Cryptochrome-1 (CRY1) is a FAD-binding transcriptional repressor in the mammalian circadian clock that binds CLOCK:BMAL1 to inhibit E-box-driven transcription and regulate rhythmic gene expression; it also modulates metabolic and glucocorticoid signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: UniProt-curated localization includes nuclear and cytoplasmic CRY1. Reason: Subcellular location annotations report cytoplasmic and nuclear CRY1. Supporting Evidence: UniProtKB:Q16526 SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:22798407, |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: UniProt-curated localization includes nuclear and cytoplasmic CRY1. Reason: Subcellular location annotations report cytoplasmic and nuclear CRY1. Supporting Evidence: UniProtKB:Q16526 SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:22798407, |
| GO:0045892 negative regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: CRY proteins repress CLOCK:BMAL1-driven transcription in the circadian loop. Reason: CRY/PER repressors inhibit CLOCK:BMAL1 transcriptional activity. Supporting Evidence: PMID:21613214 repress their own transcription by suppressing the transactivator function of |
| GO:0003677 DNA binding | IBA GO_REF:0000033 | MODIFY | Summary: Evidence supports CRY1 binding to CLOCK:BMAL1 on E-boxes, not direct DNA binding. Reason: CRY binds the CLOCK:BMAL1:E-box complex; DNA-binding TF binding is more accurate. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:21613214 CRY binds stably to the CLOCK:BMAL1:E-box ternary |
| GO:0032922 circadian regulation of gene expression | IBA GO_REF:0000033 | ACCEPT | Summary: CRY1 regulates circadian gene expression via the core transcriptional feedback loop. Reason: CRY represses CLOCK:BMAL1 activity, shaping circadian gene expression. Supporting Evidence: PMID:21613214 repress their own transcription by suppressing the transactivator function of |
| GO:0043153 entrainment of circadian clock by photoperiod | IBA GO_REF:0000033 | REMOVE | Summary: Mammalian CRY is not required for photo-entrainment; photoperiod entrainment is unsupported. Reason: Evidence indicates mammalian CRY is not required for photo-entrainment. Supporting Evidence: PMID:23133559 Arabidopsis and Drosophila CRY is a major circadian photoreceptor for light entrainment, while mammalian CRY is not required for photo-entrainment. |
| GO:0071949 FAD binding | IBA GO_REF:0000033 | ACCEPT | Summary: CRY1 binds FAD as a chromophore/cofactor. Reason: Purified hCRY1 contains FAD, supporting FAD binding. Supporting Evidence: PMID:8909283 were found to contain FAD and a pterin cofactor. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: CRY1 binds a nucleotide cofactor (FAD), consistent with nucleotide binding. Reason: FAD is a nucleotide cofactor; the term is generic but compatible with FAD binding. Supporting Evidence: UniProtKB:Q16526 Binds 1 FAD per subunit. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt-curated localization includes nuclear and cytoplasmic CRY1. Reason: Subcellular location annotations report cytoplasmic and nuclear CRY1. Supporting Evidence: UniProtKB:Q16526 SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:22798407, |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt-curated localization includes nuclear and cytoplasmic CRY1. Reason: Subcellular location annotations report cytoplasmic and nuclear CRY1. Supporting Evidence: UniProtKB:Q16526 SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:22798407, |
| GO:0009881 photoreceptor activity | IEA GO_REF:0000043 | REMOVE | Summary: Mammalian CRY is not required for photo-entrainment; photoreceptor activity is not supported. Reason: Evidence indicates mammalian CRY is not required for photo-entrainment. Supporting Evidence: PMID:23133559 Arabidopsis and Drosophila CRY is a major circadian photoreceptor for light entrainment, while mammalian CRY is not required for photo-entrainment. |
