Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods.
The protein kinase CK2 is involved in regulation of circadian rhythms in Arabidopsis.
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Overexpression of the CK2 regulatory subunit CKB3 in Arabidopsis increases CK2 activity and shortens the period of CCA1/LHY rhythmic expression, demonstrating that CK2-mediated phosphorylation of CCA1 regulates clock period in vivo.
"we show that plants overexpressing CKB3, a regulatory subunit of CK2, display increased CK2 activity and shorter periods of rhythmic expression of CCA1 and LHY."
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Overexpression of CKB3 also shortens the periods of multiple circadian clock-controlled output genes with different phase angles, indicating that CK2-CCA1 phosphorylation affects diverse clock outputs.
"overexpression of CKB3 shortened the periods of four known circadian clock-controlled genes with different phase angles, demonstrating that many clock outputs are affected."
Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes.
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Genome-wide Arabidopsis transcription factor catalog catalogues CCA1 as a sequence-specific DNA-binding MYB-related TF, providing the basis for ISS/TAS DNA-binding-TF and transcription-regulation annotations.
"Arabidopsis dedicates over 5% of its genome to code for more than 1500 transcription factors, about 45% of which are from families specific to plants."
Reciprocal regulation between TOC1 and LHY/CCA1 within the Arabidopsis circadian clock.
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LHY and CCA1 negatively regulate TOC1 expression; both proteins bind a region in the TOC1 promoter critical for its clock regulation, providing direct evidence for CCA1's cis-regulatory binding and negative regulation of an evening-phased clock gene.
"The MYB transcription factors LHY and CCA1 negatively regulate TOC1 expression. We show that both proteins bind to a region in the TOC1 promoter that is critical for its clock regulation."
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TOC1 participates in the positive regulation of LHY and CCA1 expression, completing the LHY/CCA1-TOC1 reciprocal feedback loop that is critical for clock function.
"TOC1 appears to participate in the positive regulation of LHY and CCA1 expression. Our results indicate that these interactions form a loop critical for clock function in Arabidopsis."
CK2 phosphorylation of CCA1 is necessary for its circadian oscillator function in Arabidopsis.
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CK2-mediated phosphorylation of CCA1 is required for normal circadian oscillator function in Arabidopsis; abrogating CK2-target phosphorylation sites compromises CCA1's clock function, supporting a regulated post-translational modification of CCA1 in the oscillator.
"Phosphorylation of some of the central oscillator proteins is necessary for the generation of normal circadian rhythms"
Systems approach identifies an organic nitrogen-responsive gene network that is regulated by the master clock control gene CCA1.
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Genome-wide network analysis identifies CCA1 as the central transcription factor regulating an organic-nitrogen-responsive gene network in Arabidopsis, linking the circadian clock to nitrogen metabolic gene expression.
"Genes that responded to organic N"
Circadian clock proteins LHY and CCA1 regulate SVP protein accumulation to control flowering in Arabidopsis.
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CCA1 (with LHY) represses the floral transition under both short-day and long-day photoperiods and accelerates flowering under continuous light, placing it upstream of photoperiodic flowering as a clock-output role.
"the circadian clock proteins LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) not only repressed the floral transition under short-day and long-day conditions but also accelerated flowering when the plants were grown under continuous light (LL)"
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LHY/CCA1 regulate the FT-SVP module, modulating accumulation of the flowering repressor SVP and FT expression; this is a clock-output role rather than core oscillator function for CCA1.
"Circadian clock proteins LHY and CCA1 regulate SVP protein accumulation to control flowering in Arabidopsis."
CIRCADIAN CLOCK ASSOCIATED1 and LATE ELONGATED HYPOCOTYL function synergistically in the circadian clock of Arabidopsis.
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CCA1 colocalizes with LHY in the nucleus and heterodimerizes with LHY both in vitro and in vivo, providing experimental EXP support for nuclear localization and a basis for CCA1/LHY dimerization activity.
"they also colocalize in the nucleus and heterodimerize in vitro and in vivo"
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Single cca1 and lhy mutants each show short-period rhythms, and the cca1 lhy double mutant has a still shorter period than either single, indicating only partial functional redundancy and synergistic CCA1/LHY action in the oscillator.
"cca1 lhy double mutants show an even shorter period phenotype than the cca1 single mutant, suggesting that CCA1 and LHY are only partially functionally redundant"
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CCA1 and LHY can form homodimers and are present in the same large (>400 kDa) nuclear complex in planta, supporting their assembly into a clock transcriptional module.
"CCA1 and LHY can form homodimers, and they also colocalize in the nucleus and heterodimerize in vitro and in vivo"
The role of casein kinase II in flowering time regulation has diversified during evolution.
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CCA1 is the relevant CK2 target in Arabidopsis influencing photoperiodic flowering; cross-species comparison shows that CK2's role in flowering time has diversified in evolution but the Arabidopsis CCA1-CK2 axis remains central.
"The circadian clock component CIRCADIAN CLOCK ASSOCIATED1 (CCA1) is a CK2 target in Arabidopsis, where it influences photoperiodic flowering."
