Cryptochrome (CRY/DmCRY, type I/Drosophila-type) is a FAD-binding blue-light photoreceptor that provides light input to the Drosophila circadian clock. Its core, best-established function is light-dependent entrainment: blue light absorbed by FAD drives photoreduction (via a Trp triad/tetrad) and a conformational switch (C-terminal tail undocking) that enables CRY to bind TIMELESS (TIM) and trigger TIM ubiquitination/proteasomal degradation via the E3 ligase JETLAG (JET)/CUL1, resetting the PER/TIM oscillator. This is mechanistically DISTINCT from mammalian CRY1/2 (type II), which are light-independent transcriptional repressors. In Drosophila, CRY can also act as a transcriptional repressor of CLK/CYC targets, but this is a secondary role confined to peripheral clocks. CRY additionally has non-canonical, tissue-dependent roles including light-dependent magnetosensitivity, modulation of neuronal excitability/arousal, a structural (actin/signalplex) role in eye rhabdomeres, and metabolic regulation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: UniProt-curated localization includes nuclear CRY, consistent with light-driven nuclear translocation. Reason: Subcellular location evidence indicates CRY accumulates in the nucleus after light perception, supporting nuclear localization. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm ... Nucleus. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: UniProt-curated localization includes cytoplasmic CRY. Reason: CRY is reported in cytoplasm and perinuclear region prior to nuclear translocation, supporting cytoplasmic localization. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10417378, |
| GO:0045892 negative regulation of DNA-templated transcription | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CRY can act as a transcriptional repressor of CLK/CYC-activated clock genes (Collins et al. 2006), but this is a Drosophila-specific secondary role confined to peripheral clocks, NOT the canonical mammalian-type light-independent repression. Drosophila CRY (type I) is mechanistically distinct from mammalian CRY1/2 (type II): the falcon deep research establishes that the best-established / primary function of DmCRY is as a blue-light photoreceptor that triggers light-dependent TIM degradation, whereas light-independent transcriptional repression is the defining role of the type II (mammalian) cryptochromes. The IBA inference (from the phylogenetic family) therefore over-weights a repressor role that, in flies, is non-core and peripheral. Reason: Genuine but secondary/non-core in Drosophila. Collins et al. (PMID:16527739) show repression of CLK/CYC targets is "confined to peripheral clocks" and does not significantly affect pacemaker-neuron or behavioral rhythms; the core DmCRY function is light input via TIM degradation, not transcriptional repression. Distinct from the mammalian type II cryptochrome repressor role that drives this phylogenetic inference. Supporting Evidence: UniProtKB:O77059 Genes directly activated by the transcription factors Clock (Clk) and cycle (cyc) are repressed by cry. PMID:16527739 Here we demonstrate that Drosophila CRY also functions as a transcriptional repressor. file:DROME/CRY/CRY-deep-research-falcon.md This Drosophila light-sensing role is mechanistically distinct from **vertebrate/mammalian-type (type II) cryptochromes**, which are described primarily as **light-independent transcriptional repressors** in the core clock feedback loop. |
| GO:0003677 DNA binding | IBA GO_REF:0000033 | REMOVE | Summary: CRY lacks photolyase activity and functions as a photoreceptor rather than a DNA-binding repair enzyme. Reason: Evidence indicates CRY is a blue-light photoreceptor without photolyase activity; DNA binding is not supported. Supporting Evidence: PMID:10063806 the protein is not a DNA repair enzyme but a blue-light photoreceptor. |
| GO:0032922 circadian regulation of gene expression | IBA GO_REF:0000033 | ACCEPT | Summary: CRY regulates expression of CLK/CYC target genes, consistent with circadian regulation of gene expression. Reason: Repression of clock-controlled transcription by CRY supports circadian regulation of gene expression. Supporting Evidence: UniProtKB:O77059 Genes directly activated by the transcription factors Clock (Clk) and cycle (cyc) are repressed by cry. |
| GO:0043153 entrainment of circadian clock by photoperiod | IBA GO_REF:0000033 | ACCEPT | Summary: Loss of CRY disrupts synchronization to light-dark cycles, indicating a role in photoperiod entrainment. The falcon deep research details the canonical mechanism: light-activated CRY binds TIM and triggers TIM degradation via recruitment of the E3 ubiquitin ligase Jetlag (JET)/CUL1, leading to TIM ubiquitination and proteasomal degradation, thereby resetting the PER/TIM negative arm and entraining behavioral rhythms. This is the core, best-established DmCRY function. Reason: Core biological process. CRY is the primary photoreceptor for entrainment of the fly circadian clock and acts by light-dependent TIM degradation. Supporting Evidence: UniProtKB:O77059 Flies exhibit poor synchronization to light-dark cycles and show no response to brief light pulses. PMID:37100907 the photoreceptor Cryptochrome (Cry) entrains the clock by triggering Tim degradation in light PMID:16794082 Expression of JET along with the circadian photoreceptor cryptochrome (CRY) in cultured S2R cells confers light-dependent degradation onto TIM, PMID:22080955 is the primary photoreceptor for entrainment of the fly circadian clock file:DROME/CRY/CRY-deep-research-falcon.md In the canonical pathway, light-activated CRY **binds Timeless (TIM)** and triggers **TIM degradation** via recruitment of the **E3 ubiquitin ligase Jetlag (JET)**, thereby resetting the circadian oscillator. file:DROME/CRY/CRY-deep-research-falcon.md The canonical output of CRY photoreception is **light-dependent TIM degradation** |
