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.