| GO:0019902 phosphatase binding | IEA GO_REF:0000117 | REMOVE | Summary: Phosphatase binding evidence is for hCRY2, not CRY1. Reason: The cited interaction involves hCRY2 rather than CRY1. Supporting Evidence: PMID:9383998 specifically interacted with hCRY2. |
| GO:0048511 rhythmic process | IEA GO_REF:0000043 | ACCEPT | Summary: CRY1 participates in rhythmic processes as part of the circadian clock. Reason: CRY1 is a core circadian clock component regulating rhythmic gene expression. Supporting Evidence: UniProtKB:Q16526 Transcriptional repressor which forms a core component of the |
| GO:0005515 protein binding | IPI PMID:23133559 Role of type II protein arginine methyltransferase 5 in the ... | MARK AS OVER ANNOTATED | Summary: CRY1 interacts with PRMT5, but the generic protein binding term is too broad. Reason: The study reports a specific PRMT5 interaction rather than nonspecific binding. Supporting Evidence: PMID:23133559 interacting molecule of CRY1. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: High-throughput interactome study; generic protein binding term is not informative for CRY1. Reason: Proteome-scale AP-MS reports many candidate interactions and does not validate a specific CRY1 binding partner. Supporting Evidence: PMID:28514442 BioPlex 2.0 contains more than 29,000 previously unknown co-associations |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Proteome-scale interactome mapping is too nonspecific for a generic protein-binding annotation. Reason: The study reports large-scale interaction networks rather than a specific CRY1 binding partner. Supporting Evidence: PMID:33961781 we have created two proteome-scale, cell-line-specific |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: CRY proteins repress CLOCK:BMAL1-driven transcription in the circadian loop. Reason: CRY/PER repressors inhibit CLOCK:BMAL1 transcriptional activity. Supporting Evidence: PMID:21613214 repress their own transcription by suppressing the transactivator function of |
| GO:0003690 double-stranded DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: Evidence supports CRY1 binding to CLOCK:BMAL1 on E-boxes, not direct DNA binding. Reason: CRY binds the CLOCK:BMAL1:E-box complex; DNA-binding TF binding is more accurate. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:21613214 CRY binds stably to the CLOCK:BMAL1:E-box ternary |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | REMOVE | Summary: Human CRY1 is primarily nuclear/cytoplasmic; mitochondrial localization is not established. Reason: Available human evidence supports cytoplasmic/nuclear localization; mitochondrial localization is from mouse CRY1. Supporting Evidence: UniProtKB:Q16526 SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:22798407, PMID:9801304 mCRY1 is localized in mitochondria |
| GO:0006094 gluconeogenesis | IEA GO_REF:0000107 | MODIFY | Summary: CRY1 inhibits gluconeogenic gene expression rather than catalyzing gluconeogenesis. Reason: Evidence supports negative regulation of gluconeogenesis. Proposed replacements: negative regulation of gluconeogenesis Supporting Evidence: PMID:20852621 gluconeogenic gene expression by blocking glucagon-mediated increases in |
| GO:0006111 regulation of gluconeogenesis | IEA GO_REF:0000107 | MODIFY | Summary: CRY1 represses gluconeogenic gene expression via glucagon/cAMP signaling. Reason: Evidence supports negative regulation rather than generic regulation. Proposed replacements: negative regulation of gluconeogenesis Supporting Evidence: PMID:20852621 gluconeogenic gene expression by blocking glucagon-mediated increases in |
| GO:0009416 response to light stimulus | IEA GO_REF:0000107 | REMOVE | Summary: Mammalian CRY is not required for photo-entrainment, so light response is unsupported. Reason: Evidence indicates mammalian CRY is not required for photo-entrainment. Supporting Evidence: PMID:23133559 Arabidopsis and Drosophila CRY is a major circadian photoreceptor for light entrainment, while mammalian CRY is not required for photo-entrainment. |