| GO:0071949 FAD binding | IBA GO_REF:0000033 | ACCEPT | Summary: CRY binds FAD as the principal blue-light chromophore/cofactor in the photolyase homology region (PHR). The falcon deep research notes that FAD binding is both photochemical (it is the chromophore that absorbs blue light) and a structural requirement for CRY to reach a signaling-competent native fold. Reason: Core molecular function. UniProt-curated cofactor annotations specify one FAD per subunit, and FAD binding is essential for both photoreception and folding. Supporting Evidence: UniProtKB:O77059 Binds 1 FAD per subunit. PMID:24297896 contains a C-terminal tail (CTT) helix that binds beside a FAD cofactor PDB:8DD7 FAD (Subject of Investigation/LOI) file:DROME/CRY/CRY-deep-research-falcon.md cryptochromes have a conserved **photolyase homology region (PHR)** that binds **FAD** as the principal blue-light chromophore file:DROME/CRY/CRY-deep-research-falcon.md FAD binding is not only photochemical but also a structural requirement** to reach a signaling-competent native fold. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: CRY binds a flavin adenine dinucleotide cofactor, supporting nucleotide binding. Reason: FAD is a nucleotide cofactor; the term is generic but consistent with known cofactor binding. Supporting Evidence: UniProtKB:O77059 Binds 1 FAD per subunit. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt-curated localization includes nuclear CRY. Reason: Subcellular location annotations indicate nuclear accumulation after light perception. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm ... Nucleus. PMID:18663237 CRY is present in both the nucleus and the cytoplasm of these neurons, |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt-curated localization includes cytoplasmic CRY. Reason: CRY localizes to cytoplasm and perinuclear region prior to nuclear translocation. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10417378, PMID:18663237 CRY is present in both the nucleus and the cytoplasm of these neurons, |
| GO:0009416 response to light stimulus | IEA GO_REF:0000117 | ACCEPT | Summary: CRY expression and function are light regulated, supporting a response to light stimulus. Reason: Light-regulated expression and photoreceptor function indicate response to light stimulus. Supporting Evidence: UniProtKB:O77059 Regulation of expression by light suggests a role in photoreception for locomotor activity rhythms. |
| GO:0009881 photoreceptor activity | IEA GO_REF:0000043 | ACCEPT | Summary: CRY is a blue-light-dependent photoreceptor in the circadian system. The falcon deep research establishes that this is the best-established/core function of DmCRY: blue light absorbed by FAD drives photoreduction via a Trp triad/tetrad, producing a conformational change (CTT undocking) that enables light-dependent TIM binding and JET-dependent TIM degradation, resetting the circadian oscillator. Reason: UniProt function description explicitly identifies CRY as a blue-light-dependent regulator in the circadian loop; falcon synthesis confirms photoreceptor activity as the core molecular function. Supporting Evidence: UniProtKB:O77059 Blue light-dependent regulator that is the input of the circadian feedback loop. PMID:21187431 Cryptochrome (CRY) is a blue-light sensitive flavoprotein that functions as the primary circadian photoreceptor in Drosophila melanogaster. PMID:10839367 encodes a critical circadian photoreceptor in Drosophila. file:genes/DROME/CRY/CRY-deep-research-cyberian.md Cryptochrome (CRY) is a blue light-sensitive flavoprotein that serves as the primary dedicated circadian photoreceptor in file:DROME/CRY/CRY-deep-research-falcon.md blue-light absorption by **FAD** drives photoreduction via a **Trp triad/tetrad** |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: CRY accumulates in the perinuclear region before nuclear translocation. Reason: The perinuclear accumulation is documented as part of CRY light-dependent trafficking. Supporting Evidence: UniProtKB:O77059 Accumulates in the perinuclear region about one hour before translocation into the nucleus. |
| GO:0048511 rhythmic process | IEA GO_REF:0000043 | ACCEPT | Summary: CRY functions within the circadian feedback loop, supporting a rhythmic process annotation. Reason: CRY is a blue-light-dependent regulator in the circadian feedback loop. Supporting Evidence: UniProtKB:O77059 Blue light-dependent regulator that is the input of the circadian feedback loop. |
| GO:0005515 protein binding | IPI PMID:17418796 The Drosophila circadian network is a seasonal timer. | MARK AS OVER ANNOTATED | Summary: The cited study is focused on circadian network/photoperiod effects and does not present direct CRY binding assays; light-dependent CRY-TIM interaction is documented elsewhere. Reason: Protein binding is overly generic and the PMID cited does not provide direct binding evidence for CRY. Specific interactions (e.g., CRY–TIM) are better captured with partner-specific evidence when available. Supporting Evidence: PMID:17418796 Previous work in Drosophila has defined two populations of circadian brain neurons, morning cells (M-cells) and evening cells (E-cells), PMID:10417378 CRY and TIM are part of the same complex and directly interact in yeast in a light-dependent fashion. |
| GO:0005829 cytosol | IDA PMID:10417378 Light-dependent sequestration of TIMELESS by CRYPTOCHROME. | ACCEPT | Summary: CRY can be detected in cytoplasm as well as nucleus. Reason: Cytoplasmic accumulation is documented in studies of CRY localization; nuclear localization does not exclude cytosolic presence. Supporting Evidence: PMID:10417378 PER/TIM and CRY influence the subcellular distribution of these protein complexes, which reside primarily in the nucleus after the perception of a light signal. PMID:14960620 it accumulated in both the nucleus and the cytoplasm, including some neuritic projections. |
