GID1A (Q9MAA7) — Arabidopsis thaliana — curation notes

Identity and overview

• GID1A = GA INSENSITIVE DWARF1A, locus At3g05120. Synonyms CXE10 (carboxylesterase 10), GID1L1.
• Soluble nuclear gibberellin (GA) receptor; one of three Arabidopsis paralogs (GID1A/B/C), orthologs of rice OsGID1.
• Belongs to the carboxylesterase / hormone-sensitive lipase (HSL, 'GDXG' lipolytic enzyme) superfamily with an α/β-hydrolase fold, but functions as a hormone RECEPTOR, NOT as a catalytically active hydrolase.

Function: GA receptor, not an active hydrolase

• "GID1 was first described in rice as a nuclear localized protein similar to hormone-sensitive lipase family without hydrolase activity" PMID:24961590.
• All three recombinant AtGID1 proteins bind bioactive GA with higher affinity to GA4 PMID:16709201.
• Crystal structure of GID1A–GA–GAI(DELLA) ternary complex: GID1A binds GA in a deep pocket covered by its N-terminal helical switch, which then binds DELLA PMID:19037309. GID1 is called a "nuclear receptor" here PMID:19037309.
• => hydrolase activity (GO:0016787, IEA from InterPro) is a spurious over-annotation derived from the lipase/esterase fold and should be removed. The UniProt EC=3.-.-.- is nominal; the catalytic Ser is not functional as a hydrolase in vivo.

Mechanism / signaling

• GA-bound GID1 interacts with DELLA repressors (GAI, RGA, RGL1, RGL2, RGL3) in a GA-dependent manner; this is the receptor's effector step [UniProt SUBUNIT; PMID:17194763 "GA enhances the interaction between GID1 and DELLA proteins... the N-terminal sequence containing the DELLA domain is necessary for GID1 binding"].
• The GA–GID1–DELLA complex promotes DELLA interaction with the SLY1 F-box of SCF(SLY1), leading to DELLA polyubiquitination and 26S proteasomal degradation, derepressing GA responses PMID:17194763.
• GA-GID1 can also downregulate DELLA repression without degradation (proteolysis-independent) PMID:18827182.
• GID1A acts as a POSITIVE regulator of the GA signaling pathway PMID:17194763.
• The DELLA domain is the "receiver domain" for activated GID1A PMID:17416730.

Genetics / redundancy / phenotypes

• Single gid1 mutants ~ no/normal visible phenotype (UniProt DISRUPTION PHENOTYPE; PMID:17194763, PMID:17521411). Triple gid1a gid1b gid1c is an extreme GA-insensitive dwarf, non-germinating, GA-unresponsive PMID:17521411, PMID:17416730.
• GID1A makes the strongest single contribution; gid1a gid1c reduced stem height; gid1a gid1b reduced male fertility (functional specialization within redundancy) PMID:17194763.
• Floral organ development defects in the triple mutant PMID:17194763 — supports floral organ morphogenesis BP.

Fruit-set / fertility (PMID:24961590)

• "GID1A plays a major role during fruit-set and growth, whereas GID1B and GID1C have specific roles in seed development and pod elongation" PMID:24961590.
• GID1A expressed throughout the pistil PMID:24961590.
• Supports fruit morphogenesis (GO:0048530) and positive regulation of fertilization (GO:1905516) for GID1A. The GOA IGI/IMP set (with GID1B Q9LYC1, GID1C Q940G6) reflects genetic redundancy analysis in this paper.
• NOTE on the negated annotation: GOA line "NOT|involved_in response to gibberellin (IGI, with Q9LYC1=RGL2... actually Q9LYC1 is GID1C? check)". The NOT annotation (with UniProtKB:Q9LYC1) and the non-negated IGI (with Q940G6) come from this fruit-set redundancy study; the NOT likely reflects a specific double-mutant combination where GID1A did not show a measurable contribution (redundancy masking). Treated cautiously / KEEP_AS_NON_CORE-style.

Subcellular localization

• UniProt: Nucleus (by similarity, ECO:0000250). GID1 repeatedly described as a NUCLEAR receptor [PMID:19037309; PMID:24961590].
• Experimental GID1A-GFP/localization detected in BOTH nucleus and cytoplasm [GOA PMID:17416730 IDA: located_in nucleus AND cytoplasm]. Nuclear-cytoplasmic distribution is consistent with GA perception and DELLA (nuclear) interaction.
• TAIR ISM (GO_REF:0000122, AtSubP prediction) nucleus — redundant computational support for nucleus.