| GO:0014823 response to activity | IEA GO_REF:0000107 | REMOVE | Summary: No evidence found linking CRY1 to response to activity. Reason: Accessible sources do not report CRY1 involvement in activity response. Supporting Evidence: UniProtKB:Q16526 Transcriptional repressor which forms a core component of the |
| GO:0016922 nuclear receptor binding | IEA GO_REF:0000120 | ACCEPT | Summary: CRY1 interacts with nuclear receptors such as the glucocorticoid receptor. Reason: Cryptochromes bind the glucocorticoid receptor in a ligand-dependent manner. Supporting Evidence: PMID:22170608 cryptochromes 1 and 2, interact with the glucocorticoid receptor |
| GO:0019900 kinase binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Direct kinase binding evidence was not found in accessible sources. Reason: No direct kinase-binding assays were located in the available references. |
| GO:0019901 protein kinase binding | IEA GO_REF:0000107 | UNDECIDED | Summary: Direct kinase binding evidence was not found in accessible sources. Reason: No direct kinase-binding assays were located in the available references. |
| GO:0019915 lipid storage | IEA GO_REF:0000107 | REMOVE | Summary: No direct evidence found for CRY1 in lipid storage. Reason: Available references emphasize circadian regulation and gluconeogenesis rather than lipid storage. Supporting Evidence: UniProtKB:Q16526 Transcriptional repressor which forms a core component of the |
| GO:0031397 negative regulation of protein ubiquitination | IEA GO_REF:0000107 | REMOVE | Summary: CRY1 is ubiquitinated by SCF(FBXL3), indicating it is a substrate not a regulator. Reason: Evidence shows CRY1 is ubiquitinated and degraded rather than regulating ubiquitination. Supporting Evidence: PMID:17463251 Cry1 and Cry2 proteins are ubiquitinated and degraded |
| GO:0031398 positive regulation of protein ubiquitination | IEA GO_REF:0000107 | REMOVE | Summary: CRY1 is a ubiquitination substrate rather than a positive regulator. Reason: CRY1 is ubiquitinated and degraded via SCF(FBXL3). Supporting Evidence: PMID:17463251 Cry1 and Cry2 proteins are ubiquitinated and degraded |
| GO:0032868 response to insulin | IEA GO_REF:0000107 | ACCEPT | Summary: CRY1 influences insulin sensitivity in metabolic settings. Reason: Cry1 overexpression improves insulin sensitivity in insulin-resistant mice. Supporting Evidence: PMID:20852621 improved insulin sensitivity in insulin-resistant db/db mice |
| GO:0032922 circadian regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: CRY1 regulates circadian gene expression via the core transcriptional feedback loop. Reason: CRY represses CLOCK:BMAL1 activity, shaping circadian gene expression. Supporting Evidence: PMID:21613214 repress their own transcription by suppressing the transactivator function of |
| GO:0033762 response to glucagon | IEA GO_REF:0000107 | ACCEPT | Summary: CRY1 modulates glucagon-stimulated signaling during fasting. Reason: Cry1 reduces glucagon-mediated increases in cAMP. Supporting Evidence: PMID:20852621 gluconeogenic gene expression by blocking glucagon-mediated increases in |
| GO:0042593 glucose homeostasis | IEA GO_REF:0000107 | ACCEPT | Summary: CRY1 contributes to glucose homeostasis. Reason: Loss of cryptochromes causes glucose intolerance and altered corticosterone levels. Supporting Evidence: PMID:22170608 results in glucose intolerance and constitutively |
| GO:0042752 regulation of circadian rhythm | IEA GO_REF:0000107 | ACCEPT | Summary: CRY1 is a core circadian clock repressor. Reason: CRY1/2 encode inhibitors of CLOCK:BMAL1 in the feedback loop. Supporting Evidence: PMID:17463251 encode inhibitors of the Clock-Bmal1 complex |
| GO:0042754 negative regulation of circadian rhythm | IEA GO_REF:0000107 | ACCEPT | Summary: CRY1 represses CLOCK:BMAL1 as part of the negative limb of the clock. Reason: CRY1/2 inhibit CLOCK:BMAL1 in a negative-feedback loop. Supporting Evidence: PMID:17463251 encode inhibitors of the Clock-Bmal1 complex |
