id: O82132
gene_symbol: DREB2A
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:3702
  label: Arabidopsis thaliana
description: >-
  DREB2A is a sequence-specific DNA-binding transcription factor of the AP2/ERF
  superfamily (ERF/DREB subfamily) in Arabidopsis thaliana. Through its single
  AP2/ERF DNA-binding domain it recognizes the dehydration-responsive
  element/C-repeat (DRE/CRT) cis-element (core motif A/GCCGAC, with a preference
  for ACCGAC) in the promoters of stress-inducible genes and activates their
  transcription via an acidic C-terminal transactivation domain. It is a
  nuclear protein and a central regulator of the ABA-independent branch of
  drought-, high-salinity- and heat-stress-responsive gene expression. DREB2A
  activity is tightly controlled post-translationally: a central negative
  regulatory domain (NRD, containing a PEST sequence) targets the protein for
  ubiquitination by the RING E3 ligases DRIP1 and DRIP2 and degradation by the
  26S proteasome under non-stress conditions, while stress (notably heat)
  stabilizes the protein in the nucleus. A constitutively active form lacking
  the NRD (DREB2A-CA) confers strong drought and heat tolerance when
  overexpressed. Under heat stress DREB2A induces the heat-stress regulatory
  cascade, including the heat-shock transcription factor gene HsfA3, and
  cooperates with a DPB3-1/NF-YA2/NF-YB3 trimer to selectively activate
  heat-stress target genes.
existing_annotations:
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Electronic InterPro2GO annotation for the AP2/ERF DNA-binding domain.
      DREB2A is a bona fide DNA-binding protein, so this is correct, but it is
      a general parent of the more informative experimentally supported
      DNA-binding transcription factor activity / DRE-element binding.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general; subsumed by the specific sequence-specific
      DNA-binding transcription factor activity and DRE/CRT cis-regulatory
      region binding annotations.
    supported_by:
    - reference_id: file:ARATH/DREB2A/DREB2A-uniprot.txt
      supporting_text: "DNA_BIND        78..135"
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Electronic InterPro2GO annotation of AP2/ERF transcription factor
      activity, consistent with the experimentally demonstrated function.
    action: ACCEPT
    reason: >-
      DREB2A is an experimentally validated DNA-binding transcription factor;
      this electronic annotation is corroborated by IDA (PMID:9707537) and ISS
      annotations to the same term.
    supported_by:
    - reference_id: PMID:9707537
      supporting_text: >-
        Both the DREB1A and DREB2A proteins specifically bound to the DRE
        sequence in vitro and activated the transcription of the
        b-glucuronidase reporter gene driven by the DRE sequence in Arabidopsis
        leaf protoplasts.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic subcellular-location mapping placing DREB2A in the nucleus,
      consistent with multiple IDA observations and its role as a transcription
      factor.
    action: ACCEPT
    reason: >-
      Nuclear localization is experimentally confirmed (GFP-DREB2A in nucleus,
      N-terminal NLS); the electronic annotation is correct.
    supported_by:
    - reference_id: PMID:16617101
      supporting_text: >-
        Synthetic green fluorescent protein gave a strong signal in the nucleus
        under unstressed control conditions when fused to constitutive active
        DREB2A
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Electronic InterPro2GO annotation of transcriptional regulation. Correct
      but general; experimental data specifically support positive regulation
      of transcription.
    action: KEEP_AS_NON_CORE
    reason: >-
      General process term subsumed by the more specific positive regulation of
      DNA-templated transcription annotation supported by IDA.
    supported_by:
    - reference_id: PMID:9707537
      supporting_text: >-
        activated the transcription of the b-glucuronidase reporter gene driven
        by the DRE sequence in Arabidopsis leaf protoplasts
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18552202
  qualifier: enables
  review:
    summary: >-
      IPI interaction with DRIP1 (Q9M9Y4) / DRIP2 (Q94AY3), RING E3 ubiquitin
      ligases that ubiquitinate DREB2A and target it for proteasomal
      degradation. A real, important interaction, but "protein binding" is an
      uninformative molecular-function term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction is experimentally supported and biologically central
      (post-translational control of DREB2A), but per curation guidelines
      GO:0005515 is too generic to represent a molecular function. The
      regulatory consequence is captured elsewhere; not endorsed as core.