GARU / stability (PMID:29042542)

• GID1 protein is itself a substrate of the RING E3 ligase GARU; GID1A interacts with GARU (basis of the IPI protein binding annotation and IDA nucleus). PMID:29042542. GID1A localized to nucleus in this study (IDA).

Hypoxia HEP (PMID:31519798)

• Genome-wide epigenome-to-translatome survey of hypoxia/reoxygenation in seedlings; GID1A appears as one of many regulated transcripts. This is a high-throughput expression pattern (HEP) annotation, not direct functional evidence that GID1A acts in the hypoxia response. Mark as over-annotated / non-core.

Phytohormone network (PMID:32612234)

• Large-scale Y2H phytohormone protein interaction network; source of several IPI protein-binding interactions (incl. IMPA3 O04294, MES17 Q9SG92). High-throughput; supports DELLA + other interactions but protein binding is uninformative.

Interaction partners (from GOA IPI WITH/FROM + UniProt INTERACTION)

• DELLAs: GAI (Q9LQT8), RGA (Q9SLH3), RGL1 (Q9C8Y3), RGL2 (Q8GXW1), RGL3 (Q9LF53) — GA-dependent, the core effector interactions.
• GID2/SLY-related Q9STX3 (GID2), AFPH2 Q9SV55, IMPA3 O04294 (importin alpha 3), MES17 Q9SG92.

Curation decisions summary

• MF core: gibberellin binding (GO:0010331, IDA) — ACCEPT as core. No GO term "gibberellin receptor activity" exists (verified absent in OLS GO); propose as new term.
• hydrolase activity (GO:0016787) — REMOVE (fold-based mis-annotation; protein has no hydrolase activity).
• protein binding (GO:0005515, many IPI) — uninformative; KEEP_AS_NON_CORE (documents DELLA + other interactions) but not core; better captured by signaling BP and a future "GA-activated receptor / DELLA binding" MF.
• BP core: gibberellin-mediated signaling pathway (GO:0010476) + positive regulation of GA signaling (GO:0009939) — ACCEPT.
• response to gibberellin (GO:0009739) — ACCEPT (multiple lines), redundant with signaling.
• floral organ morphogenesis / fruit morphogenesis / positive regulation of fertilization — developmental outputs of GA signaling; KEEP_AS_NON_CORE (pleiotropic, redundant with paralogs).
• cellular response to hypoxia (GO:0071456, HEP) — MARK_AS_OVER_ANNOTATED.
• nucleus / cytoplasm — ACCEPT (nucleus core; cytoplasm experimentally observed).

Deep research synthesis (Falcon / Edison Scientific report)

The Falcon deep-research report (GID1A-deep-research-falcon.md) corroborates and extends the existing review with no contradictions. Key points used to strengthen the review:

• Non-enzymatic receptor confirmed: "the receptor lacks key catalytic features and shows no detectable hydrolase activity in a model substrate assay (p-nitrophenyl acetate)" — reinforces the REMOVE decision on GO:0016787 hydrolase activity (Ueguchi-Tanaka et al. 2007; Alabadí & Sun 2025).
• Ligand binding / GA4 selectivity: "GA4 is highlighted as the highest-affinity GA and the most effective for driving GID1–DELLA complex formation in planta" — supports GO:0010331 gibberellin binding (core MF).
• Allosteric lid mechanism: GA binding "creates hydrophobic surfaces needed for DELLA binding" (closes N-terminal lid; engages DELLA, LExLE, VHYNP motifs) — supports the receptor mechanism / proposed gibberellin receptor activity term.
• Two-mode DELLA suppression: proteolysis-dependent (cryo-EM GA3–GID1A–RGA–SLY1–ASK1 quaternary complex, ~2.72 Å, Dahal et al. 2025 PNAS) AND proteolysis-independent ("GA-bound GID1 can reduce DELLA repression without necessarily inducing DELLA degradation") — supports GO:0009939 and the GA-mediated signaling core function.
• Nucleocytoplasmic localization: "GFP-tagged Arabidopsis GID1A localized to both nucleus and cytoplasm, and this distribution was not altered by GA or paclobutrazol treatment" — supports both nucleus (GO:0005634) and cytoplasm (GO:0005737).
• New mechanistic detail (2025): GA–GID1A binding to the DELLA GRAS region can compete with IDD transcription-factor binding (Y3H attenuation of IDD1–RGA), extending DELLA neutralization beyond degradation. Captured as context; no new GO ID added.

