DREB2A (At5g05410, UniProt O82132) — Gene Review Notes

Arabidopsis thaliana DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 2A.
AP2/ERF-family transcription factor. ORF/locus AT5G05410; synonym ERF045.

Summary of biology

DREB2A is a sequence-specific DNA-binding transcription factor of the AP2/ERF
superfamily (ERF/DREB subfamily) that binds the dehydration-responsive
element / C-repeat (DRE/CRT) cis-element, core motif A/GCCGAC, in target gene
promoters and activates their transcription. It is a master regulator of the
ABA-independent branch of drought-, high-salinity- and heat-stress-responsive
gene expression in Arabidopsis. A central negative regulatory domain (NRD; the
~30 aa region between residues 136-165, containing a PEST sequence) targets the
protein for ubiquitin-mediated degradation by the RING E3 ligases DRIP1/DRIP2
and the 26S proteasome; deletion of this region produces a constitutively active
form (DREB2A-CA) that confers drought and heat tolerance. Under heat stress
DREB2A is stabilized and induces the heat-stress regulatory cascade, including
the heat-shock transcription factor gene HsfA3.

DNA binding / TF activity / nucleus (core functions)

Drought / water deprivation / osmotic stress

Heat stress / heat acclimation

Post-translational regulation / degradation (DRIP1/DRIP2)

Protein-protein interactions (GO:0005515 IPI annotations)

These are real, experimentally supported interactions but "protein binding"
(GO:0005515) is uninformative as a molecular function. Underlying interactors:
- DRIP1 (Q9M9Y4) / DRIP2 (Q94AY3) — RING E3 ligases. PMID:18552202
- RCD1 (Q8RY59) — Radical-induced Cell Death1; SLiM-mediated binding to the
RCD1 RST domain. PMID:27881680 and [PMID:19548978 RCD1/SRO1].
- MED25 (Q7XYY2 / Q7XYY2-1) — Mediator subunit; interaction reported, with NMR
structural data on a DREB2A peptide (PDB 5OAP, residues 255-272). PMID:21536906, PMID:22447446
- DPB3-1 / NF-YC10 (Q9LN09) — heat-stress coactivator. PMID:25490919
- DOG1 (A0SVK0) and IMPA6 (Q9FWY7) — large-scale interactome. PMID:32612234

UniProt INTERACTION block confirms DOG1, DRIP1, IMPA6, MED25, RCD1.
[file:ARATH/DREB2A/DREB2A-uniprot.txt "O82132; Q9M9Y4: DRIP1; NbExp=4"]

Target-promoter binding annotations (GO:0000976, IPI, WITH AGI loci)

Multiple TAIR annotations to "transcription cis-regulatory region binding"
(GO:0000976) with WITH-field AGI loci come from large yeast-one-hybrid /
gene-regulatory-network screens (enhanced Y1H, secondary cell wall network,
nitrogen network, PXY/vascular network, PRC2 regulation, plant-defense network).
These document DREB2A binding to specific target promoters and support the
sequence-specific DNA-binding TF function, although several of the networks
(secondary cell wall, vascular development, nitrogen metabolism, PRC2) are
contexts where DREB2A is a node in a large Y1H matrix rather than an established
in planta regulator. [PMID:22037706 Enhanced Y1H], [PMID:25533953 secondary cell wall GRN], [PMID:31806676 PXY vascular network], [PMID:30356219 nitrogen network], [PMID:27650334 PRC2], [PMID:25352272 plant-defense promoter integration].

Weaker / expression-readout annotations (candidates for non-core or over-annotation)

Provenance / IEA backbone annotations

Conclusions for review actions

Core: GO:0003700 (DNA-binding TF activity), GO:0000976 (DRE/CRT cis-regulatory
region binding), GO:0005634 (nucleus), GO:0045893 (positive regulation of
transcription), GO:0009414 (response to water deprivation), GO:0009408 (response
to heat). DNA binding (GO:0003677) and regulation of transcription (GO:0006355)
are accepted as correct but general/non-core electronic backbone.
The eight GO:0005515 "protein binding" IPI annotations are real interactions but
uninformative as MF; mark over-annotated (do not endorse as core).
UV-B, H2O2, hypoxia, heat-acclimation are expression-readout associations →
keep as non-core.