    supported_by:
    - reference_id: PMID:18552202
      supporting_text: >-
        DRIP1 and DRIP2 act as novel negative regulators in drought-responsive
        gene expression by targeting DREB2A to 26S proteasome proteolysis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19548978
  qualifier: enables
  review:
    summary: >-
      IPI interaction with RCD1 (Q8RY59), a hub protein mediating stress and
      developmental responses. Real interaction but uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Experimentally supported interaction, but GO:0005515 is too generic to be
      a useful molecular function for DREB2A.
    supported_by:
    - reference_id: PMID:19548978
      supporting_text: >-
        Unequally redundant RCD1 and SRO1 mediate stress and developmental
        responses and interact with transcription factors.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21536906
  qualifier: enables
  review:
    summary: >-
      IPI interaction with the Mediator subunit MED25 (Q7XYY2-1), consistent
      with DREB2A recruiting the Mediator complex during transcriptional
      activation. Real interaction but uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Supported interaction, but GO:0005515 is too generic to represent a
      molecular function.
    supported_by:
    - reference_id: PMID:21536906
      supporting_text: >-
        The Arabidopsis thaliana Med25 mediator subunit integrates
        environmental cues to control plant development.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32612234
  qualifier: enables
  review:
    summary: >-
      IPI interactions from a large-scale phytohormone protein interaction
      network (DOG1 A0SVK0 and IMPA6 Q9FWY7). Real interactions but
      uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      High-throughput interactome interactions; GO:0005515 is too generic to be
      a useful molecular function.
    supported_by:
    - reference_id: PMID:32612234
      supporting_text: Extensive signal integration by the phytohormone protein network.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22447446
  qualifier: enables
  review:
    summary: >-
      IPI interaction with MED25 (Q7XYY2) characterized structurally (DREB2A
      disordered region undergoing conformational changes on DNA/MED25 binding;
      PDB 5OAP). Real interaction but uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Supported interaction with structural data, but GO:0005515 is too generic
      to represent a molecular function.
    supported_by:
    - reference_id: PMID:22447446
      supporting_text: >-
        Interactions between DNA, transcriptional regulator Dreb2a and the
        Med25 mediator subunit from Arabidopsis thaliana involve conformational
        changes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27881680
  qualifier: enables
  review:
    summary: >-
      IPI interaction with RCD1 (Q8RY59) via a short linear motif in the DREB2A
      disordered region binding the RCD1 RST domain. Real interaction but
      uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Supported SLiM-mediated interaction, but GO:0005515 is too generic to be
      a useful molecular function.
    supported_by:
    - reference_id: PMID:27881680
      supporting_text: >-
        Structures and Short Linear Motif of Disordered Transcription Factor
        Regions Provide Clues to the Interactome of the Cellular Hub Protein
        Radical-induced Cell Death1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25490919
  qualifier: enables
  review:
    summary: >-
      IPI interaction with DPB3-1/NF-YC10 (Q9LN09), the heat-stress-specific
      coactivator. Real interaction but uninformative MF term.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Experimentally supported interaction central to heat-stress regulation,
      but GO:0005515 is too generic to represent a molecular function.
    supported_by:
    - reference_id: PMID:25490919
      supporting_text: >-
        we identified DNA POLYMERASE II SUBUNIT B3-1 (DPB3-1)
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:25490919
  qualifier: located_in
  review:
    summary: >-
      Direct (IDA) nuclear localization of DREB2A, where it interacts with
      DPB3-1 during heat stress. Core localization.
    action: ACCEPT
    reason: >-
      Experimentally confirmed nuclear localization, consistent with TF
      function.
    supported_by:
    - reference_id: PMID:25490919
      supporting_text: NF-YB3 and DPB3-1 form a trimer with NF-YA2 in the nucleus
    - reference_id: file:ARATH/DREB2A/DREB2A-deep-research-falcon.md
      supporting_text: >-
        DREB2A functions primarily in the **nucleus**
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IDA
  original_reference_id: PMID:25490919
  qualifier: involved_in
  review:
    summary: >-
      DREB2A functions in the heat-stress response, cooperating with the
      DPB3-1/NF-YA2/NF-YB3 trimer to enhance heat-stress-inducible target gene
      expression (e.g. HsfA3). Core biological process.
    action: ACCEPT
    reason: >-
      Heat-stress role is well established by gain- and loss-of-function and
      complex-formation data.
    supported_by:
    - reference_id: PMID:25490919
      supporting_text: >-
        the identified trimer enhances heat stress-inducible gene expression
        during heat stress responses in cooperation with DREB2A
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IDA
  original_reference_id: PMID:25490919
  qualifier: involved_in
  review:
    summary: >-
      DREB2A positively regulates transcription of stress-inducible target
      genes; in the heat-stress complex it synergistically activates the HsfA3
      promoter. Core function as a transcriptional activator.
