TOC1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000160 phosphorelay signal transduction system	IEA GO_REF:0000002	REMOVE	Summary: Electronic annotation propagated from the response-regulator receiver-domain InterPro signature. TOC1 is a pseudo-response regulator whose receiver-like domain lacks the conserved phospho-accepting aspartate, so it cannot participate in the His-to-Asp phosphorelay that defines this term. Reason: GO:0000160 is defined as a histidine-kinase autophosphorylation to aspartate phosphotransfer cascade. TOC1 lacks the catalytic Asp (Glu-71) and acts as a DNA-binding transcriptional repressor, not a phosphorelay component. This is an over-propagated electronic annotation from the family-level receiver-domain signature and is biologically incorrect for TOC1. Supporting Evidence: file:ARATH/TOC1/TOC1-uniprot.txt Lacks the phospho-accepting Asp (here Glu-71), present in the receiver domain, which is one of the conserved features of the two- component response regulators (ARRs) family. PMID:18055606 The pseudo receiver domain shows high similarity to receiver domains of two-component response regulators but lacks the key Asp residue that accepts a phosphoryl group to modulate the activity of the protein. file:ARATH/TOC1/TOC1-deep-research-falcon.md proteins are plant clock components that resemble two-component response regulators but are generally treated as transcriptional regulators rather than enzymatic phosphorelay proteins
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Nuclear localization is well established for TOC1 and is consistent with its role as a DNA-binding transcriptional repressor. This electronic annotation agrees with multiple experimental IDA annotations. Reason: TOC1 is a nuclear protein with a CCT-domain NLS and is experimentally shown to be nuclear-localized; the IEA agrees with IDA evidence. Supporting Evidence: PMID:18562312 Each PRR protein examined is nuclear-localized and is differentially phosphorylated over the circadian cycle.
GO:0007623 circadian rhythm	IEA GO_REF:0000117	ACCEPT	Summary: TOC1 is a core component of the circadian oscillator; its mutation alters the period of many circadian rhythms. This electronic annotation is consistent with strong experimental evidence. Reason: TOC1 is a central clock component whose loss shortens circadian period; involvement in circadian rhythm is firmly established. Supporting Evidence: PMID:10926537 The toc1 mutation causes shortened circadian rhythms in light-grown Arabidopsis plants.
GO:0009736 cytokinin-activated signaling pathway	IEA GO_REF:0000002	REMOVE	Summary: Electronic annotation propagated from the ARR-like InterPro family signature. TOC1 is a pseudo-response regulator with no role in cytokinin signaling, and it lacks the phospho-accepting Asp required for the cytokinin two-component phosphorelay. Reason: GO:0009736 is the cytokinin two-component signaling cascade ending in transcription. TOC1 is not a cytokinin-signaling response regulator (those are the type-A/type-B ARRs); it lacks the catalytic Asp and there is no experimental evidence linking TOC1 to cytokinin signaling. This is an over-propagated electronic annotation from the receiver-domain family signature. Supporting Evidence: file:ARATH/TOC1/TOC1-uniprot.txt Lacks the phospho-accepting Asp (here Glu-71), present in the receiver domain, which is one of the conserved features of the two- component response regulators (ARRs) family.
GO:0005515 protein binding	IPI PMID:11828029 The APRR1/TOC1 quintet implicated in circadian rhythms of Ar...	KEEP AS NON CORE	Summary: IntAct-derived protein interaction (with PIL1). True interaction but the generic protein binding term is uninformative as a molecular function. Reason: TOC1 interacts with many clock and bHLH partners, but bare protein binding does not capture a specific molecular function; retained as non-core supporting evidence.
GO:0005515 protein binding	IPI PMID:14654842 Targeted degradation of TOC1 by ZTL modulates circadian func...	KEEP AS NON CORE	Summary: Interaction with ZTL/ADO1, the F-box protein that targets TOC1 for SCF(ZTL) proteasomal degradation. Biologically meaningful but captured here only as generic protein binding. Reason: TOC1-ZTL interaction underlies TOC1 turnover, but the generic protein binding term is uninformative as a molecular function.
GO:0005515 protein binding	IPI PMID:15310821 Identification of ASK and clock-associated proteins as molec...	KEEP AS NON CORE	Summary: Interaction with ADO2/LKP2 (and ADO1/ZTL), members of the ZTL/LKP2 family of clock-associated F-box photoreceptors. Reason: True clock-relevant interaction, but bare protein binding is uninformative as a molecular function.
