family_id: PANTHER:PTHR10648 family_name: SERINE/THREONINE-PROTEIN PHOSPHATASE PP2A 65 KDA REGULATORY SUBUNIT preferred_name: PP2A/PP4 regulatory scaffold proteins summary: HEAT-repeat regulatory scaffolds organize phosphatase complexes. PP2A A subunits assemble catalytic and regulatory partners; the retrieved family also includes PP4 regulatory proteins. Scaffold binding is distinct from catalytic dephosphorylation. functional_coherence: HETEROGENEOUS coherence_reason: PP2A holoenzyme assembly supports heteromeric protein association for the wheat target. Neuronal locations cannot be transferred into wheat, although they may describe animal family members. Centromeric and chromosome-segregation roles require the relevant complex and organism; antigen binding is not implied by a viral protein binding a phosphatase scaffold. subfamilies: - subfamily_id: PANTHER:PTHR10648:SF4 label: PROTEIN PHOSPHATASE 2 (FORMERLY 2A), REGULATORY SUBUNIT A, BETA ISOFORM-RELATED description: Recorded placement of F6LAX4. PP2A holoenzyme assembly supports heteromeric protein association for the wheat target. Neuronal locations cannot be transferred into wheat, although they may describe animal family members. Centromeric and chromosome-segregation roles require the relevant complex and organism; antigen binding is not implied by a viral protein binding a phosphatase scaffold. representative_members: - id: UniProtKB:F6LAX4 gene_symbol: F6LAX4 organism: Triticum aestivum gene_review: genes/WHEAT/F6LAX4/F6LAX4-ai-review.yaml term_assessments: - assessed_term: id: GO:0046982 label: protein heterodimerization activity scope: UNRESOLVED scope_reason: PP2A structures directly establish a scaffold-catalytic-subunit heterodimer, and both alpha and beta A-subunit branches have that association role. The wider family includes PP4 regulatory proteins and distinct assemblies. Protein association is supported beyond the wheat exemplar, but a complete set of branches satisfying the particular heterodimerization relation has not been delimited. supported_by: - reference_id: PMID:17174897 supporting_text: "The PP2A holoenzyme consists of a heterodimeric core \nenzyme" - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: DR InterPro; IPR051023; PP2A_Regulatory_Subunit_A. - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT DOMAIN 276..351 - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT /note="Phosphatase PP2A regulatory subunit A/Splicing - reference_id: file:genes/human/PPP2R1A/PPP2R1A-uniprot.txt supporting_text: 'CC -!- FUNCTION: The PR65 subunit of protein phosphatase 2A serves as a CC scaffolding molecule to coordinate the assembly of the catalytic CC subunit and a variable regulatory B subunit' - assessed_term: id: GO:0043025 label: neuronal cell body scope: UNRESOLVED scope_reason: Neuronal cell-body localization can apply to animal phosphatase scaffolds expressed in neurons, but wheat has no neuronal cell body. The conserved PP2A assembly interface does not establish this tissue-specific location. The animal branches with localization evidence need separate delimitation from the plant and fungal members. supported_by: - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: DR InterPro; IPR051023; PP2A_Regulatory_Subunit_A. - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT DOMAIN 276..351 - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT /note="Phosphatase PP2A regulatory subunit A/Splicing - assessed_term: id: GO:0007059 label: chromosome segregation scope: UNRESOLVED scope_reason: PP2A and PP4 complexes can regulate chromosome segregation through different substrates and targeting partners. The holoenzyme structures establish assembly, not chromosome-segregation involvement of every scaffold in every tissue. A partner- and branch-resolved physiological assignment is required. supported_by: - reference_id: PMID:17174897 supporting_text: "The PP2A holoenzyme consists of a heterodimeric core \nenzyme" - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: DR InterPro; IPR051023; PP2A_Regulatory_Subunit_A. - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT DOMAIN 276..351 - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT /note="Phosphatase PP2A regulatory subunit A/Splicing - assessed_term: id: GO:0043005 label: neuron projection scope: UNRESOLVED scope_reason: Neuron projections are animal cellular structures and cannot be transferred to the wheat member. A phosphatase scaffold may be recruited to them by neuronal partners, but that recruitment is separate from conserved holoenzyme assembly. No exhaustive set of projection-localized family branches is established. supported_by: - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: DR InterPro; IPR051023; PP2A_Regulatory_Subunit_A. - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT DOMAIN 276..351 - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT /note="Phosphatase PP2A