PPP2CB encodes the beta isoform of the catalytic subunit of protein phosphatase 2A (PP2A), a major serine/threonine phosphatase (EC 3.1.3.16). PP2Acbeta is the minor catalytic isoform (~97% identical to the alpha isoform PPP2CA, which is ~10x more abundant). The catalytic subunit uses a bimetallic Mn2+ active site to dephosphorylate phosphoserine and phosphothreonine residues on protein substrates. PP2A functions as a heterotrimeric holoenzyme consisting of a scaffold A subunit, catalytic C subunit, and one of many regulatory B subunits that confer substrate specificity and subcellular localization. Combinatorial assembly of subunit isoforms generates >70 distinct PP2A holoenzymes. PP2Acbeta is predominantly cytoplasmic and nuclear, and is also a component of the STRIPAK complex. C-terminal Leu-309 methylation by LCMT1 (reversed by PME-1) is a key regulatory mechanism controlling B subunit selection and holoenzyme assembly. PP2A opposes kinase signaling in numerous pathways including cell cycle, Wnt/beta-catenin, Ras/MAPK, NF-kappaB, and PI3K/Akt, and is a major regulator of tau phosphorylation in brain.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004722 protein serine/threonine phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PPP2CB is a well-established serine/threonine phosphoprotein phosphatase. This is the core molecular function of the protein, supported by extensive biochemical evidence and phylogenetic analysis across eukaryotes. The IBA annotation is well supported by broad phylogenetic conservation. Reason: This is the defining molecular function of PPP2CB. The protein catalyzes dephosphorylation of phosphoserine and phosphothreonine residues using a bimetallic active site. Supported by UniProt EC 3.1.3.16 assignment, deep research review, and phylogenetic inference. Supporting Evidence: PMID:8206937 Methylation of PP2Ac subunit, in vitro, increases its activity toward both phosphorylase a and a phosphopeptide. PMID:2849765 The nucleotide sequence of the cDNA encoding the human lung protein phosphatase 2A beta catalytic subunit. |
| GO:0000278 mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: PP2A holoenzymes (with B55 and B56 regulatory subunits) play essential roles in mitotic cell cycle regulation, opposing CDK-mediated phosphorylation during cell cycle transitions. The IBA annotation is phylogenetically well-supported. Reason: PP2A is a central regulator of mitotic cell cycle progression. PP2A-B55 and PP2A-B56 are required for mitotic exit, opposing CDK substrates. UniProt lists roles in kinetochore/centromere and spindle pole localization during mitosis. The phylogenetic inference is appropriate. Supporting Evidence: PMID:27880917 complementary affinity purification and proximity-based interaction proteomics approaches to generate a physical interactome for 140 human proteins harboring phosphatase catalytic domains |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PPP2CB is active in the cytosol, consistent with its role as a major cytoplasmic phosphatase. The IBA annotation is well supported by both phylogenetic evidence and experimental localization data. Reason: Cytosolic localization of PP2A catalytic subunits is well established. UniProt lists cytoplasm as a subcellular location for PPP2CB. Reactome pathways also place PPP2CB in cytosol for various signaling events. Supporting Evidence: PMID:16541025 PP2A colocalizes with shugoshin at centromeres and is required for centromeric protection. |
| GO:0000775 chromosome, centromeric region | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation derived from UniProt subcellular location vocabulary. UniProt cites PMID:16541025 (Kitajima et al. 2006) showing PP2A localizes to centromeres in prometaphase cells via interaction with SGO1. Reason: The localization is experimentally supported. UniProt states: "In prometaphase cells, but not in anaphase cells, localizes at centromeres." This is based on PMID:16541025 which directly demonstrated PP2A-SGO1 interaction at centromeres. Supporting Evidence: PMID:16541025 a specific subtype of serine/threonine protein phosphatase 2A (PP2A) associating with human shugoshin. PP2A colocalizes with shugoshin at centromeres |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location. UniProt states PP2A is found at spindle poles during mitosis, based on PMID:16541025. Reason: Spindle pole localization during mitosis is documented in UniProt subcellular location, which cites PMID:16541025. Consistent with PP2A role in mitotic regulation. Supporting Evidence: PMID:16541025 crucial--particularly at centromeres--for proper chromosome segregation in mitosis and meiosis |