| GO:0007623 circadian rhythm | IPI PMID:10417378 Light-dependent sequestration of TIMELESS by CRYPTOCHROME. | ACCEPT | Summary: CRY acts as a circadian photoreceptor interacting with core clock components, supporting a role in circadian rhythm. Reason: The paper explicitly describes CRY as a circadian photoreceptor acting via core clock components, consistent with circadian rhythm involvement. Supporting Evidence: PMID:10417378 Thus, CRY acts as a circadian photoreceptor by directly interacting with core components of the circadian clock. |
| GO:0007623 circadian rhythm | IMP PMID:11357134 A new role for cryptochrome in a Drosophila circadian oscill... | ACCEPT | Summary: CRY mediates light input to circadian oscillators in brain and peripheral tissues, supporting circadian rhythm function. Reason: The abstract states CRY acts as a photoreceptor mediating light input to circadian oscillators, indicating a role in circadian rhythms. Supporting Evidence: PMID:11357134 In Drosophila, cryptochrome (CRY) acts as a photoreceptor that mediates light input to circadian oscillators in both brain and peripheral tissue. |
| GO:0007623 circadian rhythm | IGI PMID:9845370 The cryb mutation identifies cryptochrome as a circadian pho... | ACCEPT | Summary: The cryb mutation identifies cryptochrome as a circadian photoreceptor, consistent with circadian rhythm involvement. Reason: Genetic evidence from cryb mutants establishes cryptochrome as a circadian photoreceptor in Drosophila. Supporting Evidence: PMID:9845370 The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. |
| GO:0009881 photoreceptor activity | IDA PMID:10417378 Light-dependent sequestration of TIMELESS by CRYPTOCHROME. | ACCEPT | Summary: CRY is described as a circadian photoreceptor acting via light-dependent interactions with core clock components. Reason: The cited study explicitly characterizes CRY as a circadian photoreceptor, supporting photoreceptor activity. Supporting Evidence: PMID:10417378 Thus, CRY acts as a circadian photoreceptor by directly interacting with core components of the circadian clock. |
| GO:0007623 circadian rhythm | IMP PMID:9845369 CRY, a Drosophila clock and light-regulated cryptochrome, is... | ACCEPT | Summary: CRY is a major contributor to circadian rhythm resetting and photosensitivity, supporting circadian rhythm involvement. Reason: The abstract directly links CRY to circadian rhythm resetting, which is central to circadian rhythm processes. Supporting Evidence: PMID:9845369 CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity. |
| GO:0009637 response to blue light | IMP PMID:9845369 CRY, a Drosophila clock and light-regulated cryptochrome, is... | ACCEPT | Summary: CRY mediates blue-light-evoked neuronal responses in pacemaker neurons, supporting a response to blue light. Reason: Blue-light responsiveness is explicitly reported for CRY in pacemaker neurons; the original study supports CRY as a photosensitive cryptochrome. Supporting Evidence: PMID:28489826 Loss of either cry or rh7 caused minor defects in photoentrainment, whereas loss of both caused profound impairment PMID:9845369 All characterized family members are directly photosensitive and include plant blue light photoreceptors. |
| GO:0043153 entrainment of circadian clock by photoperiod | IGI PMID:28840790 A New Rhodopsin Influences Light-dependent Daily Activity Pa... | ACCEPT | Summary: Genetic interaction data support CRY contributions to photoentrainment and synchronization to light-dark cycles. Reason: The cited study reports altered synchronization in blue light and stronger effects when cryptochrome-based light input is absent; additional evidence shows cry loss affects photoentrainment. Supporting Evidence: PMID:28840790 However, in blue light (470 nm), Rh70 mutants needed significantly longer to synchronize than wild-type controls, PMID:28489826 Loss of either cry or rh7 caused minor defects in photoentrainment, whereas loss of both caused profound impairment |
| GO:0032922 circadian regulation of gene expression | IMP PMID:28489826 A rhodopsin in the brain functions in circadian photoentrain... | ACCEPT | Summary: CRY contributes to circadian clock regulation and acts as a transcriptional repressor of clock-controlled genes. Reason: Photoentrainment phenotypes in cry mutants support circadian regulation, and CRY represses CLK/CYC-driven transcription. Supporting Evidence: PMID:28489826 Loss of either cry or rh7 caused minor defects in photoentrainment, whereas loss of both caused profound impairment PMID:16527739 Drosophila CRY also functions as a transcriptional repressor. |
| GO:0032922 circadian regulation of gene expression | IGI PMID:28489826 A rhodopsin in the brain functions in circadian photoentrain... | ACCEPT | Summary: Genetic interaction data link CRY to circadian regulation and transcriptional repression. Reason: cry-dependent photoentrainment plus CRY transcriptional repression supports circadian regulation of gene expression. Supporting Evidence: PMID:28489826 Loss of either cry or rh7 caused minor defects in photoentrainment, whereas loss of both caused profound impairment PMID:16527739 Drosophila CRY also functions as a transcriptional repressor. |
| GO:0043153 entrainment of circadian clock by photoperiod | IMP PMID:28489826 A rhodopsin in the brain functions in circadian photoentrain... | ACCEPT | Summary: CRY contributes to photoentrainment of the circadian clock. Reason: Loss of cry impairs photoentrainment, especially when combined with loss of rh7. Supporting Evidence: PMID:28489826 Loss of either cry or rh7 caused minor defects in photoentrainment, whereas loss of both caused profound impairment |
| GO:0043153 entrainment of circadian clock by photoperiod | IGI PMID:28489826 A rhodopsin in the brain functions in circadian photoentrain... | ACCEPT | Summary: Genetic interaction evidence supports CRY-dependent photoentrainment. Reason: Combined loss of cry and rh7 causes strong defects in photoentrainment. Supporting Evidence: PMID:28489826 Loss of either cry or rh7 caused minor defects in photoentrainment, whereas loss of both caused profound impairment |