regulatory subunit A/Splicing - assessed_term: id: GO:0000775 label: chromosome, centromeric region scope: UNRESOLVED scope_reason: Centromeric localization requires the appropriate chromosome-targeting complex; it is not entailed by being the PP2A A scaffold. The available structural evidence identifies subunit interfaces without establishing centromere residence for the wheat protein or all PP4-related members. Specific localization and partner evidence are needed. supported_by: - reference_id: PMID:17174897 supporting_text: "The PP2A holoenzyme consists of a heterodimeric core \nenzyme" - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: DR InterPro; IPR051023; PP2A_Regulatory_Subunit_A. - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT DOMAIN 276..351 - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT /note="Phosphatase PP2A regulatory subunit A/Splicing - assessed_term: id: GO:1990405 label: protein antigen binding scope: UNRESOLVED scope_reason: SV40 small t antigen directly binds PP2A A subunit, but that interaction does not by itself establish immune antigen-recognition activity. The substrate name antigen must not be used as the functional definition of protein antigen binding. No family-wide antigen-recognition mechanism is supported, while the ordinary viral-protein/scaffold interaction remains valid. supported_by: - reference_id: PMID:17608567 supporting_text: 'ST directly interacts with the PP2A scaffolding A subunit' - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: DR InterPro; IPR051023; PP2A_Regulatory_Subunit_A. - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT DOMAIN 276..351 - reference_id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt supporting_text: FT /note="Phosphatase PP2A regulatory subunit A/Splicing node_assessments: - node_id: PANTHER:PTN000068762 asserted_term: id: GO:0005829 label: cytosol evidence: IRD negated: true seeds: - id: PANTHER:PTN000068663 label: PTN000068663 (ancestral IBD node; IRD source) paint_snapshot: '20250902' node_taxon: id: NCBITaxon:3702 label: Arabidopsis thaliana assessment: LOSS_CONTRADICTED assessment_reason: >- PTN000068762 is a single leaf, Arabidopsis PP2AA3 (Q38951, AT1G13320, SF36). The IRD blocks the cytosol IBD on the eukaryotic PP2A scaffold-subunit node PTN000068663, and both rows carry the same date (2025-09-02). AT1G13320 is one of the three seeds of that cytosol IBD (with Drosophila Pp2A-29B and mouse Ppp2r1a), so the IRD negates the localization of the protein that seeded it, and nothing below re-annotates cytosol. The seed evidence is the PP2AA3 IDA from PMID:22404109 (abstract-only). The abstract states that all three Arabidopsis A subunits are in both the nucleus and the cytosol. That is the expected place for the scaffolding A subunit of a cytosolic and nuclear serine/threonine phosphatase holoenzyme. The paralogs PP2AA1 and PP2AA2 are outside this single-leaf clade, and no sequence or experimental reason is recorded that would set PP2AA3 apart. The IRD should be retracted. If the intent was to stop a nuclear-only call, that is not the term it blocks, since the nucleus IBD also covers PP2AA3. supported_by: - reference_id: PMID:22404109 supporting_text: we demonstrate that HDA14, ELP3 and the PP2A A-subunits A1, A2 and A3 all reside in both the nucleus and cytosol of the cell. references: - id: PMID:17174897 title: Structure of the protein phosphatase 2A holoenzyme. - id: PMID:17608567 title: Structural basis of PP2A inhibition by small t antigen. - id: PMID:22404109 title: "Arabidopsis thaliana histone deacetylase 14 (HDA14) is an \u03b1-tubulin deacetylase that associates with PP2A and enriches in the microtubule fraction with the putative histone acetyltransferase ELP3." - id: file:genes/WHEAT/F6LAX4/F6LAX4-uniprot.txt - id: file:interpro/panther/PTHR10648/PTHR10648-entries.csv - id: file:interpro/panther/PTHR10648/PTHR10648-paint.tsv - id: file:genes/human/PPP2R1A/PPP2R1A-uniprot.txt review_status: COMPLETE reviewed_by: codex review_date: '2026-10-06' notes: 'WHEAT/F6LAX4: requested accession F6LAX4; current record F6LAX4; sequence length 587; source cohort ARGO50. Family boundaries were assessed using the fetched member set and the cited domain, literature and analytical evidence. Gene-review verdicts and ARBA assertions are not independent validation. PANTHER subfamily labels and membership are recorded from the frozen UniProt records and panther.obo; they do not by themselves prove functional uniformity within a subfamily. PAINT rows were inspected as ancestral assertions, but node placement is not adjudicated without the relevant descendant tree/alignment. No residue requirement is encoded without a verified sequence-version anchor. A target-level refutation is not a family-wide NOT_APPLICABLE judgment. Exact protein-name-only predictions are treated as family-identification hypotheses rather than invented GO predictions.'