| GO:0004722 protein serine/threonine phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated annotation from multiple IEA methods confirming protein serine/threonine phosphatase activity. Redundant with IBA and TAS annotations for the same term but independently valid. Reason: Correct core function. This IEA annotation is consistent with the more authoritative IBA and TAS annotations for the same GO term. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location. PPP2CB has been experimentally shown to localize to the nucleus, consistent with its role in nuclear phosphatase activity and its description as predominantly cytoplasmic and nuclear. Reason: Nuclear localization is well supported. UniProt cites PMID:16541025 and also states PPP2CB is nucleoplasmic (IDA from HPA). Deep research confirms PPP2CB is predominantly cytoplasmic and nuclear. Supporting Evidence: PMID:16541025 PP2A colocalizes with shugoshin at centromeres and is required for centromeric protection |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for cytoplasm localization. Broader than cytosol but still correct. PPP2CB is well established as a cytoplasmic protein. Reason: Cytoplasm is a broader parent term of cytosol. PPP2CB is well established in both cytosol and cytoplasm. Consistent with IBA cytosol annotation and UniProt subcellular location. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA from InterPro domain mapping. Hydrolase activity is correct but too general for a protein whose specific phosphatase activity is well characterized. The more specific GO:0004722 annotations exist. Reason: While very broad, hydrolase activity is technically correct as a parent of phosphatase activity. The more specific GO:0004722 annotations also exist. This IEA is acceptable as a domain-based annotation even though more informative terms are present. |
| GO:0090443 FAR/SIN/STRIPAK complex | IEA GO_REF:0000117 | ACCEPT | Summary: IEA from ARBA machine learning model predicting STRIPAK complex membership. This is consistent with experimental evidence from PMID:18782753 (IDA annotation also present). Reason: Correct annotation. PPP2CB was experimentally identified as part of the STRIPAK complex in PMID:18782753, and a separate IDA annotation exists. This IEA is redundant but valid. |
| GO:0005515 protein binding | IPI PMID:10698523 GSK-3beta-dependent phosphorylation of adenomatous polyposis... | MARK AS OVER ANNOTATED | Summary: IPI based on interaction with AXIN2 (Q9Y2T1). The study showed PP2A complexed with Axin dephosphorylates APC in Wnt signaling. The interaction is functionally meaningful (Wnt pathway regulation) but annotated as generic protein binding. Reason: Protein binding is uninformative. The interaction with AXIN2 reflects PP2A recruitment to the beta-catenin destruction complex. A more informative annotation would capture the specific functional context (e.g., phosphatase activity in the Wnt pathway), but that is a BP annotation, not MF. The IPI evidence does not support a more specific MF term than protein binding. Supporting Evidence: PMID:10698523 the heterodimeric form of protein phosphatase 2A (PP2A) directly bound to Axin, and PP2A complexed with Axin dephosphorylated APC phosphorylated by GSK-3beta |
| GO:0005515 protein binding | IPI PMID:16085932 A novel, evolutionarily conserved protein phosphatase comple... | MARK AS OVER ANNOTATED | Summary: IPI based on interaction with TIPRL (O75663). The study characterized a PP4 complex involved in cisplatin sensitivity. TIPRL is a known PP2A interactor and phosphatase regulator. Annotated as generic protein binding. Reason: Protein binding is uninformative. TIPRL interaction with PP2A catalytic subunits is part of the phosphatase regulatory network, but the GO term does not capture the functional significance. The primary study focused on PP4, not PP2A. Supporting Evidence: PMID:16085932 Using a combination of tandem affinity purification tagging and mass spectrometry, we characterized a novel, evolutionarily conserved protein phosphatase 4 (PP4)-containing complex |
| GO:0005515 protein binding | IPI PMID:18782753 A PP2A phosphatase high density interaction network identifi... | MARK AS OVER ANNOTATED | Summary: IPI for interaction with IGBP1/alpha4 (P78318) and STRIP1 (Q5VSL9) from the PP2A high-density interaction network study that defined the STRIPAK complex. These are well-established PP2A complex components. Reason: Protein binding is uninformative. Both IGBP1 and STRIP1 are functional PP2A-associated proteins. The interactions are better captured by the STRIPAK complex (GO:0090443) and PP2A complex (GO:0000159) annotations. Supporting Evidence: PMID:18782753 STRIPAK contains the PP2A catalytic (PP2Ac) and scaffolding (PP2A A) subunits, the striatins (PP2A regulatory B''' subunits), the striatin-associated protein Mob3, the novel proteins STRIP1 and STRIP2 |
