UniProt: P93024 (ARFE_ARATH). Gene: ARF5; synonyms IAA24, MP; locus At1g19850. 902 aa.
ARF5/MONOPTEROS is a B3-domain AUXIN RESPONSE FACTOR (ARF) transcription factor that functions as a
sequence-specific transcriptional activator. It binds auxin response elements (AuxREs; the
5'-TGTCTC-3' motif) in the promoters of auxin-responsive genes and activates their transcription.
ARF5 is one of only ~5 of the 23 Arabidopsis ARFs that act as transcriptional activators (the rest are
repressors) PMID:21734647.
It is essential for embryonic apical-basal axis (body axis) formation, root meristem initiation, and
vascular patterning, and acts post-embryonically in vascular development, leaf vascular patterning,
flower primordium initiation, and meristem maintenance.
ARF5 forms homodimers and heterodimers with Aux/IAA repressors.
- Interacts with IAA12/BODENLOS (BDL) — Y2H, inhibits MP in root meristem initiation
PMID:12101120.
- Interacts with IAA17/AXR3 (heterodimerization via domain III) PMID:11283339.
- IntAct: IAA1 (P49677), IAA12 (Q38830), IAA13 (Q38831), IAA14 (Q38832), IAA19 (O24409), self (P93024).
- Large-scale interactome confirms ARF5 interacts with many Aux/IAAs and homodimerizes [PMID:22096563 "the transcription activator ARF5 stood out among the tested ARFs to interact with 10 Aux/IAA proteins"; PMID:21734647].
- IAA19 (MSG2) interaction reported in PMID:14729917 context (ARF-Aux/IAA interaction via CTD; this paper is primarily on ARF7/NPH4 but IntAct used it for ARF5-IAA19).
- IAA14/SLR interaction context PMID:16236149 (IntAct, Q38832).
- Self-dimerization / identical protein binding [PMID:24485461 (structural homodimer), PMID:21734647, PMID:22096563].
Note: GO:0005515 "protein binding" annotations all derive from these IntAct/TAIR interaction datasets.
These are mostly Aux/IAA repressors. Per curation guidelines, bare "protein binding" is uninformative;
the informative MF is GO:0140297 "DNA-binding transcription factor binding" (ARF5 binds Aux/IAA
transcriptional repressors / co-binds with chromatin remodelers) and GO:0042802 "identical protein
binding" (homodimerization is functionally meaningful for DNA binding per PMID:24485461).
PMID:26460543 protein-binding annotation: MP recruits SWI/SNF chromatin remodeling ATPases (BRM/SYD)
PMID:26460543. The TAIR annotation links AT2G28290 (SYD) and AT2G46020 (BRM).
In low auxin, Aux/IAA proteins (e.g. BDL/IAA12) bound to the MP C-terminal domain recruit TOPLESS
co-repressor and HDA19 histone deacetylase, blocking activation; auxin triggers Aux/IAA degradation,
freeing MP and allowing SWI/SNF recruitment PMID:26460543. MP autoregulates its own expression and
that of BDL PMID:21478855.
GO:0009942 (longitudinal axis specification) and GO:0010051 (xylem/phloem pattern formation) are the
classic mp loss-of-function phenotypes (Przemeck 1996) — strong IMP support.
Core MF: sequence-specific DNA-binding transcriptional activator acting at AuxRE elements (auxin-activated).
Core BP: auxin-activated signaling pathway controlling embryonic axis/vascular/meristem patterning.
Core CC: nucleus.
NEW: GO:0140297 DNA-binding transcription factor binding (binds Aux/IAA repressors); GO:0001228 / activator-class
RNA Pol II activity considered but GO:0003700 already captures activator TF activity. Add
GO:0009734 auxin-activated signaling pathway (in UniProt DR line, IEA:UniProtKB-KW) — but this is not in GOA tsv,
so add as NEW with KW support.
The Falcon deep-research report (file:ARATH/ARF5/ARF5-deep-research-falcon.md) fully corroborates the
existing review and adds recent (2023-2024) mechanistic context; it did not surface any evidence that
weakens prior decisions, and no UNDECIDED annotations were present to resolve.
Key corroborating points used as supported_by evidence:
- Core identity/function: "MP/ARF5 is a nuclear auxin-dependent transcriptional activator that binds
AuxREs and drives developmental gene programs." Acts "in the nucleus as a terminal effector of the
nuclear auxin pathway (NAP), translating auxin levels into transcriptional outputs at
AuxRE-containing cis-regulatory elements." Supports GO:0003700, GO:0005634, GO:0006355, GO:0009733.
- DNA binding via B3: DBD "containing a B3 subdomain that recognizes AuxREs, plus additional DBD
substructures that enable dimerization and cooperative binding." Supports GO:0003677 MODIFY rationale.
- Homodimerization: "For MP/ARF5, homodimerization is described as required for promoter binding and in
vivo specificity." Supports GO:0042802.
- Auxin gating / NAP mechanism: "Increased auxin promotes TIR1/AFB-mediated Aux/IAA degradation,
releasing MP/ARF5 to activate transcription." "At low auxin, BDL/IAA12 binds MP/ARF5 and recruits
TPL/TPR co-repressors and HDA19 to maintain repression." Supports GO:0009734 (NEW) and the
GO:0140297 Aux/IAA-binding core function.
- Chromatin coupling: "Activated MP/ARF5 then associates with chromatin remodelers and histone
acetylation machinery to induce transcription" (BRM/SYD SWI/SNF remodelers). Supports the
cis-regulatory binding core function and the proposed_new_term rationale.
