Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000159 protein phosphatase type 2A complex	IBA GO_REF:0000033	ACCEPT	Summary: PPP2R1A is the core scaffolding subunit of the PP2A complex. Multiple crystal structures demonstrate it as an integral component of the PP2A heterotrimer (PMID:17055435, PMID:17174897). This is the defining function of this protein. Reason: PPP2R1A is the major scaffolding A subunit of PP2A, forming the core dimer with the catalytic C subunit and recruiting regulatory B subunits. This annotation is directly supported by structural and biochemical evidence. Supporting Evidence: PMID:17055435 The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a 36 kDa catalytic subunit. PMID:17174897 The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit.
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: PPP2R1A localizes to the nucleus as part of multiple PP2A complexes, including the INTAC complex which functions on chromatin (PMID:33243860, PMID:34004147). UniProt annotation confirms nuclear localization with experimental evidence. Reason: Nuclear localization is well-supported by multiple experimental studies showing PPP2R1A in the nucleus as part of INTAC and other PP2A complexes. Supporting Evidence: PMID:33243860 we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC PMID:30611118 CRTC3 interacts with B55 PP2A holoenzymes via a conserved PP2A-binding region
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: PPP2R1A is a widely expressed scaffold protein present in the cytoplasm. UniProt annotation confirms cytoplasmic localization by similarity (UniProtKB:Q32PI5). Reason: Cytoplasmic localization is expected and well-supported for the major PP2A scaffold. PP2A holoenzymes are found in both cytoplasm and nucleus.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: PPP2R1A is present in the cytosol as part of PP2A holoenzymes. Consistent with the cytoplasm annotation and supported by multiple Reactome pathway entries. Reason: Cytosolic localization is well-established for PP2A holoenzymes containing PPP2R1A as scaffold subunit.
GO:0019888 protein phosphatase regulator activity	IBA GO_REF:0000033	ACCEPT	Summary: PPP2R1A serves as the scaffolding subunit that organizes the PP2A holoenzyme, thereby regulating phosphatase activity by determining which B subunit (and therefore which substrates) are engaged. This is its core molecular function. Reason: As the scaffold that assembles the PP2A holoenzyme, PPP2R1A directly regulates phosphatase activity by controlling holoenzyme composition and substrate access. This is an appropriate MF term for a non-catalytic regulatory subunit. Supporting Evidence: PMID:17174897 The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit.
GO:0051225 spindle assembly	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: PP2A is involved in mitotic processes including chromosome segregation and centromeric localization of Sgo1 (PMID:16580887). The role in spindle assembly is plausible through PP2A-mediated dephosphorylation of mitotic regulators, and is supported by Reactome annotations linking PP2A to centrosome maturation and mitotic spindle organization. Reason: While PP2A has roles in mitosis, spindle assembly is a downstream consequence of PP2A holoenzyme activity with specific B subunits, not a core function of PPP2R1A itself. The IBA annotation is reasonable given conservation but represents a non-core biological process for this scaffold subunit.
GO:0051754 meiotic sister chromatid cohesion, centromeric	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: PP2A-B56 complexes play a conserved role in protecting centromeric cohesion during meiosis. PMID:16580887 demonstrates PP2A's role at centromeres for chromosome segregation, though this study focused on mitosis. The meiotic role is inferred phylogenetically from yeast/fly data. Reason: Meiotic centromeric cohesion is a conserved function of PP2A across eukaryotes, and the IBA inference is phylogenetically sound. However, this is a specialized meiosis-specific process rather than a core function of the PPP2R1A scaffold. Supporting Evidence: PMID:16580887 PP2A localizes to centromeres in a Bub1-dependent manner. The Sgo1-PP2A interaction is required for centromeric localization of Sgo1 and proper chromosome segregation in human cells.
GO:0000775 chromosome, centromeric region	IEA GO_REF:0000044	ACCEPT	Summary: IEA mapping from UniProt subcellular location. Supported by experimental data showing PP2A localizes to centromeres during mitosis (PMID:16580887). Reason: Centromeric localization is experimentally confirmed by Tang et al. 2006 showing PP2A localization to centromeres in a Bub1-dependent manner. Supporting Evidence: PMID:16580887 PP2A localizes to centromeres in a Bub1-dependent manner.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: IEA mapping from UniProt subcellular location. Nuclear localization is experimentally confirmed by multiple studies (PMID:33243860, PMID:30611118). Reason: Consistent with IBA annotation and experimental evidence for nuclear PP2A functions including INTAC complex.
GO:0005694 chromosome	IEA GO_REF:0000044	ACCEPT	Summary: IEA mapping from UniProt. PPP2R1A localizes to chromosomes/chromatin as part of the INTAC complex (PMID:33243860, PMID:34004147) and to centromeres during mitosis (PMID:16580887). Reason: Chromosome localization is supported by experimental data for both INTAC and centromeric PP2A functions.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: IEA mapping from UniProt subcellular location. Consistent with IBA annotation. Reason: Cytoplasmic localization is well-established for PP2A holoenzymes.
GO:0016328 lateral plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: IEA mapping from UniProt. Based on experimental data from PMID:15525651 showing colocalization with Galpha12 at the lateral cell membrane in Caco-2 cells. Reason: Supported by the experimental IDA annotation from PMID:15525651 showing lateral plasma membrane localization. Supporting Evidence: PMID:15525651 Endogenous Aalpha and Galpha(12) colocalized by immunofluorescent microscopy in Caco-2 cells and in neurons.
GO:0030425 dendrite	IEA GO_REF:0000044	ACCEPT	Summary: IEA mapping from UniProt. Based on experimental data from PMID:15525651 showing PPP2R1A in dendrites of neurons. Reason: Supported by the experimental IDA annotation from PMID:15525651. Supporting Evidence: PMID:15525651 Endogenous Aalpha and Galpha(12) colocalized by immunofluorescent microscopy in Caco-2 cells and in neurons.
GO:0005515 protein binding	IPI PMID:11504734 Interaction between protein phosphatase 5 and the A subunit ...	MARK AS OVER ANNOTATED	Summary: Interaction between PPP2R1A and protein phosphatase 5 (PP5/PPP5C). This study shows PP5 forms a heterotrimeric complex with PP2A A and C subunits. The interaction is specific and functionally relevant to phosphatase regulation. Reason: Protein binding is too vague for the scaffolding role of PPP2R1A. The actual function is better captured by the protein phosphatase regulator activity annotation.
GO:0005515 protein binding	IPI PMID:11591705 Protein phosphatase 2A interacts with and directly dephospho...	MARK AS OVER ANNOTATED	Summary: Interaction with RelA/NF-kB. PP2A directly dephosphorylates RelA. PPP2R1A serves as scaffold for this interaction. Reason: Protein binding is too vague. The scaffolding function is already captured by protein phosphatase regulator activity.
GO:0005515 protein binding	IPI PMID:15761952 Single-step Strep-tag purification for the isolation and ide...	MARK AS OVER ANNOTATED	Summary: Identified in a Strep-tag purification approach for protein complex isolation. High-throughput interaction data. Reason: Protein binding is uninformative. This HT study simply confirms PPP2R1A is in complexes, already captured by PP2A complex annotation.
GO:0005515 protein binding	IPI PMID:16044149 Activation of the protein kinase B pathway by the HPV-16 E7 ...	MARK AS OVER ANNOTATED	Summary: Interaction between HPV-16 E7 oncoprotein and PP2A involving the A subunit. Relevant to viral hijacking of PP2A. Reason: Protein binding is too vague. The interaction with viral oncoproteins is a known feature of PP2A but not a core function of PPP2R1A.
GO:0005515 protein binding	IPI PMID:16764867 Interaction of nucleoredoxin with protein phosphatase 2A.	MARK AS OVER ANNOTATED	Summary: Interaction with nucleoredoxin (NXN), which associates with PP2A. Reason: Protein binding is uninformative for PPP2R1A. The scaffolding function is already captured.
GO:0005515 protein binding	IPI PMID:17055435 Structure of protein phosphatase 2A core enzyme bound to tum...	MARK AS OVER ANNOTATED	Summary: Crystal structure of PP2A core enzyme showing direct interaction between A and C subunits. Key structural study. Reason: While the A-C interaction is fundamental, protein binding is too vague. This is already captured by the PP2A complex annotation.
GO:0005515 protein binding	IPI PMID:17245430 A specific PP2A regulatory subunit, B56gamma, mediates DNA d...	MARK AS OVER ANNOTATED	Summary: PP2A-B56gamma mediates p53 dephosphorylation at Thr55. PPP2R1A serves as scaffold for the B56gamma-containing holoenzyme. Reason: Protein binding is uninformative. The scaffolding role is already captured.
GO:0005515 protein binding	IPI PMID:17274953 Methylation of the C-terminal leucine residue of the PP2A ca...	MARK AS OVER ANNOTATED	Summary: Study on methylation of PP2A C subunit and binding of B subunit PR55/B. PPP2R1A as scaffold. Reason: Protein binding is too vague for the scaffolding interaction with B subunits.
GO:0005515 protein binding	IPI PMID:17374643 Mechanisms of the HRSL3 tumor suppressor function in ovarian...	MARK AS OVER ANNOTATED	Summary: Interaction with PLA2G16/HRSL3 tumor suppressor, which may decrease PP2A activity. Reason: Protein binding is uninformative. One of many proteins interacting with PPP2R1A as PP2A scaffold.
GO:0005515 protein binding	IPI PMID:17529992 Structural and biochemical insights into the regulation of p...	MARK AS OVER ANNOTATED	Summary: Structural/biochemical study of SV40 small t antigen interaction with PP2A. Small t binds the A subunit to displace B subunits. Reason: Protein binding is too vague. Viral oncoprotein interaction is well-known but not a core function.
GO:0005515 protein binding	IPI PMID:17540176 The tumor suppressor PP2A Abeta regulates the RalA GTPase.	MARK AS OVER ANNOTATED	Summary: PP2A Abeta regulates RalA GTPase. This study focuses on PPP2R1B not PPP2R1A. Reason: Protein binding is uninformative. The interaction is likely through the PP2A complex scaffold function.
GO:0005515 protein binding	IPI PMID:17632056 CIP2A inhibits PP2A in human malignancies.	MARK AS OVER ANNOTATED	Summary: CIP2A inhibits PP2A. PPP2R1A interacts with CIP2A as part of PP2A complex. Reason: Protein binding is too vague. CIP2A interaction reflects PP2A regulation, not a specific PPP2R1A function.
GO:0005515 protein binding	IPI PMID:18394995 Structural mechanism of demethylation and inactivation of pr...	MARK AS OVER ANNOTATED	Summary: Structural mechanism of PP2A demethylation and inactivation by PME-1. PPP2R1A as part of the complex. Reason: Protein binding is uninformative. PME-1 interaction is with the PP2A complex.
GO:0005515 protein binding	IPI PMID:18715871 PP4R4/KIAA1622 forms a novel stable cytosolic complex with p...	MARK AS OVER ANNOTATED	Summary: PP4R4/KIAA1622 forms a complex with PP4. PPP2R1A interaction may reflect shared subunit usage. Reason: Protein binding is uninformative and may reflect promiscuous HT interaction data.
GO:0005515 protein binding	IPI PMID:18782753 A PP2A phosphatase high density interaction network identifi...	MARK AS OVER ANNOTATED	Summary: PP2A phosphatase high density interaction network identifying STRIPAK complex. PPP2R1A is a core STRIPAK component. Reason: Protein binding is too vague. The STRIPAK complex membership is captured by the FAR/SIN/STRIPAK complex annotation.
GO:0005515 protein binding	IPI PMID:19156129 An integrated workflow for charting the human interaction pr...	MARK AS OVER ANNOTATED	Summary: Integrated workflow charting the PP2A interaction proteome. Large-scale interaction mapping. Reason: Protein binding from large-scale proteomics is uninformative for this well-characterized scaffold.
GO:0005515 protein binding	IPI PMID:19293187 PME-1 protects extracellular signal-regulated kinase pathway...	MARK AS OVER ANNOTATED	Summary: PME-1 protects ERK pathway from PP2A inactivation in glioma. PPP2R1A interacts as PP2A scaffold. Reason: Protein binding is too vague. The PP2A scaffolding function is already captured.
GO:0005515 protein binding	IPI PMID:19915589 The chromosomal association of condensin II is regulated by ...	MARK AS OVER ANNOTATED	Summary: Noncatalytic function of PP2A in chromosomal association of condensin II. PPP2R1A as PP2A scaffold. Reason: Protein binding is uninformative. This reflects a downstream PP2A function.
GO:0005515 protein binding	IPI PMID:20711181 Live-cell imaging RNAi screen identifies PP2A-B55alpha and i...	MARK AS OVER ANNOTATED	Summary: RNAi screen identifying PP2A-B55alpha as key mitotic exit regulator. PPP2R1A as scaffold. Reason: Protein binding is too vague. Mitotic functions are downstream of PP2A holoenzyme activity.
GO:0005515 protein binding	IPI PMID:21075311 B55β-associated PP2A complex controls PDK1-directed myc sign...	MARK AS OVER ANNOTATED	Summary: B55beta-associated PP2A controls PDK1-directed Myc signaling. PPP2R1A as scaffold. Reason: Protein binding is uninformative for the scaffold subunit.
GO:0005515 protein binding	IPI PMID:21460856 ATM-mediated phosphorylation activates the tumor-suppressive...	MARK AS OVER ANNOTATED	Summary: ATM-mediated phosphorylation activates B56gamma-PP2A tumor suppressor. PPP2R1A as scaffold. Reason: Protein binding is too vague. The scaffolding role is already captured.
GO:0005515 protein binding	IPI PMID:22167190 Identification and characterization of an alternatively spli...	MARK AS OVER ANNOTATED	Summary: Identification of alternatively spliced PPP2CA isoform. Interaction with PPP2R1A as expected. Reason: Protein binding is uninformative. A-C interaction is already captured by PP2A complex annotation.
GO:0005515 protein binding	IPI PMID:23555304 Dynamic circadian protein-protein interaction networks predi...	MARK AS OVER ANNOTATED	Summary: Circadian protein-protein interaction networks. HT interaction study. Reason: Protein binding from HT circadian interaction study is uninformative.
GO:0005515 protein binding	IPI PMID:25150978 An extracellular-matrix-specific GEF-GAP interaction regulat...	MARK AS OVER ANNOTATED	Summary: ECM-specific GEF-GAP interaction regulates Rho GTPase crosstalk. Indirect PP2A involvement. Reason: Protein binding is uninformative. Likely reflects indirect PP2A complex interaction.
GO:0005515 protein binding	IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ...	MARK AS OVER ANNOTATED	Summary: In situ proximity ligation assay profiling endogenous PPIs in pathway networks. Reason: Protein binding from PLA assay is uninformative for the scaffold subunit.
GO:0005515 protein binding	IPI PMID:25438055 AMBRA1 links autophagy to cell proliferation and tumorigenes...	MARK AS OVER ANNOTATED	Summary: AMBRA1 links autophagy to c-Myc dephosphorylation via PP2A. PPP2R1A as scaffold. Reason: Protein binding is too vague. The PP2A scaffolding function is already captured.
GO:0005515 protein binding	IPI PMID:26496610 A human interactome in three quantitative dimensions organiz...	MARK AS OVER ANNOTATED	Summary: Human interactome in three quantitative dimensions. Large-scale interaction study. Reason: Protein binding from large-scale interactome study is uninformative.
GO:0005515 protein binding	IPI PMID:26829474 Acetylation of Aurora B by TIP60 ensures accurate chromosoma...	MARK AS OVER ANNOTATED	Summary: Acetylation of Aurora B by TIP60 for chromosome segregation. PP2A interaction. Reason: Protein binding is uninformative. Reflects downstream PP2A mitotic function.
GO:0005515 protein binding	IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis...	MARK AS OVER ANNOTATED	Summary: Organelle-specific protein landscape. Large-scale localization/interaction study. Reason: Protein binding from large-scale study is uninformative.
GO:0005515 protein binding	IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas...	MARK AS OVER ANNOTATED	Summary: Phenotypic and interaction profiling of human phosphatases. Large-scale study. Reason: Protein binding from large-scale phosphatase profiling is uninformative.
GO:0005515 protein binding	IPI PMID:28330616 Systematic Analysis of Human Protein Phosphatase Interaction...	MARK AS OVER ANNOTATED	Summary: Systematic analysis of human protein phosphatase interactions and dynamics. Reason: Protein binding from systematic phosphatase interaction study is uninformative.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Extensive disruption of protein interactions by genetic variants. Population genetics study. Reason: Protein binding from variant interaction disruption study is uninformative.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Reference map of human binary protein interactome. Large-scale Y2H study. Reason: Protein binding from large-scale binary interactome is uninformative.
GO:0005515 protein binding	IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro...	MARK AS OVER ANNOTATED	Summary: Kinase interaction network. Large-scale study. Reason: Protein binding from kinase interaction network study is uninformative.
GO:0005515 protein binding	IPI PMID:33633399 Cryo-EM structure of the Hippo signaling integrator human ST...	MARK AS OVER ANNOTATED	Summary: Cryo-EM structure of STRIPAK complex containing PPP2R1A. Key structural study. Reason: Protein binding is too vague. The STRIPAK complex membership is captured by FAR/SIN/STRIPAK complex annotation.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Dual proteome-scale networks. Large-scale interactome study. Reason: Protein binding from large-scale interactome is uninformative.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	MARK AS OVER ANNOTATED	Summary: OpenCell endogenous tagging cartography. Large-scale localization study. Reason: Protein binding from large-scale tagging study is uninformative.
GO:0005515 protein binding	IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei...	MARK AS OVER ANNOTATED	Summary: Systematic discovery of mutation-directed neo-protein-protein interactions in cancer. Reason: Protein binding from cancer neo-PPI study is uninformative for core function.
GO:0005515 protein binding	IPI PMID:37761890 Novel Variants of PPP2R1A in Catalytic Subunit Binding Domai...	MARK AS OVER ANNOTATED	Summary: Novel PPP2R1A variants in catalytic subunit binding domain. Disease variants affecting A-C interaction. Reason: Protein binding is too vague. The A-C interaction is captured by PP2A complex annotation.
GO:0005515 protein binding	IPI PMID:38123684 Cryo-EM structures of PP2A:B55-FAM122A and PP2A:B55-ARPP19.	MARK AS OVER ANNOTATED	Summary: Cryo-EM structures of PP2A:B55 complexes with FAM122A and ARPP19. Key structural study showing PPP2R1A in PP2A holoenzyme. Reason: Protein binding is too vague. The scaffolding function is captured by PP2A complex and protein phosphatase regulator activity annotations.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Multimodal cell maps. Large-scale study. Reason: Protein binding from large-scale cell mapping is uninformative.
GO:0005515 protein binding	IPI PMID:8617797 Identification of a novel protein phosphatase 2A regulatory ...	MARK AS OVER ANNOTATED	Summary: Identification of novel PP2A regulatory subunit highly expressed in muscle. PPP2R1A interaction with B subunits. Reason: Protein binding is too vague. A-B subunit interaction is captured by PP2A complex annotation.
GO:0005515 protein binding	IPI PMID:9857076 Identification of structural elements involved in the intera...	MARK AS OVER ANNOTATED	Summary: Structural elements in SV40 small t antigen involved in PP2A interaction. Viral oncoprotein binding to A subunit. Reason: Protein binding is too vague. Viral interaction reflects exploitation of the scaffold function.
GO:0004721 phosphoprotein phosphatase activity	IDA PMID:30595372 De Novo Mutations Affecting the Catalytic Cα Subunit of PP2A...	ACCEPT	Summary: PPP2R1A contributes to phosphoprotein phosphatase activity as the scaffold subunit of the PP2A holoenzyme. The contributes_to qualifier is appropriate since PPP2R1A is not itself catalytic but enables the catalytic C subunit to function within the holoenzyme context. PMID:30595372 studies PP2A mutations in neurodevelopmental disorders. Reason: The contributes_to qualifier correctly captures that PPP2R1A is essential for PP2A holoenzyme assembly and function but is not itself the catalytic subunit. Supporting Evidence: PMID:30595372 De Novo Mutations Affecting the Catalytic Calpha Subunit of PP2A, PPP2CA, Cause Syndromic Intellectual Disability Resembling Other PP2A-Related Neurodevelopmental Disorders.
GO:0008287 protein serine/threonine phosphatase complex	IDA PMID:28167675 ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphat...	ACCEPT	Summary: PPP2R1A is a core component of the PP2A Ser/Thr phosphatase complex. PMID:28167675 shows ARPP-16 interacts with the A subunit of PP2A, confirming PPP2R1A in this complex in brain tissue. Reason: This is a parent term of GO:0000159 (protein phosphatase type 2A complex) and is appropriately applied. PPP2R1A is definitionally a component of a protein serine/threonine phosphatase complex. Supporting Evidence: PMID:28167675 ARPP-16 interacts directly with the scaffolding A subunit of the serine/threonine protein phosphatase, PP2A
GO:0005634 nucleus	NAS PMID:32647223 INTS10-INTS13-INTS14 form a functional module of Integrator ...	ACCEPT	Summary: Nuclear localization supported by PPP2R1A being part of the INTAC complex (Integrator-PP2A) which functions in the nucleus on chromatin. PMID:32647223 describes Integrator module function. Reason: Consistent with other nuclear localization annotations and INTAC complex role.
GO:0016180 snRNA processing	NAS PMID:16239144 Integrator, a multiprotein mediator of small nuclear RNA pro...	KEEP AS NON CORE	Summary: The Integrator complex mediates snRNA 3-prime end processing (PMID:16239144). PPP2R1A is part of the INTAC complex (Integrator-PP2A). However, snRNA processing is an Integrator function, and PP2A association may be primarily for transcription regulation rather than snRNA processing per se. Reason: While PPP2R1A is part of INTAC, snRNA processing is primarily an Integrator endonuclease function. The PP2A component (PPP2R1A + PPP2CA) provides phosphatase activity for CTD dephosphorylation, which is distinct from snRNA cleavage. This is a non-core function of PPP2R1A. Supporting Evidence: PMID:16239144 We show that Integrator is recruited to the U1 and U2 snRNA genes and mediates the snRNAs' 3' end processing.
GO:0034243 regulation of transcription elongation by RNA polymerase II	IDA PMID:38570683 Structural basis of Integrator-dependent RNA polymerase II t...	ACCEPT	Summary: As part of the INTAC complex, PPP2R1A scaffolds PPP2CA which dephosphorylates the Pol II CTD and DSIF/SPT5, thereby preventing transcriptional elongation (PMID:38570683, PMID:34004147). This is a well-characterized INTAC function. Reason: PPP2R1A is essential for INTAC complex assembly and the PP2A-mediated dephosphorylation of Pol II CTD that regulates transcription elongation. This is a core function of PPP2R1A-containing INTAC. Supporting Evidence: PMID:38570683 The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer.
