PPP2CA encodes the catalytic subunit alpha isoform (PP2Acalpha) of protein phosphatase 2A (PP2A), a major serine/threonine phosphatase (EC 3.1.3.16) that functions as a heterotrimer with a scaffold A subunit and a variable regulatory B subunit. Over 80 distinct PP2A holoenzymes exist, together accounting for approximately 50-70% of total cellular Ser/Thr phosphatase activity. Substrate specificity is primarily determined by the regulatory B subunit. PPP2CA also functions in two non-canonical complexes: the Integrator-PP2A (INTAC) complex, which dephosphorylates Pol II CTD at Ser2/5/7 to regulate transcription; and the STRIPAK complex, which regulates Hippo signaling by dephosphorylating MST1/2. Activity is regulated by C-terminal Leu309 methylation (by LCMT-1), tail phosphorylation (Tyr307/Thr304), and endogenous inhibitors (PABIR1/FAM122A, ARPP19, CIP2A, SET). De novo mutations cause Houge-Janssens syndrome 3 (syndromic intellectual disability).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004722 protein serine/threonine phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0000278 mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: PP2A is involved in mitotic cell cycle regulation. IBA annotation from phylogenetic analysis. Reason: PP2A has well-established roles in mitotic cell cycle including centromeric cohesin protection via SGO1/SGO2 (PMID:16541025, PMID:16580887), spindle checkpoint regulation, and G2/M checkpoint (PMID:33108758). The 2024 substrate mapping study showed PPP2CA degradation causes G2/M arrest. This IBA annotation is well-supported. Supporting Evidence: PMID:16541025 Shugoshin collaborates with protein phosphatase 2A to protect cohesin |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0000775 chromosome, centromeric region | IEA GO_REF:0000120 | ACCEPT | Summary: PPP2CA localizes to centromeric regions during prometaphase, where it protects centromeric cohesin via shugoshin. Reason: UniProt explicitly states: 'In prometaphase cells, but not in anaphase cells, localizes at centromeres' (PMID:16541025). This is supported by the SGO1/SGO2 interaction and centromeric cohesin protection function. Supporting Evidence: PMID:16541025 Shugoshin collaborates with protein phosphatase 2A to protect cohesin |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | ACCEPT | Summary: PPP2CA localizes to spindle poles during mitosis. Reason: UniProt subcellular location states: 'During mitosis, also found at spindle poles' (PMID:16541025). This is consistent with PP2A roles in mitotic regulation. |
| GO:0004722 protein serine/threonine phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: PPP2CA localizes to the nucleus, including via its role in the INTAC complex. Reason: Nuclear localization is well-established by multiple studies. UniProt cites PMID:16541025, PMID:33243860, PMID:34004147, PMID:39032490. Nuclear function includes transcription regulation via INTAC complex. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: PPP2CA associates with chromosomes, consistent with its centromeric localization and INTAC complex function on chromatin. Reason: UniProt lists Chromosome as a subcellular location (PMID:33243860, PMID:34004147). PP2A is recruited to chromatin via the Integrator complex and localizes to centromeres during mitosis (PMID:16541025). |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: PPP2CA is present in the cytoplasm. Reason: Well-established cytoplasmic localization supported by UniProt (PMID:16541025, PMID:39032490) and consistent with PP2A function in cytoplasmic signaling pathways. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000108 | ACCEPT | Summary: PPP2CA regulates transcription by RNA Polymerase II through the INTAC complex, which dephosphorylates the Pol II CTD. Reason: Well-supported by INTAC complex studies. PPP2CA dephosphorylates Pol II CTD at Ser2, Ser5, and Ser7 (PMID:33243860, PMID:34004147), thereby regulating transcription elongation. This IEA annotation based on logical inference is correct. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000002 | ACCEPT | Summary: PPP2CA has hydrolase activity as a phosphoprotein phosphatase that hydrolyzes phospho-ester bonds on serine/threonine residues. Reason: This is a correct but very broad parent term. PPP2CA is a hydrolase (phosphoester hydrolysis). More specific terms (GO:0004722) are also annotated, but this IEA annotation from InterPro is not wrong. |
| GO:0090443 FAR/SIN/STRIPAK complex | IEA GO_REF:0000117 | ACCEPT | Summary: PPP2CA is a component of the STRIPAK complex as the catalytic subunit. Reason: Cryo-EM structure of human STRIPAK at 3.2 A confirms PPP2CA (PP2AC) is a core component, directly interacting with PP2AA, STRN3, and STRIP1 (PMID:33633399). STRIPAK regulates Hippo signaling by dephosphorylating MST1/2. Supporting Evidence: PMID:33633399 STRIPAK is established as a noncanonical PP2A complex with four copies of regulatory STRN3 for enhanced signal integration |
| GO:0005515 protein binding | IPI PMID:11591705 Protein phosphatase 2A interacts with and directly dephospho... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:11839802 Integrin alpha 2 beta 1 promotes activation of protein phosp... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:12963337 Parallel purification of three catalytic subunits of the pro... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:1328865 Identification of binding sites on the regulatory A subunit ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:15467457 A dynamic equilibrium between CDKs and PP2A modulates phosph... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:15761952 Single-step Strep-tag purification for the isolation and ide... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:16044149 Activation of the protein kinase B pathway by the HPV-16 E7 ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:16085932 A novel, evolutionarily conserved protein phosphatase comple... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:16126728 Positive regulation of IkappaB kinase signaling by protein s... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:16129692 Distinct protein phosphatase 2A heterotrimers modulate growt... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:16239230 Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by prote... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:16456541 B56-containing PP2A dephosphorylate ERK and their activity i... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:16541025 Shugoshin collaborates with protein phosphatase 2A to protec... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:16764867 Interaction of nucleoredoxin with protein phosphatase 2A. | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:17055435 Structure of protein phosphatase 2A core enzyme bound to tum... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:17274953 Methylation of the C-terminal leucine residue of the PP2A ca... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:17384681 Identification of a PP2A-interacting protein that functions ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:17529992 Structural and biochemical insights into the regulation of p... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:17540176 The tumor suppressor PP2A Abeta regulates the RalA GTPase. | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:18394995 Structural mechanism of demethylation and inactivation of pr... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:18715871 PP4R4/KIAA1622 forms a novel stable cytosolic complex with p... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:18716626 Heterochromatin links to centromeric protection by recruitin... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:18782753 A PP2A phosphatase high density interaction network identifi... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:18977201 Physical association of GPR54 C-terminal with protein phosph... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:19060904 An empirical framework for binary interactome mapping. | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:19156129 An integrated workflow for charting the human interaction pr... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:19293187 PME-1 protects extracellular signal-regulated kinase pathway... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:19915589 The chromosomal association of condensin II is regulated by ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:20927323 Protein phosphatase 2A negatively regulates eukaryotic initi... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:21460856 ATM-mediated phosphorylation activates the tumor-suppressive... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:21806989 Mechanism of inhibition of PP2A activity and abnormal hyperp... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:23892082 A positive role of mammalian Tip41-like protein, TIPRL, in t... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:24126060 Over expression of PPP2R2C inhibits human glioma cells growt... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:25531779 STRIPAK components determine mode of cancer cell migration a... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:26256536 The Mechanism of ATP-Dependent Allosteric Protection of Akt ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:28330616 Systematic Analysis of Human Protein Phosphatase Interaction... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:32878885 IRF1 Promotes the Innate Immune Response to Viral Infection ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:33633399 Cryo-EM structure of the Hippo signaling integrator human ST... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:37761890 Novel Variants of PPP2R1A in Catalytic Subunit Binding Domai... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:38123684 Cryo-EM structures of PP2A:B55-FAM122A and PP2A:B55-ARPP19. | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:7592815 Identification of a new family of protein phosphatase 2A reg... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:8392071 Structure and expression of a 72-kDa regulatory subunit of p... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:8617797 Identification of a novel protein phosphatase 2A regulatory ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:9647778 Alpha 4 associates with protein phosphatases 2A, 4, and 6. | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0000159 protein phosphatase type 2A complex | IEA GO_REF:0000107 | ACCEPT | Summary: PPP2CA is a component of the protein phosphatase type 2A complex. Reason: PPP2CA is the catalytic subunit of PP2A. This is the defining complex for this protein. Supported by crystal structure (PMID:17055435), holoenzyme structure (PMID:17174897), and extensive biochemical characterization. Supporting Evidence: PMID:17055435 Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins |
| GO:0005829 cytosol | IEA GO_REF:0000107 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005886 plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation suggesting PPP2CA localizes to plasma membrane. Reason: PP2A has been reported at cell membranes in some contexts. The deep research notes localization to 'cell membrane'. However, this is not a primary localization and likely reflects B-subunit-dependent targeting to specific membrane-associated complexes. |
| GO:0043029 T cell homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PP2Acalpha is required for CD8+ T-cell homeostasis, supported by mouse conditional deletion studies. Reason: A 2024 study (Zhou et al., Eur J Immunol) showed conditional PP2Acalpha deletion in T cells causes defective CD8+ T-cell homeostasis. While biologically significant, this is a tissue-specific phenotype rather than a core molecular function. The ISS annotation is based on mouse ortholog data. |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation suggesting PPP2CA localizes to synapses. PP2A is abundant in neurons and regulates synaptic proteins. Reason: PP2A is the major phosphatase in neurons (>70% of neuronal phosphatase activity) and regulates tau phosphorylation and other synaptic proteins. Synaptic localization is plausible but represents tissue-specific function rather than core function. |