Circadian clock-associated 1 and late elongated hypocotyl regulate expression of the C-repeat binding factor (CBF) pathway in Arabidopsis.
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CCA1 (with LHY) directly binds CBF1-3 promoters (presumably at EE/CBS motifs) and circadian-regulates the CBF cold-response regulon, contributing to plant freezing tolerance as a clock-output function.
"this circadian regulation is caused by the direct action of CCA1 and LHY binding at the CBF1-3 locus—presumably at the EE, CBS, and related motifs"
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The cca1-11/lhy-21 double mutant shows impaired freezing tolerance in both nonacclimated and cold-acclimated plants, demonstrating that CCA1 contributes to cold tolerance as a clock output (best framed as circadian regulation of cold response).
"the cca1-11/lhy-21 double mutation resulted in impaired freezing tolerance in both nonacclimated and cold-acclimated plants"
Coordinated transcriptional regulation underlying the circadian clock in Arabidopsis.
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CCA1 (with LHY) directly suppresses ELF4 expression at dawn through physical interactions with the FHY3/FAR1/HY5 transcription-promoting factors at the ELF4 promoter, providing IMP support for negative regulation of circadian rhythm.
"the circadian-controlled CCA1 and LHY proteins directly suppress ELF4 expression periodically at dawn through physical interactions with these transcription-promoting factors"
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A coordinated set of light- and circadian-regulated transcription factors (FHY3, FAR1, HY5 activating; CCA1/LHY repressing) acts at the ELF4 promoter to generate its cyclic expression, providing a molecular link from light signaling to the central oscillator.
"a set of light- and circadian-regulated transcription factors act directly and coordinately at the ELF4 promoter to regulate its cyclic expression"
Accurate timekeeping is controlled by a cycling activator in Arabidopsis.
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REVEILLE8 (RVE8), a CCA1/LHY-related MYB protein, is a direct transcriptional activator of EE-containing clock and output genes; the prevailing model of the Arabidopsis clock as exclusively transcriptional repressors at the EE (where CCA1 acts) is revised to include this counter-balancing activator at the same cis-elements.
"a related Myb-like protein, REVEILLE8 (RVE8), is a direct transcriptional activator of EE-containing clock and output genes."
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Loss of RVE8 and close homologs reduces and delays evening-phased clock-gene transcripts and significantly lengthens clock period, providing context for CCA1-mediated repression versus RVE-mediated activation at shared EE promoters.
"Loss of RVE8 and its close homologs causes a delay and reduction in levels of evening-phased clock gene transcripts and significant lengthening of clock pace."
FBH1 affects warm temperature responses in the Arabidopsis circadian clock.
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FBH1 is identified as an additional regulator of the circadian clock affecting warm-temperature responses, providing the framework in which CCA1 is the dominant transcription factor for temperature compensation and warm-temperature timing.
"an important feature of the clock is the ability to maintain a relatively constant period over a range of physiological temperatures; this ability is referred to as "temperature compensation.""
Phosphorylation of Histone H2A at Serine 95: A Plant-Specific Mark Involved in Flowering Time Regulation and H2A.Z Deposition.
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Arabidopsis MLK4 phosphorylates histone H2A on serine 95 (a plant-specific modification) and regulates flowering time and H2A.Z deposition; this chromatin layer interacts with the CCA1-regulated flowering network, providing context for CCA1-controlled gene expression.
"Arabidopsis thaliana MUT9P-LIKE-KINASE (MLK4) phosphorylates histone H2A on serine 95, a plant-specific modification in the histone core domain. Mutations in MLK4 caused late flowering under long-day"
Receptor kinase FERONIA regulates flowering time in Arabidopsis.
A Myb-related transcription factor is involved in the phytochrome regulation of an Arabidopsis Lhcb gene.
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Original cloning of CCA1 as a MYB-related transcription factor that binds the Lhcb1*3 (CAB) promoter at the imperfect repeats AAA/CAATCT and is required for phytochrome-induced Lhcb1*3 expression; first identification of CCA1 as a sequence-specific cis-regulatory region binder.
"We have isolated the gene for a protein designated CCA1. This protein can bind to a region of the promoter of an Arabidopsis light-harvesting chlorophyll a/b protein gene, Lhcb1*3, which is necessary for its regulation by phytochrome."
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The MYB-related N-terminal repeat of CCA1 is required for binding to the Lhcb1*3 promoter; antisense lines reduce phytochrome induction of Lhcb1*3 specifically, establishing CCA1 as a specific transcriptional activator of Lhcb1*3 in response to red light.
"the CCA1 protein acts as a specific activator of Lhcb1*3 transcription in response to brief red illumination."
Constitutive expression of the CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) gene disrupts circadian rhythms and suppresses its own expression.
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Constitutive overexpression of CCA1 abolishes the circadian rhythms of multiple clock-output genes with different phases, causes longer hypocotyls and delayed flowering, and suppresses endogenous CCA1 and LHY expression, establishing CCA1 as part of a feedback loop closely associated with the central oscillator.