| GO:0005515 protein binding | IPI PMID:19156129 An integrated workflow for charting the human interaction pr... | MARK AS OVER ANNOTATED | Summary: IPI for interaction with IGBP1 (P78318) from an integrated PP2A interaction proteomics workflow. This is a well-characterized PP2A regulatory interaction. Reason: Protein binding is uninformative. IGBP1/alpha4 is a known PP2A chaperone/regulatory protein. Better captured by complex membership annotations. |
| GO:0005515 protein binding | IPI PMID:20969868 LIM domain protein FHL1B interacts with PP2A catalytic Ξ² sub... | MARK AS OVER ANNOTATED | Summary: IPI for interaction with FHL1B (Q13642-2). Study demonstrated FHL1B specifically interacts with PP2A catalytic beta subunit (PPP2CB) by yeast two-hybrid and co-immunoprecipitation, suggesting a novel cell-cycle regulatory pathway. Reason: Protein binding is uninformative. The FHL1B interaction is PPP2CB-specific (not shown for PPP2CA) and linked to cell cycle regulation, which is interesting but the GO term does not capture this specificity. Supporting Evidence: PMID:20969868 FHL1B was demonstrated to interact with the beta catalytic subunit (Cbeta) of a type 2A protein phosphatase (PP2A) by yeast two-hybrid screening |
| GO:0005515 protein binding | IPI PMID:25531779 STRIPAK components determine mode of cancer cell migration a... | MARK AS OVER ANNOTATED | Summary: IPI for interaction with STRIP1 (Q5VSL9) from STRIPAK complex study on cancer cell migration and metastasis. High-throughput proteomics study. Reason: Protein binding is uninformative. STRIP1 interaction is part of STRIPAK complex, better captured by GO:0090443. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: IPI for interactions with IGBP1 (P78318) and STRIP1 (Q5VSL9) from quantitative human interactome study. Large-scale proteomics. Reason: Protein binding is uninformative. Both are known PP2A complex components. High-throughput study; interactions better captured by complex annotations. |
| GO:0005515 protein binding | IPI PMID:27880917 Phenotypic and Interaction Profiling of the Human Phosphatas... | MARK AS OVER ANNOTATED | Summary: IPI for interactions with TIPRL (O75663) and IGBP1 (P78318) from comprehensive phosphatase interactome profiling. Study identified diverse mitotic regulators among phosphatase interactors. Reason: Protein binding is uninformative. Both TIPRL and IGBP1 are established PP2A regulators. The study provides valuable interactome data but protein binding does not convey functional information. Supporting Evidence: PMID:27880917 complementary affinity purification and proximity-based interaction proteomics approaches to generate a physical interactome for 140 human proteins harboring phosphatase catalytic domains |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: IPI for interaction with STRIP1 (Q5VSL9) from architecture of the human interactome study. Large-scale proteomics. Reason: Protein binding is uninformative. STRIP1 is a STRIPAK component. High-throughput study. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: IPI for interaction with FMR1/FMRP (Q06787-7) from neurodegenerative disease interactome mapping study. The interaction was identified by mass spectrometry in a large-scale screen. Reason: Protein binding is uninformative. The FMR1 interaction is from a high-throughput screen and the functional significance for PPP2CB is unclear. PP2A may dephosphorylate FMRP but this is not demonstrated in this study. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: IPI for interactions with IGBP1 (P78318) and STRIP1 (Q5VSL9) from dual proteome-scale cell-specific interactome study. Reason: Protein binding is uninformative. Both are established PP2A complex members. High-throughput study. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: IPI for interactions with IGBP1 (P78318) and STRIP1 (Q5VSL9) from the OpenCell endogenous tagging study. Large-scale proteomics. Reason: Protein binding is uninformative. Both are known PP2A/STRIPAK complex members. High-throughput study. |