- PB1-mediated interactions: "a C-terminal PB1 domain for ARF–ARF and ARF–Aux/IAA interactions."
Supports GO:0140297 (NEW).
Additional context noted but not annotated (no verifiable GO ID / outside GOA scope): ARF5 prefers the
5'-TGTCGG-3' AuxRE over canonical TGTCTC and binds paired AuxREs with spacing/orientation grammar; PB1
deletion (MPΔ / MP11ir isoform) broadens and de-auxin-sensitizes genomic binding (258 vs 3,405 promoters
in one dataset); ~4,585 direct auxin-dependent targets reported; combinatorial partner TFs (e.g. bZIP11
recruiting SAGA; GBF factors); and 2024 evolutionary work tracing the ARF DBD fold to a chromatin-regulator
(PHIP-related crypto-Tudor) origin. These refine but do not change the existing annotation decisions.
Reviewer (ai4c-agent, IMPORTANT) flagged that the NEW GO:0140297 "DNA-binding
transcription factor binding" annotation was justified by ARF5's interaction with
Aux/IAA proteins (e.g. BODENLOS/IAA12). Aux/IAA proteins are transcriptional
co-repressors that LACK a DNA-binding domain — they bind ARFs via PB1-domain
(domain III/IV) interactions. GO:0140297 requires the partner to be a DNA-binding
transcription factor, so it is not appropriate for ARF-Aux/IAA interactions.
Decision: replaced GO:0140297 with GO:0019904 "protein domain specific binding"
(verified label/def via QuickGO API: "Binding to a specific domain of a protein"),
which correctly captures the PB1-domain-mediated ARF5-Aux/IAA interaction. Updated:
- the NEW molecular-function annotation block (now GO:0019904, IPI, PMID:12101120)
- the corresponding core_functions entry
- the six REMOVE reviews of redundant GO:0005515 "protein binding" annotations that
pointed at GO:0140297, and corrected text mislabeling Aux/IAA as DNA-binding TFs.
ARF-ARF homodimerization (where the partner IS a DNA-binding TF) remains covered by
the existing GO:0042802 "identical protein binding" annotations, so no redundant
ARF-ARF term was created. Validation: ✓ Valid.
All seeded annotation payloads were preserved, including term IDs, evidence types, original sources, supporting entities and flags. The review evaluates biological claims independently of inert relationship fields. No new annotation row was added. Available genuine prior research reports were used for discovery; primary text and curated record statements were preferred for evidence. The actual Falcon and perplexity-lite fallback attempts failed (authorization/quota errors), as recorded in .cache/module-audit-logs/auxin-fetch/; no provider report was fabricated. Normal publication fetching and normal ReferenceFetcher URL recovery supplied the sources below. Canonical PMID records were not hand-edited to insert recovered text.
The annotation-reviewer workflow was applied to every row. Bare protein-binding rows are refined only where the interaction and functional partner class support a more informative term; removal of an otherwise uninformative binding row does not dispute the measured interaction. True general transcription terms are refined rather than rejected. Nuclear evidence does not establish absence from cytoplasm.
MP is an activator, supported by direct DNA recognition and native target regulation, rather than an undifferentiated ARF-family transcription factor [PMID:24485461; PMID:19369397]. The latter reports “MP binds in vivo to two AuxRE-spanning fragments in the DRN promoter”. The supported core is GO:0001216, with GO:0001222 for Aux/IAA corepressor binding and the existing cis-regulatory binding core retained. Generic binding rows for characterized Aux/IAA partners are refined to corepressor binding; the BRM/SYD interaction is refined to transcription coregulator binding because MP recruits these remodelers to target loci PMID:26460543. The 2005 IAA14 abstract foregrounds ARF7/19, which is not evidence that the curator's ARF5 interaction is wrong; independently demonstrated MP–BODENLOS binding supports the functional class PMID:12101120.
DBD homodimerization and PB1-mediated interaction assays are distinguished; an interaction-screen row need not have tested the same interface as a later DBD structure. Broad hormone response is refined to auxin response, and broad transcription regulation to the demonstrated positive direction. Developmental patterning claims remain supported context-specific roles, not excluded merely because they are outputs of transcription. Existing proposed domain-binding and auxin-signaling rows are preserved; they were not newly created in this session. Provider-summary quotations were replaced by available primary support without deleting their reference provenance.
A specific caution is retained: auxin-sensitive regulation is not a claim that all MP target loci use an invariant TPL/HDA19 complex or that every AuxRE is TGTCTC. Receptor-associated catalytic findings in other panel members are not transferred to MP.
Validation and source-closure results are recorded in .cache/module-audit-logs/auxin-arf-tpl-final-report.md; the committed helper history identifies this curation session.
Independent QA identified that the canonical PMID:14729917 extraction is truncated despite its full-text flag. The parent recovered the complete public source normally at publications/url_https___pmc.ncbi.nlm.nih.gov_articles_PMC341911_.md. Its Results/Figure 9B directly support ARF5 CTD binding to IAA19 and additional Aux/IAAs (bars 12–17). The existing binding row now uses the target-specific Results sentence. The self-binding summary distinguishes the paper’s CTD constructs from the independent DBD homodimer structure. All existing actions and raw annotation payloads are unchanged. Yeast binding capacity is not equated to a shared native developmental phenotype or an obligatory TPL-containing complex. Canonical PMID provenance is retained alongside the recovered full-source file.