    action: ACCEPT
    reason: >-
      DREB2A is a transcriptional activator (UniProt keyword Activator); direct
      transactivation demonstrated.
    supported_by:
    - reference_id: PMID:25490919
      supporting_text: >-
        The identified trimer comprising NF-YA2, NF-YB3, and DPB3-1 enhanced
        HsfA3 promoter transactivation by DREB2A
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IPI
  original_reference_id: PMID:22037706
  qualifier: enables
  review:
    summary: >-
      Enhanced yeast-one-hybrid assay detecting DREB2A binding to target
      promoter fragments. Supports the sequence-specific DRE/CRT cis-regulatory
      region binding function. Core molecular activity.
    action: ACCEPT
    reason: >-
      DREB2A binds the DRE/CRT cis-element in promoters; this Y1H-based
      promoter-binding annotation is consistent with the well-established
      DNA-binding function.
    supported_by:
    - reference_id: PMID:9707537
      supporting_text: >-
        Both the DREB1A and DREB2A proteins specifically bound to the DRE
        sequence in vitro
    - reference_id: file:ARATH/DREB2A/DREB2A-deep-research-falcon.md
      supporting_text: >-
        DREB2A recognizes **DRE/CRT** elements sharing an **A/GCCGAC core**
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IPI
  original_reference_id: PMID:25352272
  qualifier: enables
  review:
    summary: >-
      Promoter cis-regulatory binding detected in a plant-defense regulatory
      network screen. Supports DRE/CRT cis-element binding activity, though the
      defense context is a large-scale network node rather than an established
      in planta DREB2A regulon.
    action: KEEP_AS_NON_CORE
    reason: >-
      Supports the cis-regulatory binding molecular activity, but the specific
      defense-network context is peripheral to DREB2A's core abiotic-stress
      role; redundant with the core GO:0000976 annotation.
    supported_by:
    - reference_id: PMID:25352272
      supporting_text: Promoter-based integration in plant defense regulation.
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IPI
  original_reference_id: PMID:25533953
  qualifier: enables
  review:
    summary: >-
      Promoter binding detected in a secondary-cell-wall gene regulatory
      network screen. Supports cis-regulatory binding activity but in a context
      peripheral to DREB2A's established abiotic-stress function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Y1H-network node; consistent with the cis-element binding activity but
      the secondary-cell-wall context is not an established DREB2A regulon.
    supported_by:
    - reference_id: PMID:25533953
      supporting_text: An Arabidopsis gene regulatory network for secondary cell wall synthesis.
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IPI
  original_reference_id: PMID:27650334
  qualifier: enables
  review:
    summary: >-
      Promoter binding detected in a study of transcriptional regulation of
      Polycomb Repressive Complex 2 genes. Supports cis-regulatory binding
      activity in a peripheral context.
    action: KEEP_AS_NON_CORE
    reason: >-
      Network-screen binding; consistent with cis-element binding activity but
      peripheral to DREB2A's core stress role.
    supported_by:
    - reference_id: PMID:27650334
      supporting_text: >-
        Transcriptional Regulation of Arabidopsis Polycomb Repressive Complex 2
        Coordinates Cell-Type Proliferation and Differentiation.
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IPI
  original_reference_id: PMID:30356219
  qualifier: enables
  review:
    summary: >-
      Promoter binding detected in a nitrogen-associated metabolism/growth
      gene regulatory network screen. Supports cis-regulatory binding activity
      in a peripheral context.
    action: KEEP_AS_NON_CORE
    reason: >-
      Network-screen binding; consistent with cis-element binding activity but
      the nitrogen-metabolism context is not an established DREB2A regulon.
    supported_by:
    - reference_id: PMID:30356219
      supporting_text: Transcriptional regulation of nitrogen-associated metabolism and growth.
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IPI
  original_reference_id: PMID:31806676
  qualifier: enables
  review:
    summary: >-
      Promoter binding detected in a PXY-mediated vascular-development
      transcriptional network screen. Supports cis-regulatory binding activity
      in a peripheral context.
    action: KEEP_AS_NON_CORE
    reason: >-
      Network-screen binding; consistent with cis-element binding activity but
      the vascular-development context is not an established DREB2A regulon.
    supported_by:
    - reference_id: PMID:31806676
      supporting_text: >-
        A PXY-Mediated Transcriptional Network Integrates Signaling Mechanisms
        to Control Vascular Development in Arabidopsis.