| GO:0005515 protein binding | IPI PMID:9647778 Alpha 4 associates with protein phosphatases 2A, 4, and 6. | MARK AS OVER ANNOTATED | Summary: IPI for interaction with IGBP1/alpha4 (P78318). Study demonstrated alpha4 associates constitutively with both PP2A catalytic isoforms, PP4C, and PP6C. This is a well-established functional interaction where alpha4 serves as a chaperone protecting monomeric PP2A C subunit. Reason: Protein binding is uninformative. The alpha4-PP2Ac interaction is functionally important for PP2A biogenesis and stability. However, the GO term protein binding does not capture this functional role. Supporting Evidence: PMID:9647778 alpha 4, a previously identified phosphoprotein, associates constitutively with the catalytic subunits of PP4, PP6, and both isoforms of PP2A |
| GO:0000159 protein phosphatase type 2A complex | IEA GO_REF:0000107 | ACCEPT | Summary: IEA from Ensembl Compara transfer from mouse PPP2CB. PPP2CB is a catalytic subunit of the PP2A holoenzyme complex, which is its primary functional context. Reason: Core annotation. PPP2CB is a defining component of the PP2A holoenzyme complex. Strongly supported by extensive biochemical and structural evidence. Also has a TAS annotation (PMID:8206937). |
| GO:0004721 phosphoprotein phosphatase activity | IEA GO_REF:0000107 | ACCEPT | Summary: IEA from Ensembl Compara. Phosphoprotein phosphatase activity is a parent term of protein serine/threonine phosphatase activity (GO:0004722). Correct but less specific than GO:0004722. Reason: Technically correct as PPP2CB does have phosphoprotein phosphatase activity. More specific GO:0004722 annotations are also present. This broader IEA is acceptable. |
| GO:0010288 response to lead ion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transferred from rat PPP2CB (P62716) via Ensembl Compara. Based on rat studies showing PP2A activity is affected by lead exposure. Duplicate with ISS annotation below. Reason: Response to lead ion is not a core function of PPP2CB. Lead ions can inhibit PP2A activity (as they affect many metalloenzymes), but this is a toxicological response rather than a primary biological function. Keeping as non-core given the supporting evidence from rat studies. |
| GO:0031113 regulation of microtubule polymerization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transferred from rat PPP2CB via Ensembl Compara. PP2A regulates microtubule dynamics through dephosphorylation of MAPs (MAP1b, MAP2, tau). This is consistent with PP2A's role in cytoskeletal regulation. Reason: PP2A regulates microtubule polymerization indirectly by dephosphorylating microtubule-associated proteins. PMID:10640627 showed PP2A regulates MAP1b and MAP2 phosphorylation and their microtubule binding activity. This is a downstream consequence of PP2A phosphatase activity rather than a core function of PPP2CB specifically. Supporting Evidence: PMID:10640627 The inhibition of PP2A, and to a lesser extent of PP2B, was found to induce an increased phosphorylation of MAP1b and inhibit its microtubule binding activity |
| GO:0044325 transmembrane transporter binding | IEA GO_REF:0000107 | UNDECIDED | Summary: IEA transferred from rat PPP2CB via Ensembl Compara. PP2A interacts with various membrane transporters and channels to regulate their phosphorylation state. Limited direct evidence for PPP2CB specifically. Reason: The evidence for transmembrane transporter binding is based on computational transfer from rat. While PP2A can regulate transporter phosphorylation, the specificity and directness of a binding interaction is not well documented for PPP2CB specifically. Unable to verify the original rat experimental evidence. |
| GO:0046580 negative regulation of Ras protein signal transduction | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA transferred from rat PPP2CB via Ensembl Compara. PP2A dephosphorylates components of the Ras/MAPK pathway, acting as a negative regulator. This is well established for PP2A holoenzymes generally. Reason: PP2A is well established as a negative regulator of Ras/MAPK signaling, including dephosphorylation of RAF and ERK pathway components. However, this represents one of many PP2A-regulated pathways and is driven by specific B subunit combinations rather than PPP2CB specifically. Deep research review confirms PP2A antagonizes Ras/MAPK signaling. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: IDA from HPA immunofluorescence data. PPP2CB was detected in nucleoplasm by immunofluorescence. Consistent with UniProt subcellular location annotation showing nuclear localization. Reason: Nucleoplasm localization is experimentally supported by HPA immunofluorescence and consistent with UniProt subcellular location showing nuclear localization (PMID:16541025). Deep research also describes PPP2CB as predominantly cytoplasmic and nuclear. |