| GO:0042770 signal transduction in response to DNA damage | IEA GO_REF:0000107 | REMOVE | Summary: No direct evidence found for CRY1 in DNA damage response signaling. Reason: Accessible sources focus on circadian regulation and metabolism, not DNA damage signaling. Supporting Evidence: UniProtKB:Q16526 Transcriptional repressor which forms a core component of the |
| GO:0042826 histone deacetylase binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: CRY1 recruits histone deacetylases as part of transcriptional repression. Reason: CRY1 is reported to recruit HDACs during Per1 repression. Supporting Evidence: PMID:23133559 CRY1 negatively regulates Per1 gene expression by recruiting histone deacetylases (HDACs) |
| GO:0043153 entrainment of circadian clock by photoperiod | IEA GO_REF:0000107 | REMOVE | Summary: Mammalian CRY is not required for photo-entrainment; photoperiod entrainment is unsupported. Reason: Evidence indicates mammalian CRY is not required for photo-entrainment. Supporting Evidence: PMID:23133559 Arabidopsis and Drosophila CRY is a major circadian photoreceptor for light entrainment, while mammalian CRY is not required for photo-entrainment. |
| GO:0045721 negative regulation of gluconeogenesis | IEA GO_REF:0000107 | ACCEPT | Summary: CRY1 reduces gluconeogenic gene expression during fasting. Reason: Cry1 reduces fasting gluconeogenic gene expression by blocking glucagon-mediated cAMP increases. Supporting Evidence: PMID:20852621 gluconeogenic gene expression by blocking glucagon-mediated increases in |
| GO:0045722 positive regulation of gluconeogenesis | IEA GO_REF:0000107 | REMOVE | Summary: CRY1 suppresses rather than promotes gluconeogenesis. Reason: Cry1 reduces gluconeogenic gene expression, supporting negative regulation instead. Supporting Evidence: PMID:20852621 gluconeogenic gene expression by blocking glucagon-mediated increases in |
| GO:0045744 negative regulation of G protein-coupled receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: CRY1 dampens GPCR-driven cAMP signaling. Reason: Cry1 inhibits cAMP accumulation in response to GPCR activation. Supporting Evidence: PMID:20852621 Cry1 inhibited accumulation of cAMP in response to G protein-coupled receptor |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000107 | ACCEPT | Summary: CRY proteins repress CLOCK:BMAL1-driven transcription in the circadian loop. Reason: CRY/PER repressors inhibit CLOCK:BMAL1 transcriptional activity. Supporting Evidence: PMID:21613214 repress their own transcription by suppressing the transactivator function of |
| GO:0070888 E-box binding | IEA GO_REF:0000107 | MODIFY | Summary: Evidence supports CRY1 binding to CLOCK:BMAL1 on E-boxes, not direct DNA binding. Reason: CRY binds the CLOCK:BMAL1:E-box complex; DNA-binding TF binding is more accurate. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:21613214 CRY binds stably to the CLOCK:BMAL1:E-box ternary |
| GO:0140297 DNA-binding transcription factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: CRY1 binds the CLOCK:BMAL1:E-box complex via protein-protein interactions. Reason: CRY binds stably to the CLOCK:BMAL1:E-box ternary complex. Supporting Evidence: PMID:21613214 CRY binds stably to the CLOCK:BMAL1:E-box ternary |
| GO:2000001 regulation of DNA damage checkpoint | IEA GO_REF:0000107 | REMOVE | Summary: No evidence found for CRY1 regulating the DNA damage checkpoint. Reason: Available references describe circadian transcriptional roles rather than checkpoint control. Supporting Evidence: UniProtKB:Q16526 Transcriptional repressor which forms a core component of the |
| GO:2000323 negative regulation of nuclear receptor-mediated glucocorticoid signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: CRY1 broadly represses glucocorticoid receptor activity. Reason: Cryptochromes oppose glucocorticoid receptor activation and promote repression. Supporting Evidence: PMID:22170608 cryptochromes broadly oppose |