"Constitutive expression of CCA1 protein in transgenic plants abolished the circadian rhythm of several genes with dramatically different phases. These plants also had longer hypocotyls and delayed flowering"
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Endogenous CCA1 and LHY are suppressed by constitutive CCA1, indicating CCA1 autorepression and cross-repression of LHY through a negative feedback loop in the oscillator.
"the expression of both endogenous CCA1 and the related LHY gene was suppressed."
Protein kinase CK2 interacts with and phosphorylates the Arabidopsis circadian clock-associated 1 protein.
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CK2 regulatory beta subunit CKB3 was identified as a CCA1 interactor in yeast two-hybrid, and recombinant CK2 phosphorylates CCA1 in vitro; this defines the CK2-CCA1 phosphorylation axis.
"CKB3 interacts specifically with CCA1 both in a yeast two-hybrid system and in an in vitro interaction assay."
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CK2 beta-subunits stimulate CCA1 binding to the CCA1-binding site on the Lhcb1*3 promoter, indicating that CK2 modulates CCA1's DNA-binding activity in addition to its overall activity.
"CK2 beta-subunits stimulate binding of CCA1 to the CCA1 binding site on the Lhcb1*3 gene promoter, and recombinant CK2 is able to phosphorylate CCA1 in vitro."
FutureHouse Falcon research report on Arabidopsis CCA1 (UniProt P92973)
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CCA1 acts as a master regulator within the circadian clock, binding promoter regions of key clock genes to repress or promote transcription, and forming homodimers and heterodimers (particularly with LHY) critical for efficient target binding.
"CCA1 acts as a master regulator within the circadian clock. CCA1 binds to promoter regions of key clock genes to either repress or promote transcription"
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CCA1 contributes to regulation of the endoplasmic-reticulum (ER) stress response and the unfolded protein response (UPR), suggesting a clock-output role in proteostasis.
"CCA1 is involved in the regulation of endoplasmic reticulum (ER) stress responses. By modulating target genes involved in the unfolded protein response (UPR), CCA1 helps facilitate recovery from ER stress"
Falcon (Edison Scientific) deep research report on Arabidopsis CCA1 (UniProt P92973)
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CCA1 is a dawn-phased MYB/SANT-domain DNA-binding transcription factor of the core circadian oscillator that acts largely as a repressor of evening-phased clock genes and as a dual regulator of selected outputs.
"CIRCADIAN CLOCK ASSOCIATED 1 (CCA1; At2g46830; UniProt P92973) is a dawn-phased, MYB/SANT-domain DNA-binding transcription factor that functions in the **core transcription–translation feedback loops (TTFLs)** of the Arabidopsis circadian oscillator, acting largely as a repressor of evening-phased clock genes while also serving as an activator or dual regulator for selected outputs"
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CCA1's primary molecular role is sequence-specific transcriptional regulation through promoter binding, not catalysis or transport.
"CCA1’s primary molecular role is **sequence-specific transcriptional regulation** through promoter binding, rather than catalysis or transport."
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CCA1 binds canonical promoter motifs, most prominently the Evening Element (EE) and the CCA1-binding site (CBS), to regulate target gene expression.
"binds to canonical promoter motifs—most prominently the **Evening Element (EE)** and the **CCA1-binding site (CBS)**—to regulate target gene expression."
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Functional evidence places CCA1 in the nucleus, where it binds promoters and is assayed by ChIP/ChIP-seq.
"Functional evidence places CCA1 in the **nucleus**, where it binds promoters and is assayed by ChIP/ChIP-seq."
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CCA1 peaks near dawn and, with LHY, forms the morning loop of the oscillator, repressing evening-phased genes such as TOC1 in interlocked feedback.
"CCA1 peaks near **dawn** and, together with LHY, forms the **morning loop** of the Arabidopsis circadian oscillator."
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CCA1/LHY are essential for robust circadian rhythms; cca1 lhy double mutants show severe rhythmic disruption with low amplitude.
"CCA1/LHY are essential for robust circadian rhythms: single mutants often shorten period, while cca1 lhy double mutants show severe disruption/low amplitude."
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CCA1's strongest functional partner is LHY; they act redundantly and form heterodimers in vivo.
"Strongest functional partner is **LHY**; CCA1 and LHY can act redundantly and also form heterodimers in vivo."
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Up to ~30% of the transcriptome is clock-controlled under constant conditions and up to 90% with light/temperature cues, indicating the broad downstream impact of core clock TFs such as CCA1.
"A 2024 review notes that under constant conditions ~**30%** of the transcriptome can be clock-controlled, and with light/temperature cues this can reach **up to 90%**, illustrating the potentially broad downstream impact of core clock TFs such as CCA1."
Deep research on CCA1 function
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Synthesis of CCA1 literature - CCA1 is a dawn-phased MYB/SANT-domain DNA-binding transcription factor that, together with LHY, forms the morning loop of the core Arabidopsis circadian oscillator and represses evening-phased clock genes (notably TOC1) while activating selected outputs.