Earlier notes carried over from the retired AT5G05410 folder

These notes were written for the duplicate genes/ARATH/AT5G05410 review of the same protein (O82132), which was merged into this folder. Claims tagged [deep-research] come from AI deep-research summaries, not from primary papers, and have not been re-verified against the literature.

Gene Summary

DREB2A = Dehydration-Responsive Element Binding Protein 2A
CRITICAL INTEGRATOR: Drought AND Heat stress responses through distinct pathways [deep-research]

UNIQUE FUNCTION - Cross-Stress Integrator

DREB2A coordinates BOTH drought and heat stress responses through stress-specific transcriptional programs [deep-research]

Mechanism:

Primary Function

Sequence-Specific Transcription Factor (CORE)

Domain Architecture:

POST-TRANSLATIONAL REGULATION (CRITICAL MECHANISM)

Constitutive Degradation Under Normal Conditions:

Paradox: DREB2A mRNA is constitutively expressed, but protein is RAPIDLY degraded [deep-research]

DRIP1/DRIP2-Mediated Degradation:

Stress-Induced Stabilization:

Casein Kinase 1 (CK1)-Mediated Phosphorylation:

Result:

Target Genes and Transcriptional Programs

Microarray Analysis (DREB2A-CA overexpression):

Direct Target Gene Classes:

1. Late Embryogenesis Abundant (LEA) Proteins (9 genes):
2. Heat Shock Factor A3 (HSFA3):
3. Osmoprotective Genes:
4. Stress-Responsive Genes:

Stress-Dependent Target Selectivity:

Upstream Regulation

Transcriptional Induction:

Heat Stress Pathway:
Osmotic Stress Pathway:

Transcriptional Repression:

GRF7 (Growth-Regulating Factor 7):
Phosphoinositide-Specific Phospholipase C (PI-PLC):

Alternative Splicing - Regulatory Diversity

DREB2A.2 Isoform:

Functional Significance:

Protein-Protein Interactions

Cofactors (Enhance Activity):

Nuclear Factor Y (NF-Y) Complex:

Negative Regulators:

RCD1 (Radical-Induced Cell Death 1):

Subcellular Localization

Functional Roles

1. Drought and Salt Stress Tolerance (PRIMARY):

2. Heat Stress Tolerance (CO-PRIMARY):

3. ABA-Independent Osmotic Stress Pathway:

DREB2 Family Context

Arabidopsis DREB2 Subfamily:

Evolutionary Conservation:

Biotechnological Applications

Challenges:

Solutions:

Curation Strategy

  1. ACCEPT core molecular function annotations:
  2. Sequence-specific DNA binding transcription factor
  3. DNA-binding transcription factor activity
  4. cis-regulatory region sequence-specific DNA binding

  5. DRE/CRT element binding

  6. ACCEPT biological process annotations:

  7. Response to water deprivation
  8. Response to salt stress
  9. Response to heat
  10. Response to osmotic stress
  11. Cellular response to dehydration

  12. Positive regulation of transcription

  13. ACCEPT localization annotations:

  14. Nucleus (primary site of function)

  15. EMPHASIZE key features:

  16. CROSS-STRESS INTEGRATOR (drought AND heat)
  17. Post-translational regulation (DRIP1/DRIP2, CK1 phosphorylation)
  18. DREB2A → HSFA3 → HSP cascade (hierarchical)
  19. Alternative splicing (DREB2A.2 for heat stress)
  20. Stress-specific cofactors (DPB3-1 for heat targets)

  21. Constitutive degradation, stress-induced stabilization

  22. NOTE important relationships:

  23. Upstream: HSFA1a/b/d (heat), AREB/ABF (osmotic)
  24. Downstream: HSFA3 (heat), LEA proteins (drought), HSPs
  25. Negative regulators: GRF7, RCD1, DRIP1/DRIP2, PI-PLC
  26. Cofactors: DPB3-1/NF-YC (heat-specific enhancement)

Key Functional Distinctions

vs DREB1A:

vs HSFA1 Family:

vs HSFA3:

References

2026-09-27: merge of the AT5G05410 duplicate and GOA refresh

Adjudicating the rows where the two reviews disagreed (PR #3231 review)

The retired AT5G05410 review and this one gave different actions on rows still in GOA. Decisions: