CO - AI Gene Review

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0009908 flower development	IMP PMID:28526714 CONSTANS Imparts DNA Sequence Specificity to the Histone Fol...	MODIFY	Summary: The source strongly supports CO as a master regulator of flowering and FT promoter transcription, but flower development is too broad and can be mistaken for floral organ morphogenesis. Reason: Replace with the more specific Arabidopsis process supported by CO mutant, promoter-binding, and FT-expression evidence: positive regulation of long-day photoperiodism, flowering. Proposed replacements: positive regulation of long-day photoperiodism, flowering Supporting Evidence: PMID:28526714 CONSTANS (CO/B-BOX PROTEIN1 BBX1), a master flowering regulator, forms a trimer with Arabidopsis thaliana NF-YB2/NF-YC3 to efficiently bind the CORE element of the FLOWERING LOCUS T promoter. PMID:11323677 expression of CONSTANS (CO), a gene that accelerates flowering in response to long days, is modulated by the circadian clock and day length. file:ARATH/CO/CO-deep-research-falcon.md CO is a sequence-specific transcriptional activator required for robust FT induction during inductive photoperiods.
GO:0009909 regulation of flower development	IMP PMID:11323677 CONSTANS mediates between the circadian clock and the contro...	MODIFY	Summary: The annotation captures the correct developmental direction, but the paper is specifically about CO linking the circadian clock/day length to flowering time through FT. Reason: The best replacement is positive regulation of long-day photoperiodism, flowering, which avoids over-broad flower development wording while preserving the supported CO role. Proposed replacements: positive regulation of long-day photoperiodism, flowering Supporting Evidence: PMID:11323677 expression of CONSTANS (CO), a gene that accelerates flowering in response to long days, is modulated by the circadian clock and day length.
GO:0010018 far-red light signaling pathway	IMP PMID:18667727 Regulation of CONSTANS and FLOWERING LOCUS T expression in r...	MODIFY	Summary: Far-red-enriched light changes CO transcript/protein abundance and CO is required for the flowering response, but the evidence places CO downstream in light-quality-regulated flowering rather than as a far-red signal transduction component. Reason: Use response to far red light for this evidence; CO responds to and is regulated by far-red-enriched light in the flowering pathway, but is not a photoreceptor or core far-red signaling pathway component. Proposed replacements: response to far red light Supporting Evidence: PMID:18667727 Consistent with the model that FREL promotes flowering through CO, mutants for co or gigantea, which are required for CO transcript accumulation, are relatively insensitive to FREL.
GO:0010218 response to far red light	IMP PMID:18790998 Acceleration of flowering during shade avoidance in Arabidop...	KEEP AS NON CORE	Summary: Low red:far-red shade conditions require CO for full acceleration of flowering in long days and enhance CO expression/activity. Reason: This is a supported environmental-response annotation, but it is secondary to CO's core role as a clock/light-gated transcriptional activator in long-day photoperiodic flowering. Supporting Evidence: PMID:18790998 A low red to far-red ratio required the photoperiod-pathway genes GIGANTEA (GI) and CONSTANS (CO) to fully accelerate flowering in long days and did not promote flowering in short days.
GO:0003677 DNA binding	IPI PMID:33693873 Structural insights into the multivalent binding of the Arab...	MODIFY	Summary: CO-NF-Y directly binds specific FT promoter cis-elements, but generic DNA binding is less informative than the demonstrated RNA polymerase II cis-regulatory sequence-specific promoter binding. Reason: Replace with RNA polymerase II cis-regulatory region sequence-specific DNA binding to capture CO recognition of TGTG-containing CORE/P elements in the FT promoter. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:33693873 the four previously characterized cis-elements in the FT promoter proximal region, CORE1, CORE2, P1, and P2, are all direct CO binding sites.
GO:0003700 DNA-binding transcription factor activity	ISS PMID:11118137 Arabidopsis transcription factors: genome-wide comparative a...	MODIFY	Summary: CO is now well supported as a DNA-binding transcription factor, but the original ISS source is a genome-wide transcription factor survey and the cached abstract does not expose CO-specific supporting evidence. Reason: The broad annotation is biologically plausible but should be replaced by the more informative CO-specific Pol II transcriptional activator term. The original source evidence is weak and abstract-only locally, so the modification relies on later direct biochemical and genetic evidence. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:11118137 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. PMID:28526714 Here, we demonstrated that the master flowering regulator CO interacts physically with NF-Y histone-like subunit dimers to form a novel DNA binding sequence-specific trimeric complex, NF-CO
GO:0003700 DNA-binding transcription factor activity	IDA PMID:28526714 CONSTANS Imparts DNA Sequence Specificity to the Histone Fol...	MODIFY	Summary: Direct biochemical and genetic evidence supports CO as a sequence-specific NF-CO transcriptional activator acting at the FT promoter, but GO:0003700 is now too broad. Reason: Replace with DNA-binding transcription activator activity, RNA polymerase II-specific to reflect CO-dependent activation of FT and other Pol II target genes. Proposed replacements: DNA-binding transcription activator activity, RNA polymerase II-specific Supporting Evidence: PMID:28526714 Here, we demonstrated that the master flowering regulator CO interacts physically with NF-Y histone-like subunit dimers to form a novel DNA binding sequence-specific trimeric complex, NF-CO PMID:10834834 Four early target genes of CO were identified using a steroid-inducible version of the protein.