| GO:0048512 circadian behavior | IMP PMID:28489826 A rhodopsin in the brain functions in circadian photoentrain... | ACCEPT | Summary: CRY affects circadian behavioral outputs via photoentrainment pathways. Reason: cry loss disrupts photoentrainment and alters behavioral responses to light cycles. Supporting Evidence: PMID:28489826 Loss of either cry or rh7 caused minor defects in photoentrainment, whereas loss of both caused profound impairment |
| GO:0048512 circadian behavior | IGI PMID:28489826 A rhodopsin in the brain functions in circadian photoentrain... | ACCEPT | Summary: Genetic interaction between cry and rh7 affects circadian behavioral entrainment. Reason: Combined mutations show profound behavioral photoentrainment defects. Supporting Evidence: PMID:28489826 Loss of either cry or rh7 caused minor defects in photoentrainment, whereas loss of both caused profound impairment |
| GO:0071482 cellular response to light stimulus | IMP PMID:28489826 A rhodopsin in the brain functions in circadian photoentrain... | ACCEPT | Summary: CRY mediates cellular light responses in pacemaker neurons. Reason: Light-evoked neuronal responses depend on CRY, supporting cellular response to light stimulus. Supporting Evidence: PMID:28489826 Loss of either cry or rh7 caused minor defects in photoentrainment, whereas loss of both caused profound impairment |
| GO:0005654 nucleoplasm | TAS Reactome:R-DME-432371 | ACCEPT | Summary: Reactome places CRY in nucleoplasm during circadian signaling. Reason: UniProt subcellular location evidence includes nuclear CRY. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm ... Nucleus. |
| GO:0005654 nucleoplasm | TAS Reactome:R-DME-432378 | ACCEPT | Summary: Reactome places CRY in nucleoplasm during clock-regulatory steps. Reason: Nuclear localization of CRY is documented in curated UniProt annotations. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm ... Nucleus. |
| GO:0005654 nucleoplasm | TAS Reactome:R-DME-432424 | ACCEPT | Summary: Reactome annotates CRY in nucleoplasm for TIM-related steps. Reason: CRY translocates to the nucleus after light perception. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm ... Nucleus. |
| GO:0005654 nucleoplasm | TAS Reactome:R-DME-432652 | ACCEPT | Summary: Reactome assigns CRY to nucleoplasm, consistent with light-induced nuclear localization. Reason: Curated localization places CRY in the nucleus. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm ... Nucleus. |
| GO:0005829 cytosol | TAS Reactome:R-DME-432401 | ACCEPT | Summary: Reactome assigns CRY to cytosol in light-input pathway steps. Reason: Cytosolic localization of CRY is supported by UniProt curated evidence. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10417378, |
| GO:0005829 cytosol | TAS Reactome:R-DME-432426 | ACCEPT | Summary: Reactome assigns CRY to cytosol during TIM-related interactions. Reason: Cytoplasmic localization is curated for CRY. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10417378, |
| GO:0005829 cytosol | TAS Reactome:R-DME-432428 | ACCEPT | Summary: Reactome assigns CRY to cytosol during degradation steps. Reason: CRY is documented in cytosolic compartments before nuclear translocation. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10417378, |
| GO:0005829 cytosol | TAS Reactome:R-DME-432593 | ACCEPT | Summary: Reactome assigns CRY to cytosol in ubiquitination steps. Reason: Cytosolic localization of CRY is supported by curated UniProt evidence. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10417378, |
| GO:0005829 cytosol | TAS Reactome:R-DME-881988 | ACCEPT | Summary: Reactome assigns CRY to cytosol for phosphorylation steps. Reason: CRY is documented in cytosol/perinuclear regions prior to nuclear translocation. Supporting Evidence: UniProtKB:O77059 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10417378, |
| GO:0045187 regulation of circadian sleep/wake cycle, sleep | IMP PMID:25148297 Effects of light interruption on sleep and viability of Dros... | ACCEPT | Summary: Disruption of CRY rhythms by nocturnal light affects sleep regulation. Reason: Light interruption dampens CRY rhythms and impacts sleep, indicating CRY involvement in circadian sleep/wake regulation. Supporting Evidence: PMID:25148297 the discontinuous light stimulation damped the daily rhythm of a circadian light-sensitive protein cryptochrome both at the mRNA and protein levels, |
| GO:0005515 protein binding | IPI PMID:24297896 Flavin reduction activates Drosophila cryptochrome. | MARK AS OVER ANNOTATED | Summary: TIM binds dCRY in light, but the generic protein-binding term is uninformative. Reason: The paper supports specific CRY-TIM interaction; use of a generic binding term is over-annotated. Supporting Evidence: PMID:24297896 the corresponding peptide binds dCRY in light and protects the flavin from oxidation |
| GO:0043153 entrainment of circadian clock by photoperiod | IMP PMID:22306971 Rhodopsin 5- and Rhodopsin 6-mediated clock synchronization ... | ACCEPT | Summary: CRY contributes to light synchronization of the circadian clock. Reason: The study notes that cryptochrome in brain clock neurons contributes to clock synchronization. Supporting Evidence: PMID:22306971 the blue-light photoreceptor Cryptochrome expressed within the brain clock neurons contribute to this clock synchronization. |
| GO:0043153 entrainment of circadian clock by photoperiod | IGI PMID:22306971 Rhodopsin 5- and Rhodopsin 6-mediated clock synchronization ... | ACCEPT | Summary: Genetic data in the context of light synchronization support CRY-dependent photoentrainment. Reason: Cryptochrome contributes to clock synchronization alongside visual photoreceptors. Supporting Evidence: PMID:22306971 the blue-light photoreceptor Cryptochrome expressed within the brain clock neurons contribute to this clock synchronization. |