| GO:0050811 GABA receptor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation suggesting PPP2CA binds GABA receptors. PP2A has been implicated in regulation of GABA receptor phosphorylation in neurons. Reason: PP2A is known to regulate GABA receptor phosphorylation state in neurons, which is consistent with the very high abundance of PP2A in neuronal tissue (>70% of neuronal phosphatases). However, this is one of many substrate interactions and not a core defining function of PPP2CA. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PP2A negatively regulates PI3K/AKT signaling by dephosphorylating AKT1 at Ser-473. Reason: PP2A dephosphorylation of AKT1 is supported by UniProt ('Together with RACK1 adapter, mediates dephosphorylation of AKT1 at Ser-473') and by PMID:21806946 (IMP). The 2024 T-cell study also implicates mTORC1 and AKT as PP2A downstream nodes. However, AKT regulation is one of many signaling roles of PP2A. |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: PP2A catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting NLRP3 inflammasome assembly (by similarity from mouse). Reason: UniProt states 'Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity)'. This is based on mouse ortholog data and represents one of many substrate-specific effects. Not a core function. |
| GO:1904539 negative regulation of glycolytic process through fructose-6-phosphate | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA annotation suggesting PPP2CA negatively regulates glycolysis through fructose-6-phosphate. Reason: This is a very specific metabolic process annotation from Ensembl Compara (IEA). While PP2A may regulate glycolytic enzymes via dephosphorylation, this is a downstream pleiotropic effect rather than a core function. |
| GO:0004721 phosphoprotein phosphatase activity | IDA PMID:30595372 De Novo Mutations Affecting the Catalytic CΞ± Subunit of PP2A... | ACCEPT | Summary: PPP2CA contributes phosphoprotein phosphatase activity as part of the PP2A holoenzyme complex. Reason: PPP2CA provides the catalytic phosphatase activity within the PP2A complex. The contributes_to qualifier is appropriate since the holoenzyme is required for full substrate-directed activity. The more specific GO:0004722 is also annotated. Supporting Evidence: PMID:30595372 PP2A, PPP2CA, Cause Syndromic Intellectual Disability |
| GO:0008287 protein serine/threonine phosphatase complex | IDA PMID:28167675 ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphat... | ACCEPT | Summary: PPP2CA is part of a protein serine/threonine phosphatase complex. Reason: PPP2CA functions in the PP2A complex, which is a serine/threonine phosphatase complex. This is a general cellular component term that is correct. PMID:28167675 identifies ARPP-16 as a PP2A inhibitor in the context of a serine/threonine phosphatase complex. |
| GO:0005634 nucleus | NAS PMID:32647223 INTS10-INTS13-INTS14 form a functional module of Integrator ... | ACCEPT | Summary: PPP2CA localizes to the nucleus, including via its role in the INTAC complex. Reason: Nuclear localization is well-established by multiple studies. UniProt cites PMID:16541025, PMID:33243860, PMID:34004147, PMID:39032490. Nuclear function includes transcription regulation via INTAC complex. |
| GO:0016180 snRNA processing | NAS PMID:16239144 Integrator, a multiprotein mediator of small nuclear RNA pro... | KEEP AS NON CORE | Summary: PPP2CA is linked to snRNA processing through the Integrator complex, which is involved in snRNA 3' end processing. Reason: The Integrator complex mediates snRNA 3' end processing (PMID:16239144). PPP2CA is part of the INTAC complex (Integrator + PP2A), but the endonuclease rather than the phosphatase module is primarily responsible for snRNA cleavage. PPP2CA's role in snRNA processing is indirect via its association with Integrator. |
| GO:0034243 regulation of transcription elongation by RNA polymerase II | IDA PMID:38570683 Structural basis of Integrator-dependent RNA polymerase II t... | ACCEPT | Summary: PPP2CA regulates transcription elongation by RNA polymerase II through the INTAC complex. Reason: Within the INTAC complex, PPP2CA dephosphorylates Pol II CTD and SUPT5H/SPT5, thereby preventing transcriptional elongation (PMID:38570683, PMID:34004147). This is a well-established function of the INTAC complex. |
| GO:0035330 regulation of hippo signaling | NAS PMID:33633399 Cryo-EM structure of the Hippo signaling integrator human ST... | KEEP AS NON CORE | Summary: PPP2CA regulates Hippo signaling through its role in the STRIPAK complex. Reason: This is the parent term of GO:0035331 (negative regulation of hippo signaling). Since the more specific child term is already annotated, this broader term is redundant but not incorrect. Hippo regulation is one of many pathways modulated by PP2A. |
| GO:0097706 vascular endothelial cell response to oscillatory fluid shear stress | TAS Reactome:R-HSA-9860927 | MARK AS OVER ANNOTATED | Summary: Reactome annotation linking PP2A to endothelial cell response to oscillatory shear stress. Reason: This is a highly specific process term from Reactome. While PP2A may participate in signaling downstream of PIEZO1/integrins, this level of specificity likely represents an over-annotation. PPP2CA is a general phosphatase, not specifically evolved for shear stress response. |
| GO:0004722 protein serine/threonine phosphatase activity | TAS Reactome:R-HSA-9865226 | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0160240 RNA polymerase II transcription initiation surveillance | IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po... | ACCEPT | Summary: PPP2CA participates in RNA polymerase II transcription initiation surveillance as part of the INTAC complex. Reason: The INTAC complex drives premature transcription termination of unfavorably configured transcripts by dephosphorylating Pol II CTD and SUPT5H/SPT5. This represents a quality checkpoint during transcription elongation (PMID:33243860, PMID:34004147, PMID:37080207, PMID:38570683). UniProt describes PPP2CA as 'Key mediator of a quality checkpoint during transcription elongation as part of the Integrator-PP2A (INTAC) complex'. |
| GO:0160240 RNA polymerase II transcription initiation surveillance | IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c... | ACCEPT | Summary: PPP2CA participates in RNA polymerase II transcription initiation surveillance as part of the INTAC complex. Reason: The INTAC complex drives premature transcription termination of unfavorably configured transcripts by dephosphorylating Pol II CTD and SUPT5H/SPT5. This represents a quality checkpoint during transcription elongation (PMID:33243860, PMID:34004147, PMID:37080207, PMID:38570683). UniProt describes PPP2CA as 'Key mediator of a quality checkpoint during transcription elongation as part of the Integrator-PP2A (INTAC) complex'. |