GO:0005515 protein binding	IPI PMID:17138697 CONSTANS and the CCAAT box binding complex share a functiona...	MODIFY	Summary: CO interacts with NF-Y/HAP histone-fold transcription factor subunits, a functionally important interaction for FT regulation, but generic protein binding is not informative. Reason: Replace with RNA polymerase II-specific DNA-binding transcription factor binding, reflecting CO's binding to NF-Y components in a Pol II flowering transcription complex. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:17138697 CONSTANS (CO), which promotes Arabidopsis flowering, interacts with At HAP3 and At HAP5 in yeast, in vitro, and in planta.
GO:0005515 protein binding	IPI PMID:18296627 COP1-mediated ubiquitination of CONSTANS is implicated in cr...	MODIFY	Summary: The paper supports direct CO-COP1 interaction and COP1-mediated CO ubiquitination/degradation; generic protein binding should be replaced by a more specific E3 ligase binding term. Reason: CO is a substrate/regulatory target of the COP1 ubiquitin ligase, so ubiquitin protein ligase binding is the informative molecular function. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:18296627 COP1 physically interacts with CO and functions as an E3 ligase, ubiquitinating CO in vitro and reducing CO levels in vivo.
GO:0005515 protein binding	IPI PMID:18388858 Arabidopsis COP1 shapes the temporal pattern of CO accumulat...	MODIFY	Summary: COP1 binds the C-terminal region of CO and regulates the timing of CO accumulation, but the seeded term is uninformative. Reason: Replace generic protein binding with ubiquitin protein ligase binding because COP1 is the E3 ligase that mediates dark-period CO degradation. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:18388858 COP1 and CO interact in vivo and in vitro through the C-terminal region of CO.
GO:0005515 protein binding	IPI PMID:18587275 Isolation of CONSTANS as a TGA4/OBF4 interacting protein.	MODIFY	Summary: OBF4/TGA4 is reported as a CO-interacting bZIP transcription factor that may regulate FT with CO, but generic protein binding is too broad. Reason: Replace with DNA-binding transcription factor binding, the more specific activity represented by binding to the OBF4/TGA4 transcription factor. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:18587275 We identified CONSTANS (CO), a positive regulator of floral induction, as an OBF4-interacting protein, in a yeast two-hybrid library screen.
GO:0005515 protein binding	IPI PMID:21798944 Evidence for network evolution in an Arabidopsis interactome...	REMOVE	Summary: The GOA row is based on a high-throughput interactome map and lists BBX32 as the interacting entity, but the cached article text does not contain the exact CO-BBX32 pair or experimental details for this interaction. Reason: Removal concerns only the uninformative protein binding term, not the validity of the interaction; the specific CO-BBX32 pair could not be verified from the cached text, but the term would be uninformative either way. High-throughput Y2H interactome pair (CO-BBX32) with no CO-specific functional follow-up in this paper; the informative CO interactions (NF-YB/NF-YC, COP1, FKF1) are captured by other rows and core functions. Supporting Evidence: PMID:21798944 We describe a proteome-wide binary protein-protein interaction map for the interactome network of the plant Arabidopsis thaliana containing about 6200 highly reliable interactions between about 2700 proteins.
GO:0005515 protein binding	IPI PMID:24127609 PHYTOCHROME-DEPENDENT LATE-FLOWERING accelerates flowering t...	REMOVE	Summary: PHL interacts with CO in a red-light-dependent phyB-PHL-CO regulatory complex; the generic protein binding term is uninformative and is removed in favour of describing this regulation in the CO narrative. Reason: Removal concerns only the uninformative protein binding term, not the validity of the interaction. The interaction is real and biologically relevant to CO stability and flowering regulation, but the available ontology term is too generic to add functional meaning as a standalone GO molecular function. Supporting Evidence: PMID:24127609 in the presence of phyB under red light, PHL interacted with CO as well.
GO:0005515 protein binding	IPI PMID:26801684 DELLA proteins physically interact with CONSTANS to regulate...	REMOVE	Summary: DELLA proteins physically bind CO and inhibit CO-NF-YB2 interaction, but the generic protein binding term does not capture the regulatory nature of this GA/photoperiod crosstalk. Reason: Removal concerns only the uninformative protein binding term, not the validity of the interaction. This is useful interaction evidence for the narrative, but not a precise GO molecular function for CO without a more specific transcriptional coregulator-binding term. Supporting Evidence: PMID:26801684 DELLA proteins physically interact with CONSTANS (CO).