| GO:0071949 FAD binding | IDA PMID:23746849 Structures of Drosophila cryptochrome and mouse cryptochrome... | ACCEPT | Summary: dCRY is a FAD-dependent photoreceptor. Reason: Structural analysis identifies dCRY as FAD-dependent, supporting FAD binding. Supporting Evidence: PMID:23746849 Drosophila cryptochrome (dCRY) is a FAD-dependent circadian photoreceptor, |
| GO:0050958 magnetoreception | IMP PMID:20098414 Animal cryptochromes mediate magnetoreception by an unconven... | KEEP AS NON CORE | Summary: CRY mediates light-dependent magnetoreception. The falcon deep research frames this as a non-canonical, tissue-dependent CRY function: cry mutants lose magnetic-field- dependent behaviors, with proposed radical-pair photochemistry tied to flavin redox. Reason: Genuine but non-core. Magnetosensitivity is a proposed/secondary CRY function relative to the canonical circadian photoreceptor / TIM-degradation role, and the underlying radical-pair mechanism remains a hypothesis. Supporting Evidence: PMID:20098414 the light-dependent magnetic sense of Drosophila melanogaster is mediated by the ultraviolet (UV)-A/blue light photoreceptor cryptochrome (Cry) file:DROME/CRY/CRY-deep-research-falcon.md CRY-dependent magnetosensitivity is frequently discussed in Drosophila, with reviews summarizing that cry mutants lose magnetic-field-dependent behaviors |
| GO:0071000 response to magnetism | IMP PMID:20098414 Animal cryptochromes mediate magnetoreception by an unconven... | KEEP AS NON CORE | Summary: CRY is required for light-dependent responses to magnetic fields. Per falcon, this is a non-canonical CRY function relative to the core circadian photoreceptor role. Reason: CRY-dependent magnetosensory responses under UV-A/blue light are genuine but secondary to the core circadian photoreceptor / TIM-degradation function. Supporting Evidence: PMID:20098414 the light-dependent magnetic sense of Drosophila melanogaster is mediated by the ultraviolet (UV)-A/blue light photoreceptor cryptochrome (Cry) file:DROME/CRY/CRY-deep-research-falcon.md CRY-dependent magnetosensitivity is frequently discussed in Drosophila, with reviews summarizing that cry mutants lose magnetic-field-dependent behaviors |
| GO:0009785 blue light signaling pathway | IMP PMID:10063806 A putative blue-light receptor from Drosophila melanogaster. | ACCEPT | Summary: CRY is a blue-light photoreceptor that lacks photolyase activity. Reason: The study characterizes CRY as a blue-light photoreceptor, supporting a role in blue-light signaling. Supporting Evidence: PMID:10063806 the protein is not a DNA repair enzyme but a blue-light photoreceptor. |
| GO:0009649 entrainment of circadian clock | IDA PMID:21135155 Cryptochrome-positive and -negative clock neurons in Drosoph... | ACCEPT | Summary: CRY is a key component for preferential entrainment to light. Reason: The study shows CRY-positive neurons preferentially entrain to light cycles. Supporting Evidence: PMID:21135155 CRY is a key component for the preferential entrainment to light. |
| GO:0042752 regulation of circadian rhythm | IDA PMID:21135155 Cryptochrome-positive and -negative clock neurons in Drosoph... | ACCEPT | Summary: CRY participates in light synchronization of circadian rhythms. Reason: CRY is required for light-driven entrainment of circadian rhythms in clock neurons. Supporting Evidence: PMID:21135155 The blue-light photoreceptive protein Cryptochrome (CRY) plays an important role in the light synchronization of the Drosophila circadian clock. |
| GO:0005515 protein binding | IPI PMID:10417378 Light-dependent sequestration of TIMELESS by CRYPTOCHROME. | MARK AS OVER ANNOTATED | Summary: CRY interacts with TIM in a light-dependent complex, but generic protein binding is over-annotated. The falcon deep research provides the specific structural basis: a 2023 cryo-EM structure shows TIM inserts its N-terminus into the CRY flavin pocket, replacing the autoinhibitory C-terminal tail (CTT) and forming the major interface. Reason: The evidence supports specific light-dependent CRY-TIM interaction rather than nonspecific protein binding. Supporting Evidence: PMID:10417378 CRY and TIM are part of the same complex and directly interact in yeast in a light-dependent fashion. file:DROME/CRY/CRY-deep-research-falcon.md TIM inserts its N-terminus into the CRY flavin pocket**, replacing the CRY CTT and forming a major interface. |
| GO:0071000 response to magnetism | IMP PMID:18641630 Cryptochrome mediates light-dependent magnetosensitivity in ... | KEEP AS NON CORE | Summary: CRY is necessary for light-dependent magnetosensitive responses. Per falcon, this is a non-canonical CRY function relative to the core circadian photoreceptor role. Reason: Cry-deficient flies lack magnetic responses under light, but magnetosensitivity is a secondary function relative to the core circadian photoreceptor / TIM-degradation role. Supporting Evidence: PMID:18641630 the ultraviolet-A/blue-light photoreceptor cryptochrome (Cry) is necessary for light-dependent magnetosensitive responses in Drosophila melanogaster. file:DROME/CRY/CRY-deep-research-falcon.md CRY-dependent magnetosensitivity is frequently discussed in Drosophila, with reviews summarizing that cry mutants lose magnetic-field-dependent behaviors |
| GO:0009649 entrainment of circadian clock | IMP PMID:18044989 Light activates output from evening neurons and inhibits out... | ACCEPT | Summary: CRY mediates light input that resets the circadian oscillator. The falcon deep research adds mechanistic detail: TIM then associates with CRY and JET/CUL1, leading to TIM ubiquitination and proteasomal degradation; a 2023 cryo-EM structure shows TIM inserts its N-terminus into the CRY flavin pocket, replacing the autoinhibitory CTT. Reason: Light-activated CRY binding to TIM promotes degradation and clock resetting, supporting entrainment. Core biological process. Supporting Evidence: PMID:18044989 Light-activated CRY binds to the TIMELESS (TIM) protein and induces its degradation, which is likely to reset the molecular oscillator file:DROME/CRY/CRY-deep-research-falcon.md TIM then associates with CRY and **JET/CUL1**, leading to **TIM ubiquitination and proteasomal degradation** |