No UNDECIDED annotations were present, so none required resolution. No new GO annotation could be added with a verifiable GOA/UniProt ID (a dedicated "gibberellin receptor activity" MF still does not exist in GO and remains in proposed_new_terms). The report does not contradict the negated response to gibberellin annotation (redundancy masking) or the hypoxia HEP over-annotation call. New references: Shani et al. 2024 (Plant Physiol), Alabadí & Sun 2025 (Annu Rev Plant Biol), Dahal et al. 2025 (PNAS) — cited within the falcon report rather than added as standalone PMIDs.

2026-10-06 re-review (consistency with GID1B/GID1C)

• Fixed the PMID:18827182 IGI row: the WITH locus AT4G02780 is GA1 (ent-copalyl diphosphate synthase, ga1-3 background), not SLY1.
• Fixed the PMID:17194763 protein-binding summary: Q9STX3 is SLY1/GID2, not RGL2.
• The NOT|involved_in response to gibberellin row (IGI with GID1B, PMID:24961590) is now REMOVE, as on GID1B/GID1C. It is contradicted by receptor biochemistry PMID:16709201 and by the same paper PMID:24961590.
• All GO:0005515 rows changed from KEEP_AS_NON_CORE to REMOVE under the protein-binding policy. No informative MF exists for receptor-DELLA binding, and being a GARU substrate is not a GID1A molecular function.

2026-10-15 OpenScientist hypothesis run: catalytic inactivity

Report: GID1A-hypotheses/gid1a-catalytic-inactivity/openscientist.md (3 iterations, ~21 min). The hypothesis was: "GID1A is a catalytically inactive HSL/AADAC-family alpha/beta-hydrolase whose catalytic His position is a Val." Its local bioinformatics was withheld from the prompt. GID1A has no -bioinformatics/ folder; the comparison point is the PTHR23024 (GID1) family review in PR #5027.

Verdict from the run: supported (strongly).
- Needleman-Wunsch alignments against human AADAC (P22760) and HSL (Q05469) both place the active enzymes' catalytic His on GID1A Val319. The equivalent residues are GID1B Asn338 and GID1C Ile317.
- Parsing PDB 2ZSH, the run reports that no His nitrogen lies within 8.5 Å of the Ser191 Oγ.

Checked here against GID1A-uniprot.txt:
- The residue claims are correct. Positions 191/289/319 are S/D/V. Residues 113-115 are the HGG oxyanion motif. The nucleophile elbow is AGDSSGG.
- UniProt annotates only two ACT_SITE residues, 191 and 289, and no catalytic His. This corroborates the absence of an annotated general base; the Val at 319 itself comes from the sequence, not from the active-site annotation. It agrees with the Val319 finding in the PTHR23024 family review (PR #5027).
- I did not re-run the alignments or the PDB distance measurements.
- The paralog residues (GID1B Asn338, GID1C Ile317 at the AADAC His373 position) are the residue-level basis for the GID1B review's IBA hydrolase REMOVE. That row's propagation_review gives the source status SUPPORTS_SOURCE_BUT_NOT_TARGET to the PAINT node PANTHER:PTN009058710, not to AADAC; AADAC (P22760) is one of the active esterases in the IBA's with/from list that seeded the node.

Errors in the report, not to be propagated:
- It says GID1B and GID1C have "no GA-binding MF" and only GO:0016787. This is false. Both GOA files and both reviews carry GO:0010331 gibberellin binding.
- Its triad comparison table marks the GID1B acid as Asp, although its own Finding 1 footnote says the GID1B acid position fell in an alignment gap.
- It says no primary paper reports the presence or absence of esterase activity. The original rice GID1 paper is cited as describing the protein as HSL-like "without hydrolase activity" PMID:24961590. The Falcon deep-research file reports a negative p-nitrophenyl acetate assay. So the "no residual activity" clause has at least a published negative claim behind it. I have not verified the primary assay, because PMID:16193045 has no cached text.

Curation consequence: no action changes. GO:0016787 hydrolase activity (IEA, GO_REF:0000002) is already REMOVE in this review; the report is now cited as a reference and in that row's supported_by as residue-level support. The proposed "gibberellin receptor activity" MF still has no GO term.

2026-10-20: ported fixes from the parallel review branch

Dropped the NEW GO:0009939 positive regulation of GA-mediated signaling row (IGI, PMID:17194763). No GID1 paralog carries GO:0009939; all carry GO:0010476 gibberellin mediated signaling pathway, which GID1A already has. The second core function now uses GO:0010476 with proposed_molecular_function "gibberellin receptor activity" (the existing proposed_new_terms entry), which distinguishes it from the GA-binding core function.