- term:
    id: GO:0071456
    label: cellular response to hypoxia
  evidence_type: HEP
  original_reference_id: PMID:31519798
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      High-throughput expression/epigenome study in which heat-stress
      transcripts (a category that includes DREB2A) are progressively
      upregulated during hypoxia. This is a transcript-level expression
      association (HEP), not evidence that DREB2A function is required for the
      hypoxia response.
    action: KEEP_AS_NON_CORE
    reason: >-
      HEP inference from a high-throughput expression pattern; a transcript
      association rather than a demonstrated DREB2A function in hypoxia. Retain
      as non-core rather than remove, as the evidence is a legitimate (if weak)
      expression-based inference.
    supported_by:
    - reference_id: PMID:31519798
      supporting_text: Hypoxia promoted a progressive upregulation of heat stress transcripts
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISM
  original_reference_id: GO_REF:0000122
  qualifier: located_in
  review:
    summary: >-
      Sequence-based (AtSubP) prediction of nuclear localization, consistent
      with the multiple experimental IDA observations.
    action: ACCEPT
    reason: >-
      Predicted nuclear localization, corroborated by multiple experimental
      nuclear IDA annotations.
    supported_by:
    - reference_id: PMID:16617101
      supporting_text: >-
        Synthetic green fluorescent protein gave a strong signal in the nucleus
        under unstressed control conditions when fused to constitutive active
        DREB2A
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:21443605
  qualifier: located_in
  review:
    summary: >-
      Direct nuclear localization reported in a subcellular-localization
      compendium of hydrogen-peroxide-induced proteins. Consistent with TF
      function.
    action: ACCEPT
    reason: >-
      Experimentally observed nuclear localization, corroborating the core
      nuclear annotation.
    supported_by:
    - reference_id: PMID:21443605
      supporting_text: A subcellular localization compendium of hydrogen peroxide-induced proteins.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:18552202
  qualifier: located_in
  review:
    summary: >-
      Direct (IDA) nuclear localization of DREB2A, where it interacts with the
      RING E3 ligases DRIP1/DRIP2. Core localization.
    action: ACCEPT
    reason: >-
      Experimentally confirmed nuclear localization.
    supported_by:
    - reference_id: PMID:18552202
      supporting_text: >-
        C3HC4 RING domain–containing proteins that interact with the DREB2A
        protein in the nucleus
- term:
    id: GO:0010224
    label: response to UV-B
  evidence_type: IEP
  original_reference_id: PMID:18266923
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Annotation that DREB2A is a UV-B-responsive gene. The originally cited paper
      (PMID:18266923) characterizes a novel UV-B cis-element (UVBox) on the ANAC13
      promoter and does not itself mention DREB2A, so it is miscited for this
      annotation; however, DREB2A's UV-B responsiveness is independently supported
      (HY5-dependent UV-B induction, PMID:14739338).
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but peripheral: DREB2A is a UV-B-induced transcript, not an effector that
      drives the UV-B response; its core role is ABA-independent drought/heat
      transcriptional regulation. The original GOA reference (PMID:18266923) is miscited
      (it does not mention DREB2A), so support is re-anchored to PMID:14739338, which
      documents HY5-dependent UV-B induction of DREB2A. Kept as non-core (consistent with
      the parallel GO:0010224 IGI annotation) rather than removed, since the underlying
      UV-B-responsiveness is genuine.
    additional_reference_ids:
    - PMID:14739338
    supported_by:
    - reference_id: PMID:14739338
      supporting_text: loss of HY5 impairs the UV-B-responsive expression of several genes
- term:
    id: GO:0010224
    label: response to UV-B
  evidence_type: IGI
  original_reference_id: PMID:14739338
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      DREB2A (At5g05410) is a UV-B-induced transcript whose induction is
      impaired in the hy5 mutant. This documents DREB2A as a downstream
      UV-B-responsive gene (genetic dependence on HY5), not that DREB2A
      function drives the UV-B response.
    action: KEEP_AS_NON_CORE
    reason: >-
      Expression-readout / genetic-interaction association; DREB2A is a UV-B
      target gene rather than an effector of the response. Non-core.