| GO:0050958 magnetoreception | IMP PMID:19355790 Cryptochrome mediates light-dependent magnetosensitivity of ... | KEEP AS NON CORE | Summary: CRY-dependent magnetic sensitivity of the circadian clock supports magnetoreception. Per falcon, this is a non-canonical, tissue-dependent CRY function relative to the core circadian photoreceptor / TIM-degradation role. Reason: Magnetic field effects on the clock are light- and CRY-dependent, but magnetosensitivity is a secondary/proposed function, not the core circadian photoreceptor role. Supporting Evidence: PMID:19355790 Drosophila's circadian clock is sensitive to magnetic fields and that this sensitivity depends on light activation of CRY and on the applied field strength file:DROME/CRY/CRY-deep-research-falcon.md CRY-dependent magnetosensitivity is frequently discussed in Drosophila, with reviews summarizing that cry mutants lose magnetic-field-dependent behaviors |
| GO:0005634 nucleus | IDA PMID:18399544 Cryptochrome is present in the compound eyes and a subset of... | ACCEPT | Summary: CRY localizes to the nucleus in light/dark conditions. Reason: Independent evidence shows nuclear accumulation of CRY in brain neurons. Supporting Evidence: PMID:14960620 it accumulated in both the nucleus and the cytoplasm, including some neuritic projections. |
| GO:0005737 cytoplasm | IDA PMID:18399544 Cryptochrome is present in the compound eyes and a subset of... | ACCEPT | Summary: CRY localizes to cytoplasm in brain neurons. Reason: Independent evidence shows cytoplasmic accumulation of CRY in light/dark conditions. Supporting Evidence: PMID:14960620 it accumulated in both the nucleus and the cytoplasm, including some neuritic projections. |
| GO:0003913 DNA photolyase activity | IMP NOT PMID:10063806 A putative blue-light receptor from Drosophila melanogaster. | ACCEPT | Summary: CRY lacks DNA photolyase activity (negated). Reason: Recombinant CRY does not show photolyase activity for CPD or 6-4 photoproducts. Supporting Evidence: PMID:10063806 The recombinant protein did not show photolyase activity for either cyclobutane pyrimidine dimers or 6-4 photoproducts in vitro |
| GO:0005515 protein binding | IPI PMID:11448767 Light-dependent interaction between Drosophila CRY and the c... | MARK AS OVER ANNOTATED | Summary: CRY interacts with PER in a light-dependent manner, but the generic binding term is over-annotated. Reason: The evidence supports a specific CRY-PER interaction rather than nonspecific protein binding. Supporting Evidence: PMID:11448767 revealed a dimerization between PER and CRY. |
| GO:0009881 photoreceptor activity | IMP PMID:10417378 Light-dependent sequestration of TIMELESS by CRYPTOCHROME. | ACCEPT | Summary: CRY is described as a circadian photoreceptor. Reason: The study explicitly characterizes CRY as a circadian photoreceptor acting via core clock components. Supporting Evidence: PMID:10417378 Thus, CRY acts as a circadian photoreceptor by directly interacting with core components of the circadian clock. |
| GO:0009881 photoreceptor activity | IMP PMID:18597555 Human and Drosophila cryptochromes are light activated by fl... | ACCEPT | Summary: Cryptochromes function as blue-light signaling receptors. Reason: The study describes cryptochromes as flavoprotein blue-light signaling receptors. Supporting Evidence: PMID:18597555 Cryptochromes are a class of flavoprotein blue-light signaling receptors found in plants, animals, and humans |
| GO:0009882 blue light photoreceptor activity | IMP PMID:10063806 A putative blue-light receptor from Drosophila melanogaster. | ACCEPT | Summary: CRY is a blue-light photoreceptor. The falcon deep research confirms this as the core molecular function: DmCRY is a Drosophila-type/type I cryptochrome that functions primarily as a blue-light photoreceptor for circadian clock entrainment, mechanistically distinct from the light-independent mammalian-type (type II) cryptochromes. Reason: Recombinant CRY lacks photolyase activity and is characterized as a blue-light photoreceptor; this is the core molecular function. Supporting Evidence: PMID:10063806 suggesting that the protein is not a DNA repair enzyme but a blue-light photoreceptor. file:DROME/CRY/CRY-deep-research-falcon.md functions primarily as a **blue-light photoreceptor** for circadian clock entrainment |
| GO:0009882 blue light photoreceptor activity | IMP PMID:10233998 An extraretinally expressed insect cryptochrome with similar... | ACCEPT | Summary: DCry is identified as a candidate blue-light photoreceptor in Drosophila. Reason: The study identifies DCry as a blue-light photoreceptor linked to circadian entrainment. Supporting Evidence: PMID:10233998 We now have identified and characterized a candidate blue light photoreceptor gene in Drosophila (DCry) |
| GO:0009882 blue light photoreceptor activity | IMP PMID:17298948 A novel photoreaction mechanism for the circadian blue light... | ACCEPT | Summary: dCRY functions as a blue-light photoreceptor. Reason: The study describes dCRY as a blue light photoreceptor involved in clock synchronization. Supporting Evidence: PMID:17298948 Drosophila cryptochrome (dCRY) is a blue light photoreceptor that is involved in the synchronization of the circadian clock with the environmental light-dark cycle |
| GO:0009882 blue light photoreceptor activity | IMP PMID:9845369 CRY, a Drosophila clock and light-regulated cryptochrome, is... | ACCEPT | Summary: CRY contributes to photosensitivity in the circadian system. Reason: The study links CRY to circadian photosensitivity and light-dependent resetting. Supporting Evidence: PMID:9845369 CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity. |
| GO:0042752 regulation of circadian rhythm | IMP PMID:10233998 An extraretinally expressed insect cryptochrome with similar... | ACCEPT | Summary: DCry dosage affects blue-light resetting of circadian locomotor rhythms. Reason: Changes in DCry gene dosage alter blue-light resetting responses. Supporting Evidence: PMID:10233998 changes in DCry gene dosage are associated predictably with alterations of the blue light resetting response for the circadian rhythm of adult locomotor activity. |