| GO:2000850 negative regulation of glucocorticoid secretion | IEA GO_REF:0000107 | ACCEPT | Summary: Cryptochromes restrain glucocorticoid levels in vivo. Reason: Loss of cryptochromes leads to constitutively high corticosterone. Supporting Evidence: PMID:22170608 results in glucose intolerance and constitutively |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | MODIFY | Summary: CRY1 is nuclear, but nucleoplasm is more specific than supported. Reason: Evidence supports nuclear localization without nucleoplasm specificity. Proposed replacements: nucleus Supporting Evidence: UniProtKB:Q16526 SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:22798407, |
| GO:0007623 circadian rhythm | ISS GO_REF:0000024 | ACCEPT | Summary: CRY1 functions in the core circadian clock. Reason: CRY1 is a core component of the circadian clock mechanism. Supporting Evidence: UniProtKB:Q16526 Transcriptional repressor which forms a core component of the |
| GO:0009416 response to light stimulus | ISS GO_REF:0000024 | REMOVE | Summary: Mammalian CRY is not required for photo-entrainment, so light response is unsupported. Reason: Evidence indicates mammalian CRY is not required for photo-entrainment. Supporting Evidence: PMID:23133559 Arabidopsis and Drosophila CRY is a major circadian photoreceptor for light entrainment, while mammalian CRY is not required for photo-entrainment. |
| GO:0014823 response to activity | ISS GO_REF:0000024 | REMOVE | Summary: No evidence found linking CRY1 to response to activity. Reason: Accessible sources do not report CRY1 involvement in activity response. Supporting Evidence: UniProtKB:Q16526 Transcriptional repressor which forms a core component of the |
| GO:0005515 protein binding | IPI PMID:30530698 Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modula... | MODIFY | Summary: CRY1 binds the nuclear receptor HNF4A; a nuclear receptor binding term is more appropriate. Reason: Evidence supports interaction with a nuclear receptor rather than generic protein binding. Proposed replacements: nuclear receptor binding Supporting Evidence: PMID:30530698 we noted a robust binding between core clock proteins and the HNF4A protein |
| GO:0005515 protein binding | IPI PMID:26431207 CUL4-DDB1-CDT2 E3 Ligase Regulates the Molecular Clock Activ... | MARK AS OVER ANNOTATED | Summary: CRY1 is ubiquitinated by the CUL4-DDB1-CDT2 ligase; generic protein binding is too broad. Reason: The evidence describes CRY1 as a ubiquitination substrate rather than a general binding activity. Supporting Evidence: PMID:26431207 ubiquitinates CRY1 and promotes its |
| GO:0005634 nucleus | IDA PMID:26431207 CUL4-DDB1-CDT2 E3 Ligase Regulates the Molecular Clock Activ... | ACCEPT | Summary: UniProt-curated localization includes nuclear CRY1. Reason: Subcellular location annotations indicate nuclear localization; PMID:26431207 does not contradict this. Supporting Evidence: UniProtKB:Q16526 SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:22798407, PMID:26431207 ubiquitinates CRY1 and promotes its |
| GO:0031398 positive regulation of protein ubiquitination | ISS GO_REF:0000024 | REMOVE | Summary: CRY1 is a ubiquitination substrate rather than a positive regulator. Reason: CRY1 is ubiquitinated and degraded via SCF(FBXL3). Supporting Evidence: PMID:17463251 Cry1 and Cry2 proteins are ubiquitinated and degraded |
| GO:0045721 negative regulation of gluconeogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: CRY1 reduces gluconeogenic gene expression during fasting. Reason: Cry1 reduces fasting gluconeogenic gene expression by blocking glucagon-mediated cAMP increases. Supporting Evidence: PMID:20852621 gluconeogenic gene expression by blocking glucagon-mediated increases in |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:23133559 Role of type II protein arginine methyltransferase 5 in the ... | ACCEPT | Summary: CRY1 participates in transcriptional repression within the circadian feedback loop. Reason: PER/CRY complexes inhibit CLOCK/BMAL1 transcriptional activity. Supporting Evidence: PMID:23133559 complexes inhibit the transcriptional activity of the CLOCK/BMAL1 heterodimer |