GO:0005515 protein binding	IPI PMID:17704763 ZEITLUPE is a circadian photoreceptor stabilized by GIGANTEA...	KEEP AS NON CORE	Summary: Interaction within the ZTL/GIGANTEA module of the clock (ZTL stabilized by GI). Reason: True interaction, but generic protein binding is uninformative as a molecular function.
GO:0005515 protein binding	IPI PMID:18055606 PRR3 Is a vascular regulator of TOC1 stability in the Arabid...	KEEP AS NON CORE	Summary: Interaction with PRR3/APRR3, which binds TOC1 and protects it from ZTL-mediated degradation in the vasculature. Reason: Biologically meaningful (TOC1 stability regulation) but captured only as generic protein binding. Supporting Evidence: PMID:18055606 PRR3 was able to bind to TOC1 in yeast and in plants and to perturb TOC1 interaction with ZEITLUPE (ZTL), which targets TOC1 for proteasome-dependent degradation.
GO:0005515 protein binding	IPI PMID:20407420 PRR5 regulates phosphorylation, nuclear import and subnuclea...	KEEP AS NON CORE	Summary: Interaction with PRR5, which promotes TOC1 nuclear import, phosphorylation and subnuclear foci formation. Reason: Biologically meaningful (TOC1 nuclear accumulation) but captured only as generic protein binding. Supporting Evidence: PMID:20407420 both proteins interact in vitro and in vivo through their conserved N-termini. TOC1-PRR5 oligomerization enhances TOC1 nuclear accumulation
GO:0005515 protein binding	IPI PMID:21798944 Evidence for network evolution in an Arabidopsis interactome...	KEEP AS NON CORE	Summary: Large-scale Arabidopsis interactome (binary Y2H) interaction. Generic protein binding, uninformative as molecular function. Reason: High-throughput interaction; bare protein binding is uninformative as a molecular function.
GO:0005515 protein binding	IPI PMID:28650476 CrY2H-seq: a massively multiplexed assay for deep-coverage i...	KEEP AS NON CORE	Summary: Large-scale CrY2H-seq interactome interaction. Generic protein binding, uninformative as molecular function. Reason: High-throughput interaction; bare protein binding is uninformative as a molecular function.
GO:0005515 protein binding	IPI PMID:32612234 Extensive signal integration by the phytohormone protein net...	KEEP AS NON CORE	Summary: Phytohormone protein interaction network screen interaction. Generic protein binding, uninformative as molecular function. Reason: High-throughput interaction; bare protein binding is uninformative as a molecular function.
GO:0003677 DNA binding	IDA PMID:32165445 Pseudo Response Regulators Regulate Photoperiodic Hypocotyl ...	ACCEPT	Summary: TOC1 (and other PRRs) directly bind the G-box cis-elements of the PIF4 and PIF5 promoters to repress their transcription, supporting direct DNA binding. Reason: Direct DNA binding by TOC1 is experimentally demonstrated (EMSA / promoter binding); a core molecular property of TOC1 as a DNA-binding repressor. Supporting Evidence: PMID:32165445 PRRs directly bind the promoters of PHYTOCHROME-INTERACTING FACTOR4 (PIF4) and PIF5 to repress their expression, hence PRRs act as transcriptional repressors of the positive growth regulators PIF4 and PIF5
GO:0005634 nucleus	ISM GO_REF:0000122	ACCEPT	Summary: Sequence-based (AtSubP) prediction of nuclear localization, consistent with the CCT-domain NLS and experimental nuclear localization. Reason: Agrees with experimental IDA nucleus annotations and the known CCT-domain NLS. Supporting Evidence: PMID:18562312 Each PRR protein examined is nuclear-localized and is differentially phosphorylated over the circadian cycle.
GO:0010468 regulation of gene expression	IMP PMID:23638299 Accurate timekeeping is controlled by a cycling activator in...	MODIFY	Summary: TOC1 regulates expression of clock genes within the oscillator network (it represses morning genes CCA1/LHY and is itself activated by RVE8). Correct but a general term; a more specific negative-regulation term better captures TOC1 function. Reason: TOC1 acts specifically as a transcriptional repressor of its target genes; the generic regulation of gene expression can be made more specific to negative regulation of transcription, consistent with the repressor evidence. Proposed replacements: negative regulation of transcription by RNA polymerase II Supporting Evidence: PMID:23638299 which in turn represses expression of CCA1 and LHY
GO:0003677 DNA binding	IDA PMID:22315425 Arabidopsis circadian clock protein, TOC1, is a DNA-binding ...	ACCEPT	Summary: Purified TOC1 binds DNA directly through its CCT domain (T1ME/TGTG and related motifs). This is a core molecular property establishing TOC1 as a DNA-binding protein. Reason: Direct in vitro DNA binding by purified TOC1 via the CCT domain is firmly demonstrated; a core molecular function. Supporting Evidence: PMID:22315425 Purified TOC1 binds directly to DNA through its CCT domain, which is similar to known DNA-binding domains. file:ARATH/TOC1/TOC1-deep-research-falcon.md TOC1 is experimentally supported as a DNA-binding transcription factor, with DNA binding and regulatory activity dependent on the CCT domain
