id: F6LAX4 gene_symbol: LOC123103357 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:4565 label: Triticum aestivum description: > F6LAX4 is the bread wheat (Triticum aestivum) scaffolding A subunit (PR65 type) of protein phosphatase 2A (PP2A), encoded by a homoeologous locus set on chromosome group 5 (TraesCS5A02G168400, TraesCS5B02G165200, TraesCS5D02G172700). The 587-residue, ~65 kDa protein consists almost entirely of tandem HEAT repeats that fold into a horseshoe-shaped alpha-helical solenoid. It has no catalytic activity. In the PP2A holoenzyme the A subunit binds the catalytic C subunit to form the A-C core dimer and provides the platform on which a variable regulatory B subunit (B55, B'/B56 or B''/PR72 type) docks, so the A subunit holds the heterotrimer together and, by permitting assembly of different holoenzymes, governs PP2A activity, substrate choice and subcellular targeting. Grass genomes encode a single lineage of A subunits that is co-orthologous to the three Arabidopsis A subunits (RCN1/PP2AA1, PP2AA2, PP2AA3); the Arabidopsis proteins are found in both the nucleus and the cytosol and, through the PP2A holoenzymes they scaffold, act in auxin transport, hormone signalling and development. No experimental study of the wheat protein itself has been reported. existing_annotations: - term: id: GO:0000159 label: protein phosphatase type 2A complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: The A subunit is an obligate structural component of the PP2A heterotrimer, so membership of the protein phosphatase type 2A complex is the defining cellular component of F6LAX4. action: ACCEPT reason: The IBA derives from the PAINT IBD on the eukaryote-level scaffold node PTN000068663, seeded by experimental annotations from budding and fission yeast, fly, worm, mouse, human, Candida and Dictyostelium A subunits. F6LAX4 descends from this node (PANTHER PTHR10648, and the re-review phylogeny places it with all other plant A subunits inside the conserved scaffold clade), carries the full HEAT-repeat solenoid, and has no sign of divergence. Structural work shows the scaffolding subunit is one of the two subunits of the PP2A core enzyme. Accepted as core. supported_by: - reference_id: PMID:17174897 supporting_text: The PP2A holoenzyme consists of a heterodimeric core - reference_id: PMID:17174897 supporting_text: enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a - reference_id: file:WHEAT/F6LAX4/F6LAX4-bioinformatics/RESULTS-rereview.md supporting_text: F6LAX4 is a co-ortholog of all three - term: id: GO:0019888 label: protein phosphatase regulator activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: The A subunit has no catalytic activity; it regulates PP2A by assembling the catalytic C subunit with alternative regulatory B subunits, which determines holoenzyme activity and substrate specificity. Protein phosphatase regulator activity is the standard MF for PP2A A and B subunits. action: ACCEPT reason: The IBA derives from the PAINT IBD at PTN000068596 (seeded by human PPP2R1A, fly Pp2A-29B and worm A subunits), the node that also carries the scaffold-activity IBD. F6LAX4 lies inside this clade. GO:0019888 is the existing GO class for this role (the PP2A-specific regulator term GO:0008601 is no longer a separate class); the more precise structural description of what the A subunit does is captured by the NEW protein complex scaffold activity row below, which complements rather than replaces this term. supported_by: - reference_id: file:human/PPP2R1A/PPP2R1A-uniprot.txt record_section: ["CC:FUNCTION"] supporting_text: The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit - reference_id: file:WHEAT/F6LAX4/F6LAX4-deep-research-falcon.md supporting_text: enable recruitment of different B subunits, thereby indirectly controlling **substrate specificity**, **localization**, and **activity modulation** of PP2A holoenzymes. - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: All three Arabidopsis A subunits, which are co-orthologs of F6LAX4, have been shown to reside in both the nucleus and the cytosol. action: ACCEPT reason: Although this row is an ARBA prediction, the same localization is supported phylogenetically (PAINT IBD for nucleus on the eukaryote scaffold node PTN000068663 is seeded by AT1G13320, AT1G25490 and AT3G25800, i.e. all three Arabidopsis A subunits, plus yeast, fly, worm and human members) and experimentally for the Arabidopsis co-orthologs. A soluble scaffold of a phosphatase with nuclear substrates is expected in the nucleus. supported_by: - reference_id: PMID:22404109 supporting_text: A-subunits A1, A2 and A3 all reside in both the nucleus and cytosol of the cell. - reference_id: file:WHEAT/F6LAX4/F6LAX4-bioinformatics/RESULTS-rereview.md supporting_text: F6LAX4 is a co-ortholog of all three - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: Correct but less specific than the evidence supports; the