| GO:1902996 regulation of neurofibrillary tangle assembly | TAS PMID:16262633 Contributions of protein phosphatases PP1, PP2A, PP2B and PP... | KEEP AS NON CORE | Summary: TAS annotation based on a study showing PP2A is the major tau phosphatase in human brain (~71% of total tau phosphatase activity), and PP2A activity is decreased in AD brain, correlating with tau hyperphosphorylation and neurofibrillary tangle formation. Reason: While PP2A is clearly the major tau phosphatase, this represents a downstream physiological consequence of PP2A phosphatase activity in brain rather than a core function of PPP2CB. Additionally, the study used PP2A generally (likely predominantly PPP2CA given its higher expression in brain). The annotation is not wrong but represents a non-core, tissue-specific function. Supporting Evidence: PMID:16262633 PP2A, PP1, PP5 and PP2B accounted for approximately 71%, approximately 11%, approximately 10% and approximately 7%, respectively, of the total tau phosphatase activity of human brain |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IGI PMID:28159925 miRNA-1246 induces pro-inflammatory responses in mesenchymal... | KEEP AS NON CORE | Summary: IGI annotation from a study showing miR-1246 directly targets PPP2CB, and PPP2CB knockdown increases p65/NF-kappaB levels in MSCs. The IGI evidence is based on interaction with RELA/p65 (Q04206). Reason: The study provides evidence that PPP2CB negatively regulates NF-kappaB signaling, but in a specific cellular context (MSCs in tumor microenvironment). PPP2CB knockdown increased RELA expression and total p65 levels but did not directly increase phospho-p65. The effect on pro-inflammatory cytokines required additional TNFalpha stimulation. This represents a non-core, context-dependent function. Supporting Evidence: PMID:28159925 Knock-down of PPP2CB significantly increased RELA expression PMID:28159925 knock-down of either PRKAR1A or PPP2CB led to a significant up-regulation of total p65 in MSCs whereas phosphorylation of p65 at Ser536 remained unaffected |
| GO:0090443 FAR/SIN/STRIPAK complex | IDA PMID:18782753 A PP2A phosphatase high density interaction network identifi... | ACCEPT | Summary: IDA annotation showing PPP2CB is part of the STRIPAK complex, based on iterative affinity purification/mass spectrometry in human cells. The study defined the STRIPAK complex and identified PPP2CB as a core component. Reason: Well-supported experimental evidence. The study used iterative AP-MS to identify PPP2CB in the STRIPAK complex, which contains PP2A catalytic and scaffolding subunits, striatins, MOB4, STRIP1/2, PDCD10, and STE20 kinases. This is a core complex for PPP2CB function. Supporting Evidence: PMID:18782753 STRIPAK contains the PP2A catalytic (PP2Ac) and scaffolding (PP2A A) subunits, the striatins (PP2A regulatory B''' subunits), the striatin-associated protein Mob3, the novel proteins STRIP1 and STRIP2 |
| GO:0010629 negative regulation of gene expression | IGI PMID:28159925 miRNA-1246 induces pro-inflammatory responses in mesenchymal... | MARK AS OVER ANNOTATED | Summary: IGI annotation (with TNFalpha P01375) showing PPP2CB acts upstream of negative regulation of gene expression. Based on the miR-1246/PPP2CB study in MSCs where PPP2CB knockdown combined with TNFalpha enhanced expression of pro-inflammatory genes. Reason: This annotation is overly broad. The study showed PPP2CB knockdown combined with TNFalpha increases IL-6, CCL2, CCL5 transcription in MSCs. This means PPP2CB normally negatively regulates expression of these specific inflammatory genes, but the term "negative regulation of gene expression" is too generic. Additionally, the qualifier is acts_upstream_of rather than involved_in, indicating indirect effects. Supporting Evidence: PMID:28159925 knock-down of PPP2CB in combination with TNFalpha stimulation phenocopied the miR-1246-enhanced transcriptional response of IL-6 |
| GO:0010629 negative regulation of gene expression | IMP PMID:28159925 miRNA-1246 induces pro-inflammatory responses in mesenchymal... | MARK AS OVER ANNOTATED | Summary: IMP annotation showing PPP2CB is involved in negative regulation of gene expression, based on the same miR-1246 study in MSCs. Reason: Same concern as the IGI annotation above. The term is too broad. The evidence shows PPP2CB normally suppresses inflammatory gene expression in MSCs, but this is a very general biological process annotation that does not capture specificity. The NF-kappaB annotation (GO:0043124) is more specific and informative. Supporting Evidence: PMID:28159925 knock-down of PPP2CB significantly decreased releases of IL-6 and CCL2 |