GO:0005515 protein binding	IPI PMID:27015278 MicroProtein-Mediated Recruitment of CONSTANS into a TOPLESS...	REMOVE	Summary: miP1a/miP1b bind CO and recruit TOPLESS corepressor machinery to repress FT induction, but generic protein binding is not an appropriate functional annotation. Reason: Removal concerns only the uninformative protein binding term, not the validity of the interaction. The evidence belongs in the CO regulatory mechanism narrative. A generic protein binding GO term would obscure the specific microProtein/TOPLESS repression mechanism and should not be retained as a standalone function. Supporting Evidence: PMID:27015278 Both miP1a and miP1b interact with CO in yeast, in vitro and in planta.
GO:0005515 protein binding	IPI PMID:28526714 CONSTANS Imparts DNA Sequence Specificity to the Histone Fol...	MODIFY	Summary: CO physically interacts with NF-Y histone fold subunits in the NF-CO DNA binding complex; generic protein binding is less informative than specific binding to RNA polymerase II transcription factor components. Reason: Replace with RNA polymerase II-specific DNA-binding transcription factor binding, reflecting CO's functional interaction with NF-YB/NF-YC subunits. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:28526714 CO physically interacts with the same HFD surface required for NF-YA association
GO:0005515 protein binding	IPI PMID:28650476 CrY2H-seq: a massively multiplexed assay for deep-coverage i...	REMOVE	Summary: The GOA row summarizes multiple high-throughput CrY2H-seq CO interactions with BBX/NF-Y transcription factors, but the cached paper text does not expose the exact interaction table for these pairs. Reason: Removal concerns only the uninformative protein binding term, not the validity of the interaction; the specific pairs could not be verified from the cached text, but the term would be uninformative either way. High-throughput CrY2H-seq pairs with BBX/NF-Y factors; the functionally established CO-NF-Y trimer is captured separately from targeted studies, and this generic term adds no information. Supporting Evidence: PMID:28650476 By performing ten independent screens testing a total of 36 million binary interaction combinations, and uncovering a network of 8,577 interactions among 1,453 transcription factors
GO:0005515 protein binding	IPI PMID:33082412 B-box transcription factor 28 regulates flowering by interac...	MODIFY	Summary: BBX28 interacts with CO and reduces CO recruitment to the FT locus, providing a specific transcription-factor interaction rather than generic protein binding. Reason: Replace with DNA-binding transcription factor binding because the interacting partner is a B-box transcription factor regulating CO-dependent FT expression. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:33082412 the interaction between BBX28 and CO decreases the recruitment of CO to FT locus without affecting the transcriptional activation activity of CO.
GO:0005515 protein binding	IPI PMID:33693873 Structural insights into the multivalent binding of the Arab...	MODIFY	Summary: CO binds NF-YB/NF-YC in the structural CO-NF-Y promoter-binding complex; generic protein binding is too broad. Reason: Replace with RNA polymerase II-specific DNA-binding transcription factor binding, matching the structural CO-NF-Y transcriptional regulatory complex. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:33693873 Structural analysis of CO in complex with NUCLEAR FACTOR-YB/YC (NF-YB/YC) and the CORE2 or CORE1 elements revealed the molecular basis for the specific recognition of the shared TGTG motifs.
GO:0008270 zinc ion binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: CO contains two B-box zinc finger domains with predicted zinc-binding residues, consistent with UniProt/InterPro domain evidence. Reason: Zinc ion binding is a conserved structural feature of the BBX domains and supports protein folding/interaction capacity, but it is not the main biological function of CO. Supporting Evidence: file:interpro/panther/PTHR31319/PTHR31319-entries.csv Q39057,Zinc finger protein CONSTANS,protein,3702,Arabidopsis thaliana,Arabidopsis thaliana (Mouse-ear cress),CO,373,PTHR31319:SF82,ZINC FINGER PROTEIN CONSTANS,True
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000108	MODIFY	Summary: CO clearly regulates transcription, but the inferred term is too broad for a nuclear sequence-specific activator of RNA polymerase II target genes such as FT. Reason: Replace with positive regulation of transcription by RNA polymerase II, which better reflects CO-dependent activation of FT and other early target transcripts. Proposed replacements: positive regulation of transcription by RNA polymerase II Supporting Evidence: PMID:10834834 Four early target genes of CO were identified using a steroid-inducible version of the protein.