GO:0035330 regulation of hippo signaling	NAS PMID:33633399 Cryo-EM structure of the Hippo signaling integrator human ST...	ACCEPT	Summary: PPP2R1A is part of the STRIPAK complex which negatively regulates Hippo signaling by dephosphorylating MST1/2 kinases (PMID:33633399). Reason: Regulation of Hippo signaling through the STRIPAK complex is a well-established function. The STRIPAK structure shows PPP2R1A as a core component. Supporting Evidence: PMID:33633399 The striatin-interacting phosphatase and kinase (STRIPAK) complex is a large, multisubunit protein phosphatase 2A (PP2A) assembly that integrates diverse cellular signals in the Hippo pathway to regulate cell proliferation and survival.
GO:0160240 RNA polymerase II transcription initiation surveillance	IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po...	ACCEPT	Summary: INTAC complex (containing PPP2R1A) functions as a quality checkpoint during transcription, driving premature termination of unfavorable transcripts by dephosphorylating Pol II CTD (PMID:33243860). Reason: Core function of PPP2R1A as part of the INTAC complex. Well-supported by structural and functional data. Supporting Evidence: PMID:33243860 The INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription.
GO:0160240 RNA polymerase II transcription initiation surveillance	IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c...	ACCEPT	Summary: The PP2A-Integrator-CDK9 axis fine-tunes transcription. PPP2R1A as part of INTAC dephosphorylates Pol II CTD to regulate transcription elongation decisions (PMID:34004147). Reason: Consistent with PMID:33243860. PPP2R1A is essential for INTAC function. Supporting Evidence: PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer.
GO:0160240 RNA polymerase II transcription initiation surveillance	IDA PMID:38570683 Structural basis of Integrator-dependent RNA polymerase II t...	ACCEPT	Summary: Structural basis of Integrator-dependent Pol II termination. PPP2R1A is part of the INTAC complex shown in multiple functional states (PMID:38570683). Reason: Further structural confirmation of PPP2R1A role in INTAC-mediated transcription initiation surveillance. Supporting Evidence: PMID:38570683 we present three cryo-electron microscopy structures of the complete Integrator-PP2A complex in different functional states.
GO:0160232 INTAC complex	IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po...	ACCEPT	Summary: PPP2R1A is a core component of the INTAC complex, the Integrator-PP2A assembly identified in this landmark study (PMID:33243860). Reason: PPP2R1A is definitionally part of INTAC as it provides the PP2A scaffold. Supporting Evidence: PMID:33243860 we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC.
GO:0160232 INTAC complex	IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c...	ACCEPT	Summary: Confirms PPP2R1A as component of INTAC in context of the PP2A-Integrator-CDK9 transcription axis (PMID:34004147). Reason: Consistent with PMID:33243860. PPP2R1A is a core INTAC component.
GO:0160232 INTAC complex	IDA PMID:34762484 Structural basis of Integrator-mediated transcription regula...	ACCEPT	Summary: Structural basis of Integrator-mediated transcription regulation confirms PPP2R1A in the INTAC pretermination complex bound to paused Pol II (PMID:34762484). Reason: High-resolution structural evidence for PPP2R1A in INTAC. Supporting Evidence: PMID:34762484 Integrator and protein phosphatase 2A (PP2A) form a complex that dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent RNA, and terminates transcription.
GO:0160232 INTAC complex	IDA PMID:36869814 Structural basis of INTAC-regulated transcription.	ACCEPT	Summary: Structural basis of INTAC-regulated transcription. PPP2R1A confirmed as component of INTAC (PMID:36869814). Reason: Additional structural study confirming PPP2R1A in INTAC complex.
GO:0160232 INTAC complex	IDA PMID:38570683 Structural basis of Integrator-dependent RNA polymerase II t...	ACCEPT	Summary: Complete Integrator-PP2A structures in multiple functional states confirm PPP2R1A as core INTAC component (PMID:38570683). Reason: Latest structural evidence for PPP2R1A in INTAC. Supporting Evidence: PMID:38570683 we present three cryo-electron microscopy structures of the complete Integrator-PP2A complex in different functional states.
GO:0000785 chromatin	IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po...	ACCEPT	Summary: PPP2R1A localizes to chromatin as part of the INTAC complex, which is recruited to chromatin at transcription pause sites (PMID:33243860). Reason: Chromatin localization is well-supported by INTAC structural and functional studies showing the complex acts on chromatin-associated Pol II.
GO:0000785 chromatin	IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c...	ACCEPT	Summary: PPP2R1A on chromatin as part of INTAC for transcription regulation (PMID:34004147). Reason: Consistent with PMID:33243860. Chromatin association via INTAC complex.
GO:0005634 nucleus	IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po...	ACCEPT	Summary: Nuclear localization as part of INTAC complex (PMID:33243860). Reason: Consistent with other nuclear localization annotations. INTAC functions in nucleus.
GO:0005634 nucleus	IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c...	ACCEPT	Summary: Nuclear localization confirmed by PP2A-Integrator-CDK9 study (PMID:34004147). Reason: Consistent with INTAC function in nucleus.
GO:0019888 protein phosphatase regulator activity	IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po...	ACCEPT	Summary: PPP2R1A scaffolds PPP2CA within the INTAC complex, enabling its phosphatase activity on Pol II CTD (PMID:33243860). This is the core molecular function. Reason: Direct experimental evidence that PPP2R1A regulates PP2A phosphatase activity within the INTAC complex.
GO:0019888 protein phosphatase regulator activity	IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c...	ACCEPT	Summary: PPP2R1A scaffolds PP2A phosphatase activity in the Integrator-CDK9 axis (PMID:34004147). Reason: Consistent with core scaffold function enabling PP2A phosphatase regulation.
GO:0035331 negative regulation of hippo signaling	IDA PMID:33633399 Cryo-EM structure of the Hippo signaling integrator human ST...	ACCEPT	Summary: STRIPAK complex containing PPP2R1A dephosphorylates MST1/2 to negatively regulate Hippo signaling (PMID:33633399). The cryo-EM structure shows PPP2R1A as integral to STRIPAK assembly. Reason: Well-supported by structural and functional data. PPP2R1A as STRIPAK scaffold enables PP2A-mediated negative regulation of Hippo pathway. Supporting Evidence: PMID:33633399 STRIPAK is a key negative regulator of the Hippo pathway that controls tissue homeostasis and suppresses tumorigenesis
GO:0090443 FAR/SIN/STRIPAK complex	IDA PMID:18782753 A PP2A phosphatase high density interaction network identifi...	ACCEPT	Summary: PPP2R1A is a core component of the STRIPAK complex, first identified in this landmark proteomics study (PMID:18782753). Reason: PPP2R1A is the PP2A scaffold subunit (PP2A A) of the STRIPAK complex. The original discovery paper confirms its membership. Supporting Evidence: PMID:18782753 Here we define a novel large multiprotein assembly, referred to as the striatin-interacting phosphatase and kinase (STRIPAK) complex. STRIPAK contains the PP2A catalytic (PP2Ac) and scaffolding (PP2A A) subunits
GO:0090443 FAR/SIN/STRIPAK complex	IDA PMID:33633399 Cryo-EM structure of the Hippo signaling integrator human ST...	ACCEPT	Summary: Cryo-EM structure of STRIPAK confirms PPP2R1A as core component (PMID:33633399). Reason: High-resolution structural confirmation of PPP2R1A in STRIPAK. Supporting Evidence: PMID:33633399 The PP2AA-C heterodimer interacts with one end of the STRN3 CC tetramer through the first HEAT-repeat of PP2AA.
GO:0035556 intracellular signal transduction	NAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero...	KEEP AS NON CORE	Summary: PP2A is a major regulator of numerous signaling pathways (PMID:11007961). PPP2R1A as scaffold enables diverse PP2A holoenzymes to regulate multiple signaling cascades. Reason: Intracellular signal transduction is too broad and vague. While PP2A regulates many signaling pathways, this term does not capture the specific scaffolding role of PPP2R1A. More specific pathway annotations are preferred.
GO:0043029 T cell homeostasis	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Transferred from ortholog data. UniProt notes that PP2A-mediated AKT1 dephosphorylation is essential for regulatory T-cell homeostasis (by similarity). This is a downstream consequence of PP2A activity. Reason: T cell homeostasis is a downstream pleiotropic consequence of PP2A activity in specific immune cell contexts, not a core function of the PPP2R1A scaffold.
GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: PP2A dephosphorylates AKT1, negatively regulating PI3K/AKT signaling. Transferred from ortholog data. PPP2R1A cancer mutations can lead to constitutive AKT phosphorylation. Reason: While PP2A-mediated AKT dephosphorylation is well-established, this is a downstream consequence of specific PP2A holoenzyme activity, not a core function of the PPP2R1A scaffold subunit itself.
GO:0005515 protein binding	IPI PMID:15525651 Galpha12 directly interacts with PP2A: evidence FOR Galpha12...	MARK AS OVER ANNOTATED	Summary: Galpha12 directly interacts with PPP2R1A. The interaction promotes PP2A activation and dephosphorylation of tau. Reason: Protein binding is too vague. The functional consequence (PP2A activation) is the informative part.
GO:0016328 lateral plasma membrane	IDA PMID:15525651 Galpha12 directly interacts with PP2A: evidence FOR Galpha12...	ACCEPT	Summary: PPP2R1A colocalizes with Galpha12 at the lateral cell membrane in Caco-2 cells and neurons (PMID:15525651). Reason: Experimental evidence from immunofluorescence showing lateral membrane localization, consistent with PP2A function in cell polarity contexts. Supporting Evidence: PMID:15525651 Endogenous Aalpha and Galpha(12) colocalized by immunofluorescent microscopy in Caco-2 cells and in neurons.
GO:0043005 neuron projection	IDA PMID:15525651 Galpha12 directly interacts with PP2A: evidence FOR Galpha12...	ACCEPT	Summary: PPP2R1A detected in neuron projections by immunofluorescence in primary neurons (PMID:15525651). Reason: Direct experimental evidence for neuronal projection localization. Supporting Evidence: PMID:15525651 Endogenous Aalpha and Galpha(12) colocalized by immunofluorescent microscopy in Caco-2 cells and in neurons.
GO:0043025 neuronal cell body	IDA PMID:15525651 Galpha12 directly interacts with PP2A: evidence FOR Galpha12...	ACCEPT	Summary: PPP2R1A detected in neuronal cell body by immunofluorescence (PMID:15525651). Reason: Direct experimental evidence for neuronal cell body localization. Supporting Evidence: PMID:15525651 Endogenous Aalpha and Galpha(12) colocalized by immunofluorescent microscopy in Caco-2 cells and in neurons.
GO:0005515 protein binding	IPI PMID:17974561 Tesk1 interacts with Spry2 to abrogate its inhibition of ERK...	MARK AS OVER ANNOTATED	Summary: Tesk1 interacts with Spry2 to abrogate ERK phosphorylation inhibition. PPP2R1A interaction with SPRY2. Reason: Protein binding is too vague. PP2A dephosphorylation of SPRY2 is the functional consequence.
GO:0005515 protein binding	IPI PMID:30611118 Mitogenic Signals Stimulate the CREB Coactivator CRTC3 throu...	MARK AS OVER ANNOTATED	Summary: CRTC3 interacts with PP2A for dephosphorylation and nuclear translocation. PPP2R1A is part of the B55 PP2A holoenzyme. Reason: Protein binding is too vague. The PP2A scaffolding function is already captured.
GO:0005634 nucleus	IDA PMID:30611118 Mitogenic Signals Stimulate the CREB Coactivator CRTC3 throu...	ACCEPT	Summary: PPP2R1A is part of PP2A holoenzymes that dephosphorylate CRTC3, promoting nuclear translocation (PMID:30611118). Reason: Nuclear localization experimentally confirmed in the context of CRTC3 regulation.
GO:0005515 protein binding	IPI PMID:27588481 FAM122A, a new endogenous inhibitor of protein phosphatase 2...	MARK AS OVER ANNOTATED	Summary: FAM122A directly interacts with PPP2R1A and B55alpha, inhibiting PP2A phosphatase activity. Reason: Protein binding is too vague. The interaction with a PP2A inhibitor reflects the scaffold role already captured.
GO:0005515 protein binding	IPI PMID:28174209 Oncoprotein CIP2A is stabilized via interaction with tumor s...	MARK AS OVER ANNOTATED	Summary: CIP2A is stabilized via interaction with PP2A/B56. PPP2R1A as scaffold subunit. Reason: Protein binding is too vague. The PP2A scaffolding function is already captured.
GO:1990405 protein antigen binding	IPI PMID:9847399 Binding specificity of protein phosphatase 2A core enzyme fo...	ACCEPT	Summary: PPP2R1A binds viral T antigens (SV40 small t, polyoma middle T) which displace regulatory B subunits. PMID:9847399 maps specific binding determinants on the A subunit. Reason: T antigen binding is a well-characterized property of PPP2R1A. This is more informative than generic protein binding as it describes a specific molecular interaction relevant to viral oncogenesis. Supporting Evidence: PMID:9847399 some amino acids are involved in the binding of all types of B subunits, whereas others are specifically involved in the binding of one or two types of B subunits. T-antigen-binding specificity does not correlate with that of a particular type of B subunit.
GO:0070062 extracellular exosome	HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres...	MARK AS OVER ANNOTATED	Summary: PPP2R1A detected in exosomes from prostatic secretions by proteomics (PMID:23533145). This is likely nonspecific detection of an abundant cytoplasmic protein in exosomes. Reason: Exosomal localization from HDA proteomics likely reflects nonspecific inclusion of an abundant cytoplasmic protein. This does not represent a core function or primary localization of PPP2R1A.
GO:0005829 cytosol	TAS Reactome:R-HSA-1295599	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-1295609	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-1295613	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-1295622	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-1295632	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-1549564	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-2574840	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-2574845	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-2995388	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-3000310	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-3000319	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-380272	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-380283	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-380294	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-380303	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-380311	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-380316	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-380455	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-380508	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-5617816	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-5626220	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-5626223	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-5626227	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-5626228	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-5626681	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-5626699	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-5638009	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-8853405	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-8853419	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-927813	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-927830	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-927836	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-934559	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0005829 cytosol	TAS Reactome:R-HSA-9667965	ACCEPT	Summary: Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic as a core component of PP2A holoenzymes involved in various Reactome pathways. Reason: Cytosolic localization is well-established for PP2A holoenzymes. Redundant with IBA cytosol annotation but each represents a different Reactome pathway context.
GO:0000159 protein phosphatase type 2A complex	IDA PMID:17055435 Structure of protein phosphatase 2A core enzyme bound to tum...	ACCEPT	Summary: Crystal structure of PP2A core enzyme directly demonstrates PPP2R1A as scaffold subunit of the PP2A complex (PMID:17055435). Reason: High-resolution structural evidence. PPP2R1A is definitionally part of PP2A. Supporting Evidence: PMID:17055435 The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a 36 kDa catalytic subunit.
GO:0000159 protein phosphatase type 2A complex	IDA PMID:17174897 Structure of the protein phosphatase 2A holoenzyme.	ACCEPT	Summary: Crystal structure of PP2A holoenzyme with B56 confirms PPP2R1A as scaffold subunit (PMID:17174897). Reason: Definitive structural evidence for PPP2R1A in PP2A holoenzyme. Supporting Evidence: PMID:17174897 The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit.
GO:0000775 chromosome, centromeric region	IDA PMID:16580887 PP2A is required for centromeric localization of Sgo1 and pr...	ACCEPT	Summary: PP2A localizes to centromeres in a Bub1-dependent manner for Sgo1 localization and chromosome segregation (PMID:16580887). Reason: Direct experimental evidence for centromeric localization of PP2A containing PPP2R1A. Supporting Evidence: PMID:16580887 PP2A localizes to centromeres in a Bub1-dependent manner.
GO:0005515 protein binding	IPI PMID:16580887 PP2A is required for centromeric localization of Sgo1 and pr...	MARK AS OVER ANNOTATED	Summary: PP2A interaction with Sgo1 at centromeres. PPP2R1A depletion causes chromosome missegregation. Reason: Protein binding is too vague. The centromeric function is better captured by chromosome segregation and centromeric region annotations.
GO:0007059 chromosome segregation	IDA PMID:16580887 PP2A is required for centromeric localization of Sgo1 and pr...	KEEP AS NON CORE	Summary: PPP2R1A depletion causes chromosome missegregation. PP2A is required for centromeric Sgo1 localization and proper chromosome segregation (PMID:16580887). Reason: While experimentally validated, chromosome segregation is a downstream consequence of PP2A centromeric activity with specific B subunits. It is not the core scaffolding function of PPP2R1A. Supporting Evidence: PMID:16580887 Depletion of Plk1 by RNA interference (RNAi) restores centromeric localization of Sgo1 and prevents chromosome missegregation in cells depleted of PP2A_Aalpha.
GO:0005515 protein binding	IPI PMID:9847399 Binding specificity of protein phosphatase 2A core enzyme fo...	MARK AS OVER ANNOTATED	Summary: Binding specificity of PP2A core enzyme for regulatory B subunits and T antigens. Key study showing A subunit mutations affect B subunit binding differentially. Reason: Protein binding is too vague. The scaffolding function and B subunit binding specificity are better captured by PP2A complex and protein phosphatase regulator activity annotations.
GO:0046982 protein heterodimerization activity	IPI PMID:9847399 Binding specificity of protein phosphatase 2A core enzyme fo...	ACCEPT	Summary: PPP2R1A heterodimerizes with the catalytic C subunit to form the PP2A core enzyme (PMID:9847399). This is a specific molecular function. Reason: Heterodimerization with the catalytic C subunit is a core molecular function of PPP2R1A, more informative than generic protein binding. The A-C heterodimerization is the foundation of PP2A assembly. Supporting Evidence: PMID:9847399 The core enzyme of protein phosphatase 2A is composed of a regulatory subunit A and a catalytic subunit C.
GO:0000159 protein phosphatase type 2A complex	TAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero...	ACCEPT	Summary: Review article confirming PPP2R1A as PP2A scaffold (PMID:11007961). Reason: Well-established core function. Consistent with IBA and IDA annotations.
GO:0005634 nucleus	NAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero...	ACCEPT	Summary: Nuclear localization noted in PP2A review (PMID:11007961). Consistent with multiple experimental annotations. Reason: Consistent with other nuclear localization annotations.
GO:0005739 mitochondrion	NAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero...	MARK AS OVER ANNOTATED	Summary: Mitochondrial localization mentioned in PP2A review (PMID:11007961). PP2A has been reported at mitochondria in some contexts but this is not well- established as a primary localization for PPP2R1A. Reason: Mitochondrial localization is not well-supported as a primary site for PPP2R1A. NAS evidence from a general review is weak. No specific experimental data for PPP2R1A at mitochondria in the available literature.
GO:0005829 cytosol	TAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero...	ACCEPT	Summary: Cytosolic localization from PP2A review (PMID:11007961). Reason: Consistent with well-established cytosolic PP2A function.
GO:0015630 microtubule cytoskeleton	NAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero...	KEEP AS NON CORE	Summary: PP2A has roles at the microtubule cytoskeleton, particularly in mitosis (centrosome maturation, spindle assembly). NAS from review (PMID:11007961). Reason: Microtubule cytoskeleton association is a downstream consequence of PP2A activity in mitotic contexts. Not a core function of the PPP2R1A scaffold.
GO:0016020 membrane	NAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero...	KEEP AS NON CORE	Summary: Membrane localization from PP2A review (PMID:11007961). PP2A can associate with membranes through certain B subunits and interactors. Reason: Membrane association is context-dependent and driven by specific B subunits or interactors. Not a primary localization for the scaffold subunit.
GO:0040008 regulation of growth	NAS PMID:11360189 Absence of PPP2R1A mutations in Wilms tumor.	MARK AS OVER ANNOTATED	Summary: PMID:11360189 examines PPP2R1A mutations in Wilms tumor context, noting PP2A importance in fetal kidney growth. No mutations found in PPP2R1A. Reason: Regulation of growth is too vague and represents a broad downstream consequence of PP2A activity. The cited paper found NO PPP2R1A mutations in Wilms tumor, weakening the annotation. Growth regulation is a pleiotropic effect, not a specific function of PPP2R1A.
GO:0045595 regulation of cell differentiation	NAS PMID:11360189 Absence of PPP2R1A mutations in Wilms tumor.	MARK AS OVER ANNOTATED	Summary: PMID:11360189 mentions PP2A role in kidney differentiation context. The paper found no PPP2R1A mutations in Wilms tumor. Reason: Regulation of cell differentiation is too broad and vague. The cited paper is a negative mutational study. Differentiation effects are pleiotropic downstream consequences of PP2A activity with specific B subunits.
GO:0065003 protein-containing complex assembly	TAS PMID:9989501 The structure of the protein phosphatase 2A PR65/A subunit r...	ACCEPT	Summary: PPP2R1A is the scaffold that assembles PP2A holoenzyme complexes. The crystal structure at 2.3 A reveals how 15 HEAT repeats organize the assembly platform (PMID:9989501). Reason: Protein-containing complex assembly is a core function of PPP2R1A as the scaffolding subunit that organizes PP2A holoenzyme formation. Supporting Evidence: PMID:9989501 The PR65/A subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit, generating functionally diverse heterotrimers.