GO:0003700 DNA-binding transcription factor activity	IDA PMID:22315425 Arabidopsis circadian clock protein, TOC1, is a DNA-binding ...	MODIFY	Summary: TOC1 acts as a sequence-specific DNA-binding transcriptional repressor; DNA binding via the CCT domain is necessary for its repression of CCA1/LHY. This is the core molecular function of TOC1. Reason: TOC1 is demonstrated to bind DNA and act specifically as a transcriptional REPRESSOR (Gal4/UAS repression assays), with DNA binding necessary for repression of Pol II target genes such as CCA1/LHY. The generic 'DNA-binding transcription factor activity' is therefore better represented by the repressor-specific child term GO:0001227 (DNA-binding transcription repressor activity, RNA polymerase II-specific). Proposed replacements: DNA-binding transcription repressor activity, RNA polymerase II-specific Supporting Evidence: PMID:22315425 we use the Gal4/UAS system in Arabidopsis to show that TOC1 acts as a general transcriptional repressor, and that repression activity is in the pseudoreceiver domain of the protein. PMID:22315425 mutation or deletion of the CCT domain prevents this repression showing that DNA-binding is necessary for TOC1 action. file:ARATH/TOC1/TOC1-deep-research-falcon.md current consensus supports repressor activity as the safest core GO interpretation.
GO:0010629 negative regulation of gene expression	IDA PMID:22315425 Arabidopsis circadian clock protein, TOC1, is a DNA-binding ...	ACCEPT	Summary: TOC1 represses CCA1/LHY expression; chemical induction/overexpression of TOC1 causes repression of these targets. Correct; reflects TOC1's repressor activity. Reason: TOC1 negatively regulates expression of its target genes (CCA1/LHY), directly demonstrated by induction experiments. Supporting Evidence: PMID:22315425 Chemical induction and transient overexpression of TOC1 in Arabidopsis seedlings cause repression of CCA1 / LHY expression
GO:0005634 nucleus	IDA PMID:18562312 Post-translational regulation of the Arabidopsis circadian c...	ACCEPT	Summary: Direct experimental evidence that TOC1 (PRR1) is nuclear-localized. Core localization consistent with its transcriptional repressor function. Reason: Direct experimental demonstration of nuclear localization of TOC1. Supporting Evidence: PMID:18562312 Each PRR protein examined is nuclear-localized and is differentially phosphorylated over the circadian cycle. file:ARATH/TOC1/TOC1-deep-research-falcon.md TOC1 is nuclear localized, consistent with promoter binding and transcriptional repression functions.
GO:0006355 regulation of DNA-templated transcription	TAS PMID:12068096 Two-component signal transduction pathways in Arabidopsis.	ACCEPT	Summary: General transcriptional regulation annotation derived from a two-component signaling review. TOC1's transcriptional regulation is now known to be direct and repressive; the term is correct but general. Reason: TOC1 regulates DNA-templated transcription; the term is accurate though general. Note the supporting review is a broad two-component overview rather than a TOC1- specific functional study. Supporting Evidence: PMID:12068096 a response regulator that mediates the output
GO:0000976 transcription cis-regulatory region binding	IDA NOT PMID:19286557 A functional genomics approach reveals CHE as a component of...	ACCEPT	Summary: Negated annotation reflecting the 2009 finding that TOC1 did not bind the CCA1 promoter (TCP-binding-site region) directly by EMSA/Y1H and was instead recruited via CHE. Later work (2012) showed TOC1 does bind other elements (T1ME/G-box) directly via the CCT domain, so this negation is specific to that promoter region/assay context. Reason: The published negative result is valid as stated (no direct TOC1 binding detected to the CCA1 promoter region tested). It does not contradict the later positive DNA-binding annotations, which concern different cis-elements and assays. Per guidance, an experimental annotation is retained rather than removed. Supporting Evidence: PMID:19286557 A direct interaction of TOC1 with the CCA1 promoter was investigated by electrophoretic mobility shift assays and the yeast one-hybrid system, but no binding was detected using these approaches (data not shown), suggesting that TOC1 is unable to bind directly to the CCA1 promoter.
