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).
| 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 B55Ξ²-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 CΞ± 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. |
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