundantly in regulating CRY2-dependent flowering
- id: PMID:24780222
  title: Quantitative real-time kinetics of optogenetic proteins CRY2 and CIB1/N using single-molecule
    tools.
  findings:
  - statement: CRY2 photoactivation drives association with CIB1.
    supporting_text: Upon illumination, CRY2 is photoactivated to contact and associate with CIB1.
- id: PMID:25428980
  title: Cellular metabolites enhance the light sensitivity of Arabidopsis cryptochrome through alternate
    electron transfer pathways.
  findings:
  - statement: Cellular metabolites affect Arabidopsis cryptochrome light sensitivity through electron-transfer
      routes.
    supporting_text: Cellular metabolites enhance the light sensitivity of Arabidopsis cryptochrome through
      alternate electron transfer pathways.
- id: PMID:25792146
  title: The blue light-dependent phosphorylation of the CCE domain determines the photosensitivity of
    Arabidopsis CRY2.
  findings:
  - statement: Blue-light-dependent phosphorylation of the CCE domain regulates CRY2 photosensitivity.
    supporting_text: CRY2 undergoes blue light-dependent phosphorylation in multiple serine residues of
      the CCE domain
- id: PMID:26179959
  title: Blue-light dependent ROS formation by Arabidopsis cryptochrome-2 may contribute toward its signaling
    role.
  findings: []
- id: PMID:26724867
  title: Cryptochromes Interact Directly with PIFs to Control Plant Growth in Limiting Blue Light.
  findings:
  - statement: CRY1/CRY2 directly contact PIF4 and PIF5 to control growth under limiting blue light.
    supporting_text: CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription
      factors, PIF4 and PIF5.
- id: PMID:27846570
  title: Photoactivation and inactivation of Arabidopsis cryptochrome 2.
  findings:
  - statement: Blue-light-dependent CRY2 homodimerization is required for physiological activation.
    supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
      to become physiologically active.
- id: PMID:28492234
  title: Molecular basis for blue light-dependent phosphorylation of Arabidopsis cryptochrome 2.
  findings: []
- id: PMID:28633330
  title: The asparagine-rich protein NRP interacts with the Verticillium effector PevD1 and regulates
    the subcellular localization of cryptochrome 2.
  findings: []
- id: PMID:32398826
  title: Structural insights into BIC-mediated inactivation of Arabidopsis cryptochrome 2.
  findings:
  - statement: Crystal structures of the CRY2 PHR (photolyase-homology) domain with bound FAD and of the
      BIC2-CRY2N complex reveal how BIC inactivates the FAD-bound photoreceptor.
    supporting_text: Here, we report crystal structures of CRY2N (CRY2 PHR domain) and the BIC2-CRY2N complex
      with resolutions of 2.7 and 2.5 Å, respectively.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified crystal structure (PDB 6K8I) of FAD-bound Arabidopsis CRY2 and its BIC
      complex.
- id: PMID:32661061
  title: Photoexcited Cryptochrome2 Interacts Directly with TOE1 and TOE2 in Flowering Regulation.
  findings: []
- id: PMID:36396657
  title: CRY2 interacts with CIS1 to regulate thermosensory flowering via FLM alternative splicing.
  findings: []
- id: PMID:36508461
  title: A role for brassinosteroid signalling in decision-making processes in the Arabidopsis seedling.
  findings: []
- id: PMID:9565033
  title: Cryptochrome blue-light photoreceptors of Arabidopsis implicated in phototropism.
  findings:
  - statement: Cryptochromes contribute to Arabidopsis phototropism.
    supporting_text: cryptochrome is one of the photoreceptors mediating phototropism in plants.
- id: file:ARATH/CRY2/CRY2-deep-research-falcon.md
  title: Falcon deep research summary for Arabidopsis CRY2
  findings:
  - statement: Deep research synthesis identifies CRY2 as a nuclear plant blue-light photoreceptor with
      FAD-dependent photochemistry, condensate/photobody behavior, and flowering/growth outputs.
- id: file:ARATH/CRY2/CRY2-uniprot.txt
  title: UniProtKB record for Arabidopsis CRY2 (Q96524)
  findings:
  - statement: UniProt summarizes CRY2 as a photoreceptor mediating blue-light inhibition of hypocotyl
      elongation and photoperiodic control of floral initiation.
- id: file:interpro/panther/PTHR11455/PTHR11455-notes.md
  title: PANTHER PTHR11455 cryptochrome family notes
  findings:
  - statement: PANTHER family PTHR11455 contains both signaling cryptochromes and repair photolyases,
      so family-level IBA photolyase annotations require caution.
core_functions:
- description: CRY2 acts as a nuclear FAD-dependent blue-light photoreceptor. Blue light promotes CRY2
    photoactivation, homodimerization/oligomerization, nuclear photobody formation, and partner interactions
    that drive blue-light signaling, low-blue-light growth responses, and photoperiodic flowering through
    CO/FT and CIB-dependent mechanisms.
  molecular_function:
    id: GO:0009882
    label: blue light photoreceptor activity
  directly_involved_in:
  - id: GO:0009785
    label: blue light signaling pathway
  - id: GO:0010244
    label: response to low fluence blue light stimulus by blue low-fluence system
  - id: GO:0048574
    label: long-day photoperiodism, flowering
  - id: GO:2000028
    label: regulation of photoperiodism, flowering
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0016604
    label: nuclear body
  supported_by:
  - reference_id: PMID:22311776
    supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
      ubiquitination, photobody formation, and degradation in the nucleus
  - reference_id: PMID:27846570
    supporting_text: Arabidopsis cryptochrome 2 (CRY2) undergoes blue light-dependent homodimerization
      to become physiologically active.
  - reference_id: PMID:21514160
    supporting_text: SPA1 acts as a signaling molecule to mediate CRY2-dependent control of CO protein
      stability, FT transcription, and floral initiation in response to blue light.
  - reference_id: PMID:26724867
    supporting_text: CRY1 and CRY2 perceive this change and respond by directly contacting two bHLH transcription
      factors, PIF4 and PIF5.
  - reference_id: file:ARATH/CRY2/CRY2-deep-research-falcon.md
    supporting_text: 'Arabidopsis thaliana CRY2 (UniProt: Q96524) is a plant blue-light photoreceptor'
proposed_new_terms:
- proposed_name: cryptochrome photobody
  proposed_definition: A nuclear body formed by photoactivated cryptochrome photoreceptors in response
    to blue light and associated with cryptochrome signaling, phosphorylation, ubiquitination, partner
    colocalization, or turnover.
  justification: CRY2 annotations currently use the broad nuclear body term, while the UniProt-derived
    PML body mapping is inappropriate for Arabidopsis. A plant cryptochrome photobody term would capture
    the specific light-induced CRY2 compartment supported by multiple studies.
  proposed_parent:
    id: GO:0016604
    label: nuclear body
  supported_by:
  - reference_id: PMID:21514160
    supporting_text: blue light enhances colocalization of the CRY2 and MycSPA1 proteins in the nuclear
      bodies
  - reference_id: PMID:22311776
    supporting_text: CRY2 is a constitutive nuclear protein that undergoes blue-light-dependent phosphorylation,
      ubiquitination, photobody formation, and degradation in the nucleus
suggested_questions:
- question: Should GO represent Arabidopsis CRY2 photobodies with a dedicated cryptochrome photobody cellular-component
    term rather than PML body or generic nuclear body?
  experts:
  - Lin C
  - Zuo Z
  - Yu X
- question: For CRY2-mediated chromatin compaction/decompaction annotations, should curation prefer downstream
    regulation terms over direct chromatin remodeling terminology?
  experts:
  - Tessadori F
  - van Zanten M
suggested_experiments:
- experiment_type: curation/ontology review
  hypothesis: CRY2 photobodies are distinct enough from generic nuclear bodies to warrant a GO cellular-component
    child term.
  description: Compare CRY2 photobody composition, light dependence, dynamics, and partner colocalization
    across PMID:21514160, PMID:22311776, PMID:27846570, and recent condensate studies; define term boundaries
    and synonym needs.
- experiment_type: targeted genetic and imaging assay
  hypothesis: CRY2 affects chromatin organization indirectly through photoreceptor signaling partners
    rather than by direct chromatin remodeling activity.
  description: Measure chromatin compaction and floral-transition markers in cry2, CIB/SPAs, and photobody-defective
    CRY2 mutants under matched blue-light conditions, paired with CRY2 chromatin-proximity or CUT&Tag
    assays.