GO:0005515 protein binding	IPI PMID:19286557 A functional genomics approach reveals CHE as a component of...	KEEP AS NON CORE	Summary: Interaction with TCP21/CHE, which recruits TOC1 to the CCA1 promoter. Biologically meaningful but captured only as generic protein binding. Reason: TOC1-CHE interaction links TOC1 to CCA1 regulation, but bare protein binding is uninformative as a molecular function. Supporting Evidence: PMID:19286557 we observed a direct protein-protein interaction between TOC1 and the N-terminal domain of CHE
GO:0005634 nucleus	TAS PMID:19286557 A functional genomics approach reveals CHE as a component of...	ACCEPT	Summary: TOC1 is reported as nuclear-localized in this study, consistent with multiple other nucleus annotations. Reason: Consistent with extensive experimental evidence for nuclear localization. Supporting Evidence: PMID:19286557 Both proteins are nuclear localized
GO:0006351 DNA-templated transcription	TAS PMID:19286557 A functional genomics approach reveals CHE as a component of...	MODIFY	Summary: TOC1 participates in transcriptional regulation, but GO:0006351 (the transcription process itself, the act of RNA synthesis) is not the appropriate term for a sequence-specific transcriptional repressor; a regulation-of-transcription term is correct. Reason: TOC1 is a transcriptional regulator (repressor), not part of the basal RNA synthesis machinery. The annotation should be to regulation of transcription, not to the transcription process per se. Proposed replacements: regulation of DNA-templated transcription
GO:0005634 nucleus	IDA PMID:10926537 Cloning of the Arabidopsis clock gene TOC1, an autoregulator...	ACCEPT	Summary: Original TOC1 cloning paper reporting a nuclear protein. Core localization. Reason: Early direct evidence that TOC1 encodes a nuclear protein; consistent with all later evidence. Supporting Evidence: PMID:10926537 The TOC1 gene was isolated and found to encode a nuclear protein
GO:0010031 circumnutation	IMP PMID:15908440 Circadian rhythm of circumnutation in inflorescence stems of...	KEEP AS NON CORE	Summary: toc1 mutants shorten the period of circadian circumnutation, indicating TOC1 influences this clock output. This is a downstream physiological output of clock function rather than a core molecular role of TOC1. Reason: Circumnutation rhythm is a circadian output affected by clock disruption in toc1 mutants; a genuine but non-core, downstream process. Supporting Evidence: PMID:15908440 toc1 appears to shorten the period and elf3 causes an arrhythmic phenotype in circumnutation speed in LL
GO:0007623 circadian rhythm	TAS PMID:11100772 Circadian waves of expression of the APRR1/TOC1 family of ps...	ACCEPT	Summary: TOC1/APRR1 expression cycles with a circadian rhythm and is part of the sequential PRR expression wave proposed to underlie the clock. Core involvement in circadian rhythm. Reason: Strong evidence that TOC1 is a circadian clock component subject to circadian regulation. Supporting Evidence: PMID:11100772 all these members of the APRR1/TOC1 family (APRR1, APRR3, APRR5, APRR7, and APRR9) are subjected to a circadian rhythm at the level of transcription
GO:0007623 circadian rhythm	IEP PMID:10926537 Cloning of the Arabidopsis clock gene TOC1, an autoregulator...	ACCEPT	Summary: TOC1 expression is circadianly regulated and toc1 mutation alters circadian period; supports involvement in circadian rhythm. Reason: TOC1 is itself circadianly regulated and participates in a feedback loop controlling clock-regulated rhythms. Supporting Evidence: PMID:10926537 TOC1 is itself circadianly regulated and participates in a feedback loop to control its own expression.
GO:0006355 regulation of DNA-templated transcription	ISS PMID:10926537 Cloning of the Arabidopsis clock gene TOC1, an autoregulator...	ACCEPT	Summary: Sequence-based inference (CONSTANS-family basic motif plus acidic domain) that TOC1 functions in transcriptional regulation. Subsequently confirmed experimentally. Reason: TOC1's role in regulation of DNA-templated transcription, inferred from its CCT and acidic motifs, is now experimentally established. Supporting Evidence: PMID:10926537 two motifs that suggest a role in transcriptional regulation

Gene Description

Existing Annotations Review

Core Functions

Sequence-specific DNA-binding transcriptional repressor that binds DNA directly through its CCT domain (e.g. T1ME/TGTG and related G-box/ME elements) and represses transcription of target genes, with DNA binding required for repression.

Core evening-phased component of the circadian oscillator that represses the morning genes CCA1 and LHY, completing the central transcriptional feedback loop that generates ~24 h rhythms; toc1 mutation shortens circadian period.

Direct transcriptional repressor of PIF4 and PIF5 within the PRR family, binding their promoters to control circadian/photoperiodic hypocotyl growth.

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