| GO:0042752 regulation of circadian rhythm | IMP PMID:17298948 A novel photoreaction mechanism for the circadian blue light... | ACCEPT | Summary: dCRY participates in synchronization of the circadian clock to light-dark cycles. Reason: The study links dCRY photoreceptor function to circadian clock synchronization. Supporting Evidence: PMID:17298948 Drosophila cryptochrome (dCRY) is a blue light photoreceptor that is involved in the synchronization of the circadian clock with the environmental light-dark cycle |
| GO:0042752 regulation of circadian rhythm | IMP PMID:9845369 CRY, a Drosophila clock and light-regulated cryptochrome, is... | ACCEPT | Summary: CRY contributes to circadian rhythm resetting. Reason: The study identifies CRY as a major contributor to circadian rhythm resetting and photosensitivity. Supporting Evidence: PMID:9845369 CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity. |
| GO:0042752 regulation of circadian rhythm | IMP PMID:9845370 The cryb mutation identifies cryptochrome as a circadian pho... | ACCEPT | Summary: cryb mutants show impaired synchronization to light-dark cycles. Reason: Genetic loss of CRY affects circadian light synchronization, supporting regulation of circadian rhythm. Supporting Evidence: PMID:9845370 Behaviorally, cryb exhibits poor synchronization to light-dark cycles in genetic backgrounds that cause external blindness |
| GO:0045892 negative regulation of DNA-templated transcription | IMP PMID:16527739 Drosophila CRYPTOCHROME is a circadian transcriptional repre... | KEEP AS NON CORE | Summary: Collins et al. directly demonstrate that Drosophila CRY can repress CLK/CYC-driven transcription, but the effect is "confined to peripheral clocks" and does not significantly affect pacemaker-neuron molecular or behavioral rhythms. This is a genuine but secondary role; the falcon deep research frames the primary/best-established DmCRY function as the blue-light photoreceptor that triggers light-dependent TIM degradation, mechanistically distinct from the mammalian type II repressor role. Reason: Direct experimental evidence (IMP) for repressor activity is solid, but it is a peripheral-clock-specific, non-core function in Drosophila. The canonical core function is light input via TIM degradation, not transcriptional repression. Supporting Evidence: PMID:16527739 Drosophila CRY also functions as a transcriptional repressor. file:DROME/CRY/CRY-deep-research-falcon.md A 2020 expert review by Foley & Emery frames Drosophila CRY as a multi-functional photoreceptor whose **best-established** role is circadian entrainment via **light-dependent TIM degradation** |
| GO:0050660 flavin adenine dinucleotide binding | IDA PMID:10063806 A putative blue-light receptor from Drosophila melanogaster. | ACCEPT | Summary: Recombinant CRY binds a flavin adenine dinucleotide chromophore. Reason: The study reports FAD as a chromophore in purified CRY. Supporting Evidence: PMID:10063806 Purified recombinant protein contained a flavin adenine dinucleotide chromophore. |
| GO:0050660 flavin adenine dinucleotide binding | IDA PMID:17298948 A novel photoreaction mechanism for the circadian blue light... | ACCEPT | Summary: dCRY contains FAD as a bound cofactor. Reason: Biochemical analysis shows FAD(ox) in purified dCRY. Supporting Evidence: PMID:17298948 insect cell-purified dCRY contains flavin adenine dinucleotide in its oxidized state (FAD(ox)) and residual amounts of methenyltetrahydrofolate |
| GO:0050660 flavin adenine dinucleotide binding | IMP PMID:18597555 Human and Drosophila cryptochromes are light activated by fl... | ACCEPT | Summary: Light induces redox changes in flavin bound to CRY. Reason: Photoreduction of bound flavin implies FAD binding. Supporting Evidence: PMID:18597555 Cryptochromes are a class of flavoprotein blue-light signaling receptors found in plants, animals, and humans |
| GO:0050980 detection of light stimulus involved in magnetoreception | IMP PMID:18641630 Cryptochrome mediates light-dependent magnetosensitivity in ... | KEEP AS NON CORE | Summary: Light-dependent magnetosensitivity requires CRY, indicating light detection linked to magnetoreception. Per falcon, this is a non-canonical CRY function relative to the core circadian photoreceptor role. Reason: CRY is necessary for light-dependent magnetic responses, but this magnetosensory detection is secondary to the core circadian photoreceptor / TIM-degradation function. Supporting Evidence: PMID:18641630 the ultraviolet-A/blue-light photoreceptor cryptochrome (Cry) is necessary for light-dependent magnetosensitive responses in Drosophila melanogaster. file:DROME/CRY/CRY-deep-research-falcon.md CRY-dependent magnetosensitivity is frequently discussed in Drosophila, with reviews summarizing that cry mutants lose magnetic-field-dependent behaviors |
| GO:0042752 regulation of circadian rhythm | IDA PMID:16510731 Functional analysis of circadian pacemaker neurons in Drosop... | ACCEPT | Summary: CRY contributes to regulation of circadian rhythm, and this study highlights light-responsive pacemaker neuron behavior. Reason: Pacemaker neuron light responses are consistent with CRY-dependent circadian regulation supported by additional literature. Supporting Evidence: PMID:16510731 respond differently to light and can be completely desynchronized from one another by constant light PMID:9845369 CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity. |
| GO:0007602 phototransduction | IMP PMID:18056988 Animal type 1 cryptochromes. Analysis of the redox state of ... | MODIFY | Summary: The study supports CRY as a circadian photoreceptor, but phototransduction is broader than demonstrated. Reason: Evidence supports photoreceptor activity, not a complete phototransduction cascade annotation. Proposed replacements: photoreceptor activity Supporting Evidence: PMID:18056988 Type 1 CRYs, the prototype of which is the Drosophila CRY, that is known to be a circadian photoreceptor. |