Core Functions

PPP2R1A is the scaffolding A subunit of PP2A that organizes the catalytic C subunit and diverse regulatory B subunits into functional holoenzymes, thereby regulating phosphatase activity and substrate specificity. The A subunit does not have catalytic activity itself but enables it by assembling the holoenzyme. As part of canonical PP2A trimers, it contributes to Ser/Thr phosphatase activity on diverse substrates including signaling kinases and transcription factors.

Molecular Function:

protein phosphatase regulator activity

Directly Involved In:

protein-containing complex assembly

Cellular Locations:

cytosol nucleus

In Complex:

protein phosphatase type 2A complex

Supporting Evidence:

PMID:17055435
The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a 36 kDa catalytic subunit.
PMID:17174897
The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit.
PMID:9989501
The PR65/A subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit, generating functionally diverse heterotrimers.

As part of the INTAC complex (Integrator-PP2A), PPP2R1A scaffolds PPP2CA which dephosphorylates the Pol II CTD at Ser2, Ser5, and Ser7, driving premature transcription termination. This represents a quality checkpoint function during transcription initiation, distinct from canonical PP2A holoenzyme activities.

Molecular Function:

protein phosphatase regulator activity

Directly Involved In:

RNA polymerase II transcription initiation surveillance regulation of transcription elongation by RNA polymerase II

Cellular Locations:

chromatin nucleus

In Complex:

INTAC complex

Supporting Evidence:

PMID:33243860
we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC. The INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription.
PMID:38570683
we present three cryo-electron microscopy structures of the complete Integrator-PP2A complex in different functional states.

As part of the STRIPAK complex, PPP2R1A scaffolds PP2A phosphatase activity that dephosphorylates MST1/2 Hippo kinases, negatively regulating the Hippo signaling pathway. STRIPAK is a noncanonical PP2A assembly with striatin as the regulatory B subunit.

Molecular Function:

protein phosphatase regulator activity

Directly Involved In:

negative regulation of hippo signaling

Cellular Locations:

cytosol

In Complex:

FAR/SIN/STRIPAK complex

Supporting Evidence:

PMID:33633399
The striatin-interacting phosphatase and kinase (STRIPAK) complex is a large, multisubunit protein phosphatase 2A (PP2A) assembly that integrates diverse cellular signals in the Hippo pathway to regulate cell proliferation and survival.
PMID:18782753
Here we define a novel large multiprotein assembly, referred to as the striatin-interacting phosphatase and kinase (STRIPAK) complex. STRIPAK contains the PP2A catalytic (PP2Ac) and scaffolding (PP2A A) subunits

References

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:11007961

Type 2A protein phosphatase, the complex regulator of numerous signaling pathways.

PMID:11360189

Absence of PPP2R1A mutations in Wilms tumor.

PMID:11504734

Interaction between protein phosphatase 5 and the A subunit of protein phosphatase 2A: evidence for a heterotrimeric form of protein phosphatase 5.

PMID:11591705

Protein phosphatase 2A interacts with and directly dephosphorylates RelA.

PMID:15525651

Galpha12 directly interacts with PP2A: evidence FOR Galpha12-stimulated PP2A phosphatase activity and dephosphorylation of microtubule-associated protein, tau.

PMID:15761952

Single-step Strep-tag purification for the isolation and identification of protein complexes from mammalian cells.

PMID:16044149

Activation of the protein kinase B pathway by the HPV-16 E7 oncoprotein occurs through a mechanism involving interaction with PP2A.

PMID:16239144

Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II.

PMID:16580887

PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation.

PMID:16764867

Interaction of nucleoredoxin with protein phosphatase 2A.

PMID:17055435

Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins.

PMID:17174897

Structure of the protein phosphatase 2A holoenzyme.

PMID:17245430

A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55.

PMID:17274953

Methylation of the C-terminal leucine residue of the PP2A catalytic subunit is unnecessary for the catalytic activity and the binding of regulatory subunit (PR55/B).

PMID:17374643

Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells.

PMID:17529992

Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40.

PMID:17540176

The tumor suppressor PP2A Abeta regulates the RalA GTPase.

PMID:17632056

CIP2A inhibits PP2A in human malignancies.

PMID:17974561

Tesk1 interacts with Spry2 to abrogate its inhibition of ERK phosphorylation downstream of receptor tyrosine kinase signaling.

PMID:18394995

Structural mechanism of demethylation and inactivation of protein phosphatase 2A.

PMID:18715871

PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4.

PMID:18782753

A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein.

PMID:19156129

An integrated workflow for charting the human interaction proteome: insights into the PP2A system.

PMID:19293187

PME-1 protects extracellular signal-regulated kinase pathway activity from protein phosphatase 2A-mediated inactivation in human malignant glioma.

PMID:19915589

The chromosomal association of condensin II is regulated by a noncatalytic function of PP2A.

PMID:20711181

Live-cell imaging RNAi screen identifies PP2A-B55alpha and importin-beta1 as key mitotic exit regulators in human cells.

PMID:21075311

B55β-associated PP2A complex controls PDK1-directed myc signaling and modulates rapamycin sensitivity in colorectal cancer.

PMID:21460856

ATM-mediated phosphorylation activates the tumor-suppressive function of B56γ-PP2A.

PMID:22167190

Identification and characterization of an alternatively spliced isoform of the human protein phosphatase 2Aα catalytic subunit.

PMID:23533145

In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.

PMID:23555304

Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions.

PMID:25150978

An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

PMID:25241761

Using an in situ proximity ligation assay to systematically profile endogenous protein-protein interactions in a pathway network.

PMID:25438055

AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation.

PMID:26496610

A human interactome in three quantitative dimensions organized by stoichiometries and abundances.

PMID:26829474

Acetylation of Aurora B by TIP60 ensures accurate chromosomal segregation.

PMID:27173435

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms.

PMID:27588481

FAM122A, a new endogenous inhibitor of protein phosphatase 2A.

PMID:27880917

Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators.

PMID:28167675

ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase).

PMID:28174209

Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56.

PMID:28330616

Systematic Analysis of Human Protein Phosphatase Interactions and Dynamics.

PMID:30595372

De Novo Mutations Affecting the Catalytic Cα Subunit of PP2A, PPP2CA, Cause Syndromic Intellectual Disability Resembling Other PP2A-Related Neurodevelopmental Disorders.

PMID:30611118

Mitogenic Signals Stimulate the CREB Coactivator CRTC3 through PP2A Recruitment.

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32647223

INTS10-INTS13-INTS14 form a functional module of Integrator that binds nucleic acids and the cleavage module.

PMID:32707033

Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.

PMID:33243860

Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase.

PMID:33633399

Cryo-EM structure of the Hippo signaling integrator human STRIPAK.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34004147

The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer.

PMID:34762484

Structural basis of Integrator-mediated transcription regulation.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:35512704

Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.

PMID:36869814

Structural basis of INTAC-regulated transcription.

PMID:37761890

Novel Variants of PPP2R1A in Catalytic Subunit Binding Domain and Genotype-Phenotype Analysis in Neurodevelopmentally Delayed Patients.

PMID:38123684

Cryo-EM structures of PP2A:B55-FAM122A and PP2A:B55-ARPP19.

PMID:38570683

Structural basis of Integrator-dependent RNA polymerase II termination.

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

PMID:8617797

Identification of a novel protein phosphatase 2A regulatory subunit highly expressed in muscle.

PMID:9847399

Binding specificity of protein phosphatase 2A core enzyme for regulatory B subunits and T antigens.

PMID:9857076

Identification of structural elements involved in the interaction of simian virus 40 small tumor antigen with protein phosphatase 2A.

PMID:9989501

The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs.

Reactome:R-HSA-1295599

SPRY2 translocates to the plasma membrane

Reactome:R-HSA-1295609

SRC phosphorylates SPRY2 on Y55 and Y227

Reactome:R-HSA-1295613

SPRY2 binds GRB2

Reactome:R-HSA-1295622

SPRY2 binds CBL

Reactome:R-HSA-1295632

PPA2A dephosphorylates SPRY2

Reactome:R-HSA-1549564

PPTN11 dephosphorylates SPRY2

Reactome:R-HSA-2574840

AJUBA facilitates AURKA autophosphorylation

Reactome:R-HSA-2574845

AJUBA binds centrosome-associated AURKA

Reactome:R-HSA-2995388

PP2A dephosphorylates BANF1

Reactome:R-HSA-3000310

AURKA phosphorylates PLK1

Reactome:R-HSA-3000319

BORA binds PLK1 and AURKA

Reactome:R-HSA-380272

Plk1-mediated phosphorylation of Nlp

Reactome:R-HSA-380283

Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome

Reactome:R-HSA-380294

Loss of C-Nap-1 from centrosomes

Reactome:R-HSA-380303

Dissociation of Phospho-Nlp from the centrosome

Reactome:R-HSA-380311

Recruitment of Plk1 to centrosomes

Reactome:R-HSA-380316

Association of NuMA with microtubules

Reactome:R-HSA-380455

Recruitment of CDK11p58 to the centrosomes

Reactome:R-HSA-380508

Translocation of NuMA to the centrosomes

Reactome:R-HSA-5617816

RAB3IP stimulates nucleotide exchange on RAB8A

Reactome:R-HSA-5626220

C2CD3 binds the mother centriole

Reactome:R-HSA-5626223

C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole

Reactome:R-HSA-5626227

CP110 and CEP97 dissociate from the centriole

Reactome:R-HSA-5626228

The distal appendage proteins recruit TTBK2

Reactome:R-HSA-5626681

Recruitment of transition zone proteins

Reactome:R-HSA-5626699

MARK4 binds ODF2 in the centriole

Reactome:R-HSA-5638009

CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body

Reactome:R-HSA-8853405

TPX2 binds AURKA at centrosomes

Reactome:R-HSA-8853419

TPX2 promotes AURKA autophosphorylation

Reactome:R-HSA-927813

p-4S-UPF1 recruits SMG5, SMG7, SMG6, PNRC2, DCP1A, and PP2A

Reactome:R-HSA-927830

Decay of mRNA in SMG6:SMG5:SMG7:mRNA complex

Reactome:R-HSA-927836

SMG6 hydrolyzes mRNA with premature termination codon

Reactome:R-HSA-934559

SPRY2 is phosphorylated by phosphorylated MNK1

Reactome:R-HSA-9667965

ANKLE2 binds PP2A

Deep Research

Falcon

(PPP2R1A-deep-research-falcon.md)

Research Report: Functional Annotation of Human **PPP2R1A** (UniProt **P30153**)—PP2A Scaffold Subunit Aα (PR65α) Falcon Edison Scientific Literature 22 citations 2026-03-07T19:24:41.937827

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Functional Annotation of Human PPP2R1A (UniProt P30153)—PP2A Scaffold Subunit Aα (PR65α)

1. Target identity verification (gene/protein disambiguation)

PPP2R1A (UniProt P30153) encodes the serine/threonine-protein phosphatase 2A (PP2A) 65 kDa regulatory subunit A alpha isoform, also known as PR65α / PP2A-Aα, in Homo sapiens. The collected literature consistently describes PPP2R1A as the non-catalytic scaffold (“A”) subunit of PP2A, built from HEAT repeats that organize binding of PP2A catalytic (“C”) and regulatory (“B”) subunits, matching the UniProt description and domain expectations (HEAT/ARM-like solenoid scaffold) (peris2023regulationandrole pages 2-4, ramaswamy2015therapeuticreactivationof pages 1-2, pavan2016designsynthesisand pages 20-25).