Gene Description

Proposed New Ontology Terms

cryptochrome photobody

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Arabidopsis thaliana CRY2 (UniProt: Q96524; locus At1g04400) — Functional Annotation

1) Target identity verification (CRITICAL)

2) Key concepts and definitions (current understanding)

2.1 Cryptochromes (CRYs)

2.2 PHR and CCE domains

2.3 Photobodies and liquid–liquid phase separation (LLPS)

3) Molecular function of CRY2: photochemistry → conformational change → oligomerization/condensation → signaling

3.1 Primary photochemistry (FAD-centered photocycle)

3.2 Oligomerization, photobodies, and LLPS

4) Subcellular localization

5) Pathways and biological processes controlled by CRY2

5.1 Photoperiodic flowering: CRY2 → CIBs/FT (and CO stabilization via COP1/SPA)

5.2 Hypocotyl elongation and early seedling development

5.3 Circadian-associated outputs

6) Regulation of CRY2 activity and abundance (phosphorylation, ubiquitination, proteasomal degradation)

7) Quantitative data and statistics (recent studies prioritized where available)

7.1 ATP binding and modulation of CRY2 photochemistry (biochemical parameter)

7.2 Blue-light-dependent degradation kinetics (example time course)

7.3 Photochemistry time constants and spectral antagonism

7.4 Growth phenotype effect size (example)

8) Recent developments and latest research highlights (2023–2024 priority)

8.1 2023: CRY2 condensates link light perception to epitranscriptomic regulation

8.2 2024: Integration with growth-control networks and COP1/SPA logic

9) Current applications and real-world implementations

9.1 Optogenetics: CRY2/CIB as a light-inducible dimerization tool

10) Expert synthesis and interpretation (authoritative perspectives)

Evidence summary table

Source notes, URLs, and publication dates

Limitations of the retrieved evidence set

Citations

📄 View Raw YAML