    supported_by:
    - reference_id: PMID:14739338
      supporting_text: loss of HY5 impairs the UV-B-responsive expression of several genes
- term:
    id: GO:0010286
    label: heat acclimation
  evidence_type: IEP
  original_reference_id: PMID:16807682
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Transcript-level induction of DREB2-subfamily genes during heat
      acclimation in suspension cultures, suggesting cross-talk between heat and
      dehydration signaling. Expression-based association consistent with the
      established heat role but not a functional knockout result here.
    action: KEEP_AS_NON_CORE
    reason: >-
      IEP expression association; biologically consistent with DREB2A's heat
      role but not the strongest evidence. Retain as non-core.
    supported_by:
    - reference_id: PMID:16807682
      supporting_text: >-
        of DREB2 (dehydration responsive element-binding factor 2) subfamily
        genes and
- term:
    id: GO:0042542
    label: response to hydrogen peroxide
  evidence_type: IEP
  original_reference_id: PMID:17030801
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      The cited reference is the dual drought/heat-function paper; hydrogen
      peroxide response is not its focus and is not established as a DREB2A
      function there. Treated as a peripheral expression-based association.
    action: KEEP_AS_NON_CORE
    reason: >-
      IEP expression-based association lacking strong functional support for an
      H2O2-specific role; retain as non-core rather than remove.
    supported_by:
    - reference_id: PMID:17030801
      supporting_text: >-
        Dual function of an Arabidopsis transcription factor DREB2A in
        water-stress-responsive and heat-stress-responsive gene expression.
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IMP
  original_reference_id: PMID:17030801
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Loss- and gain-of-function evidence that DREB2A functions in the
      heat-stress response: DREB2A-CA overexpressors gain thermotolerance and
      dreb2a knockouts lose it. Core biological process.
    action: ACCEPT
    reason: >-
      Strong genetic (IMP) evidence for a DREB2A role in heat-stress response.
    supported_by:
    - reference_id: PMID:17030801
      supporting_text: >-
        Thermotolerance was significantly increased in plants overexpressing
        DREB2A CA and decreased in DREB2A knockout plants. Collectively, these
        results indicate that DREB2A functions in both water and HS-stress
        responses.
    - reference_id: file:ARATH/DREB2A/DREB2A-deep-research-falcon.md
      supporting_text: >-
        DREB2A is also strongly supported as a regulator of heat-responsive gene
        expression and thermotolerance
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IDA
  original_reference_id: PMID:9707537
  qualifier: enables
  review:
    summary: >-
      Direct demonstration that DREB2A binds the DRE sequence and activates
      DRE-driven reporter transcription. Core molecular function.
    action: ACCEPT
    reason: >-
      DREB2A is an experimentally validated DNA-binding transcription factor.
    supported_by:
    - reference_id: PMID:9707537
      supporting_text: >-
        Both the DREB1A and DREB2A proteins specifically bound to the DRE
        sequence in vitro and activated the transcription of the
        b-glucuronidase reporter gene driven by the DRE sequence in Arabidopsis
        leaf protoplasts.
    - reference_id: file:ARATH/DREB2A/DREB2A-deep-research-falcon.md
      supporting_text: >-
        DREB2A is a **sequence-specific DNA-binding transcription factor**.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16617101
  qualifier: located_in
  review:
    summary: >-
      Direct nuclear localization of GFP-DREB2A in Arabidopsis; the protein
      carries an N-terminal NLS. Core localization.
    action: ACCEPT
    reason: >-
      Experimentally confirmed nuclear localization.
    supported_by:
    - reference_id: PMID:16617101
      supporting_text: >-
        Synthetic green fluorescent protein gave a strong signal in the nucleus
        under unstressed control conditions when fused to constitutive active
        DREB2A
- term:
    id: GO:0009414
    label: response to water deprivation
  evidence_type: IMP
  original_reference_id: PMID:16617101
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Functional analysis showing DREB2A (via DREB2A-CA gain-of-function)
      regulates many water-stress-inducible genes and confers drought
      tolerance. Core biological process.
    action: ACCEPT
    reason: >-
      Well-established role of DREB2A in the drought/water-deprivation response.
    supported_by:
    - reference_id: PMID:16617101
      supporting_text: >-
        Overexpression of constitutive active DREB2A resulted in significant
        drought stress tolerance but only slight freezing tolerance in
        transgenic Arabidopsis plants.