| GO:0160240 RNA polymerase II transcription initiation surveillance | IDA PMID:37080207 INTAC endonuclease and phosphatase modules differentially re... | ACCEPT | Summary: PPP2CA participates in RNA polymerase II transcription initiation surveillance as part of the INTAC complex. Reason: The INTAC complex drives premature transcription termination of unfavorably configured transcripts by dephosphorylating Pol II CTD and SUPT5H/SPT5. This represents a quality checkpoint during transcription elongation (PMID:33243860, PMID:34004147, PMID:37080207, PMID:38570683). UniProt describes PPP2CA as 'Key mediator of a quality checkpoint during transcription elongation as part of the Integrator-PP2A (INTAC) complex'. |
| GO:0160240 RNA polymerase II transcription initiation surveillance | IDA PMID:38570683 Structural basis of Integrator-dependent RNA polymerase II t... | ACCEPT | Summary: PPP2CA participates in RNA polymerase II transcription initiation surveillance as part of the INTAC complex. Reason: The INTAC complex drives premature transcription termination of unfavorably configured transcripts by dephosphorylating Pol II CTD and SUPT5H/SPT5. This represents a quality checkpoint during transcription elongation (PMID:33243860, PMID:34004147, PMID:37080207, PMID:38570683). UniProt describes PPP2CA as 'Key mediator of a quality checkpoint during transcription elongation as part of the Integrator-PP2A (INTAC) complex'. |
| GO:0160232 INTAC complex | IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po... | ACCEPT | Summary: PPP2CA is a component of the INTAC (Integrator-PP2A) complex. Reason: PPP2CA is the phosphatase component of the INTAC complex, confirmed by cryo-EM structures (PMID:33243860, PMID:34762484, PMID:36869814, PMID:38570683) and functional studies (PMID:34004147, PMID:37080207). UniProt confirms PPP2CA as 'Phosphatase component of the Integrator-PP2A (INTAC) complex'. 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: PPP2CA is a component of the INTAC (Integrator-PP2A) complex. Reason: PPP2CA is the phosphatase component of the INTAC complex, confirmed by cryo-EM structures (PMID:33243860, PMID:34762484, PMID:36869814, PMID:38570683) and functional studies (PMID:34004147, PMID:37080207). UniProt confirms PPP2CA as 'Phosphatase component of the Integrator-PP2A (INTAC) complex'. 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:34762484 Structural basis of Integrator-mediated transcription regula... | ACCEPT | Summary: PPP2CA is a component of the INTAC (Integrator-PP2A) complex. Reason: PPP2CA is the phosphatase component of the INTAC complex, confirmed by cryo-EM structures (PMID:33243860, PMID:34762484, PMID:36869814, PMID:38570683) and functional studies (PMID:34004147, PMID:37080207). UniProt confirms PPP2CA as 'Phosphatase component of the Integrator-PP2A (INTAC) complex'. 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:36869814 Structural basis of INTAC-regulated transcription. | ACCEPT | Summary: PPP2CA is a component of the INTAC (Integrator-PP2A) complex. Reason: PPP2CA is the phosphatase component of the INTAC complex, confirmed by cryo-EM structures (PMID:33243860, PMID:34762484, PMID:36869814, PMID:38570683) and functional studies (PMID:34004147, PMID:37080207). UniProt confirms PPP2CA as 'Phosphatase component of the Integrator-PP2A (INTAC) complex'. 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:37080207 INTAC endonuclease and phosphatase modules differentially re... | ACCEPT | Summary: PPP2CA is a component of the INTAC (Integrator-PP2A) complex. Reason: PPP2CA is the phosphatase component of the INTAC complex, confirmed by cryo-EM structures (PMID:33243860, PMID:34762484, PMID:36869814, PMID:38570683) and functional studies (PMID:34004147, PMID:37080207). UniProt confirms PPP2CA as 'Phosphatase component of the Integrator-PP2A (INTAC) complex'. 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:38570683 Structural basis of Integrator-dependent RNA polymerase II t... | ACCEPT | Summary: PPP2CA is a component of the INTAC (Integrator-PP2A) complex. Reason: PPP2CA is the phosphatase component of the INTAC complex, confirmed by cryo-EM structures (PMID:33243860, PMID:34762484, PMID:36869814, PMID:38570683) and functional studies (PMID:34004147, PMID:37080207). UniProt confirms PPP2CA as 'Phosphatase component of the Integrator-PP2A (INTAC) complex'. Supporting Evidence: PMID:33243860 we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC |
| GO:0031113 regulation of microtubule polymerization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PP2A regulates microtubule polymerization, consistent with its role as the major phosphatase for microtubule-associated proteins. Reason: UniProt states 'PP2A is the major phosphatase for microtubule-associated proteins (MAPs)' (PMID:22613722). MAP dephosphorylation affects microtubule dynamics. However, this is one of many PP2A functions and not the core defining function. ISS annotation from ortholog data. |
| GO:0090090 negative regulation of canonical Wnt signaling pathway | IMP PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | KEEP AS NON CORE | Summary: PP2A negatively regulates canonical Wnt signaling. PMID:20080667 shows DAB2IP modulates PP2A-GSK3B interaction affecting Wnt/beta-catenin pathway. Reason: PP2A interacts with AXIN1 (PMID:9920888) and GSK3B (PMID:20080667) in the Wnt pathway context. However, Wnt signaling regulation is one of many pathways modulated by PP2A and is not a core function of PPP2CA itself. |
| GO:0000785 chromatin | IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po... | ACCEPT | Summary: PPP2CA associates with chromatin as part of the INTAC complex. Reason: PPP2CA is recruited to chromatin via its association with the Integrator complex (PMID:33243860, PMID:34004147). UniProt states: 'Recruited to chromatin and transcription pause-release checkpoint via its association with the Integrator complex'. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II |
| GO:0000785 chromatin | IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c... | ACCEPT | Summary: PPP2CA associates with chromatin as part of the INTAC complex. Reason: PPP2CA is recruited to chromatin via its association with the Integrator complex (PMID:33243860, PMID:34004147). UniProt states: 'Recruited to chromatin and transcription pause-release checkpoint via its association with the Integrator complex'. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c... | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0005634 nucleus | IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po... | ACCEPT | Summary: PPP2CA localizes to the nucleus, including via its role in the INTAC complex. Reason: Nuclear localization is well-established by multiple studies. UniProt cites PMID:16541025, PMID:33243860, PMID:34004147, PMID:39032490. Nuclear function includes transcription regulation via INTAC complex. |