Arabidopsis co-orthologs are cytosolic, and the PAINT cytosol IBD on the eukaryote scaffold node covers F6LAX4. action: MODIFY proposed_replacement_terms: - id: GO:0005829 label: cytosol reason: Cytosol (part_of cytoplasm) is supported by direct localization of Arabidopsis PP2A-A1, A2 and A3 and by the PAINT IBD for GO:0005829 at PTN000068663 (seeded by AT1G13320, fly Pp2A-29B and mouse Ppp2r1a), which UniProt already shows as an IBA on this entry. The PAINT IRD at PTN000068762 that negates cytosol is a single-leaf node for Arabidopsis PP2AA3 and does not cover the grass lineage; the PTHR10648 family review argues that IRD is itself contradicted by the PP2AA3 data. Refining to cytosol is therefore warranted. supported_by: - reference_id: PMID:22404109 supporting_text: A-subunits A1, A2 and A3 all reside in both the nucleus and cytosol of the cell. - term: id: GO:0032991 label: protein-containing complex evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: part_of review: summary: True (the A subunit is part of the PP2A holoenzyme) but uninformative, since the accepted GO:0000159 protein phosphatase type 2A complex already entails it. action: TOO_GENERAL reason: Previously marked MARK_AS_OVER_ANNOTATED, but the claim is not an over-annotation, it is simply a root-level complex term subsumed by GO:0000159, which is ACCEPTed in this review. TOO_GENERAL is the action defined for exactly this case. supported_by: - reference_id: PMID:17174897 supporting_text: enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a - term: id: GO:0140378 label: protein complex scaffold activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: The A subunit is the structural scaffold that holds the PP2A heterotrimer together, which is the definition of protein complex scaffold activity. action: NEW reason: PAINT curators placed an IBD for GO:0140378 on PTN000068596 (seed human PPP2R1A, dated 2026-06-03), the same ancestral node from which F6LAX4 receives its GO:0019888 IBA, so this IBA is expected to propagate to F6LAX4 in the next GOA release; it is absent from the fetched GOA snapshot only because of its date. The term describes what the A subunit itself does (it is an integral member of the complex that holds it together) rather than a downstream consequence. F6LAX4 retains the complete HEAT-repeat solenoid on which both the C and B subunits dock. supported_by: - reference_id: PMID:17174897 supporting_text: The regulatory B'/B56/PR61 subunit simultaneously interacts with the catalytic - reference_id: file:human/PPP2R1A/PPP2R1A-uniprot.txt record_section: ["CC:FUNCTION"] supporting_text: The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit - reference_id: file:WHEAT/F6LAX4/F6LAX4-uniprot.txt record_section: ["DR:InterPro"] supporting_text: DR InterPro; IPR051023; PP2A_Regulatory_Subunit_A. references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: - statement: Phylogenetic (IBA) annotations from GO_Central. GO:0000159 comes from the eukaryote scaffold node PTN000068663 and GO:0019888 from PTN000068596; PTN000068596 also carries a GO:0140378 protein complex scaffold activity IBD (2026-06-03) not yet in the fetched GOA. The BP IBDs at PTN000068664 (spindle assembly; meiotic sister chromatid cohesion, centromeric) are on an animal/fungal subclade and were not propagated to F6LAX4. reference_review: relevance: HIGH correctness: VERIFIED review_notes: > Node placements checked against interpro/panther/PTHR10648/PTHR10648-paint.tsv in the 2026-10-20 re-review. - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: - statement: ARBA rule-based (IEA) annotations assigning nucleus (GO:0005634), cytoplasm (GO:0005737) and protein-containing complex (GO:0032991). reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: > Automated ARBA mappings. Not used as evidence for themselves; the localizations are independently supported by PAINT IBDs and by PMID:22404109 for the Arabidopsis co-orthologs. - id: file:WHEAT/F6LAX4/F6LAX4-deep-research-falcon.md title: Deep-research report (falcon / Edison Scientific Literature) - functional annotation of wheat PP2A scaffolding A subunit (F6LAX4 / LOC123103357). findings: - statement: No primary literature characterizes this wheat gene; functional annotation is family-level inference grounded in canonical PP2A-A structure-function evidence. - statement: The PP2A A subunit is a HEAT-repeat alpha-solenoid that binds the catalytic C subunit and recruits regulatory B subunits, controlling substrate specificity, localization and activity of PP2A holoenzymes. - statement: Arabidopsis RCN1/PP2AA1 functions in auxin distribution and root development, with redundancy among the three A subunits. reference_review: relevance: HIGH correctness: VERIFIED review_notes: > LLM deep-research synthesis; it transparently states that no wheat-specific literature exists. In the 2026-10-20 re-review it is retained but primary support was shifted to