| GO:0043153 entrainment of circadian clock by photoperiod | ISS GO_REF:0000024 | REMOVE | Summary: Mammalian CRY is not required for photo-entrainment; photoperiod entrainment is unsupported. Reason: Evidence indicates mammalian CRY is not required for photo-entrainment. Supporting Evidence: PMID:23133559 Arabidopsis and Drosophila CRY is a major circadian photoreceptor for light entrainment, while mammalian CRY is not required for photo-entrainment. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:12397359 Dec1 and Dec2 are regulators of the mammalian molecular cloc... | ACCEPT | Summary: CRY proteins inhibit Per transcription in the circadian feedback loop. Reason: The study states Cry proteins inhibit Per transcription. Supporting Evidence: PMID:12397359 Cry proteins to inhibit Per transcription |
| GO:0031397 negative regulation of protein ubiquitination | ISS GO_REF:0000024 | REMOVE | Summary: CRY1 is ubiquitinated by SCF(FBXL3), indicating it is a substrate not a regulator. Reason: Evidence shows CRY1 is ubiquitinated and degraded rather than regulating ubiquitination. Supporting Evidence: PMID:17463251 Cry1 and Cry2 proteins are ubiquitinated and degraded |
| GO:0005515 protein binding | IPI PMID:20852621 Cryptochrome mediates circadian regulation of cAMP signaling... | MARK AS OVER ANNOTATED | Summary: CRY1 interacts with G(s)Ξ± in GPCR signaling; generic protein binding is too broad. Reason: Evidence supports a specific interaction with G(s)Ξ± rather than nonspecific binding. Supporting Evidence: PMID:20852621 modulate GPCR activity directly through interaction with |
| GO:0006094 gluconeogenesis | ISS GO_REF:0000024 | MODIFY | Summary: CRY1 inhibits gluconeogenic gene expression rather than catalyzing gluconeogenesis. Reason: Evidence supports negative regulation of gluconeogenesis. Proposed replacements: negative regulation of gluconeogenesis Supporting Evidence: PMID:20852621 gluconeogenic gene expression by blocking glucagon-mediated increases in |
| GO:0033762 response to glucagon | ISS GO_REF:0000024 | ACCEPT | Summary: CRY1 modulates glucagon-stimulated signaling during fasting. Reason: Cry1 reduces glucagon-mediated increases in cAMP. Supporting Evidence: PMID:20852621 gluconeogenic gene expression by blocking glucagon-mediated increases in |
| GO:0045744 negative regulation of G protein-coupled receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: CRY1 dampens GPCR-driven cAMP signaling. Reason: Cry1 inhibits cAMP accumulation in response to GPCR activation. Supporting Evidence: PMID:20852621 Cry1 inhibited accumulation of cAMP in response to G protein-coupled receptor |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: UniProt-curated localization includes nuclear and cytoplasmic CRY1. Reason: Subcellular location annotations report cytoplasmic and nuclear CRY1. Supporting Evidence: UniProtKB:Q16526 SUBCELLULAR LOCATION: Cytoplasm. Nucleus {ECO:0000269|PubMed:22798407, |
| GO:0042770 signal transduction in response to DNA damage | ISS GO_REF:0000024 | REMOVE | Summary: No direct evidence found for CRY1 in DNA damage response signaling. Reason: Accessible sources focus on circadian regulation and metabolism, not DNA damage signaling. Supporting Evidence: UniProtKB:Q16526 Transcriptional repressor which forms a core component of the |
| GO:2000001 regulation of DNA damage checkpoint | ISS GO_REF:0000024 | REMOVE | Summary: No evidence found for CRY1 regulating the DNA damage checkpoint. Reason: Available references describe circadian transcriptional roles rather than checkpoint control. Supporting Evidence: UniProtKB:Q16526 Transcriptional repressor which forms a core component of the |