| GO:0005634 nucleus | IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c... | ACCEPT | Summary: PPP2CA localizes to the nucleus, including via its role in the INTAC complex. Reason: Nuclear localization is well-established by multiple studies. UniProt cites PMID:16541025, PMID:33243860, PMID:34004147, PMID:39032490. Nuclear function includes transcription regulation via INTAC complex. |
| GO:0180006 RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity | IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po... | ACCEPT | Summary: PPP2CA has RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity as part of the INTAC complex. Reason: PMID:33243860 demonstrates that INTAC dephosphorylates Pol II CTD at Ser2 (as well as Ser5 and Ser7). This specific phosphatase activity is a core function within the INTAC complex. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0180006 RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity | IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c... | ACCEPT | Summary: PPP2CA has RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity as part of the INTAC complex. Reason: PMID:33243860 demonstrates that INTAC dephosphorylates Pol II CTD at Ser2 (as well as Ser5 and Ser7). This specific phosphatase activity is a core function within the INTAC complex. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0180007 RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity | IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po... | ACCEPT | Summary: PPP2CA has RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity as part of the INTAC complex. Reason: PMID:33243860 demonstrates INTAC dephosphorylates Pol II CTD at Ser5. This specific phosphatase activity is well-supported. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0180007 RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity | IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c... | ACCEPT | Summary: PPP2CA has RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity as part of the INTAC complex. Reason: PMID:33243860 demonstrates INTAC dephosphorylates Pol II CTD at Ser5. This specific phosphatase activity is well-supported. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0180008 RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity | IDA PMID:33243860 Identification of Integrator-PP2A complex (INTAC), an RNA po... | ACCEPT | Summary: PPP2CA has RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity as part of the INTAC complex. Reason: PMID:33243860 demonstrates INTAC dephosphorylates Pol II CTD at Ser7. This specific phosphatase activity is well-supported. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0180008 RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity | IDA PMID:34004147 The PP2A-Integrator-CDK9 axis fine-tunes transcription and c... | ACCEPT | Summary: PPP2CA has RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity as part of the INTAC complex. Reason: PMID:33243860 demonstrates INTAC dephosphorylates Pol II CTD at Ser7. This specific phosphatase activity is well-supported. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0005634 nucleus | IDA PMID:39032490 Cytoplasmic binding partners of the Integrator endonuclease ... | ACCEPT | Summary: PPP2CA localizes to the nucleus, including via its role in the INTAC complex. Reason: Nuclear localization is well-established by multiple studies. UniProt cites PMID:16541025, PMID:33243860, PMID:34004147, PMID:39032490. Nuclear function includes transcription regulation via INTAC complex. |
| GO:0005829 cytosol | IDA PMID:39032490 Cytoplasmic binding partners of the Integrator endonuclease ... | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0035331 negative regulation of hippo signaling | IDA PMID:33633399 Cryo-EM structure of the Hippo signaling integrator human ST... | KEEP AS NON CORE | Summary: PPP2CA, as part of the STRIPAK complex, negatively regulates Hippo signaling by dephosphorylating MST1/2 kinases. Reason: PP2A-STRIPAK dephosphorylates MST1/2 T-loop, restraining Hippo pathway activation (PMID:33633399, PMID:29063833). This is a well-characterized function of the STRIPAK complex but is one of many signaling pathways regulated by PP2A, not the core defining function. Supporting Evidence: PMID:33633399 STRIPAK is a key negative regulator of the Hippo pathway |
| GO:0090443 FAR/SIN/STRIPAK complex | IDA PMID:33633399 Cryo-EM structure of the Hippo signaling integrator human ST... | ACCEPT | Summary: PPP2CA is a component of the STRIPAK complex as the catalytic subunit. Reason: Cryo-EM structure of human STRIPAK at 3.2 A confirms PPP2CA (PP2AC) is a core component, directly interacting with PP2AA, STRN3, and STRIP1 (PMID:33633399). STRIPAK regulates Hippo signaling by dephosphorylating MST1/2. Supporting Evidence: PMID:33633399 STRIPAK is established as a noncanonical PP2A complex with four copies of regulatory STRN3 for enhanced signal integration |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:29063833 SAV1 promotes Hippo kinase activation through antagonizing t... | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0005737 cytoplasm | IDA PMID:29063833 SAV1 promotes Hippo kinase activation through antagonizing t... | ACCEPT | Summary: PPP2CA is present in the cytoplasm. Reason: Well-established cytoplasmic localization supported by UniProt (PMID:16541025, PMID:39032490) and consistent with PP2A function in cytoplasmic signaling pathways. |
| GO:0035331 negative regulation of hippo signaling | IDA PMID:29063833 SAV1 promotes Hippo kinase activation through antagonizing t... | KEEP AS NON CORE | Summary: PPP2CA, as part of the STRIPAK complex, negatively regulates Hippo signaling by dephosphorylating MST1/2 kinases. Reason: PP2A-STRIPAK dephosphorylates MST1/2 T-loop, restraining Hippo pathway activation (PMID:33633399, PMID:29063833). This is a well-characterized function of the STRIPAK complex but is one of many signaling pathways regulated by PP2A, not the core defining function. Supporting Evidence: PMID:33633399 STRIPAK is a key negative regulator of the Hippo pathway |
| GO:0090443 FAR/SIN/STRIPAK complex | IDA PMID:29063833 SAV1 promotes Hippo kinase activation through antagonizing t... | ACCEPT | Summary: PPP2CA is a component of the STRIPAK complex as the catalytic subunit. Reason: Cryo-EM structure of human STRIPAK at 3.2 A confirms PPP2CA (PP2AC) is a core component, directly interacting with PP2AA, STRN3, and STRIP1 (PMID:33633399). STRIPAK regulates Hippo signaling by dephosphorylating MST1/2. Supporting Evidence: PMID:33633399 STRIPAK is established as a noncanonical PP2A complex with four copies of regulatory STRN3 for enhanced signal integration |
| GO:0035556 intracellular signal transduction | NAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero... | KEEP AS NON CORE | Summary: PPP2CA/PP2A is involved in intracellular signal transduction through dephosphorylation of multiple signaling proteins. Reason: While PP2A is a major regulator of signal transduction pathways (Wnt, Hippo, MAPK, mTOR, AKT), this term is very broad. The core function is protein dephosphorylation; signal transduction is a downstream consequence. |
| GO:0004722 protein serine/threonine phosphatase activity | TAS PMID:21131359 Nuclear tau, a key player in neuronal DNA protection. | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0043029 T cell homeostasis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PP2Acalpha is required for CD8+ T-cell homeostasis, supported by mouse conditional deletion studies. Reason: A 2024 study (Zhou et al., Eur J Immunol) showed conditional PP2Acalpha deletion in T cells causes defective CD8+ T-cell homeostasis. While biologically significant, this is a tissue-specific phenotype rather than a core molecular function. The ISS annotation is based on mouse ortholog data. |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PP2A negatively regulates PI3K/AKT signaling by dephosphorylating AKT1 at Ser-473. Reason: PP2A dephosphorylation of AKT1 is supported by UniProt ('Together with RACK1 adapter, mediates dephosphorylation of AKT1 at Ser-473') and by PMID:21806946 (IMP). The 2024 T-cell study also implicates mTORC1 and AKT as PP2A downstream nodes. However, AKT regulation is one of many signaling roles of PP2A. |
| GO:1900227 positive regulation of NLRP3 inflammasome complex assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: PP2A catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting NLRP3 inflammasome assembly (by similarity from mouse). Reason: UniProt states 'Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity)'. This is based on mouse ortholog data and represents one of many substrate-specific effects. Not a core function. |
| GO:0004725 protein tyrosine phosphatase activity | IDA PMID:15525651 Galpha12 directly interacts with PP2A: evidence FOR Galpha12... | MARK AS OVER ANNOTATED | Summary: PMID:15525651 reports that Galpha12 stimulates PP2A activity ~300%. The GO annotation claims protein tyrosine phosphatase activity, but the abstract discusses general PP2A stimulation and tau dephosphorylation (a Ser/Thr substrate). PP2A is canonically a Ser/Thr phosphatase. Reason: While PMID:15525651 reports in vitro phosphotyrosine phosphatase activity for PP2A, this is not the canonical or well-established function. PP2A is universally recognized as a Ser/Thr phosphatase (EC 3.1.3.16). The tyrosine phosphatase activity reported in this single study may represent a minor or artificial in vitro activity. The UniProt entry does not list tyrosine phosphatase activity. Supporting Evidence: PMID:15525651 approximately 300% stimulation of PP2A activity |
| GO:0051898 negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:21806946 Neurotensin signaling activates microRNAs-21 and -155 and Ak... | KEEP AS NON CORE | Summary: PP2A negatively regulates PI3K/AKT signaling by dephosphorylating AKT1 at Ser-473. Reason: PP2A dephosphorylation of AKT1 is supported by UniProt ('Together with RACK1 adapter, mediates dephosphorylation of AKT1 at Ser-473') and by PMID:21806946 (IMP). The 2024 T-cell study also implicates mTORC1 and AKT as PP2A downstream nodes. However, AKT regulation is one of many signaling roles of PP2A. |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:25438055 AMBRA1 links autophagy to cell proliferation and tumorigenes... | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:30513302 AMBRA1 Controls Regulatory T-Cell Differentiation and Homeos... | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:2000045 regulation of G1/S transition of mitotic cell cycle | IDA PMID:25438055 AMBRA1 links autophagy to cell proliferation and tumorigenes... | KEEP AS NON CORE | Summary: PMID:25438055 shows PPP2CA/PP2A dephosphorylates MYC (via AMBRA1), promoting MYC degradation and thereby regulating G1/S transition. Reason: Cell cycle regulation is a major PP2A function, and G1/S transition regulation via MYC dephosphorylation is well-supported (PMID:25438055). However, this is one of many cell cycle roles and the broader mitotic cell cycle term is already accepted. |
| GO:0006470 protein dephosphorylation | IMP PMID:33108758 CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promote... | ACCEPT | Summary: PPP2CA catalyzes protein dephosphorylation as its core biological process. Reason: Protein dephosphorylation is the central biological process catalyzed by PPP2CA/PP2A. Supported by extensive evidence including substrate mapping (deep research: 6,280 phosphopeptides increased upon PPP2CA degradation), individual substrate studies (PMID:33108758 for WEE1, PMID:25438055 for MYC, PMID:30513302 for FOXO3), and the EC number 3.1.3.16. |
| GO:0005515 protein binding | IPI PMID:17974561 Tesk1 interacts with Spry2 to abrogate its inhibition of ERK... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:30595372 De Novo Mutations Affecting the Catalytic CΞ± Subunit of PP2A... | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0005515 protein binding | IPI PMID:30595372 De Novo Mutations Affecting the Catalytic CΞ± Subunit of PP2A... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:30611118 Mitogenic Signals Stimulate the CREB Coactivator CRTC3 throu... | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0005515 protein binding | IPI PMID:30611118 Mitogenic Signals Stimulate the CREB Coactivator CRTC3 throu... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0048156 tau protein binding | NAS PMID:28386764 Roles of tau protein in health and disease. | KEEP AS NON CORE | Summary: PP2A is reported to dephosphorylate tau and to bind tau, relevant to neurodegeneration. Reason: PP2A is described as a major tau phosphatase (PMID:10640627, PMID:16262633, PMID:28386764). While tau dephosphorylation is biologically important, it is one of many PP2A substrates and not a core defining function. Tau binding is context-dependent and mediated by specific holoenzymes (B55 family). |