| GO:0009881 photoreceptor activity | IMP PMID:18056988 Animal type 1 cryptochromes. Analysis of the redox state of ... | ACCEPT | Summary: Drosophila CRY is a circadian photoreceptor. Reason: The paper explicitly describes Drosophila CRY as a circadian photoreceptor. Supporting Evidence: PMID:18056988 Type 1 CRYs, the prototype of which is the Drosophila CRY, that is known to be a circadian photoreceptor. |
| GO:0050660 flavin adenine dinucleotide binding | IDA PMID:18056988 Animal type 1 cryptochromes. Analysis of the redox state of ... | ACCEPT | Summary: Type 1 CRYs contain FAD when purified. Reason: The study reports FAD in purified insect CRYs including Drosophila. Supporting Evidence: PMID:18056988 Cryptochromes from all four sources contain FAD(ox) when purified, and the flavin is readily reduced to FAD(*-) by light |
| GO:0043153 entrainment of circadian clock by photoperiod | IMP PMID:14960620 Novel features of cryptochrome-mediated photoreception in th... | ACCEPT | Summary: CRY mediates photic input to the circadian clock. Reason: The study identifies cryptochrome as a photopigment in brain clock neurons affecting light responses. Supporting Evidence: PMID:14960620 The other involves a presumptive photopigment, cryptochrome (cry), expressed in lateral brain neurons that control behavioral rhythms |
| GO:0045475 locomotor rhythm | IMP PMID:17068124 Veela defines a molecular link between Cryptochrome and Time... | KEEP AS NON CORE | Summary: CRY-dependent light input affects behavioral rhythmicity. Reason: The study reports maintenance of behavioral rhythmicity under constant light in CRY pathway variants, consistent with locomotor rhythm modulation. Supporting Evidence: PMID:17068124 these genetically altered flies maintain behavioral and molecular rhythmicity under constant-light conditions that usually stop the clock |
| GO:0009649 entrainment of circadian clock | IMP PMID:15996552 Serotonin modulates circadian entrainment in Drosophila. | ACCEPT | Summary: Light entrainment involves light-induced TIM degradation in a CRY-dependent pathway. Reason: The study links light entrainment to TIM degradation and notes interaction with CRY pathway components. Supporting Evidence: PMID:15996552 Entrainment of the Drosophila circadian clock to light involves the light-induced degradation of the clock protein timeless (TIM). |
| GO:0005634 nucleus | IDA PMID:10417378 Light-dependent sequestration of TIMELESS by CRYPTOCHROME. | ACCEPT | Summary: CRY-containing complexes reside primarily in the nucleus after light perception. Reason: The study describes nuclear localization of CRY/PER/TIM complexes after light. Supporting Evidence: PMID:10417378 PER/TIM and CRY influence the subcellular distribution of these protein complexes, which reside primarily in the nucleus after the perception of a light signal. |
| GO:0009416 response to light stimulus | IMP PMID:15258584 A constitutively active cryptochrome in Drosophila melanogas... | ACCEPT | Summary: Light-activated CRY regulates circadian photoresponses. Reason: The study directly links CRY activation by light to circadian photoresponses. Supporting Evidence: PMID:15258584 Light-activated cryptochrome (CRY) regulates circadian photoresponses in Drosophila melanogaster. |
| GO:0009588 UV-A, blue light phototransduction | ISS PMID:10233998 An extraretinally expressed insect cryptochrome with similar... | ACCEPT | Summary: DCry is an extraretinal blue-light photoreceptor implicated in circadian photoresponses. Reason: The study identifies DCry as a blue-light photoreceptor in brain clock neurons. Supporting Evidence: PMID:10233998 We now have identified and characterized a candidate blue light photoreceptor gene in Drosophila (DCry) |
| GO:0009649 entrainment of circadian clock | IMP PMID:12417651 The extraretinal eyelet of Drosophila: development, ultrastr... | ACCEPT | Summary: Light entrainment involves the eyelet and cryptochrome pathways. Reason: The study reports that eyelet together with cryptochrome mediates phase delays in entrainment. Supporting Evidence: PMID:12417651 eyelet together with cryptochrome mainly mediates phase delays. |
| GO:0042332 gravitaxis | IMP PMID:12042820 Identification of genes involved in Drosophila melanogaster ... | KEEP AS NON CORE | Summary: cry mutants show altered geotaxis scores, supporting a role in gravitaxis. This is a pleiotropic behavioral effect rather than the core circadian photoreceptor function; the falcon deep research does not feature gravitaxis among CRY's well-established roles. Reason: The full text reports that homozygous cry mutants significantly increase geotaxis scores, but this is a downstream/pleiotropic behavioral phenotype, not a core function. Supporting Evidence: PMID:12042820 genes that contribute to the complex, polygenic behavior of geotaxis |
| GO:0043153 entrainment of circadian clock by photoperiod | IMP PMID:15258584 A constitutively active cryptochrome in Drosophila melanogas... | ACCEPT | Summary: CRY activation by light affects circadian photoresponses and entrainment. Reason: Light-activated CRY regulates photoresponses consistent with photoperiod entrainment. Supporting Evidence: PMID:15258584 Light-activated cryptochrome (CRY) regulates circadian photoresponses in Drosophila melanogaster. |
| GO:0043153 entrainment of circadian clock by photoperiod | IMP PMID:16361445 Disruption of Cryptochrome partially restores circadian rhyt... | ACCEPT | Summary: Light entraining signals require CRY-dependent pathways. Reason: The study states that cryptochrome-mediated pathways provide entraining light signals to the clock. Supporting Evidence: PMID:16361445 cryptochrome are also critical in providing the circadian clock with entraining light signals from the environment |
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