2. Key concepts and definitions (current understanding)

2.1 PP2A holoenzyme architecture and the role of PPP2R1A

PP2A is a major Ser/Thr phosphatase that typically functions as a heterotrimer consisting of:
- a scaffold A subunit (PPP2R1A/Aα or PPP2R1B/Aβ),
- a catalytic C subunit (PPP2CA or PPP2CB), and
- one of many regulatory B subunits that confer substrate specificity and subcellular targeting (peris2023regulationandrole pages 2-4, pavan2016designsynthesisand pages 15-20).

PPP2R1A’s primary molecular function is scaffolding/assembly: it binds the catalytic C subunit to form the AC core dimer and provides the binding platform for B subunits, which largely determine what the holoenzyme dephosphorylates and where it acts in the cell (peris2023regulationandrole pages 2-4, ramaswamy2015therapeuticreactivationof pages 1-2).

A schematic of PP2A holoenzyme modularity (AC core plus different B-subunits, including B56 isoforms) is shown in Peris et al. 2023 (Figure 1A) (peris2023regulationandrole media 44652bd9).

2.2 Structural domains: HEAT-repeat scaffold and interaction interfaces

PPP2R1A/PR65α is composed of 15 tandem HEAT repeats forming an extended curved solenoid scaffold (thapa2021structuralinsightof pages 11-16, pavan2016designsynthesisand pages 20-25). Multiple sources converge on the interaction topology:
- C-terminal HEAT repeats (≈11–15): major interface for catalytic C subunit binding (thapa2021structuralinsightof pages 11-16, ramaswamy2015therapeuticreactivationof pages 1-2).
- N-terminal HEAT repeats (≈1–10): primary interface for regulatory B subunit binding (thapa2021structuralinsightof pages 11-16, ramaswamy2015therapeuticreactivationof pages 1-2).

At the PP2A core interface, extensive noncovalent interactions stabilize the AC core; one structural description notes stabilization by “15 intermolecular hydrogen bonds and significant van der Waals contacts” between scaffold A and catalytic C (thapa2021structuralinsightof pages 16-19). In the context of B56-family binding, HEAT repeats 2–8 are described as engaging B56 subunits, and the A–B interaction is characterized as relatively loose without the catalytic subunit present (thapa2021structuralinsightof pages 16-19).

2.3 What PPP2R1A does not do (enzyme activity clarification)

PPP2R1A is not the catalytic phosphatase. The C subunit performs the chemical reaction (dephosphorylation of Ser/Thr residues). PPP2R1A’s role is to assemble and stabilize the catalytic machinery while enabling regulatory B subunits to impose substrate and localization constraints (peris2023regulationandrole pages 2-4, ramaswamy2015therapeuticreactivationof pages 1-2).

3. PP2A biogenesis and regulation relevant to PPP2R1A

3.1 Assembly intermediates and maturation factors

A substantial fraction of PP2A exists as AC core dimer; one review estimates ~one-third of PP2A species are A–C only (without a B subunit) (verbinnen2021proteinphosphatase2a pages 1-5). Holoenzyme biogenesis involves multiple chaperones/enzymes and regulated C-tail modifications. In neurodevelopment-focused synthesis, assembly intermediates can include stabilizing proteins (e.g., alpha4, TIPRL1, PME-1) and factors promoting assembly of active holoenzymes such as LCMT1 and PTPA, described as indispensable for generating/assembling active PP2A holoenzymes (verbinnen2021proteinphosphatase2a pages 1-5).

3.2 2024 structural advance: methylation-independent trimer assembly

A major recent development is the 2024 structural/biochemical reconstitution by Wachter et al. (JBC; April 2024; https://doi.org/10.1016/j.jbc.2024.107268) demonstrating that PPP2R1A-containing trimers can assemble without detectable requirement for C-terminal methylation under their in vitro conditions.

Key quantitative points:
- Recombinant complexes from insect cells were only ~6–8% methylated at the PP2A C-terminal leucine by MS; after LCMT1 treatment methylation increased to ~30–40% (wachter2024structuralcharacterizationof pages 2-4).
- Nevertheless, methylated vs unmethylated Aα–B55α–Cα and Aα–B56ε–Cα complexes showed similar phosphatase activity, supporting that methylation was dispensable for both assembly and activity in these assays (wachter2024structuralcharacterizationof pages 2-4).
- The authors solved an X-ray crystal structure at 3.1 Å of the unmethylated Aα–B56ε–Cα trimer, reporting substantial interface areas (A–B ≈ 1384 Å²; B–C ≈ 1294 Å²) and strong agreement with an AlphaFold2-Multimer model (RMSD ~1.047 Å) (wachter2024structuralcharacterizationof pages 2-4).

Interpretation: while PP2A C-tail methylation has been widely considered to bias holoenzyme composition, the 2024 work provides direct structural evidence that canonical PPP2R1A-containing trimers can form spontaneously in vitro with minimal methylation and retain enzymatic function, refining current models of how PPP2R1A scaffolds holoenzymes (wachter2024structuralcharacterizationof pages 1-2, wachter2024structuralcharacterizationof pages 2-4).

4. Cellular localization (where PPP2R1A acts)

PPP2R1A should be understood as a widely expressed scaffold whose effective localization is emergent from holoenzyme composition. Regulatory B subunits are repeatedly emphasized as key determinants of subcellular localization and substrate access for PP2A holoenzymes (peris2023regulationandrole pages 2-4). A neurodevelopmental review highlights that PPP2R1A (Aα) is expressed at substantially higher levels than Aβ in brain and increases during development, consistent with broad cellular roles in neuronal tissues (verbinnen2021proteinphosphatase2a pages 1-5).

Direct high-resolution, PPP2R1A-specific compartment assignment is not provided in the extracted text segments; however, localization differences among PP2A holoenzymes are discussed in relation to subunit composition (e.g., isoform-dependent cytoplasmic/nuclear distributions for certain regulatory subunits) (thapa2021structuralinsightof pages 16-19, verbinnen2021proteinphosphatase2a pages 1-5).

5. Biological processes and pathway involvement (mechanistic framing)

5.1 Pathway-level roles of PPP2R1A-containing PP2A holoenzymes

PPP2R1A-containing PP2A complexes are described as broad tumor-suppressive regulators affecting cell cycle and many signaling processes (peris2023regulationandrole pages 2-4). Pathway examples cited in the retrieved evidence include:
- PI3K/AKT signaling: PP2A can dephosphorylate/inactivate AKT, opposing pro-survival signaling; PPP2R1A mutations that disrupt holoenzyme formation can lead to constitutive AKT phosphorylation (thapa2021structuralinsightof pages 11-16, pavan2016designsynthesisand pages 25-29).
- MAPK and Wnt/β-catenin pathways: PP2A activity is described as capable of dampening MAPK and Wnt/β-catenin signaling outputs (pavan2016designsynthesisand pages 25-29).
- Cell cycle control: distinct B subunits (e.g., B55 vs B56 family members) are associated with different cell-cycle transition controls, consistent with the principle that PPP2R1A’s scaffold role enables variable specificity through B-subunit selection (pavan2016designsynthesisand pages 25-29, peris2023regulationandrole pages 2-4).

5.2 Substrate specificity: driven by regulatory B subunits (with examples)

Because PPP2R1A is a scaffold, substrate specificity is primarily imposed by the regulatory B subunits rather than by PPP2R1A itself (peris2023regulationandrole pages 2-4). One neurodevelopment-focused synthesis notes that B55-family PP2A complexes show a preference for dephosphorylating Ser-Pro and Thr-Pro motifs and recognize basic stretches near the dephosphorylation site (verbinnen2021proteinphosphatase2a pages 1-5). This is a key practical annotation point: PPP2R1A’s functional “specificity” is mostly indirect, via which B subunits can bind the scaffolded AC core.

6. Disease relevance and real-world applications

6.1 Cancer: recurrent PPP2R1A alterations and clinical genomics

PPP2R1A is recurrently altered in cancer, consistent with PP2A’s role as a tumor suppressor (peris2023regulationandrole pages 2-4, ramaswamy2015therapeuticreactivationof pages 1-2). Reported mechanisms include mutations that weaken binding to B subunits (and sometimes C), shifting signaling outputs such as AKT phosphorylation (thapa2021structuralinsightof pages 11-16, ramaswamy2015therapeuticreactivationof pages 1-2).

Recent clinical statistic (2024): In 187 p53-abnormal (p53abn) endometrial cancers, PPP2R1A mutations occurred in 29% of cases in a study combining shallow whole-genome sequencing and targeted panel sequencing (Clinical Cancer Research; March 2024; https://doi.org/10.1158/1078-0432.ccr-23-3689) (jamieson2024targetedandshallow pages 1-2). The same study frames p53abn endometrial cancers as highly aggressive and reports that the integrated approach identified potential therapeutic opportunities in 75% of patients (jamieson2024targetedandshallow pages 1-2).

Additional cancer statistics/mechanisms summarized in the extracted evidence include:
- PPP2R1A mutation frequency reported as up to 43.2% in uterine/type II serous endometrial cancer in a structural review excerpt (thapa2021structuralinsightof pages 11-16).
- PPP2R1A levels reported as reduced ~10-fold in ~43% of human gliomas in the same excerpt (thapa2021structuralinsightof pages 11-16).

Real-world implementation: These cohort-level mutation frequencies support use of PPP2R1A status in molecular profiling and stratification of tumors (e.g., endometrial cancer subtyping) and motivate therapies that aim to restore PP2A tumor-suppressive function, either by reactivating PP2A activity or by correcting disrupted holoenzyme assembly dynamics (ramaswamy2015therapeuticreactivationof pages 1-2, jamieson2024targetedandshallow pages 1-2).

6.2 Neurodevelopmental disorders (NDDs) / intellectual disability

An authoritative review focused on PP2A mutations in brain and neurologic disease highlights PPP2R1A among PP2A genes with mutations causally involved in neurodevelopmental disorders and intellectual disability, emphasizing that altered holoenzyme assembly and specificity are key mechanistic themes (Biochemical Society Transactions; July 2021; https://doi.org/10.1042/BST20201313) (verbinnen2021proteinphosphatase2a pages 1-5).

While the extracted text does not enumerate specific PPP2R1A patient variants, it supports the expert framing that perturbations of PPP2R1A-dependent PP2A assembly can affect brain development and neurologic function (verbinnen2021proteinphosphatase2a pages 1-5).

7. Expert synthesis and authoritative interpretation

7.1 Functional annotation statement (high-confidence)

PPP2R1A (PP2A-Aα/PR65α) is a HEAT-repeat scaffold that builds the PP2A catalytic platform by binding PP2Ac to form the AC core and recruiting diverse regulatory B subunits that specify substrates and subcellular targeting. This statement is directly supported across multiple reviews and structural descriptions (peris2023regulationandrole pages 2-4, ramaswamy2015therapeuticreactivationof pages 1-2, pavan2016designsynthesisand pages 20-25).

7.2 Why PPP2R1A is frequently disease-relevant

Because PPP2R1A controls which B subunits can assemble and stabilize a functional PP2A holoenzyme, PPP2R1A variants can act as “assembly lesions”: they may selectively disrupt certain PP2A holoenzymes (e.g., B56-associated complexes), thereby biasing phosphorylation states of key signaling proteins (e.g., AKT) without eliminating all PP2A function (thapa2021structuralinsightof pages 11-16, ramaswamy2015therapeuticreactivationof pages 1-2).

7.3 2023–2024 shift in mechanistic understanding

Peris et al. (2023; BBA Reviews on Cancer; September 2023; https://doi.org/10.1016/j.bbcan.2023.188953) emphasizes the centrality of scaffold-mediated assembly and how post-translational regulation of the catalytic subunit tail biases B-subunit choice (peris2023regulationandrole pages 2-4). Wachter et al. (2024) adds a key nuance: canonical PPP2R1A trimers can assemble spontaneously in an unmethylated state in vitro, and AlphaFold2-Multimer can closely recapitulate a PPP2R1A-containing trimer interface at near-atomic accuracy (wachter2024structuralcharacterizationof pages 2-4). Together, these sources support a modern view that PPP2R1A scaffolding is robust, and that regulatory layers (including methylation) may be more about tuning holoenzyme repertoires in cells than being an absolute requirement for assembly (peris2023regulationandrole pages 2-4, wachter2024structuralcharacterizationof pages 2-4).

8. Summary artifact

Category	Key points	Best supporting citations
Identity/structure	• PPP2R1A encodes PP2A scaffold Aα (PR65α); 15 HEAT repeats forming a curved ARM/HEAT solenoid; A–C interface at HEAT 11–15; A–B interface at HEAT 1–10 • Scaffold organizes AC core and positions B subunits to define specificity	(thapa2021structuralinsightof pages 11-16, thapa2021structuralinsightof pages 16-19)
Molecular function	• Non-catalytic scaffold that assembles the catalytic C with regulatory B subunits to form active heterotrimeric PP2A holoenzymes • B subunits dictate substrate selection and subcellular targeting while Aα provides docking surfaces	(peris2023regulationandrole pages 2-4, pavan2016designsynthesisand pages 15-20, verbinnen2021proteinphosphatase2a pages 1-5)
Assembly/biogenesis regulation	• Core AC dimers and assembly intermediates stabilized by alpha4/TIPRL1/PME-1; LCMT1 methylation and PTPA promote formation of active holoenzymes • 2024 structural work shows unmethylated Aα–B55α–Cα and Aα–B56ε–Cα trimers assemble spontaneously and retain activity; methylation is dispensable for assembly in vitro	(verbinnen2021proteinphosphatase2a pages 1-5, wachter2024structuralcharacterizationof pages 1-2, wachter2024structuralcharacterizationof pages 2-4, wachter2024structuralcharacterizationof pages 6-7)
Localization	• Aα-scaffolded holoenzymes localize to cytosol and nucleus; distribution and membrane association are governed by partnering C and B subunits (isoform- and context-dependent)	(thapa2021structuralinsightof pages 16-19, verbinnen2021proteinphosphatase2a pages 1-5)
Pathways/processes	• Regulates cell cycle transitions and DNA damage responses • Negatively modulates PI3K/AKT, MAPK, and Wnt/β-catenin signaling via B subunit–specified holoenzymes	(peris2023regulationandrole pages 2-4, pavan2016designsynthesisand pages 15-20)
Disease relevance	• Recurrent somatic mutations in endometrial/uterine serous carcinoma; PPP2R1A acts as a tumor suppressor within PP2A • PPP2R1A variants implicated in neurodevelopmental disorders/intellectual disability (Houge–Janssens spectrum)	(jamieson2024targetedandshallow pages 1-2, thapa2021structuralinsightof pages 11-16, verbinnen2021proteinphosphatase2a pages 1-5)
Recent 2023–2024 advances	• 3.1 Å X-ray structure of unmethylated Aα–B56ε–Cα trimers; AF2-Multimer accurately predicts PP2A trimer interfaces • Methylation of PP2Ac L309 increases with LCMT1 but is not required for trimer assembly/activity in vitro • PPP2R1A mutated in 29% (54/187) of p53abn endometrial cancers	(wachter2024structuralcharacterizationof pages 1-2, wachter2024structuralcharacterizationof pages 2-4, wachter2024structuralcharacterizationof pages 6-7, jamieson2024targetedandshallow pages 1-2)
Quantitative/statistics	• 15 HEAT repeats; B subunits encoded by ~15 genes generating >40 isoforms; core AC dimer constitutes ~1/3 of PP2A species; Aα predominates (~90% of holoenzymes) • PPP2R1A mutations up to 43.2% in uterine/type II serous endometrial cancer; PPP2R1A reduced ~10-fold in ~43% of gliomas • PPP2R1A mutated in 29% of p53abn endometrial cancers (n=187)	(pavan2016designsynthesisand pages 20-25, peris2023regulationandrole pages 2-4, verbinnen2021proteinphosphatase2a pages 1-5, thapa2021structuralinsightof pages 11-16, jamieson2024targetedandshallow pages 1-2)

Table: Concise functional annotation of human PPP2R1A (PP2A scaffold Aα) spanning structure, role in PP2A assembly, localization, pathways, disease links, and 2023–2024 findings. Quantitative data and citations enable quick reference and verification.