| GO:0042593 glucose homeostasis | ISS GO_REF:0000024 | ACCEPT | Summary: CRY1 contributes to glucose homeostasis. Reason: Loss of cryptochromes causes glucose intolerance and altered corticosterone levels. Supporting Evidence: PMID:22170608 results in glucose intolerance and constitutively |
| GO:2000323 negative regulation of nuclear receptor-mediated glucocorticoid signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: CRY1 broadly represses glucocorticoid receptor activity. Reason: Cryptochromes oppose glucocorticoid receptor activation and promote repression. Supporting Evidence: PMID:22170608 cryptochromes broadly oppose |
| GO:0016922 nuclear receptor binding | IPI PMID:22170608 Cryptochromes mediate rhythmic repression of the glucocortic... | ACCEPT | Summary: CRY1/2 interact with the glucocorticoid receptor in a ligand-dependent manner. Reason: The study reports cryptochromes binding the glucocorticoid receptor. Supporting Evidence: PMID:22170608 cryptochromes 1 and 2, interact with the glucocorticoid receptor |
| GO:0005515 protein binding | IPI PMID:21613214 Biochemical analysis of the canonical model for the mammalia... | MARK AS OVER ANNOTATED | Summary: CRY binds to the CLOCK:BMAL1:E-box complex; generic protein binding is too broad. Reason: Evidence describes specific interaction with CLOCK:BMAL1 on DNA. Supporting Evidence: PMID:21613214 CRY binds stably to the CLOCK:BMAL1:E-box ternary |
| GO:0005515 protein binding | IPI PMID:21680841 A molecular mechanism for circadian clock negative feedback. | REMOVE | Summary: The cited study focuses on PER complexes and does not present CRY1 binding evidence. Reason: No CRY1 interaction evidence is provided in the abstract. Supporting Evidence: PMID:21680841 PERIOD (PER) proteins, acting in a large complex, inhibit the transcriptional |
| GO:0042754 negative regulation of circadian rhythm | ISS GO_REF:0000024 | ACCEPT | Summary: CRY1 represses CLOCK:BMAL1 as part of the negative limb of the clock. Reason: CRY1/2 inhibit CLOCK:BMAL1 in a negative-feedback loop. Supporting Evidence: PMID:17463251 encode inhibitors of the Clock-Bmal1 complex |
| GO:0032922 circadian regulation of gene expression | ISS GO_REF:0000024 | ACCEPT | Summary: CRY1 regulates circadian gene expression via the core transcriptional feedback loop. Reason: CRY represses CLOCK:BMAL1 activity, shaping circadian gene expression. Supporting Evidence: PMID:21613214 repress their own transcription by suppressing the transactivator function of |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: CRY proteins repress CLOCK:BMAL1-driven transcription in the circadian loop. Reason: CRY/PER repressors inhibit CLOCK:BMAL1 transcriptional activity. Supporting Evidence: PMID:21613214 repress their own transcription by suppressing the transactivator function of |
| GO:0005515 protein binding | IPI PMID:9383998 Human blue-light photoreceptor hCRY2 specifically interacts ... | REMOVE | Summary: The study reports PP5 interaction with hCRY2, not CRY1. Reason: Evidence is specific to CRY2, so it does not support CRY1 binding. Supporting Evidence: PMID:9383998 specifically interacted with hCRY2. |
| GO:0019902 phosphatase binding | IPI PMID:9383998 Human blue-light photoreceptor hCRY2 specifically interacts ... | REMOVE | Summary: Phosphatase binding evidence is for hCRY2, not CRY1. Reason: The study specifies PP5 interaction with hCRY2 rather than CRY1. Supporting Evidence: PMID:9383998 specifically interacted with hCRY2. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:12397359 Dec1 and Dec2 are regulators of the mammalian molecular cloc... | ACCEPT | Summary: Cry proteins inhibit Per transcription in the circadian feedback loop. Reason: Cry proteins are reported to inhibit Per transcription. Supporting Evidence: PMID:12397359 Cry proteins to inhibit Per transcription |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:14672706 A novel autofeedback loop of Dec1 transcription involved in ... | ACCEPT | Summary: PER/CRY act as negative regulators of CLOCK/BMAL-driven transcription. Reason: PER/CRY suppress CLOCK/BMAL-induced expression in the feedback loop. Supporting Evidence: PMID:14672706 PERs and CRYs suppressed the induced expression. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:15147242 Expression of the gene for Dec2, a basic helix-loop-helix tr... | ACCEPT | Summary: Cry proteins suppress Clock/Bmal-induced transcription. Reason: Cry proteins are reported to suppress Clock/Bmal-induced transcription. Supporting Evidence: PMID:15147242 suppressed Clock/Bmal-induced transcription from the Dec2 promoter. |