| GO:0005515 protein binding | IPI PMID:16258073 A direct interaction between the N terminus of adenylyl cycl... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0045121 membrane raft | IDA PMID:16258073 A direct interaction between the N terminus of adenylyl cycl... | KEEP AS NON CORE | Summary: PMID:16258073 reports PP2A catalytic subunit localizes to membrane rafts in the context of ADCY8 interaction. Reason: The ADCY8 interaction study (PMID:16258073) provides direct evidence for membrane raft localization. However, this is likely context-dependent rather than a primary localization site. |
| GO:0005515 protein binding | IPI PMID:27588481 FAM122A, a new endogenous inhibitor of protein phosphatase 2... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:28609714 MFHAS1 suppresses TLR4 signaling pathway via induction of PP... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0004721 phosphoprotein phosphatase activity | TAS PMID:28386764 Roles of tau protein in health and disease. | ACCEPT | Summary: General phosphoprotein phosphatase activity annotation for PPP2CA. Reason: This is a parent term of GO:0004722. Acceptable as a broader annotation. Supporting Evidence: PMID:30595372 PP2A, PPP2CA, Cause Syndromic Intellectual Disability |
| GO:0004722 protein serine/threonine phosphatase activity | TAS PMID:28386764 Roles of tau protein in health and disease. | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0010288 response to lead ion | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: PP2A activity is affected by lead exposure. PMID:22387731 reports lead-induced over-activation of PP2A in rat hippocampus. Reason: PMID:22387731 reports lead exposure affects PP1 and PP2A activity in rat brain. However, this describes an environmental toxicology effect rather than a biological function of PPP2CA. The protein responds to lead by being affected, but this is not a functional annotation of the gene product. |
| GO:0010288 response to lead ion | TAS PMID:22387731 Over activation of hippocampal serine/threonine protein phos... | MARK AS OVER ANNOTATED | Summary: PP2A activity is affected by lead exposure. PMID:22387731 reports lead-induced over-activation of PP2A in rat hippocampus. Reason: PMID:22387731 reports lead exposure affects PP1 and PP2A activity in rat brain. However, this describes an environmental toxicology effect rather than a biological function of PPP2CA. The protein responds to lead by being affected, but this is not a functional annotation of the gene product. |
| GO:0004722 protein serine/threonine phosphatase activity | ISS GO_REF:0000024 | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0004722 protein serine/threonine phosphatase activity | TAS PMID:10640627 Regulation of phosphorylation of neuronal microtubule-associ... | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0004722 protein serine/threonine phosphatase activity | TAS PMID:16262633 Contributions of protein phosphatases PP1, PP2A, PP2B and PP... | ACCEPT | Summary: PPP2CA is the catalytic subunit of PP2A, a well-established serine/threonine phosphatase (EC 3.1.3.16). This is the core molecular function, supported by extensive biochemical, structural, and genetic evidence. Reason: This is the primary molecular function of PPP2CA. PP2A dephosphorylates protein serine/threonine residues. Confirmed by crystal structures (PMID:17055435), enzymatic assays (PMID:1848668, PMID:30595372, PMID:30611118), and INTAC complex activity (PMID:33243860, PMID:34004147). The deep research confirms PP2A accounts for ~50-70% of total Ser/Thr phosphatase activity. Supporting Evidence: PMID:33243860 the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 |
| GO:0046982 protein heterodimerization activity | IPI PMID:9847399 Binding specificity of protein phosphatase 2A core enzyme fo... | ACCEPT | Summary: PPP2CA forms a heterodimer with the A scaffold subunit (PPP2R1A) as the PP2A core enzyme. Reason: PPP2CA forms a core heterodimer with PPP2R1A (the A subunit). This is well-established structurally (PMID:17055435, PMID:38123684) and functionally. PMID:9847399 specifically addresses binding specificity of the PP2A core enzyme. Supporting Evidence: PMID:9847399 Binding specificity of protein phosphatase 2A core enzyme for regulatory B subunits and T antigens |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: HDA annotation from PMID:20458337 identifies PPP2CA in B-cell exosomes by mass spectrometry. Reason: High-throughput proteomics data. PPP2CA was detected in exosomes but this likely reflects its high cellular abundance (~1% of total protein) rather than a specific exosomal function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295599 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295609 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295613 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295622 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295632 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1549564 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2995388 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927813 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927830 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-927836 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-934559 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9667965 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9865226 | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0005515 protein binding | IPI PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0010719 negative regulation of epithelial to mesenchymal transition | IMP PMID:20080667 Role of DAB2IP in modulating epithelial-to-mesenchymal trans... | KEEP AS NON CORE | Summary: PMID:20080667 implicates PP2A in negative regulation of epithelial-to-mesenchymal transition via DAB2IP-mediated modulation. Reason: This is a downstream consequence of PP2A-mediated signaling rather than a core function. The study (PMID:20080667) shows DAB2IP modulates PP2A activity affecting EMT, but this is a pleiotropic effect rather than a primary function. |