9. Key references (URLs and publication dates)

Peris I. et al. Regulation and role of the PP2A-B56 holoenzyme family in cancer. BBA Reviews on Cancer (Sep 2023). https://doi.org/10.1016/j.bbcan.2023.188953 (peris2023regulationandrole pages 2-4)
Wachter F. et al. Structural characterization of methylation-independent PP2A assembly guides AlphaFold2Multimer prediction of family-wide PP2A complexes. J Biol Chem (Apr 2024). https://doi.org/10.1016/j.jbc.2024.107268 (wachter2024structuralcharacterizationof pages 1-2, wachter2024structuralcharacterizationof pages 2-4)
Jamieson A. et al. Targeted and shallow whole-genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers. Clinical Cancer Research (Mar 2024). https://doi.org/10.1158/1078-0432.CCR-23-3689 (jamieson2024targetedandshallow pages 1-2)
Verbinnen I. et al. Protein Phosphatase 2A (PP2A) mutations in brain function, development, and neurologic disease. Biochemical Society Transactions (Jul 2021). https://doi.org/10.1042/BST20201313 (verbinnen2021proteinphosphatase2a pages 1-5)
Ramaswamy K. et al. Therapeutic re-activation of protein phosphatase 2A in acute myeloid leukemia. Frontiers in Oncology (Feb 2015). https://doi.org/10.3389/fonc.2015.00016 (ramaswamy2015therapeuticreactivationof pages 1-2)

Notes on evidence quality

Some extracted mechanistic and prevalence statements were found in sources with incomplete bibliographic metadata (“Unknown journal” in the retrieved corpus). These statements were used only where consistent with peer-reviewed reviews and/or where clearly framed as supportive context; the highest-confidence mechanistic and 2023–2024 advances are grounded in peer-reviewed sources listed above (peris2023regulationandrole pages 2-4, wachter2024structuralcharacterizationof pages 2-4, jamieson2024targetedandshallow pages 1-2).

References

(peris2023regulationandrole pages 2-4): Irene Peris, Silvia Romero-Murillo, Carmen Vicente, Goutham Narla, and Maria D. Odero. Regulation and role of the pp2a-b56 holoenzyme family in cancer. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1878:188953, Sep 2023. URL: https://doi.org/10.1016/j.bbcan.2023.188953, doi:10.1016/j.bbcan.2023.188953. This article has 21 citations and is from a peer-reviewed journal.
(ramaswamy2015therapeuticreactivationof pages 1-2): Kavitha Ramaswamy, Barbara Spitzer, and Alex Kentsis. Therapeutic re-activation of protein phosphatase 2a in acute myeloid leukemia. Frontiers in Oncology, Feb 2015. URL: https://doi.org/10.3389/fonc.2015.00016, doi:10.3389/fonc.2015.00016. This article has 43 citations.
(pavan2016designsynthesisand pages 20-25): V Pavan. Design, synthesis and biochemical characterization of fingolimod analogs for targeting pp2a. Unknown journal, 2016.
(pavan2016designsynthesisand pages 15-20): V Pavan. Design, synthesis and biochemical characterization of fingolimod analogs for targeting pp2a. Unknown journal, 2016.
(peris2023regulationandrole media 44652bd9): Irene Peris, Silvia Romero-Murillo, Carmen Vicente, Goutham Narla, and Maria D. Odero. Regulation and role of the pp2a-b56 holoenzyme family in cancer. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1878:188953, Sep 2023. URL: https://doi.org/10.1016/j.bbcan.2023.188953, doi:10.1016/j.bbcan.2023.188953. This article has 21 citations and is from a peer-reviewed journal.
(thapa2021structuralinsightof pages 11-16): CJ Thapa. Structural insight of pp2a inhibitor proteins and their interaction with pp2a aand b56-subunits. Unknown journal, 2021.
(thapa2021structuralinsightof pages 16-19): CJ Thapa. Structural insight of pp2a inhibitor proteins and their interaction with pp2a aand b56-subunits. Unknown journal, 2021.
(verbinnen2021proteinphosphatase2a pages 1-5): Iris Verbinnen, Pieter Vaneynde, Sara Reynhout, Lisa Lenaerts, Rita Derua, Gunnar Houge, and Veerle Janssens. Protein phosphatase 2a (pp2a) mutations in brain function, development, and neurologic disease. Biochemical Society transactions, 49:1567-1588, Jul 2021. URL: https://doi.org/10.1042/bst20201313, doi:10.1042/bst20201313. This article has 53 citations and is from a peer-reviewed journal.
(wachter2024structuralcharacterizationof pages 2-4): Franziska Wachter, Radosław P. Nowak, Scott Ficarro, J. Marto, and Eric S. Fischer. Structural characterization of methylation-independent pp2a assembly guides alphafold2multimer prediction of family-wide pp2a complexes. The Journal of Biological Chemistry, Apr 2024. URL: https://doi.org/10.1016/j.jbc.2024.107268, doi:10.1016/j.jbc.2024.107268. This article has 4 citations.
(wachter2024structuralcharacterizationof pages 1-2): Franziska Wachter, Radosław P. Nowak, Scott Ficarro, J. Marto, and Eric S. Fischer. Structural characterization of methylation-independent pp2a assembly guides alphafold2multimer prediction of family-wide pp2a complexes. The Journal of Biological Chemistry, Apr 2024. URL: https://doi.org/10.1016/j.jbc.2024.107268, doi:10.1016/j.jbc.2024.107268. This article has 4 citations.
(pavan2016designsynthesisand pages 25-29): V Pavan. Design, synthesis and biochemical characterization of fingolimod analogs for targeting pp2a. Unknown journal, 2016.
(jamieson2024targetedandshallow pages 1-2): Amy Jamieson, Juliana Sobral de Barros, Dawn R. Cochrane, J. Maxwell Douglas, Sameer Shankar, Branden J. Lynch, Samuel Leung, Spencer Martin, Janine Senz, Amy Lum, Yvette Drew, C. Blake Gilks, David G. Huntsman, and Jessica N. McAlpine. Targeted and shallow whole-genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers. Clinical Cancer Research, 30:2461-2474, Mar 2024. URL: https://doi.org/10.1158/1078-0432.ccr-23-3689, doi:10.1158/1078-0432.ccr-23-3689. This article has 19 citations and is from a highest quality peer-reviewed journal.
(wachter2024structuralcharacterizationof pages 6-7): Franziska Wachter, Radosław P. Nowak, Scott Ficarro, J. Marto, and Eric S. Fischer. Structural characterization of methylation-independent pp2a assembly guides alphafold2multimer prediction of family-wide pp2a complexes. The Journal of Biological Chemistry, Apr 2024. URL: https://doi.org/10.1016/j.jbc.2024.107268, doi:10.1016/j.jbc.2024.107268. This article has 4 citations.

Citations

thapa2021structuralinsightof pages 16-19
wachter2024structuralcharacterizationof pages 2-4
peris2023regulationandrole pages 2-4
pavan2016designsynthesisand pages 25-29
jamieson2024targetedandshallow pages 1-2
thapa2021structuralinsightof pages 11-16
ramaswamy2015therapeuticreactivationof pages 1-2
pavan2016designsynthesisand pages 20-25
pavan2016designsynthesisand pages 15-20
wachter2024structuralcharacterizationof pages 1-2
wachter2024structuralcharacterizationof pages 6-7
https://doi.org/10.1016/j.jbc.2024.107268
https://doi.org/10.1158/1078-0432.ccr-23-3689
https://doi.org/10.1042/BST20201313
https://doi.org/10.1016/j.bbcan.2023.188953
https://doi.org/10.1158/1078-0432.CCR-23-3689
https://doi.org/10.3389/fonc.2015.00016
https://doi.org/10.1016/j.bbcan.2023.188953,
https://doi.org/10.3389/fonc.2015.00016,
https://doi.org/10.1042/bst20201313,
https://doi.org/10.1016/j.jbc.2024.107268,
https://doi.org/10.1158/1078-0432.ccr-23-3689,

📚 Additional Documentation

Notes

(PPP2R1A-notes.md)

PPP2R1A Research Notes

Gene Identity

Gene: PPP2R1A (HGNC:9302)
UniProt: P30153
Protein: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PR65-alpha, PP2A-Aalpha)
Family: Phosphatase 2A regulatory subunit A family

Core Function Summary

PPP2R1A encodes the major scaffolding (A-alpha) subunit of protein phosphatase 2A (PP2A). The protein contains 15 tandem HEAT repeats forming an elongated horseshoe-shaped structure PMID:9989501.

The primary molecular function is scaffolding: the C-terminal HEAT repeats (11-15) bind the catalytic C subunit (PPP2CA/PPP2CB), while the N-terminal repeats (1-10) bind regulatory B subunits PMID:17055435. This generates the PP2A holoenzyme heterotrimer.

PPP2R1A is NOT the catalytic phosphatase -- PPP2CA/PPP2CB perform the actual dephosphorylation. PPP2R1A is the structural scaffold that assembles the holoenzyme.

Key Complexes

PP2A core dimer: PPP2R1A + PPP2CA/PPP2CB (AC dimer) PMID:17055435
PP2A holoenzyme trimer: PPP2R1A + C subunit + one of many B subunits (B55/B56/PR72/striatin families) PMID:17174897
INTAC complex: Integrator + PP2A-AC, a noncanonical PP2A holoenzyme for transcription regulation PMID:33243860
STRIPAK complex: PP2AA-C + striatins + STRIP1/2 + MOB4, a noncanonical PP2A complex for Hippo signaling PMID:33633399
FAR/SIN/STRIPAK complex: Same as STRIPAK in yeast/metazoan nomenclature PMID:18782753

Subcellular Localization

Cytoplasm/Cytosol: Primary location, by similarity and supported by multiple studies
Nucleus: Experimental evidence via INTAC complex and CRTC3 studies [PMID:33243860, PMID:34004147, PMID:30611118]
Chromatin: As part of INTAC complex for transcription regulation [PMID:33243860, PMID:34004147]
Centromere: During mitosis, for Sgo1 localization and chromosome segregation PMID:16580887
Lateral plasma membrane: In neurons, colocalizes with Galpha12 PMID:15525651
Dendrites/neuronal cell body: In neurons PMID:15525651

Biological Processes

Transcription initiation surveillance / premature transcription termination: As part of INTAC complex [PMID:33243860, PMID:34004147, PMID:38570683]
snRNA processing: Integrator complex role PMID:16239144
Chromosome segregation: Centromeric PP2A protects cohesion PMID:16580887
Hippo signaling regulation: As STRIPAK component, negatively regulates Hippo pathway PMID:33633399
Cell signaling: General PP2A-mediated dephosphorylation of signaling proteins (AKT, ERK, etc.)

Disease Associations

Cancer: Somatic mutations in endometrial/uterine serous carcinoma (up to 43% frequency), breast cancer, gliomas
Houge-Janssens syndrome 2 (MIM:616362): Neurodevelopmental disorder with intellectual disability PMID:37761890

Key Literature References

PMID:9989501 - Crystal structure of PR65/A subunit, 15 HEAT repeats
PMID:17055435 - Crystal structure of PP2A core enzyme
PMID:17174897 - Crystal structure of PP2A holoenzyme with B56
PMID:33243860 - Discovery of INTAC complex
PMID:34004147 - PP2A-Integrator-CDK9 axis in transcription
PMID:33633399 - Cryo-EM of STRIPAK complex
PMID:16580887 - PP2A at centromeres for chromosome segregation
PMID:9847399 - Binding specificity of A subunit for B subunits and T antigens
PMID:38123684 - Cryo-EM of PP2A:B55 complexes
PMID:38570683 - INTAC in RNA Pol II termination