| GO:0010804 negative regulation of tumor necrosis factor-mediated signaling pathway | IGI PMID:28159925 miRNA-1246 induces pro-inflammatory responses in mesenchymal... | KEEP AS NON CORE | Summary: IGI annotation showing PPP2CB acts upstream of negative regulation of TNF-mediated signaling. Based on the miR-1246 study where PPP2CB knockdown combined with TNFalpha enhances inflammatory responses. Reason: The evidence supports that PPP2CB negatively regulates TNF-mediated signaling in MSCs. PPP2CB knockdown released negative feedback on IL-6 transcription after TNFalpha stimulation. However, this is a context-dependent effect in MSCs and represents a non-core function. Supporting Evidence: PMID:28159925 knock-down of PPP2CB in combination with TNFalpha stimulation phenocopied the miR-1246-enhanced transcriptional response of IL-6 in combination with TNFalpha |
| GO:0004722 protein serine/threonine phosphatase activity | TAS PMID:8206937 The catalytic subunit of protein phosphatase 2A is carboxyl-... | ACCEPT | Summary: TAS annotation from the study that demonstrated carboxyl methylation of PP2A catalytic subunit in vivo. The paper confirms PP2Ac phosphatase activity toward phosphorylase a and phosphopeptide substrates. Reason: Core molecular function, directly supported by the cited publication which demonstrated PP2Ac enzymatic activity. Supporting Evidence: PMID:8206937 Methylation of PP2Ac subunit, in vitro, increases its activity toward both phosphorylase a and a phosphopeptide |
| GO:0048156 tau protein binding | NAS PMID:28386764 Roles of tau protein in health and disease. | KEEP AS NON CORE | Summary: NAS annotation based on a comprehensive review of tau protein roles in health and disease. PP2A is well established as the major tau phosphatase, which implies physical binding to tau. Reason: PP2A does bind and dephosphorylate tau protein, but this is primarily documented for PP2A holoenzymes in brain (likely predominantly PPP2CA-containing). The NAS evidence from a review article is weak. Tau binding is a substrate interaction for PP2A rather than a core binding function. Keeping as non-core given that PP2A-tau interaction is well established in the broader literature. Supporting Evidence: PMID:28386764 Tau is well established as a microtubule-associated protein in neurons PMID:16262633 PP2A is the major tau phosphatase that regulates its phosphorylation at multiple sites in human brain |
| GO:0010288 response to lead ion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS annotation transferred from rat PPP2CB (P62716) by curator judgment. PP2A activity can be affected by lead exposure, as lead interferes with the metalloenzyme's active site. Reason: Consistent with the IEA annotation for the same term. Response to lead ion is a toxicological response rather than a core function. The ISS transfer from rat is appropriate given near-identical sequence. |
| GO:0004722 protein serine/threonine phosphatase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation transferred from rat PPP2CB (P62716). Core phosphatase activity, redundant with other annotations for the same term. Reason: Correct core function. ISS transfer from rat is fully appropriate given near-100% sequence identity between human and rat PPP2CB. |
| GO:0004722 protein serine/threonine phosphatase activity | TAS PMID:10640627 Regulation of phosphorylation of neuronal microtubule-associ... | ACCEPT | Summary: TAS annotation from a study on PP2A regulation of MAP1b and MAP2 phosphorylation in rat brain. Confirms PP2A serine/threonine phosphatase activity toward neuronal substrates. Reason: Core molecular function. The study directly demonstrated PP2A phosphatase activity toward MAP substrates. Supporting Evidence: PMID:10640627 PP2A might be the major PP that participates in regulation of the phosphorylation of MAP1b and MAP2 and their biological activities |
| GO:0004722 protein serine/threonine phosphatase activity | TAS PMID:16262633 Contributions of protein phosphatases PP1, PP2A, PP2B and PP... | ACCEPT | Summary: TAS annotation from the tau phosphorylation study. PP2A accounts for ~71% of tau phosphatase activity in human brain. Reason: Core molecular function. The study quantitatively demonstrated PP2A phosphatase activity toward tau. Supporting Evidence: PMID:16262633 PP2A, PP1, PP5 and PP2B accounted for approximately 71%, approximately 11%, approximately 10% and approximately 7%, respectively, of the total tau phosphatase activity of human brain |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295599 | ACCEPT | Summary: TAS from Reactome pathway for SPRY2 translocation to plasma membrane. Places PPP2CB in cytosol as part of Spry regulation of FGF signaling. Reason: Cytosol localization is correct and well-supported. Reactome annotation reflects PPP2CB involvement in SPRY2/FGF signaling regulation in the cytosol. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295609 | ACCEPT | Summary: TAS from Reactome pathway for SRC phosphorylation of SPRY2. Places PPP2CB in cytosol. Reason: Cytosol localization is correct. Redundant with other cytosol annotations but valid from Reactome evidence. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295613 | ACCEPT | Summary: TAS from Reactome pathway for SPRY2-GRB2 binding. Places PPP2CB in cytosol. Reason: Cytosol localization is correct. Redundant with other cytosol annotations but valid. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295622 | ACCEPT | Summary: TAS from Reactome pathway for SPRY2-CBL binding. Places PPP2CB in cytosol. Reason: Cytosol localization is correct. Redundant with other cytosol annotations but valid. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295632 | ACCEPT | Summary: TAS from Reactome pathway for PP2A dephosphorylation of SPRY2. This directly reflects PP2A phosphatase activity in the cytosol acting on the SPRY2 substrate. Reason: Cytosol localization is correct and directly relevant to PP2A function. This Reactome entry describes the actual dephosphorylation reaction catalyzed by PP2A on SPRY2. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1549564 | ACCEPT | Summary: TAS from Reactome pathway for PTPN11 dephosphorylation of SPRY2. Places PPP2CB in cytosol. Reason: Cytosol localization is correct. Redundant with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-934559 | ACCEPT | Summary: TAS from Reactome pathway for SPRY2 phosphorylation by MNK1. Places PPP2CB in cytosol. Reason: Cytosol localization is correct. Redundant with other cytosol annotations. |
| GO:0005515 protein binding | IPI PMID:21784977 Zinc finger protein tristetraprolin interacts with CCL3 mRNA... | MARK AS OVER ANNOTATED | Summary: IPI for interaction with TTP/ZFP36 (P26651). The study focused on TTP regulation of CCL3 mRNA and tissue inflammation. The interaction with PPP2CB was likely identified as part of a broader interactome screen. Reason: Protein binding is uninformative. The TTP-PPP2CB interaction may reflect PP2A regulation of TTP phosphorylation (TTP activity is regulated by phosphorylation), but the study focused on TTP-mRNA interactions, not PP2A function. Supporting Evidence: PMID:21784977 Zinc finger protein tristetraprolin (TTP) modulates macrophage inflammatory activity by destabilizing cytokine mRNAs |
| GO:0000159 protein phosphatase type 2A complex | TAS PMID:8206937 The catalytic subunit of protein phosphatase 2A is carboxyl-... | ACCEPT | Summary: TAS annotation from the carboxyl-methylation study, which demonstrated PP2A exists as a complex with methylated catalytic subunit. The study worked with PP2A holoenzyme from MCF7 cells. Reason: Core annotation. PPP2CB is a defining component of the PP2A complex. The study directly worked with PP2A holoenzyme complexes. Supporting Evidence: PMID:8206937 Treatment of extracts from human breast cancer (MCF7) cells with either alkali or ethanol increased immunoreactivity of PP2Ac subunit severalfold |
| GO:0006470 protein dephosphorylation | TAS PMID:2849765 The nucleotide sequence of the cDNA encoding the human lung ... | ACCEPT | Summary: TAS annotation from the original cDNA cloning paper for human PPP2CB. The paper established PPP2CB as a phosphatase catalytic subunit. Reason: Core biological process. Protein dephosphorylation is the fundamental reaction catalyzed by PPP2CB. This is directly supported by the identification of PPP2CB as a PP2A catalytic subunit. Supporting Evidence: PMID:2849765 The nucleotide sequence of the cDNA encoding the human lung protein phosphatase 2A beta catalytic subunit |
| GO:0046872 metal ion binding | IEA GO_REF:0000043 | NEW | Summary: PPP2CB requires two Mn2+ ions at its active site for catalytic activity. Metal ion binding is inherent to its phosphatase mechanism. This annotation is present in UniProt GO lines but was not in the GOA TSV extract; adding as it appears in UniProt. Reason: PPP2CB uses a bimetallic Mn2+ active site for catalysis. UniProt lists multiple Mn2+ binding sites (residues 57, 59, 85, 117, 167, 241) and includes metal ion binding as a GO annotation. This is a core aspect of the catalytic mechanism. Supporting Evidence: PMID:10318862 substitution of glutamine for either of two putative active site histidines in the PP2A C subunit results in inactivation of PP2A |
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