| GO:0000159 protein phosphatase type 2A complex | IDA PMID:17055435 Structure of protein phosphatase 2A core enzyme bound to tum... | ACCEPT | Summary: PPP2CA is a component of the protein phosphatase type 2A complex. Reason: PPP2CA is the catalytic subunit of PP2A. This is the defining complex for this protein. Supported by crystal structure (PMID:17055435), holoenzyme structure (PMID:17174897), and extensive biochemical characterization. Supporting Evidence: PMID:17055435 Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins |
| GO:0000159 protein phosphatase type 2A complex | IDA PMID:17174897 Structure of the protein phosphatase 2A holoenzyme. | ACCEPT | Summary: PPP2CA is a component of the protein phosphatase type 2A complex. Reason: PPP2CA is the catalytic subunit of PP2A. This is the defining complex for this protein. Supported by crystal structure (PMID:17055435), holoenzyme structure (PMID:17174897), and extensive biochemical characterization. Supporting Evidence: PMID:17055435 Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins |
| GO:0005515 protein binding | IPI PMID:17485487 Tripin/hSgo2 recruits MCAK to the inner centromere to correc... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:16580887 PP2A is required for centromeric localization of Sgo1 and pr... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0005515 protein binding | IPI PMID:17245430 A specific PP2A regulatory subunit, B56gamma, mediates DNA d... | MARK AS OVER ANNOTATED | Summary: Generic protein binding annotation for PPP2CA based on experimental protein-protein interaction data. Reason: Per curation guidelines, protein binding (GO:0005515) is uninformative and does not describe the actual function of PPP2CA. PPP2CA interacts with numerous proteins as part of its role as a phosphatase catalytic subunit (A subunits, B subunits, substrates, regulators, viral oncoproteins). More specific molecular function terms should be used. The interactions themselves are well-documented but this GO term adds no functional insight. |
| GO:0000159 protein phosphatase type 2A complex | TAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero... | ACCEPT | Summary: PPP2CA is a component of the protein phosphatase type 2A complex. Reason: PPP2CA is the catalytic subunit of PP2A. This is the defining complex for this protein. Supported by crystal structure (PMID:17055435), holoenzyme structure (PMID:17174897), and extensive biochemical characterization. Supporting Evidence: PMID:17055435 Structure of protein phosphatase 2A core enzyme bound to tumor-inducing toxins |
| GO:0005634 nucleus | NAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero... | ACCEPT | Summary: PPP2CA localizes to the nucleus, including via its role in the INTAC complex. Reason: Nuclear localization is well-established by multiple studies. UniProt cites PMID:16541025, PMID:33243860, PMID:34004147, PMID:39032490. Nuclear function includes transcription regulation via INTAC complex. |
| GO:0005739 mitochondrion | NAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero... | KEEP AS NON CORE | Summary: NAS annotation from PMID:11007961 suggests mitochondrial localization of PP2A. Reason: Some PP2A holoenzymes have been reported to associate with mitochondria, consistent with PP2A roles in apoptosis regulation. However, this is not a primary localization and the NAS evidence code indicates non-traceable author statement. |
| GO:0005829 cytosol | TAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero... | ACCEPT | Summary: PPP2CA localizes to the cytosol, which is a well-established localization for PP2A. Reason: PP2A is present in the cytosol as supported by UniProt subcellular location (PMID:16541025, PMID:39032490), immunofluorescence, and fractionation studies. The deep research confirms PP2A localization includes cytoplasm. |
| GO:0006470 protein dephosphorylation | TAS PMID:2849764 The nucleotide sequence of the cDNA encoding the human lung ... | ACCEPT | Summary: PPP2CA catalyzes protein dephosphorylation as its core biological process. Reason: Protein dephosphorylation is the central biological process catalyzed by PPP2CA/PP2A. Supported by extensive evidence including substrate mapping (deep research: 6,280 phosphopeptides increased upon PPP2CA degradation), individual substrate studies (PMID:33108758 for WEE1, PMID:25438055 for MYC, PMID:30513302 for FOXO3), and the EC number 3.1.3.16. |
| GO:0015630 microtubule cytoskeleton | NAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero... | KEEP AS NON CORE | Summary: PP2A associates with the microtubule cytoskeleton, consistent with its role as the major MAP phosphatase. Reason: PP2A is the major phosphatase for microtubule-associated proteins (PMID:22613722). The MID1-alpha4-PP2Ac complex is described as microtubule-localized. However, this is one of many localizations. NAS evidence from review (PMID:11007961). |
| GO:0016020 membrane | NAS PMID:11007961 Type 2A protein phosphatase, the complex regulator of numero... | KEEP AS NON CORE | Summary: NAS annotation from PMID:11007961 suggests membrane localization. Reason: Very broad localization term. PP2A can associate with membranes through B-subunit targeting, but this is not a primary localization. NAS evidence from a review article. |
| GO:0040008 regulation of growth | NAS PMID:11360189 Absence of PPP2R1A mutations in Wilms tumor. | KEEP AS NON CORE | Summary: PP2A regulates cell growth through its phosphatase activity on multiple substrates. Reason: PP2A regulates cell growth through dephosphorylation of numerous signaling proteins. This is a very broad term. The NAS annotation from PMID:11360189 (a study about PPP2R1A mutations in Wilms tumor) provides indirect support. |
| GO:0045595 regulation of cell differentiation | NAS PMID:11360189 Absence of PPP2R1A mutations in Wilms tumor. | KEEP AS NON CORE | Summary: PP2A has been implicated in regulation of cell differentiation. Reason: PP2A affects cell differentiation through its broad phosphatase activity. This NAS annotation from PMID:11360189 is very general and represents a pleiotropic effect rather than a core function. |
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