📄 View Raw YAML

id: P30153
gene_symbol: PPP2R1A
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  PPP2R1A encodes the alpha isoform of the scaffolding A subunit (PR65-alpha) of
  protein phosphatase 2A (PP2A), the major serine/threonine phosphatase in eukaryotic
  cells. The protein comprises 15 tandem HEAT repeats forming an elongated horseshoe-shaped
  structure that bridges the catalytic C subunit (via HEAT repeats 11-15) and variable
  regulatory B subunits (via HEAT repeats 1-10), thereby assembling functionally diverse
  PP2A holoenzyme heterotrimers. PPP2R1A is the predominant A subunit isoform, accounting
  for approximately 90% of cellular PP2A scaffold. In addition to canonical trimeric
  PP2A
  holoenzymes, PPP2R1A participates in noncanonical PP2A assemblies including the
  INTAC
  complex (Integrator-PP2A) which regulates RNA polymerase II transcription, and the
  STRIPAK complex which integrates Hippo pathway signaling. PPP2R1A is not itself
  catalytic;
  its function is purely structural/scaffolding. Mutations are associated with endometrial
  cancer and Houge-Janssens syndrome 2 (neurodevelopmental disorder).
existing_annotations:
- term:
    id: GO:0000159
    label: protein phosphatase type 2A complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PPP2R1A is the core scaffolding subunit of the PP2A complex. Multiple crystal
      structures demonstrate it as an integral component of the PP2A heterotrimer
      (PMID:17055435, PMID:17174897). This is the defining function of this protein.
    action: ACCEPT
    reason: >-
      PPP2R1A is the major scaffolding A subunit of PP2A, forming the core dimer with
      the catalytic C subunit and recruiting regulatory B subunits. This annotation
      is
      directly supported by structural and biochemical evidence.
    supported_by:
    - reference_id: PMID:17055435
      supporting_text: >-
        The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a 36 kDa
        catalytic subunit.
    - reference_id: PMID:17174897
      supporting_text: >-
        The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises
        a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PPP2R1A localizes to the nucleus as part of multiple PP2A complexes, including
      the INTAC complex which functions on chromatin (PMID:33243860, PMID:34004147).
      UniProt annotation confirms nuclear localization with experimental evidence.
    action: ACCEPT
    reason: >-
      Nuclear localization is well-supported by multiple experimental studies showing
      PPP2R1A in the nucleus as part of INTAC and other PP2A complexes.
    supported_by:
    - reference_id: PMID:33243860
      supporting_text: >-
        we identified a complex containing Integrator and protein phosphatase 2A
        core enzyme (PP2A-AC), termed INTAC
    - reference_id: PMID:30611118
      supporting_text: >-
        CRTC3 interacts with B55 PP2A holoenzymes via a conserved PP2A-binding region
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PPP2R1A is a widely expressed scaffold protein present in the cytoplasm. UniProt
      annotation confirms cytoplasmic localization by similarity (UniProtKB:Q32PI5).
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is expected and well-supported for the major PP2A scaffold.
      PP2A holoenzymes are found in both cytoplasm and nucleus.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PPP2R1A is present in the cytosol as part of PP2A holoenzymes. Consistent with
      the cytoplasm annotation and supported by multiple Reactome pathway entries.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes containing
      PPP2R1A as scaffold subunit.
- term:
    id: GO:0019888
    label: protein phosphatase regulator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PPP2R1A serves as the scaffolding subunit that organizes the PP2A holoenzyme,
      thereby regulating phosphatase activity by determining which B subunit (and
      therefore which substrates) are engaged. This is its core molecular function.
    action: ACCEPT
    reason: >-
      As the scaffold that assembles the PP2A holoenzyme, PPP2R1A directly regulates
      phosphatase activity by controlling holoenzyme composition and substrate access.
      This is an appropriate MF term for a non-catalytic regulatory subunit.
    supported_by:
    - reference_id: PMID:17174897
      supporting_text: >-
        The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises
        a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit.
- term:
    id: GO:0051225
    label: spindle assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PP2A is involved in mitotic processes including chromosome segregation and
      centromeric localization of Sgo1 (PMID:16580887). The role in spindle assembly
      is plausible through PP2A-mediated dephosphorylation of mitotic regulators,
      and is supported by Reactome annotations linking PP2A to centrosome maturation
      and mitotic spindle organization.
    action: KEEP_AS_NON_CORE
    reason: >-
      While PP2A has roles in mitosis, spindle assembly is a downstream consequence
      of PP2A holoenzyme activity with specific B subunits, not a core function of
      PPP2R1A itself. The IBA annotation is reasonable given conservation but represents
      a non-core biological process for this scaffold subunit.
- term:
    id: GO:0051754
    label: meiotic sister chromatid cohesion, centromeric
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PP2A-B56 complexes play a conserved role in protecting centromeric cohesion
      during meiosis. PMID:16580887 demonstrates PP2A's role at centromeres for
      chromosome segregation, though this study focused on mitosis. The meiotic
      role is inferred phylogenetically from yeast/fly data.
    action: KEEP_AS_NON_CORE
    reason: >-
      Meiotic centromeric cohesion is a conserved function of PP2A across eukaryotes,
      and the IBA inference is phylogenetically sound. However, this is a specialized
      meiosis-specific process rather than a core function of the PPP2R1A scaffold.
    supported_by:
    - reference_id: PMID:16580887
      supporting_text: >-
        PP2A localizes to centromeres in a Bub1-dependent manner. The Sgo1-PP2A
        interaction is required for centromeric localization of Sgo1 and proper
        chromosome segregation in human cells.
- term:
    id: GO:0000775
    label: chromosome, centromeric region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA mapping from UniProt subcellular location. Supported by experimental data
      showing PP2A localizes to centromeres during mitosis (PMID:16580887).
    action: ACCEPT
    reason: >-
      Centromeric localization is experimentally confirmed by Tang et al. 2006 showing
      PP2A localization to centromeres in a Bub1-dependent manner.
    supported_by:
    - reference_id: PMID:16580887
      supporting_text: >-
        PP2A localizes to centromeres in a Bub1-dependent manner.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA mapping from UniProt subcellular location. Nuclear localization is
      experimentally confirmed by multiple studies (PMID:33243860, PMID:30611118).
    action: ACCEPT
    reason: >-
      Consistent with IBA annotation and experimental evidence for nuclear PP2A
      functions including INTAC complex.
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA mapping from UniProt. PPP2R1A localizes to chromosomes/chromatin as
      part of the INTAC complex (PMID:33243860, PMID:34004147) and to centromeres
      during mitosis (PMID:16580887).
    action: ACCEPT
    reason: >-
      Chromosome localization is supported by experimental data for both INTAC
      and centromeric PP2A functions.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA mapping from UniProt subcellular location. Consistent with IBA annotation.
    action: ACCEPT
    reason: >-
      Cytoplasmic localization is well-established for PP2A holoenzymes.
- term:
    id: GO:0016328
    label: lateral plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA mapping from UniProt. Based on experimental data from PMID:15525651
      showing colocalization with Galpha12 at the lateral cell membrane in Caco-2
      cells.
    action: ACCEPT
    reason: >-
      Supported by the experimental IDA annotation from PMID:15525651 showing
      lateral plasma membrane localization.
    supported_by:
    - reference_id: PMID:15525651
      supporting_text: >-
        Endogenous Aalpha and Galpha(12) colocalized by immunofluorescent
        microscopy in Caco-2 cells and in neurons.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA mapping from UniProt. Based on experimental data from PMID:15525651
      showing PPP2R1A in dendrites of neurons.
    action: ACCEPT
    reason: >-
      Supported by the experimental IDA annotation from PMID:15525651.
    supported_by:
    - reference_id: PMID:15525651
      supporting_text: >-
        Endogenous Aalpha and Galpha(12) colocalized by immunofluorescent
        microscopy in Caco-2 cells and in neurons.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11504734
  review:
    summary: >-
      Interaction between PPP2R1A and protein phosphatase 5 (PP5/PPP5C). This study
      shows PP5 forms a heterotrimeric complex with PP2A A and C subunits. The
      interaction is specific and functionally relevant to phosphatase regulation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague for the scaffolding role of PPP2R1A. The actual
      function is better captured by the protein phosphatase regulator activity annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11591705
  review:
    summary: >-
      Interaction with RelA/NF-kB. PP2A directly dephosphorylates RelA. PPP2R1A serves
      as scaffold for this interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The scaffolding function is already captured by
      protein phosphatase regulator activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15761952
  review:
    summary: >-
      Identified in a Strep-tag purification approach for protein complex isolation.
      High-throughput interaction data.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. This HT study simply confirms PPP2R1A is in
      complexes, already captured by PP2A complex annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16044149
  review:
    summary: >-
      Interaction between HPV-16 E7 oncoprotein and PP2A involving the A subunit.
      Relevant to viral hijacking of PP2A.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The interaction with viral oncoproteins is a known
      feature of PP2A but not a core function of PPP2R1A.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16764867
  review:
    summary: >-
      Interaction with nucleoredoxin (NXN), which associates with PP2A.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative for PPP2R1A. The scaffolding function is already
      captured.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17055435
  review:
    summary: >-
      Crystal structure of PP2A core enzyme showing direct interaction between A and
      C subunits. Key structural study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      While the A-C interaction is fundamental, protein binding is too vague. This
      is already captured by the PP2A complex annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17245430
  review:
    summary: >-
      PP2A-B56gamma mediates p53 dephosphorylation at Thr55. PPP2R1A serves as scaffold
      for the B56gamma-containing holoenzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. The scaffolding role is already captured.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17274953
  review:
    summary: >-
      Study on methylation of PP2A C subunit and binding of B subunit PR55/B. PPP2R1A
      as scaffold.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague for the scaffolding interaction with B subunits.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17374643
  review:
    summary: >-
      Interaction with PLA2G16/HRSL3 tumor suppressor, which may decrease PP2A activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. One of many proteins interacting with PPP2R1A
      as PP2A scaffold.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17529992
  review:
    summary: >-
      Structural/biochemical study of SV40 small t antigen interaction with PP2A.
      Small t binds the A subunit to displace B subunits.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. Viral oncoprotein interaction is well-known but
      not a core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17540176
  review:
    summary: >-
      PP2A Abeta regulates RalA GTPase. This study focuses on PPP2R1B not PPP2R1A.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. The interaction is likely through the PP2A
      complex scaffold function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17632056
  review:
    summary: >-
      CIP2A inhibits PP2A. PPP2R1A interacts with CIP2A as part of PP2A complex.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. CIP2A interaction reflects PP2A regulation, not
      a specific PPP2R1A function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18394995
  review:
    summary: >-
      Structural mechanism of PP2A demethylation and inactivation by PME-1. PPP2R1A
      as part of the complex.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. PME-1 interaction is with the PP2A complex.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18715871
  review:
    summary: >-
      PP4R4/KIAA1622 forms a complex with PP4. PPP2R1A interaction may reflect shared
      subunit usage.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative and may reflect promiscuous HT interaction
      data.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18782753
  review:
    summary: >-
      PP2A phosphatase high density interaction network identifying STRIPAK complex.
      PPP2R1A is a core STRIPAK component.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The STRIPAK complex membership is captured by
      the FAR/SIN/STRIPAK complex annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19156129
  review:
    summary: >-
      Integrated workflow charting the PP2A interaction proteome. Large-scale interaction
      mapping.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from large-scale proteomics is uninformative for this well-characterized
      scaffold.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19293187
  review:
    summary: >-
      PME-1 protects ERK pathway from PP2A inactivation in glioma. PPP2R1A interacts
      as PP2A scaffold.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The PP2A scaffolding function is already captured.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19915589
  review:
    summary: >-
      Noncatalytic function of PP2A in chromosomal association of condensin II. PPP2R1A
      as PP2A scaffold.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. This reflects a downstream PP2A function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20711181
  review:
    summary: >-
      RNAi screen identifying PP2A-B55alpha as key mitotic exit regulator. PPP2R1A
      as scaffold.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. Mitotic functions are downstream of PP2A holoenzyme
      activity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21075311
  review:
    summary: >-
      B55beta-associated PP2A controls PDK1-directed Myc signaling. PPP2R1A as scaffold.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative for the scaffold subunit.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21460856
  review:
    summary: >-
      ATM-mediated phosphorylation activates B56gamma-PP2A tumor suppressor. PPP2R1A
      as scaffold.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The scaffolding role is already captured.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22167190
  review:
    summary: >-
      Identification of alternatively spliced PPP2CA isoform. Interaction with PPP2R1A
      as expected.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. A-C interaction is already captured by PP2A
      complex annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23555304
  review:
    summary: >-
      Circadian protein-protein interaction networks. HT interaction study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from HT circadian interaction study is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25150978
  review:
    summary: >-
      ECM-specific GEF-GAP interaction regulates Rho GTPase crosstalk. Indirect PP2A
      involvement.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. Likely reflects indirect PP2A complex interaction.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25241761
  review:
    summary: >-
      In situ proximity ligation assay profiling endogenous PPIs in pathway networks.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from PLA assay is uninformative for the scaffold subunit.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25438055
  review:
    summary: >-
      AMBRA1 links autophagy to c-Myc dephosphorylation via PP2A. PPP2R1A as scaffold.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The PP2A scaffolding function is already captured.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  review:
    summary: >-
      Human interactome in three quantitative dimensions. Large-scale interaction
      study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from large-scale interactome study is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26829474
  review:
    summary: >-
      Acetylation of Aurora B by TIP60 for chromosome segregation. PP2A interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. Reflects downstream PP2A mitotic function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27173435
  review:
    summary: >-
      Organelle-specific protein landscape. Large-scale localization/interaction study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from large-scale study is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27880917
  review:
    summary: >-
      Phenotypic and interaction profiling of human phosphatases. Large-scale study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from large-scale phosphatase profiling is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28330616
  review:
    summary: >-
      Systematic analysis of human protein phosphatase interactions and dynamics.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from systematic phosphatase interaction study is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  review:
    summary: >-
      Extensive disruption of protein interactions by genetic variants. Population
      genetics study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from variant interaction disruption study is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: >-
      Reference map of human binary protein interactome. Large-scale Y2H study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from large-scale binary interactome is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32707033
  review:
    summary: >-
      Kinase interaction network. Large-scale study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from kinase interaction network study is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33633399
  review:
    summary: >-
      Cryo-EM structure of STRIPAK complex containing PPP2R1A. Key structural study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The STRIPAK complex membership is captured by
      FAR/SIN/STRIPAK complex annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: >-
      Dual proteome-scale networks. Large-scale interactome study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from large-scale interactome is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: >-
      OpenCell endogenous tagging cartography. Large-scale localization study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from large-scale tagging study is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35512704
  review:
    summary: >-
      Systematic discovery of mutation-directed neo-protein-protein interactions in
      cancer.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from cancer neo-PPI study is uninformative for core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37761890
  review:
    summary: >-
      Novel PPP2R1A variants in catalytic subunit binding domain. Disease variants
      affecting A-C interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The A-C interaction is captured by PP2A complex
      annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:38123684
  review:
    summary: >-
      Cryo-EM structures of PP2A:B55 complexes with FAM122A and ARPP19. Key structural
      study showing PPP2R1A in PP2A holoenzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The scaffolding function is captured by PP2A complex
      and protein phosphatase regulator activity annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  review:
    summary: >-
      Multimodal cell maps. Large-scale study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding from large-scale cell mapping is uninformative.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8617797
  review:
    summary: >-
      Identification of novel PP2A regulatory subunit highly expressed in muscle.
      PPP2R1A interaction with B subunits.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. A-B subunit interaction is captured by PP2A complex
      annotation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9857076
  review:
    summary: >-
      Structural elements in SV40 small t antigen involved in PP2A interaction. Viral
      oncoprotein binding to A subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. Viral interaction reflects exploitation of the
      scaffold function.
- term:
    id: GO:0004721
    label: phosphoprotein phosphatase activity
  evidence_type: IDA
  original_reference_id: PMID:30595372
  qualifier: contributes_to
  review:
    summary: >-
      PPP2R1A contributes to phosphoprotein phosphatase activity as the scaffold
      subunit of the PP2A holoenzyme. The contributes_to qualifier is appropriate
      since PPP2R1A is not itself catalytic but enables the catalytic C subunit
      to function within the holoenzyme context. PMID:30595372 studies PP2A mutations
      in neurodevelopmental disorders.
    action: ACCEPT
    reason: >-
      The contributes_to qualifier correctly captures that PPP2R1A is essential for
      PP2A holoenzyme assembly and function but is not itself the catalytic subunit.
    supported_by:
    - reference_id: PMID:30595372
      supporting_text: >-
        De Novo Mutations Affecting the Catalytic Calpha Subunit of PP2A, PPP2CA,
        Cause Syndromic Intellectual Disability Resembling Other PP2A-Related
        Neurodevelopmental Disorders.
- term:
    id: GO:0008287
    label: protein serine/threonine phosphatase complex
  evidence_type: IDA
  original_reference_id: PMID:28167675
  review:
    summary: >-
      PPP2R1A is a core component of the PP2A Ser/Thr phosphatase complex. PMID:28167675
      shows ARPP-16 interacts with the A subunit of PP2A, confirming PPP2R1A in this
      complex in brain tissue.
    action: ACCEPT
    reason: >-
      This is a parent term of GO:0000159 (protein phosphatase type 2A complex) and
      is appropriately applied. PPP2R1A is definitionally a component of a protein
      serine/threonine phosphatase complex.
    supported_by:
    - reference_id: PMID:28167675
      supporting_text: >-
        ARPP-16 interacts directly with the scaffolding A subunit of the
        serine/threonine protein phosphatase, PP2A
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:32647223
  review:
    summary: >-
      Nuclear localization supported by PPP2R1A being part of the INTAC complex
      (Integrator-PP2A) which functions in the nucleus on chromatin. PMID:32647223
      describes Integrator module function.
    action: ACCEPT
    reason: >-
      Consistent with other nuclear localization annotations and INTAC complex role.
- term:
    id: GO:0016180
    label: snRNA processing
  evidence_type: NAS
  original_reference_id: PMID:16239144
  review:
    summary: >-
      The Integrator complex mediates snRNA 3-prime end processing (PMID:16239144).
      PPP2R1A is part of the INTAC complex (Integrator-PP2A). However, snRNA
      processing is an Integrator function, and PP2A association may be primarily
      for transcription regulation rather than snRNA processing per se.
    action: KEEP_AS_NON_CORE
    reason: >-
      While PPP2R1A is part of INTAC, snRNA processing is primarily an Integrator
      endonuclease function. The PP2A component (PPP2R1A + PPP2CA) provides
      phosphatase activity for CTD dephosphorylation, which is distinct from
      snRNA cleavage. This is a non-core function of PPP2R1A.
    supported_by:
    - reference_id: PMID:16239144
      supporting_text: >-
        We show that Integrator is recruited to the U1 and U2
        snRNA genes and mediates the snRNAs' 3' end processing.
- term:
    id: GO:0034243
    label: regulation of transcription elongation by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:38570683
  review:
    summary: >-
      As part of the INTAC complex, PPP2R1A scaffolds PPP2CA which dephosphorylates
      the Pol II CTD and DSIF/SPT5, thereby preventing transcriptional elongation
      (PMID:38570683, PMID:34004147). This is a well-characterized INTAC function.
    action: ACCEPT
    reason: >-
      PPP2R1A is essential for INTAC complex assembly and the PP2A-mediated
      dephosphorylation of Pol II CTD that regulates transcription elongation.
      This is a core function of PPP2R1A-containing INTAC.
    supported_by:
    - reference_id: PMID:38570683
      supporting_text: >-
        The Integrator complex can terminate RNA polymerase II (Pol II) in the
        promoter-proximal region of genes.
    - reference_id: PMID:34004147
      supporting_text: >-
        The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted
        therapeutically in cancer.
- term:
    id: GO:0035330
    label: regulation of hippo signaling
  evidence_type: NAS
  original_reference_id: PMID:33633399
  review:
    summary: >-
      PPP2R1A is part of the STRIPAK complex which negatively regulates Hippo
      signaling by dephosphorylating MST1/2 kinases (PMID:33633399).
    action: ACCEPT
    reason: >-
      Regulation of Hippo signaling through the STRIPAK complex is a well-established
      function. The STRIPAK structure shows PPP2R1A as a core component.
    supported_by:
    - reference_id: PMID:33633399
      supporting_text: >-
        The striatin-interacting phosphatase and kinase (STRIPAK) complex is a
        large, multisubunit protein phosphatase 2A (PP2A) assembly that integrates
        diverse cellular signals in the Hippo pathway to regulate cell proliferation
        and survival.
- term:
    id: GO:0160240
    label: RNA polymerase II transcription initiation surveillance
  evidence_type: IDA
  original_reference_id: PMID:33243860
  review:
    summary: >-
      INTAC complex (containing PPP2R1A) functions as a quality checkpoint during
      transcription, driving premature termination of unfavorable transcripts by
      dephosphorylating Pol II CTD (PMID:33243860).
    action: ACCEPT
    reason: >-
      Core function of PPP2R1A as part of the INTAC complex. Well-supported by
      structural and functional data.
    supported_by:
    - reference_id: PMID:33243860
      supporting_text: >-
        The INTAC complex dephosphorylates the carboxy-terminal repeat domain of
        RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription.
- term:
    id: GO:0160240
    label: RNA polymerase II transcription initiation surveillance
  evidence_type: IDA
  original_reference_id: PMID:34004147
  review:
    summary: >-
      The PP2A-Integrator-CDK9 axis fine-tunes transcription. PPP2R1A as part of
      INTAC dephosphorylates Pol II CTD to regulate transcription elongation
      decisions (PMID:34004147).
    action: ACCEPT
    reason: >-
      Consistent with PMID:33243860. PPP2R1A is essential for INTAC function.
    supported_by:
    - reference_id: PMID:34004147
      supporting_text: >-
        The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted
        therapeutically in cancer.
- term:
    id: GO:0160240
    label: RNA polymerase II transcription initiation surveillance
  evidence_type: IDA
  original_reference_id: PMID:38570683
  review:
    summary: >-
      Structural basis of Integrator-dependent Pol II termination. PPP2R1A is part
      of the INTAC complex shown in multiple functional states (PMID:38570683).
    action: ACCEPT
    reason: >-
      Further structural confirmation of PPP2R1A role in INTAC-mediated transcription
      initiation surveillance.
    supported_by:
    - reference_id: PMID:38570683
      supporting_text: >-
        we present three cryo-electron microscopy structures of the complete
        Integrator-PP2A complex in different functional states.
- term:
    id: GO:0160232
    label: INTAC complex
  evidence_type: IDA
  original_reference_id: PMID:33243860
  review:
    summary: >-
      PPP2R1A is a core component of the INTAC complex, the Integrator-PP2A
      assembly identified in this landmark study (PMID:33243860).
    action: ACCEPT
    reason: >-
      PPP2R1A is definitionally part of INTAC as it provides the PP2A scaffold.
    supported_by:
    - reference_id: PMID:33243860
      supporting_text: >-
        we identified a complex containing Integrator and protein phosphatase 2A
        core enzyme (PP2A-AC), termed INTAC.
- term:
    id: GO:0160232
    label: INTAC complex
  evidence_type: IDA
  original_reference_id: PMID:34004147
  review:
    summary: >-
      Confirms PPP2R1A as component of INTAC in context of the PP2A-Integrator-CDK9
      transcription axis (PMID:34004147).
    action: ACCEPT
    reason: >-
      Consistent with PMID:33243860. PPP2R1A is a core INTAC component.
- term:
    id: GO:0160232
    label: INTAC complex
  evidence_type: IDA
  original_reference_id: PMID:34762484
  review:
    summary: >-
      Structural basis of Integrator-mediated transcription regulation confirms
      PPP2R1A in the INTAC pretermination complex bound to paused Pol II (PMID:34762484).
    action: ACCEPT
    reason: >-
      High-resolution structural evidence for PPP2R1A in INTAC.
    supported_by:
    - reference_id: PMID:34762484
      supporting_text: >-
        Integrator and protein phosphatase 2A (PP2A) form a complex that
        dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent
        RNA, and terminates transcription.
- term:
    id: GO:0160232
    label: INTAC complex
  evidence_type: IDA
  original_reference_id: PMID:36869814
  review:
    summary: >-
      Structural basis of INTAC-regulated transcription. PPP2R1A confirmed as
      component of INTAC (PMID:36869814).
    action: ACCEPT
    reason: >-
      Additional structural study confirming PPP2R1A in INTAC complex.
- term:
    id: GO:0160232
    label: INTAC complex
  evidence_type: IDA
  original_reference_id: PMID:38570683
  review:
    summary: >-
      Complete Integrator-PP2A structures in multiple functional states confirm
      PPP2R1A as core INTAC component (PMID:38570683).
    action: ACCEPT
    reason: >-
      Latest structural evidence for PPP2R1A in INTAC.
    supported_by:
    - reference_id: PMID:38570683
      supporting_text: >-
        we present three cryo-electron microscopy structures of the complete
        Integrator-PP2A complex in different functional states.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:33243860
  review:
    summary: >-
      PPP2R1A localizes to chromatin as part of the INTAC complex, which is
      recruited to chromatin at transcription pause sites (PMID:33243860).
    action: ACCEPT
    reason: >-
      Chromatin localization is well-supported by INTAC structural and functional
      studies showing the complex acts on chromatin-associated Pol II.
- term:
    id: GO:0000785
    label: chromatin
  evidence_type: IDA
  original_reference_id: PMID:34004147
  review:
    summary: >-
      PPP2R1A on chromatin as part of INTAC for transcription regulation (PMID:34004147).
    action: ACCEPT
    reason: >-
      Consistent with PMID:33243860. Chromatin association via INTAC complex.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:33243860
  review:
    summary: >-
      Nuclear localization as part of INTAC complex (PMID:33243860).
    action: ACCEPT
    reason: >-
      Consistent with other nuclear localization annotations. INTAC functions in nucleus.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:34004147
  review:
    summary: >-
      Nuclear localization confirmed by PP2A-Integrator-CDK9 study (PMID:34004147).
    action: ACCEPT
    reason: >-
      Consistent with INTAC function in nucleus.
- term:
    id: GO:0019888
    label: protein phosphatase regulator activity
  evidence_type: IDA
  original_reference_id: PMID:33243860
  review:
    summary: >-
      PPP2R1A scaffolds PPP2CA within the INTAC complex, enabling its phosphatase
      activity on Pol II CTD (PMID:33243860). This is the core molecular function.
    action: ACCEPT
    reason: >-
      Direct experimental evidence that PPP2R1A regulates PP2A phosphatase activity
      within the INTAC complex.
- term:
    id: GO:0019888
    label: protein phosphatase regulator activity
  evidence_type: IDA
  original_reference_id: PMID:34004147
  review:
    summary: >-
      PPP2R1A scaffolds PP2A phosphatase activity in the Integrator-CDK9 axis
      (PMID:34004147).
    action: ACCEPT
    reason: >-
      Consistent with core scaffold function enabling PP2A phosphatase regulation.
- term:
    id: GO:0035331
    label: negative regulation of hippo signaling
  evidence_type: IDA
  original_reference_id: PMID:33633399
  review:
    summary: >-
      STRIPAK complex containing PPP2R1A dephosphorylates MST1/2 to negatively
      regulate Hippo signaling (PMID:33633399). The cryo-EM structure shows
      PPP2R1A as integral to STRIPAK assembly.
    action: ACCEPT
    reason: >-
      Well-supported by structural and functional data. PPP2R1A as STRIPAK
      scaffold enables PP2A-mediated negative regulation of Hippo pathway.
    supported_by:
    - reference_id: PMID:33633399
      supporting_text: >-
        STRIPAK is a key negative regulator of the Hippo pathway that controls
        tissue homeostasis and suppresses tumorigenesis
- term:
    id: GO:0090443
    label: FAR/SIN/STRIPAK complex
  evidence_type: IDA
  original_reference_id: PMID:18782753
  review:
    summary: >-
      PPP2R1A is a core component of the STRIPAK complex, first identified in
      this landmark proteomics study (PMID:18782753).
    action: ACCEPT
    reason: >-
      PPP2R1A is the PP2A scaffold subunit (PP2A A) of the STRIPAK complex.
      The original discovery paper confirms its membership.
    supported_by:
    - reference_id: PMID:18782753
      supporting_text: >-