cached PMIDs, the human PPP2R1A UniProt curated function text and the new phylogeny; it remains cited only for one family-level statement on B-subunit-dependent specificity. - id: PMID:17174897 title: Structure of the protein phosphatase 2A holoenzyme. findings: - statement: Crystal structure of the PP2A heterotrimer showing the scaffolding subunit as one of the two subunits of the core enzyme, contacted by both catalytic and B'/B56 subunits. reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract-only cache; quotes verified against the cached abstract. Structural work on the human holoenzyme; transfer to F6LAX4 rests on its descent from the eukaryote scaffold PAINT nodes. - id: PMID:22404109 title: "Arabidopsis thaliana histone deacetylase 14 (HDA14) is an α-tubulin deacetylase that\ \ associates with PP2A and enriches in the microtubule fraction with the putative histone acetyltransferase\ \ ELP3." findings: - statement: Arabidopsis PP2A A subunits A1, A2 and A3 (co-orthologs of F6LAX4) reside in both the nucleus and the cytosol. reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract-only cache; the localization quote is from the abstract. - id: file:human/PPP2R1A/PPP2R1A-uniprot.txt title: UniProt record P30153 (human PPP2R1A) findings: - statement: Curated function text (with PubMed evidence) describing PR65 as the scaffold that coordinates assembly of the catalytic and variable B subunits. reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Human PPP2R1A is in PANTHER SF2, not SF4, so only the ancestral scaffold function shared at PAINT node PTN000068596 is transferred, not animal-specific roles. - id: file:WHEAT/F6LAX4/F6LAX4-uniprot.txt title: UniProt record F6LAX4 findings: - statement: TrEMBL PE3 entry, 587 aa, with PP2A regulatory subunit A family signatures (IPR051023, PF22646) and HEAT repeats spanning the whole protein. - id: file:WHEAT/F6LAX4/F6LAX4-bioinformatics/RESULTS-rereview.md title: F6LAX4 phylogenetic placement among PP2A scaffold A subunits (re-review) findings: - statement: F6LAX4 is full length and groups with grass A subunits; the three Arabidopsis A subunits are eudicot-specific paralogs, so F6LAX4 is a co-ortholog of all three. The PANTHER SF4 versus SF29/SF36 split between grass and Arabidopsis A subunits is a subfamily-HMM boundary, not a functional divergence. core_functions: - description: > Structural scaffold (A/PR65) subunit of the PP2A heterotrimeric holoenzyme. Its HEAT-repeat solenoid binds the catalytic C subunit to form the core dimer and docks a variable regulatory B subunit, holding the complex together and thereby regulating PP2A activity, substrate specificity and localization in the cytosol and nucleus. molecular_function: id: GO:0140378 label: protein complex scaffold activity locations: - id: GO:0005829 label: cytosol - id: GO:0005634 label: nucleus in_complex: id: GO:0000159 label: protein phosphatase type 2A complex supported_by: - reference_id: PMID:17174897 supporting_text: enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a - reference_id: file:human/PPP2R1A/PPP2R1A-uniprot.txt record_section: ["CC:FUNCTION"] supporting_text: The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit - reference_id: PMID:22404109 supporting_text: A-subunits A1, A2 and A3 all reside in both the nucleus and cytosol of the cell. - description: > Protein phosphatase regulator: by determining which regulatory B subunit joins the A-C core, the scaffold sets the activity and substrate specificity of PP2A holoenzymes. molecular_function: id: GO:0019888 label: protein phosphatase regulator activity supported_by: - reference_id: file:human/PPP2R1A/PPP2R1A-uniprot.txt record_section: ["CC:FUNCTION"] supporting_text: The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit proposed_new_terms: [] suggested_questions: - question: > Which PP2A catalytic C subunits and regulatory B subunits does the wheat A subunit assemble with in vivo, and do the 5A/5B/5D homoeologs form distinct or redundant holoenzymes? - question: > Does the single grass A-subunit lineage cover the combined roles that are split among the three eudicot paralogs (RCN1/PP2AA1, PP2AA2, PP2AA3) in Arabidopsis, for example in auxin transport and root development? suggested_experiments: - description: > Express epitope-tagged F6LAX4 in wheat (or a heterologous plant system) and identify co-purifying PP2A catalytic C and regulatory B subunits by affinity purification mass spectrometry. hypothesis: > F6LAX4 is the structural scaffold of wheat PP2A holoenzymes, bridging the catalytic C subunit and diverse regulatory B subunits. experiment_type: interactome / protein-complex characterization - description: > Test whether F6LAX4 complements the Arabidopsis rcn1 mutant root and auxin-transport phenotypes. hypothesis: > The grass A subunit is functionally equivalent to the eudicot RCN1/PP2AA1 scaffold. experiment_type: cross-species genetic complementation