    - reference_id: file:ARATH/DREB2A/DREB2A-deep-research-falcon.md
      supporting_text: >-
        A primary, experimentally supported role of DREB2A is the **regulation
        of dehydration/drought-induced gene expression**.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: ISS
  original_reference_id: PMID:11118137
  qualifier: enables
  review:
    summary: >-
      Sequence-similarity-based assignment of DNA-binding transcription factor
      activity from a genome-wide comparative analysis of Arabidopsis
      transcription factors. Corroborates the experimentally supported function.
    action: ACCEPT
    reason: >-
      Consistent with the IDA-supported DNA-binding transcription factor
      activity; correct core molecular function.
    supported_by:
    - reference_id: PMID:9707537
      supporting_text: >-
        Both the DREB1A and DREB2A proteins specifically bound to the DRE
        sequence in vitro
- term:
    id: GO:0009414
    label: response to water deprivation
  evidence_type: TAS
  original_reference_id: PMID:10809011
  qualifier: acts_upstream_of_or_within
  review:
    summary: >-
      Author-stated role of DREB2 genes as DRE-binding proteins involved in
      dehydration- and high-salinity-responsive gene expression. Core
      biological process.
    action: ACCEPT
    reason: >-
      Consistent with the strong IMP evidence for DREB2A in drought/water
      deprivation response.
    supported_by:
    - reference_id: PMID:10809011
      supporting_text: genes are induced by dehydration and high-salt stress.
core_functions:
- description: >-
    Sequence-specific DNA-binding transcription activator that binds the
    dehydration-responsive element/C-repeat (DRE/CRT) cis-element (core motif
    A/GCCGAC) in stress-inducible gene promoters and activates their
    transcription via its acidic C-terminal transactivation domain
  supported_by:
  - reference_id: PMID:9707537
    supporting_text: >-
      Both the DREB1A and DREB2A proteins specifically bound to the DRE sequence
      in vitro and activated the transcription of the b-glucuronidase reporter
      gene driven by the DRE sequence in Arabidopsis leaf protoplasts.
  - reference_id: PMID:16617101
    supporting_text: >-
      We found that the DREB2A protein could recognize not only A/GCCGACNT, but
      also A/GCCGACNA/G/C, and prefers ACCGAC to GCCGAC.
  - reference_id: file:ARATH/DREB2A/DREB2A-deep-research-falcon.md
    supporting_text: >-
      **core biochemical activity** is **sequence-specific DNA binding** to
      dehydration-responsive element/C-repeat (DRE/CRT) cis-elements with an
      **A/GCCGAC core**
  molecular_function:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  directly_involved_in:
  - id: GO:0045893
    label: positive regulation of DNA-templated transcription
  locations:
  - id: GO:0005634
    label: nucleus
- description: >-
    Master regulator of the ABA-independent branch of drought- and
    high-salinity-responsive gene expression, activating water-stress-inducible
    target genes (e.g. RD29A/RD29B, LEA-class genes) and conferring drought
    tolerance
  supported_by:
  - reference_id: PMID:16617101
    supporting_text: >-
      Overexpression of constitutive active DREB2A resulted in significant
      drought stress tolerance but only slight freezing tolerance in transgenic
      Arabidopsis plants.
  - reference_id: PMID:10809011
    supporting_text: genes are induced by dehydration and high-salt stress.
  molecular_function:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  directly_involved_in:
  - id: GO:0009414
    label: response to water deprivation
  locations:
  - id: GO:0005634
    label: nucleus
- description: >-
    Regulator of the heat-stress response: stabilized in the nucleus under heat
    stress, it induces heat-stress-inducible genes including the heat-shock
    transcription factor gene HsfA3 and cooperates with the
    DPB3-1/NF-YA2/NF-YB3 trimer to selectively activate heat-stress target
    genes, conferring thermotolerance
  supported_by:
  - reference_id: PMID:17030801
    supporting_text: >-
      Thermotolerance was significantly increased in plants overexpressing
      DREB2A CA and decreased in DREB2A knockout plants. Collectively, these
      results indicate that DREB2A functions in both water and HS-stress
      responses.
  - reference_id: PMID:25490919
    supporting_text: >-
      The identified trimer comprising NF-YA2, NF-YB3, and DPB3-1 enhanced
      HsfA3 promoter transactivation by DREB2A
  - reference_id: file:ARATH/DREB2A/DREB2A-deep-research-falcon.md
    supporting_text: >-
      DREB2A participates in a **heat-stress-specific transcriptional complex**
      with **DPB3-1/NF-YC10 and NF-Y subunits** that enhances activation of
      heat-inducible targets such as **HsfA3**
  molecular_function:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  directly_involved_in:
  - id: GO:0009408
    label: response to heat
  - id: GO:0045893
    label: positive regulation of DNA-templated transcription
  locations:
  - id: GO:0005634
    label: nucleus
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000122
  title: AtSubP analysis
  findings: []
- id: PMID:10809011
  title: Organization and expression of two Arabidopsis DREB2 genes encoding DRE-binding
    proteins involved in dehydration- and high-salinity-responsive gene expression.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Abstract-only cache; verified by PubMed. Establishes DREB2A/DREB2B as
      DRE-binding proteins induced by dehydration and high salinity. Supports
      response to water deprivation (TAS).