        Here we define a novel large multiprotein assembly, referred to as the
        striatin-interacting phosphatase and kinase (STRIPAK) complex. STRIPAK
        contains the PP2A catalytic (PP2Ac) and scaffolding (PP2A A) subunits
- term:
    id: GO:0090443
    label: FAR/SIN/STRIPAK complex
  evidence_type: IDA
  original_reference_id: PMID:33633399
  review:
    summary: >-
      Cryo-EM structure of STRIPAK confirms PPP2R1A as core component (PMID:33633399).
    action: ACCEPT
    reason: >-
      High-resolution structural confirmation of PPP2R1A in STRIPAK.
    supported_by:
    - reference_id: PMID:33633399
      supporting_text: >-
        The PP2AA-C heterodimer interacts with one end of the STRN3 CC tetramer
        through the first HEAT-repeat of PP2AA.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: NAS
  original_reference_id: PMID:11007961
  review:
    summary: >-
      PP2A is a major regulator of numerous signaling pathways (PMID:11007961).
      PPP2R1A as scaffold enables diverse PP2A holoenzymes to regulate multiple
      signaling cascades.
    action: KEEP_AS_NON_CORE
    reason: >-
      Intracellular signal transduction is too broad and vague. While PP2A regulates
      many signaling pathways, this term does not capture the specific scaffolding
      role of PPP2R1A. More specific pathway annotations are preferred.
- term:
    id: GO:0043029
    label: T cell homeostasis
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      Transferred from ortholog data. UniProt notes that PP2A-mediated AKT1
      dephosphorylation is essential for regulatory T-cell homeostasis (by
      similarity). This is a downstream consequence of PP2A activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      T cell homeostasis is a downstream pleiotropic consequence of PP2A activity
      in specific immune cell contexts, not a core function of the PPP2R1A scaffold.
- term:
    id: GO:0051898
    label: negative regulation of phosphatidylinositol 3-kinase/protein kinase B
      signal transduction
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      PP2A dephosphorylates AKT1, negatively regulating PI3K/AKT signaling.
      Transferred from ortholog data. PPP2R1A cancer mutations can lead to
      constitutive AKT phosphorylation.
    action: KEEP_AS_NON_CORE
    reason: >-
      While PP2A-mediated AKT dephosphorylation is well-established, this is a
      downstream consequence of specific PP2A holoenzyme activity, not a core
      function of the PPP2R1A scaffold subunit itself.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15525651
  review:
    summary: >-
      Galpha12 directly interacts with PPP2R1A. The interaction promotes PP2A activation
      and dephosphorylation of tau.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The functional consequence (PP2A activation) is
      the informative part.
- term:
    id: GO:0016328
    label: lateral plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:15525651
  review:
    summary: >-
      PPP2R1A colocalizes with Galpha12 at the lateral cell membrane in Caco-2 cells
      and neurons (PMID:15525651).
    action: ACCEPT
    reason: >-
      Experimental evidence from immunofluorescence showing lateral membrane
      localization, consistent with PP2A function in cell polarity contexts.
    supported_by:
    - reference_id: PMID:15525651
      supporting_text: >-
        Endogenous Aalpha and Galpha(12) colocalized by immunofluorescent
        microscopy in Caco-2 cells and in neurons.
- term:
    id: GO:0043005
    label: neuron projection
  evidence_type: IDA
  original_reference_id: PMID:15525651
  review:
    summary: >-
      PPP2R1A detected in neuron projections by immunofluorescence in primary
      neurons (PMID:15525651).
    action: ACCEPT
    reason: >-
      Direct experimental evidence for neuronal projection localization.
    supported_by:
    - reference_id: PMID:15525651
      supporting_text: >-
        Endogenous Aalpha and Galpha(12) colocalized by immunofluorescent
        microscopy in Caco-2 cells and in neurons.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IDA
  original_reference_id: PMID:15525651
  review:
    summary: >-
      PPP2R1A detected in neuronal cell body by immunofluorescence (PMID:15525651).
    action: ACCEPT
    reason: >-
      Direct experimental evidence for neuronal cell body localization.
    supported_by:
    - reference_id: PMID:15525651
      supporting_text: >-
        Endogenous Aalpha and Galpha(12) colocalized by immunofluorescent
        microscopy in Caco-2 cells and in neurons.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17974561
  review:
    summary: >-
      Tesk1 interacts with Spry2 to abrogate ERK phosphorylation inhibition. PPP2R1A
      interaction with SPRY2.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. PP2A dephosphorylation of SPRY2 is the functional
      consequence.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30611118
  review:
    summary: >-
      CRTC3 interacts with PP2A for dephosphorylation and nuclear translocation. PPP2R1A
      is part of the B55 PP2A holoenzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The PP2A scaffolding function is already captured.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:30611118
  review:
    summary: >-
      PPP2R1A is part of PP2A holoenzymes that dephosphorylate CRTC3, promoting
      nuclear translocation (PMID:30611118).
    action: ACCEPT
    reason: >-
      Nuclear localization experimentally confirmed in the context of CRTC3 regulation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27588481
  review:
    summary: >-
      FAM122A directly interacts with PPP2R1A and B55alpha, inhibiting PP2A phosphatase
      activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The interaction with a PP2A inhibitor reflects
      the scaffold role already captured.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28174209
  review:
    summary: >-
      CIP2A is stabilized via interaction with PP2A/B56. PPP2R1A as scaffold subunit.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The PP2A scaffolding function is already captured.
- term:
    id: GO:1990405
    label: protein antigen binding
  evidence_type: IPI
  original_reference_id: PMID:9847399
  review:
    summary: >-
      PPP2R1A binds viral T antigens (SV40 small t, polyoma middle T) which
      displace regulatory B subunits. PMID:9847399 maps specific binding
      determinants on the A subunit.
    action: ACCEPT
    reason: >-
      T antigen binding is a well-characterized property of PPP2R1A. This is
      more informative than generic protein binding as it describes a specific
      molecular interaction relevant to viral oncogenesis.
    supported_by:
    - reference_id: PMID:9847399
      supporting_text: >-
        some amino acids are involved in the binding of all types of B subunits,
        whereas others are specifically involved in the binding of one or two
        types of B subunits. T-antigen-binding specificity does not correlate
        with that of a particular type of B subunit.
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  review:
    summary: >-
      PPP2R1A detected in exosomes from prostatic secretions by proteomics
      (PMID:23533145). This is likely nonspecific detection of an abundant
      cytoplasmic protein in exosomes.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Exosomal localization from HDA proteomics likely reflects nonspecific
      inclusion of an abundant cytoplasmic protein. This does not represent
      a core function or primary localization of PPP2R1A.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1295599
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1295609
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1295613
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1295622
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1295632
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1549564
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2574840
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2574845
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2995388
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3000310
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3000319
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380272
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380283
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380294
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380303
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380311
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380316
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380455
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-380508
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5617816
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626220
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626223
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626227
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626228
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626681
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5626699
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5638009
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8853405
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8853419
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927813
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927830
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-927836
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-934559
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9667965
  review:
    summary: >-
      Cytosol localization from Reactome pathway annotation. PPP2R1A is cytosolic
      as a core component of PP2A holoenzymes involved in various Reactome pathways.
    action: ACCEPT
    reason: >-
      Cytosolic localization is well-established for PP2A holoenzymes. Redundant
      with IBA cytosol annotation but each represents a different Reactome pathway
      context.
- term:
    id: GO:0000159
    label: protein phosphatase type 2A complex
  evidence_type: IDA
  original_reference_id: PMID:17055435
  review:
    summary: >-
      Crystal structure of PP2A core enzyme directly demonstrates PPP2R1A as
      scaffold subunit of the PP2A complex (PMID:17055435).
    action: ACCEPT
    reason: >-
      High-resolution structural evidence. PPP2R1A is definitionally part of PP2A.
    supported_by:
    - reference_id: PMID:17055435
      supporting_text: >-
        The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a
        36 kDa catalytic subunit.
- term:
    id: GO:0000159
    label: protein phosphatase type 2A complex
  evidence_type: IDA
  original_reference_id: PMID:17174897
  review:
    summary: >-
      Crystal structure of PP2A holoenzyme with B56 confirms PPP2R1A as scaffold
      subunit (PMID:17174897).
    action: ACCEPT
    reason: >-
      Definitive structural evidence for PPP2R1A in PP2A holoenzyme.
    supported_by:
    - reference_id: PMID:17174897
      supporting_text: >-
        The PP2A holoenzyme consists of a heterodimeric core enzyme, which
        comprises a scaffolding subunit and a catalytic subunit, and a variable
        regulatory subunit.
- term:
    id: GO:0000775
    label: chromosome, centromeric region
  evidence_type: IDA
  original_reference_id: PMID:16580887
  review:
    summary: >-
      PP2A localizes to centromeres in a Bub1-dependent manner for Sgo1
      localization and chromosome segregation (PMID:16580887).
    action: ACCEPT
    reason: >-
      Direct experimental evidence for centromeric localization of PP2A
      containing PPP2R1A.
    supported_by:
    - reference_id: PMID:16580887
      supporting_text: >-
        PP2A localizes to centromeres in a Bub1-dependent manner.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16580887
  review:
    summary: >-
      PP2A interaction with Sgo1 at centromeres. PPP2R1A depletion causes chromosome
      missegregation.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The centromeric function is better captured by
      chromosome segregation and centromeric region annotations.
- term:
    id: GO:0007059
    label: chromosome segregation
  evidence_type: IDA
  original_reference_id: PMID:16580887
  review:
    summary: >-
      PPP2R1A depletion causes chromosome missegregation. PP2A is required for
      centromeric Sgo1 localization and proper chromosome segregation (PMID:16580887).
    action: KEEP_AS_NON_CORE
    reason: >-
      While experimentally validated, chromosome segregation is a downstream
      consequence of PP2A centromeric activity with specific B subunits. It is
      not the core scaffolding function of PPP2R1A.
    supported_by:
    - reference_id: PMID:16580887
      supporting_text: >-
        Depletion of Plk1 by RNA interference (RNAi) restores centromeric
        localization of Sgo1 and prevents chromosome missegregation in cells
        depleted of PP2A_Aalpha.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9847399
  review:
    summary: >-
      Binding specificity of PP2A core enzyme for regulatory B subunits and T antigens.
      Key study showing A subunit mutations affect B subunit binding differentially.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is too vague. The scaffolding function and B subunit binding
      specificity are better captured by PP2A complex and protein phosphatase regulator
      activity annotations.
- term:
    id: GO:0046982
    label: protein heterodimerization activity
  evidence_type: IPI
  original_reference_id: PMID:9847399
  review:
    summary: >-
      PPP2R1A heterodimerizes with the catalytic C subunit to form the PP2A core
      enzyme (PMID:9847399). This is a specific molecular function.
    action: ACCEPT
    reason: >-
      Heterodimerization with the catalytic C subunit is a core molecular function
      of PPP2R1A, more informative than generic protein binding. The A-C
      heterodimerization is the foundation of PP2A assembly.
    supported_by:
    - reference_id: PMID:9847399
      supporting_text: >-
        The core enzyme of protein phosphatase 2A is composed of a regulatory
        subunit A and a catalytic subunit C.
- term:
    id: GO:0000159
    label: protein phosphatase type 2A complex
  evidence_type: TAS
  original_reference_id: PMID:11007961
  review:
    summary: >-
      Review article confirming PPP2R1A as PP2A scaffold (PMID:11007961).
    action: ACCEPT
    reason: >-
      Well-established core function. Consistent with IBA and IDA annotations.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:11007961
  review:
    summary: >-
      Nuclear localization noted in PP2A review (PMID:11007961). Consistent with
      multiple experimental annotations.
    action: ACCEPT
    reason: >-
      Consistent with other nuclear localization annotations.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: NAS
  original_reference_id: PMID:11007961
  review:
    summary: >-
      Mitochondrial localization mentioned in PP2A review (PMID:11007961). PP2A
      has been reported at mitochondria in some contexts but this is not well-
      established as a primary localization for PPP2R1A.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Mitochondrial localization is not well-supported as a primary site for
      PPP2R1A. NAS evidence from a general review is weak. No specific experimental
      data for PPP2R1A at mitochondria in the available literature.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: PMID:11007961
  review:
    summary: >-
      Cytosolic localization from PP2A review (PMID:11007961).
    action: ACCEPT
    reason: >-
      Consistent with well-established cytosolic PP2A function.
- term:
    id: GO:0015630
    label: microtubule cytoskeleton
  evidence_type: NAS
  original_reference_id: PMID:11007961
  review:
    summary: >-
      PP2A has roles at the microtubule cytoskeleton, particularly in mitosis
      (centrosome maturation, spindle assembly). NAS from review (PMID:11007961).
    action: KEEP_AS_NON_CORE
    reason: >-
      Microtubule cytoskeleton association is a downstream consequence of PP2A
      activity in mitotic contexts. Not a core function of the PPP2R1A scaffold.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: NAS
  original_reference_id: PMID:11007961
  review:
    summary: >-
      Membrane localization from PP2A review (PMID:11007961). PP2A can associate
      with membranes through certain B subunits and interactors.
    action: KEEP_AS_NON_CORE
    reason: >-
      Membrane association is context-dependent and driven by specific B subunits
      or interactors. Not a primary localization for the scaffold subunit.
- term:
    id: GO:0040008
    label: regulation of growth
  evidence_type: NAS
  original_reference_id: PMID:11360189
  review:
    summary: >-
      PMID:11360189 examines PPP2R1A mutations in Wilms tumor context, noting
      PP2A importance in fetal kidney growth. No mutations found in PPP2R1A.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Regulation of growth is too vague and represents a broad downstream
      consequence of PP2A activity. The cited paper found NO PPP2R1A mutations
      in Wilms tumor, weakening the annotation. Growth regulation is a pleiotropic
      effect, not a specific function of PPP2R1A.
- term:
    id: GO:0045595
    label: regulation of cell differentiation
  evidence_type: NAS
  original_reference_id: PMID:11360189
  review:
    summary: >-
      PMID:11360189 mentions PP2A role in kidney differentiation context.
      The paper found no PPP2R1A mutations in Wilms tumor.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Regulation of cell differentiation is too broad and vague. The cited paper
      is a negative mutational study. Differentiation effects are pleiotropic
      downstream consequences of PP2A activity with specific B subunits.
- term:
    id: GO:0065003
    label: protein-containing complex assembly
  evidence_type: TAS
  original_reference_id: PMID:9989501
  review:
    summary: >-
      PPP2R1A is the scaffold that assembles PP2A holoenzyme complexes. The
      crystal structure at 2.3 A reveals how 15 HEAT repeats organize the
      assembly platform (PMID:9989501).
    action: ACCEPT
    reason: >-
      Protein-containing complex assembly is a core function of PPP2R1A as the
      scaffolding subunit that organizes PP2A holoenzyme formation.
    supported_by:
    - reference_id: PMID:9989501
      supporting_text: >-
        The PR65/A subunit of protein phosphatase 2A serves as a scaffolding
        molecule to coordinate the assembly of the catalytic subunit and a
        variable regulatory B subunit, generating functionally diverse
        heterotrimers.
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
    Location vocabulary mapping, accompanied by conservative changes to GO terms
    applied by UniProt
  findings: []
- id: PMID:11007961
  title: Type 2A protein phosphatase, the complex regulator of numerous
    signaling pathways.
  findings: []
- id: PMID:11360189
  title: Absence of PPP2R1A mutations in Wilms tumor.
  findings: []
- id: PMID:11504734
  title: 'Interaction between protein phosphatase 5 and the A subunit of protein phosphatase
    2A: evidence for a heterotrimeric form of protein phosphatase 5.'
  findings: []
- id: PMID:11591705
  title: Protein phosphatase 2A interacts with and directly dephosphorylates
    RelA.
  findings: []
- id: PMID:15525651
  title: 'Galpha12 directly interacts with PP2A: evidence FOR Galpha12-stimulated
    PP2A phosphatase activity and dephosphorylation of microtubule-associated protein,
    tau.'
  findings: []
- id: PMID:15761952
  title: Single-step Strep-tag purification for the isolation and identification
    of protein complexes from mammalian cells.
  findings: []
- id: PMID:16044149
  title: Activation of the protein kinase B pathway by the HPV-16 E7 oncoprotein
    occurs through a mechanism involving interaction with PP2A.
  findings: []
- id: PMID:16239144
  title: Integrator, a multiprotein mediator of small nuclear RNA processing,
    associates with the C-terminal repeat of RNA polymerase II.
  findings: []
- id: PMID:16580887
  title: PP2A is required for centromeric localization of Sgo1 and proper
    chromosome segregation.
  findings: []
- id: PMID:16764867
  title: Interaction of nucleoredoxin with protein phosphatase 2A.
  findings: []
- id: PMID:17055435
  title: Structure of protein phosphatase 2A core enzyme bound to tumor-inducing
    toxins.
  findings: []
- id: PMID:17174897
  title: Structure of the protein phosphatase 2A holoenzyme.
  findings: []
- id: PMID:17245430
  title: A specific PP2A regulatory subunit, B56gamma, mediates DNA
    damage-induced dephosphorylation of p53 at Thr55.
  findings: []
- id: PMID:17274953
  title: Methylation of the C-terminal leucine residue of the PP2A catalytic
    subunit is unnecessary for the catalytic activity and the binding of
    regulatory subunit (PR55/B).
  findings: []
- id: PMID:17374643
  title: Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma
    cells.
  findings: []
- id: PMID:17529992
  title: Structural and biochemical insights into the regulation of protein
    phosphatase 2A by small t antigen of SV40.
  findings: []
- id: PMID:17540176
  title: The tumor suppressor PP2A Abeta regulates the RalA GTPase.
  findings: []
- id: PMID:17632056
  title: CIP2A inhibits PP2A in human malignancies.
  findings: []
- id: PMID:17974561
  title: Tesk1 interacts with Spry2 to abrogate its inhibition of ERK
    phosphorylation downstream of receptor tyrosine kinase signaling.
  findings: []
- id: PMID:18394995
  title: Structural mechanism of demethylation and inactivation of protein
    phosphatase 2A.
  findings: []
- id: PMID:18715871
  title: PP4R4/KIAA1622 forms a novel stable cytosolic complex with
    phosphoprotein phosphatase 4.
  findings: []
- id: PMID:18782753
  title: A PP2A phosphatase high density interaction network identifies a novel
    striatin-interacting phosphatase and kinase complex linked to the cerebral
    cavernous malformation 3 (CCM3) protein.
  findings: []
- id: PMID:19156129
  title: 'An integrated workflow for charting the human interaction proteome: insights
    into the PP2A system.'
  findings: []
- id: PMID:19293187
  title: PME-1 protects extracellular signal-regulated kinase pathway activity
    from protein phosphatase 2A-mediated inactivation in human malignant glioma.
  findings: []
- id: PMID:19915589
  title: The chromosomal association of condensin II is regulated by a
    noncatalytic function of PP2A.
  findings: []
- id: PMID:20711181
  title: Live-cell imaging RNAi screen identifies PP2A-B55alpha and
    importin-beta1 as key mitotic exit regulators in human cells.
  findings: []
- id: PMID:21075311
  title: B55β-associated PP2A complex controls PDK1-directed myc signaling and
    modulates rapamycin sensitivity in colorectal cancer.
  findings: []
- id: PMID:21460856
  title: ATM-mediated phosphorylation activates the tumor-suppressive function
    of B56γ-PP2A.
  findings: []
- id: PMID:22167190
  title: Identification and characterization of an alternatively spliced isoform
    of the human protein phosphatase 2Aα catalytic subunit.
  findings: []
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed
    prostatic secretions in urine.
  findings: []
- id: PMID:23555304
  title: Dynamic circadian protein-protein interaction networks predict temporal
    organization of cellular functions.
  findings: []
- id: PMID:25150978
  title: An extracellular-matrix-specific GEF-GAP interaction regulates Rho
    GTPase crosstalk for 3D collagen migration.
  findings: []
- id: PMID:25241761
  title: Using an in situ proximity ligation assay to systematically profile
    endogenous protein-protein interactions in a pathway network.
  findings: []
- id: PMID:25438055
  title: AMBRA1 links autophagy to cell proliferation and tumorigenesis by
    promoting c-Myc dephosphorylation and degradation.
  findings: []
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by
    stoichiometries and abundances.
  findings: []
- id: PMID:26829474
  title: Acetylation of Aurora B by TIP60 ensures accurate chromosomal
    segregation.
  findings: []
- id: PMID:27173435
  title: An organelle-specific protein landscape identifies novel diseases and
    molecular mechanisms.
  findings: []
- id: PMID:27588481
  title: FAM122A, a new endogenous inhibitor of protein phosphatase 2A.
  findings: []
- id: PMID:27880917
  title: Phenotypic and Interaction Profiling of the Human Phosphatases
    Identifies Diverse Mitotic Regulators.
  findings: []
- id: PMID:28167675
  title: ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A
    Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3
    Kinase).
  findings: []
- id: PMID:28174209
  title: Oncoprotein CIP2A is stabilized via interaction with tumor suppressor
    PP2A/B56.
  findings: []
- id: PMID:28330616
  title: Systematic Analysis of Human Protein Phosphatase Interactions and
    Dynamics.
  findings: []
- id: PMID:30595372
  title: De Novo Mutations Affecting the Catalytic Cα Subunit of PP2A, PPP2CA,
    Cause Syndromic Intellectual Disability Resembling Other PP2A-Related
    Neurodevelopmental Disorders.
  findings: []
- id: PMID:30611118
  title: Mitogenic Signals Stimulate the CREB Coactivator CRTC3 through PP2A
    Recruitment.
  findings: []
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across
    the allele frequency spectrum in human populations.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32647223
  title: INTS10-INTS13-INTS14 form a functional module of Integrator that binds
    nucleic acids and the cleavage module.
  findings: []
- id: PMID:32707033
  title: Kinase Interaction Network Expands Functional and Disease Roles of
    Human Kinases.
  findings: []
- id: PMID:33243860
  title: Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II
    phosphatase.
  findings: []
- id: PMID:33633399
  title: Cryo-EM structure of the Hippo signaling integrator human STRIPAK.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the
    human interactome.
  findings: []
- id: PMID:34004147
  title: The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be
    targeted therapeutically in cancer.
  findings: []
- id: PMID:34762484
  title: Structural basis of Integrator-mediated transcription regulation.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:35512704
  title: Systematic discovery of mutation-directed neo-protein-protein
    interactions in cancer.
  findings: []
- id: PMID:36869814
  title: Structural basis of INTAC-regulated transcription.
  findings: []
- id: PMID:37761890
  title: Novel Variants of PPP2R1A in Catalytic Subunit Binding Domain and
    Genotype-Phenotype Analysis in Neurodevelopmentally Delayed Patients.
  findings: []
- id: PMID:38123684
  title: Cryo-EM structures of PP2A:B55-FAM122A and PP2A:B55-ARPP19.
  findings: []
- id: PMID:38570683
  title: Structural basis of Integrator-dependent RNA polymerase II termination.
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional
    genomics.
  findings: []
- id: PMID:8617797
  title: Identification of a novel protein phosphatase 2A regulatory subunit
    highly expressed in muscle.
  findings: []
- id: PMID:9847399
  title: Binding specificity of protein phosphatase 2A core enzyme for
    regulatory B subunits and T antigens.
  findings: []
- id: PMID:9857076
  title: Identification of structural elements involved in the interaction of
    simian virus 40 small tumor antigen with protein phosphatase 2A.
  findings: []
- id: PMID:9989501
  title: The structure of the protein phosphatase 2A PR65/A subunit reveals the
    conformation of its 15 tandemly repeated HEAT motifs.
  findings: []
- id: Reactome:R-HSA-1295599
  title: SPRY2 translocates to the plasma membrane
  findings: []
- id: Reactome:R-HSA-1295609
  title: SRC phosphorylates SPRY2 on Y55 and Y227
  findings: []
- id: Reactome:R-HSA-1295613
  title: SPRY2 binds GRB2
  findings: []
- id: Reactome:R-HSA-1295622
  title: SPRY2 binds CBL
  findings: []
- id: Reactome:R-HSA-1295632
  title: PPA2A dephosphorylates SPRY2
  findings: []
- id: Reactome:R-HSA-1549564
  title: PPTN11 dephosphorylates SPRY2
  findings: []
- id: Reactome:R-HSA-2574840
  title: AJUBA facilitates AURKA autophosphorylation
  findings: []
- id: Reactome:R-HSA-2574845
  title: AJUBA binds centrosome-associated AURKA
  findings: []
- id: Reactome:R-HSA-2995388
  title: PP2A dephosphorylates BANF1
  findings: []
- id: Reactome:R-HSA-3000310
  title: AURKA phosphorylates PLK1
  findings: []
- id: Reactome:R-HSA-3000319
  title: BORA binds PLK1 and AURKA
  findings: []
- id: Reactome:R-HSA-380272
  title: Plk1-mediated phosphorylation of Nlp
  findings: []
- id: Reactome:R-HSA-380283
  title: Recruitment of additional gamma tubulin/ gamma TuRC to the centrosome
  findings: []
- id: Reactome:R-HSA-380294
  title: Loss of C-Nap-1 from centrosomes
  findings: []
- id: Reactome:R-HSA-380303
  title: Dissociation of Phospho-Nlp from the centrosome
  findings: []
- id: Reactome:R-HSA-380311
  title: Recruitment of Plk1 to centrosomes
  findings: []
- id: Reactome:R-HSA-380316
  title: Association of NuMA with microtubules
  findings: []
- id: Reactome:R-HSA-380455
  title: Recruitment of CDK11p58 to the centrosomes
  findings: []
- id: Reactome:R-HSA-380508
  title: Translocation of NuMA to the centrosomes
  findings: []
- id: Reactome:R-HSA-5617816
  title: RAB3IP stimulates nucleotide exchange on RAB8A
  findings: []
- id: Reactome:R-HSA-5626220
  title: C2CD3 binds the mother centriole
  findings: []
- id: Reactome:R-HSA-5626223
  title: C2CD3 and OFD1 recruit 5 distal appendage proteins to the centriole
  findings: []
- id: Reactome:R-HSA-5626227
  title: CP110 and CEP97 dissociate from the centriole
  findings: []
- id: Reactome:R-HSA-5626228
  title: The distal appendage proteins recruit TTBK2
  findings: []
- id: Reactome:R-HSA-5626681
  title: Recruitment of transition zone proteins
  findings: []
- id: Reactome:R-HSA-5626699
  title: MARK4 binds ODF2 in the centriole
  findings: []
- id: Reactome:R-HSA-5638009
  title: CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal
    body
  findings: []
- id: Reactome:R-HSA-8853405
  title: TPX2 binds AURKA at centrosomes
  findings: []
- id: Reactome:R-HSA-8853419
  title: TPX2 promotes AURKA autophosphorylation
  findings: []
- id: Reactome:R-HSA-927813
  title: p-4S-UPF1 recruits SMG5, SMG7, SMG6, PNRC2, DCP1A, and PP2A
  findings: []
- id: Reactome:R-HSA-927830
  title: Decay of mRNA in SMG6:SMG5:SMG7:mRNA complex
  findings: []
- id: Reactome:R-HSA-927836
  title: SMG6 hydrolyzes mRNA with premature termination codon
  findings: []
- id: Reactome:R-HSA-934559
  title: SPRY2 is phosphorylated by phosphorylated MNK1
  findings: []
- id: Reactome:R-HSA-9667965
  title: ANKLE2 binds PP2A
  findings: []
core_functions:
- molecular_function:
    id: GO:0019888
    label: protein phosphatase regulator activity
  contributes_to_molecular_function:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  description: >-
    PPP2R1A is the scaffolding A subunit of PP2A that organizes the catalytic C subunit
    and diverse regulatory B subunits into functional holoenzymes, thereby regulating
    phosphatase activity and substrate specificity. The A subunit does not have
    catalytic activity itself but enables it by assembling the holoenzyme. As part
    of canonical PP2A trimers, it contributes to Ser/Thr phosphatase activity on
    diverse substrates including signaling kinases and transcription factors.
  directly_involved_in:
  - id: GO:0065003
    label: protein-containing complex assembly
  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:17055435
    supporting_text: >-
      The core enzyme of PP2A comprises a 65 kDa scaffolding subunit and a
      36 kDa catalytic subunit.
  - reference_id: PMID:17174897
    supporting_text: >-
      The PP2A holoenzyme consists of a heterodimeric core enzyme, which comprises
      a scaffolding subunit and a catalytic subunit, and a variable regulatory subunit.
  - reference_id: PMID:9989501
    supporting_text: >-
      The PR65/A subunit of protein phosphatase 2A serves as a scaffolding molecule
      to coordinate the assembly of the catalytic subunit and a variable regulatory
      B subunit, generating functionally diverse heterotrimers.
- molecular_function:
    id: GO:0019888
    label: protein phosphatase regulator activity
  contributes_to_molecular_function:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  description: >-
    As part of the INTAC complex (Integrator-PP2A), PPP2R1A scaffolds PPP2CA which
    dephosphorylates the Pol II CTD at Ser2, Ser5, and Ser7, driving premature
    transcription termination. This represents a quality checkpoint function during
    transcription initiation, distinct from canonical PP2A holoenzyme activities.
  directly_involved_in:
  - id: GO:0160240
    label: RNA polymerase II transcription initiation surveillance
  - id: GO:0034243
    label: regulation of transcription elongation by RNA polymerase II
  locations:
  - id: GO:0000785
    label: chromatin
  - id: GO:0005634
    label: nucleus
  in_complex:
    id: GO:0160232
    label: INTAC complex
  supported_by:
  - reference_id: PMID:33243860
    supporting_text: >-
      we identified a complex containing Integrator and protein phosphatase 2A
      core enzyme (PP2A-AC), termed INTAC. The INTAC complex dephosphorylates the
      carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7
      and thus regulates transcription.
    full_text_unavailable: true
  - reference_id: PMID:38570683
    supporting_text: >-
      we present three cryo-electron microscopy structures of the complete
      Integrator-PP2A complex in different functional states.
- molecular_function:
    id: GO:0019888
    label: protein phosphatase regulator activity
  contributes_to_molecular_function:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  description: >-
    As part of the STRIPAK complex, PPP2R1A scaffolds PP2A phosphatase activity that
    dephosphorylates MST1/2 Hippo kinases, negatively regulating the Hippo signaling
    pathway. STRIPAK is a noncanonical PP2A assembly with striatin as the regulatory
    B subunit.
  directly_involved_in:
  - id: GO:0035331
    label: negative regulation of hippo signaling
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0090443
    label: FAR/SIN/STRIPAK complex
  supported_by:
  - reference_id: PMID:33633399
    supporting_text: >-
      The striatin-interacting phosphatase and kinase (STRIPAK) complex is a large,
      multisubunit protein phosphatase 2A (PP2A) assembly that integrates diverse
      cellular signals in the Hippo pathway to regulate cell proliferation and survival.
  - reference_id: PMID:18782753
    supporting_text: >-
      Here we define a novel large multiprotein assembly, referred to as the
      striatin-interacting phosphatase and kinase (STRIPAK) complex. STRIPAK contains
      the PP2A catalytic (PP2Ac) and scaffolding (PP2A A) subunits