| GO:0042752 regulation of circadian rhythm | ISS GO_REF:0000024 | ACCEPT | Summary: CRY1 is a core circadian clock repressor. Reason: CRY1/2 encode inhibitors of CLOCK:BMAL1 in the feedback loop. Supporting Evidence: PMID:17463251 encode inhibitors of the Clock-Bmal1 complex |
| GO:0009785 blue light signaling pathway | NAS PMID:8909283 Putative human blue-light photoreceptors hCRY1 and hCRY2 are... | REMOVE | Summary: Human CRY1 is not required for photo-entrainment; blue-light signaling is not supported. Reason: Mammalian CRY is reported not to be required for photo-entrainment, so blue-light signaling is unsupported. Supporting Evidence: PMID:23133559 Arabidopsis and Drosophila CRY is a major circadian photoreceptor for light entrainment, while mammalian CRY is not required for photo-entrainment. |
| GO:0009882 blue light photoreceptor activity | NAS PMID:8909283 Putative human blue-light photoreceptors hCRY1 and hCRY2 are... | MARK AS OVER ANNOTATED | Summary: Early work suggested blue-light photoreceptor function, but mammalian CRY is not required for photo-entrainment. Reason: The photoreceptor role is speculative for mammals; later evidence indicates CRY is not required for photo-entrainment. Supporting Evidence: PMID:8909283 may function as blue-light photoreceptors in humans. PMID:23133559 Arabidopsis and Drosophila CRY is a major circadian photoreceptor for light entrainment, while mammalian CRY is not required for photo-entrainment. |
| GO:0003690 double-stranded DNA binding | IDA PMID:9801304 Characterization of photolyase/blue-light receptor homologs ... | MODIFY | Summary: CRY1 binds CLOCK:BMAL1 on E-box DNA rather than directly binding DNA. Reason: Evidence supports association with the CLOCK:BMAL1:E-box complex, not direct DNA binding. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:21613214 CRY binds stably to the CLOCK:BMAL1:E-box ternary |
| GO:0003904 deoxyribodipyrimidine photo-lyase activity | IDA NOT PMID:8909283 Putative human blue-light photoreceptors hCRY1 and hCRY2 are... | ACCEPT | Summary: CRY1 lacks cyclobutane pyrimidine dimer photolyase activity (negated). Reason: Purified hCRY1 lacks photolyase activity on cyclobutane pyrimidine dimers. Supporting Evidence: PMID:8909283 lacked photolyase activity on the |
| GO:0003914 DNA (6-4) photolyase activity | IDA NOT PMID:8909283 Putative human blue-light photoreceptors hCRY1 and hCRY2 are... | ACCEPT | Summary: CRY1 lacks (6-4) photolyase activity (negated). Reason: Purified hCRY1 lacks photolyase activity on (6-4) photoproducts. Supporting Evidence: PMID:8909283 lacked photolyase activity on the |
| GO:0005515 protein binding | IPI PMID:17463251 SCFFbxl3 controls the oscillation of the circadian clock by ... | MARK AS OVER ANNOTATED | Summary: CRY1 is an inhibitor of CLOCK:BMAL1 but generic protein binding is too broad. Reason: Evidence points to specific interactions in the clock feedback loop. Supporting Evidence: PMID:17463251 encode inhibitors of the Clock-Bmal1 complex |
| GO:0003677 DNA binding | TAS PMID:9801304 Characterization of photolyase/blue-light receptor homologs ... | MODIFY | Summary: Evidence favors interaction with CLOCK:BMAL1 on E-boxes rather than direct DNA binding. Reason: CRY binds the CLOCK:BMAL1:E-box complex, so a TF-binding term is more accurate. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:21613214 CRY binds stably to the CLOCK:BMAL1:E-box ternary |
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