- id: PMID:11118137
  title: 'Arabidopsis transcription factors: genome-wide comparative analysis among
    eukaryotes.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Genome-wide TF comparison; basis for the ISS DNA-binding transcription
      factor activity assignment. Background/contextual for DREB2A specifically.
- id: PMID:14739338
  title: Genome-wide analysis of gene expression reveals function of the bZIP transcription
    factor HY5 in the UV-B response of Arabidopsis.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Full text confirms DREB2A (At5g05410) is a UV-B-induced transcript whose
      induction depends on HY5. Supports DREB2A as a UV-B target gene, not as an
      effector of the UV-B response; basis for a non-core annotation.
- id: PMID:16617101
  title: Functional analysis of an Arabidopsis transcription factor, DREB2A, involved
    in drought-responsive gene expression.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full-text key paper. Defines the C-terminal activation domain (254-335),
      the central negative regulatory domain (136-165, PEST), DREB2A-CA, nuclear
      localization, DRE-binding specificity, and drought tolerance.
- id: PMID:16807682
  title: Gene expression profiles during heat acclimation in Arabidopsis thaliana
    suspension-culture cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Abstract-only cache; microarray heat-acclimation profiling. DREB2-subfamily
      induction is a transcript-level observation; supports a non-core heat
      acclimation association.
- id: PMID:17030801
  title: Dual function of an Arabidopsis transcription factor DREB2A in water-stress-responsive
    and heat-stress-responsive gene expression.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full-text key paper. Establishes DREB2A's dual drought/heat role,
      induction of HsfA3 and HSPs by DREB2A-CA, heat-induced stabilization, and
      thermotolerance phenotypes. The H2O2 (GO:0042542) annotation citing this
      paper is peripheral.
- id: PMID:18266923
  title: Identification of a novel cis-regulatory element for UV-B-induced transcription
    in Arabidopsis.
  findings: []
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: >-
      Abstract concerns the ANAC13 UV-B cis-elements (MRE/UVBox) and does not
      mention DREB2A; it does not directly support a DREB2A UV-B function. The
      GO:0010224 IEP annotation citing it is weakly supported (expression-based).
- id: PMID:18552202
  title: Arabidopsis DREB2A-interacting proteins function as RING E3 ligases and negatively
    regulate plant drought stress-responsive gene expression.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full-text key paper. DRIP1/DRIP2 RING E3 ligases interact with DREB2A in
      the nucleus and target it for 26S-proteasome degradation. Supports the
      nucleus IDA and DRIP1/DRIP2 interaction annotations.
- id: PMID:19548978
  title: Unequally redundant RCD1 and SRO1 mediate stress and developmental responses
    and interact with transcription factors.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      RCD1/SRO1 interact with stress-related transcription factors including
      DREB2A; basis for a protein-binding IPI (RCD1, Q8RY59).
- id: PMID:21443605
  title: A subcellular localization compendium of hydrogen peroxide-induced proteins.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Large-scale localization compendium reporting nuclear localization of
      DREB2A (IDA), corroborating the core nucleus annotation.
- id: PMID:21536906
  title: The Arabidopsis thaliana Med25 mediator subunit integrates environmental
    cues to control plant development.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Full-text available. MED25 Mediator subunit interacts with DREB2A; basis
      for a protein-binding IPI (MED25, Q7XYY2-1).
- id: PMID:22037706
  title: Enhanced Y1H assays for Arabidopsis.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Methods paper for enhanced yeast-one-hybrid; basis for a GO:0000976
      DREB2A promoter-binding annotation. Supports cis-regulatory binding
      activity.
- id: PMID:22447446
  title: Interactions between DNA, transcriptional regulator Dreb2a and the Med25
    mediator subunit from Arabidopsis thaliana involve conformational changes.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Structural study of DREB2A-MED25 and DREB2A-DNA interactions (PDB 5OAP);
      basis for a protein-binding IPI (MED25).