PPP2R1A

Gene Description

Existing Annotations Review

Core Functions

As part of the STRIPAK complex, PPP2R1A scaffolds PP2A phosphatase activity that dephosphorylates MST1/2 Hippo kinases, negatively regulating the Hippo signaling pathway. STRIPAK is a noncanonical PP2A assembly with striatin as the regulatory B subunit.

References

Deep Research

Falcon

Research Report: Functional Annotation of Human PPP2R1A (UniProt P30153)—PP2A Scaffold Subunit Aα (PR65α)

1. Target identity verification (gene/protein disambiguation)

2. Key concepts and definitions (current understanding)

2.1 PP2A holoenzyme architecture and the role of PPP2R1A

2.2 Structural domains: HEAT-repeat scaffold and interaction interfaces

2.3 What PPP2R1A does not do (enzyme activity clarification)

3. PP2A biogenesis and regulation relevant to PPP2R1A

3.1 Assembly intermediates and maturation factors

3.2 2024 structural advance: methylation-independent trimer assembly

4. Cellular localization (where PPP2R1A acts)

5. Biological processes and pathway involvement (mechanistic framing)

5.1 Pathway-level roles of PPP2R1A-containing PP2A holoenzymes

5.2 Substrate specificity: driven by regulatory B subunits (with examples)

6. Disease relevance and real-world applications

6.1 Cancer: recurrent PPP2R1A alterations and clinical genomics

6.2 Neurodevelopmental disorders (NDDs) / intellectual disability

7. Expert synthesis and authoritative interpretation

7.1 Functional annotation statement (high-confidence)

7.2 Why PPP2R1A is frequently disease-relevant

7.3 2023–2024 shift in mechanistic understanding

8. Summary artifact

9. Key references (URLs and publication dates)

Notes on evidence quality

Citations

📚 Additional Documentation

Notes

PPP2R1A Research Notes

Gene Identity

Core Function Summary

Key Complexes

Subcellular Localization

Biological Processes

Disease Associations

Key Literature References

📄 View Raw YAML