GO:0009909 regulation of flower development	IEA GO_REF:0000002	MODIFY	Summary: InterPro-to-GO mapping captures that CONSTANS-like proteins regulate flowering, but the term is too broad and not specific to CO's photoperiodic flowering role. Reason: Replace with positive regulation of long-day photoperiodism, flowering using Arabidopsis experimental evidence rather than a broad domain-only flower-development mapping. Proposed replacements: positive regulation of long-day photoperiodism, flowering Supporting Evidence: PMID:11323677 expression of CONSTANS (CO), a gene that accelerates flowering in response to long days, is modulated by the circadian clock and day length.
GO:2000028 regulation of photoperiodism, flowering	IBA GO_REF:0000033	MODIFY	Summary: The IBA term is directionally broad. In Arabidopsis, CO is a positive regulator of long-day photoperiodic flowering, while some orthologs in other species can differ in daylength effects. Reason: Replace with positive regulation of long-day photoperiodism, flowering for Arabidopsis CO, supported by species-specific experimental evidence and PANTHER placement in the CONSTANS subfamily. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN008632251 · CONSTANS clade node (angiosperms) SUPPORTS TRANSFER IBD seeded by rice CONSTANS-family regulators at a flowering-plant node; the sign-neutral parent term reflects day-length-dependent divergence across the clade. UniProtKB:Q9FDX8 · rice HD1 (Heading date 1) SUPPORTS TRANSFER HD1 regulates photoperiodic flowering with opposite sign in a short-day plant, which is why the node term is sign-neutral; the Arabidopsis-specific refinement is the long-day positive-regulation child term. UniProtKB:O82117 · rice CO3 SUPPORTS TRANSFER Supports the clade-level photoperiodic flowering-regulation function. Proposed replacements: positive regulation of long-day photoperiodism, flowering Supporting Evidence: PMID:11323677 expression of CONSTANS (CO), a gene that accelerates flowering in response to long days, is modulated by the circadian clock and day length. file:interpro/panther/PTHR31319/PTHR31319-entries.csv Q39057,Zinc finger protein CONSTANS,protein,3702,Arabidopsis thaliana,Arabidopsis thaliana (Mouse-ear cress),CO,373,PTHR31319:SF82,ZINC FINGER PROTEIN CONSTANS,True
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular-location mapping to nucleus is consistent with CO's direct nuclear DNA-binding transcriptional role. Reason: Nuclear localization is central to CO function and is independently supported by experimental localization and structural/promoter-binding studies. Supporting Evidence: PMID:27015278 GFP:CO localizes to sub-nuclear speckles
GO:0005634 nucleus	ISM GO_REF:0000122	ACCEPT	Summary: AtSubP prediction agrees with the experimental and mechanistic evidence that CO functions in the nucleus. Reason: The prediction is consistent with CO biology and redundant with stronger experimental nuclear localization and DNA-binding evidence, but the cellular component itself is correct and central to CO function. Supporting Evidence: PMID:27015278 GFP:CO localizes to sub-nuclear speckles
GO:0005634 nucleus	IDA PMID:17138697 CONSTANS and the CCAAT box binding complex share a functiona...	ACCEPT	Summary: Nuclear localization is correct for CO, but the cached PMID:17138697 text available locally is abstract-only and does not contain the localization experiment underlying this exact GOA row. Reason: The original source is abstract-only locally, so the exact localization assay cannot be checked from the cache. However, the conclusion is independently supported by direct CO localization evidence and matches the mechanistic role of CO as a nuclear transcriptional regulator. Supporting Evidence: PMID:17138697 The CCT (for CONSTANS, CONSTANS-LIKE, TOC1) domain is found in 45 Arabidopsis thaliana proteins involved in processes such as photoperiodic flowering, light signaling, and regulation of circadian rhythms. PMID:27015278 GFP:CO localizes to sub-nuclear speckles
GO:0005634 nucleus	IDA PMID:24127609 PHYTOCHROME-DEPENDENT LATE-FLOWERING accelerates flowering t...	ACCEPT	Summary: CO is nuclear, but the local cached PMID:24127609 text exposes the phyB-PHL-CO interaction and not the subcellular localization evidence for the seeded IDA row. Reason: The cached source is abstract-only locally for this localization point, so the exact assay cannot be checked from the cache. Independent direct localization evidence supports the same nuclear component and makes the annotation biologically sound. Supporting Evidence: PMID:24127609 in the presence of phyB under red light, PHL interacted with CO as well. PMID:27015278 GFP:CO localizes to sub-nuclear speckles
GO:0005634 nucleus	EXP PMID:27015278 MicroProtein-Mediated Recruitment of CONSTANS into a TOPLESS...	ACCEPT	Summary: The full cached article shows GFP-tagged CO in subnuclear speckles, consistent with CO's nuclear transcriptional regulatory function. Reason: This is directly supported experimental localization evidence and matches the core function of CO as a nuclear transcriptional activator. Supporting Evidence: PMID:27015278 GFP:CO localizes to sub-nuclear speckles

CO

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