- id: PMID:25352272
  title: Promoter-based integration in plant defense regulation.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Promoter/regulatory network screen; basis for a GO:0000976 binding
      annotation in a defense context peripheral to DREB2A's core role.
- id: PMID:25490919
  title: Arabidopsis DPB3-1, a DREB2A interactor, specifically enhances heat stress-induced
    gene expression by forming a heat stress-specific transcriptional complex with
    NF-Y subunits.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full-text key paper. DPB3-1 (NF-YC10) interacts with DREB2A; the
      DPB3-1/NF-YA2/NF-YB3 trimer enhances DREB2A transactivation of HsfA3 under
      heat stress. Supports nucleus IDA, response to heat IDA, positive
      regulation of transcription IDA, and a DPB3-1 protein-binding IPI.
- id: PMID:25533953
  title: An Arabidopsis gene regulatory network for secondary cell wall synthesis.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Secondary-cell-wall GRN screen; basis for a GO:0000976 binding annotation
      in a context peripheral to DREB2A's core abiotic-stress role.
- id: PMID:27650334
  title: Transcriptional Regulation of Arabidopsis Polycomb Repressive Complex 2 Coordinates
    Cell-Type Proliferation and Differentiation.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      PRC2-regulation network screen; basis for a GO:0000976 binding annotation
      in a peripheral context.
- id: PMID:27881680
  title: Structures and Short Linear Motif of Disordered Transcription Factor Regions
    Provide Clues to the Interactome of the Cellular Hub Protein Radical-induced Cell
    Death1.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      SLiM/structural study of disordered TF regions binding the RCD1 RST domain;
      basis for a protein-binding IPI (RCD1, Q8RY59).
- id: PMID:30356219
  title: Transcriptional regulation of nitrogen-associated metabolism and growth.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Nitrogen-metabolism GRN screen; basis for a GO:0000976 binding annotation
      in a peripheral context.
- id: PMID:31519798
  title: Integrative Analysis from the Epigenome to Translatome Uncovers Patterns
    of Dominant Nuclear Regulation during Transient Stress.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Full-text available. High-throughput hypoxia/reoxygenation study; DREB2A
      heat-stress transcripts are progressively upregulated during hypoxia.
      Basis for a weak HEP cellular-response-to-hypoxia (expression) annotation.
- id: PMID:31806676
  title: A PXY-Mediated Transcriptional Network Integrates Signaling Mechanisms to
    Control Vascular Development in Arabidopsis.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      PXY/vascular-development network screen; basis for a GO:0000976 binding
      annotation in a peripheral context.
- id: PMID:32612234
  title: Extensive signal integration by the phytohormone protein network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Large-scale phytohormone protein interaction network; basis for
      protein-binding IPIs with DOG1 (A0SVK0) and IMPA6 (Q9FWY7).
- id: PMID:9707537
  title: Two transcription factors, DREB1 and DREB2, with an EREBP/AP2 DNA binding
    domain separate two cellular signal transduction pathways in drought- and low-temperature-responsive
    gene expression, respectively, in Arabidopsis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Original DREB2A cloning paper. Demonstrates DREB2A binds DRE and activates
      DRE-driven reporter transcription; basis for the DNA-binding transcription
      factor activity IDA.
- id: file:ARATH/DREB2A/DREB2A-deep-research-falcon.md
  title: "Falcon/Edison deep research report: DREB2A"
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      AI-generated (Falcon/Edison) deep-research synthesis used as supporting
      context; trace individual claims to primary literature before treating as
      definitive.
suggested_questions:
- question: >-
    What is the precise stress-dependent post-translational modification (e.g.
    phosphorylation of the PEST/NRD region) that stabilizes DREB2A and blocks
    DRIP1/DRIP2-mediated degradation under drought versus heat stress?
- question: >-
    What determines the dehydration- versus heat-specific target-gene
    selectivity of DREB2A, given that the DPB3-1/NF-Y trimer accounts for only
    the heat-specific subset?
suggested_experiments:
- description: >-
    Genome-wide DAP-seq or ChIP-seq with stabilized DREB2A (or DREB2A-CA) under
    drought and heat conditions to define the direct, condition-specific DRE/CRT
    regulon and distinguish core targets from large-scale Y1H network hits.
- description: >-
    Phosphoproteomic mapping of the NRD/PEST region under heat and drought
    stress combined with phospho-site mutants to test which modifications
    control DRIP1/DRIP2 recognition and DREB2A stability.