PPP2R1B encodes the beta isoform of the protein phosphatase 2A (PP2A) scaffold/structural A subunit (PR65-beta). It is the minor A subunit isoform, comprising approximately 5-10% of total cellular PP2A scaffold protein (the dominant isoform being PPP2R1A/Aalpha, with ~86% sequence identity). PPP2R1B contains 15 tandem HEAT repeats that form an elongated horseshoe-shaped scaffold. Its primary molecular function is to coordinate the assembly of PP2A heterotrimeric holoenzymes by simultaneously binding the catalytic C subunit (via HEAT repeats 11-15) and one of many regulatory B subunits (via HEAT repeats 1-10). Despite its low abundance, PPP2R1B has non-redundant functions relative to PPP2R1A. Notably, PPP2R1B-containing PP2A complexes uniquely interact with and dephosphorylate the small GTPase RalA at Ser183 and Ser194, thereby inactivating RalA and suppressing transformation. PPP2R1B functions as a tumor suppressor; cancer-associated mutations (found in ~15% of lung and colon cancers) disrupt its ability to form functional PP2A holoenzymes and regulate RalA. PPP2R1B is also recruited to the dependence receptor UNC5H2/B where it facilitates PP2A-mediated dephosphorylation of DAPk, triggering apoptosis in the absence of netrin-1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000159 protein phosphatase type 2A complex | IBA GO_REF:0000033 | ACCEPT | Summary: PPP2R1B is the scaffold/structural A-beta subunit of the PP2A holoenzyme. Its defining role is to assemble the PP2A heterotrimeric complex (A-B-C). This is the core identity of the protein and is extensively supported by structural, biochemical, and genetic evidence (PMID:17540176, UniProt). The IBA annotation is phylogenetically well-grounded, based on orthologs across yeast, fly, worm, and mouse. Reason: This is the defining cellular component for PPP2R1B. The protein is a structural subunit of PP2A and exists primarily as part of this complex. UniProt states "The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit." The IBA annotation is based on strong phylogenetic evidence across multiple model organisms. Supporting Evidence: PMID:17540176 PP2A holoenzymes are composed of three subunits, a catalytic C subunit, a structural A subunit, and a regulatory B subunit PMID:17540176 the WT PP2A Abeta subunit formed heterotrimers with the catalytic Calpha and each of the regulatory B subunits tested |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: PP2A complexes are known to localize to both nucleus and cytoplasm, with localization driven primarily by the regulatory B subunit composition. Nuclear PP2A functions include cell cycle regulation, DNA damage response, and chromatin-associated processes. The IBA annotation is phylogenetically supported across fly, yeast, and plant orthologs. Reason: PP2A is well-established to function in the nucleus in various contexts. The B56 subunit family members direct PP2A to nuclear substrates. Given the role of PPP2R1B in mitotic processes (spindle assembly, sister chromatid cohesion) and its interaction with SGO1 (PMID:16541025), nuclear localization is expected. Supporting Evidence: PMID:16456541 PP2A complexes composed of B56Ξ±, B56Ξ² and B56Ι localize to the cytoplasm, whereas those composed of B56Ξ΄ and B56Ξ³ are concentrated in the nucleus |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PP2A complexes are broadly distributed in the cytoplasm. The IBA annotation is well-supported by phylogenetic evidence across multiple model organisms including fly, worm, mouse, yeast, and Dictyostelium orthologs. Reason: PP2A is well-established as a cytoplasmic phosphatase complex. PPP2R1B-containing complexes regulate cytoplasmic substrates including RalA (PMID:17540176). The B55 and some B56 family members localize PP2A to the cytoplasm. Supporting Evidence: PMID:17540176 both RalA and AΞ² were found in membrane fraction of HEK TER-AΞ² cells PMID:16456541 PP2A complexes composed of B56Ξ±, B56Ξ² and B56Ι localize to the cytoplasm |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PP2A complexes are present in the cytosol. The IBA annotation is supported by phylogenetic evidence from fly, mouse, and plant orthologs. Reason: Cytosol is a reasonable and expected localization for a soluble scaffold protein that assembles phosphatase holoenzymes. This is consistent with and more specific than the cytoplasm annotation. Both are appropriate. |
| GO:0019888 protein phosphatase regulator activity | IBA GO_REF:0000033 | ACCEPT | Summary: PPP2R1B functions as a scaffold/regulator of PP2A phosphatase activity by assembling the catalytic C subunit with regulatory B subunits into a functional holoenzyme. Without the A subunit scaffold, the holoenzyme cannot assemble properly. The IBA annotation is phylogenetically supported. Reason: This is the core molecular function annotation for PPP2R1B. As a scaffold subunit that is essential for PP2A holoenzyme assembly, it directly regulates phosphatase activity. Cancer-associated mutants that cannot assemble holoenzymes show impaired phosphatase activity (PMID:17540176). The term "protein phosphatase regulator activity" appropriately captures the scaffolding/regulatory function. Supporting Evidence: PMID:17540176 the phosphatase activity associated with mutant AΞ² (P65S, V545A, G8R, K343E or D504G) immune complexes was reduced by 48Β±5%, 70Β±7%, 68Β±9%, 52Β±4%, or 71Β±9% respectively, compared to the activity levels found with the WT AΞ² subunit |
| GO:0051225 spindle assembly | IBA GO_REF:0000033 | ACCEPT | Summary: PP2A-B56 complexes have well-established roles in spindle assembly and mitotic progression. PP2A opposes Aurora B kinase and Plk1 at kinetochores, and is required for proper chromosome bi-orientation. The IBA annotation is based on fly ortholog evidence. Reason: PP2A-B56 complexes are critical for spindle assembly and mitotic checkpoint regulation. PPP2R1B interacts with SGO1 (PMID:16541025, UniProt), a protein that recruits PP2A to centromeres to protect cohesion and regulate kinetochore-microtubule attachments. Reactome annotates PPP2R1B in multiple mitotic pathways including "Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal" and "MASTL Facilitates Mitotic Progression". While the A-alpha isoform may dominate quantitatively, the IBA annotation is phylogenetically appropriate. |
| GO:0051754 meiotic sister chromatid cohesion, centromeric | IBA GO_REF:0000033 | ACCEPT | Summary: PP2A-B56 (specifically via Shugoshin recruitment) protects centromeric cohesion during meiosis by dephosphorylating cohesin subunits, preventing their premature cleavage by separase. The IBA annotation is supported by mouse and fission yeast ortholog evidence. Reason: UniProt documents that PPP2R1B interacts with SGO1 (PMID:16541025). Shugoshin recruits PP2A to centromeres to protect cohesin during meiosis I. The title of the supporting publication is "Shugoshin collaborates with protein phosphatase 2A to protect cohesin." Reactome also annotates PPP2R1B in "Resolution of Sister Chromatid Cohesion." While this function may be more prominent for PP2A complexes containing the Aalpha isoform given its greater abundance, the phylogenetic inference from mouse and yeast is valid for the Abeta isoform as well. |
| GO:0005515 protein binding | IPI PMID:16456541 B56-containing PP2A dephosphorylate ERK and their activity i... | MODIFY | Summary: This IPI annotation reflects interaction between PPP2R1B and PPP2R5C (B56gamma, Q13362), detected by co-immunoprecipitation in the context of studying B56-containing PP2A holoenzymes that dephosphorylate ERK (PMID:16456541). This is a bona fide PP2A holoenzyme subunit interaction. Reason: The interaction with B56gamma is a genuine PP2A regulatory subunit binding event, integral to PP2A holoenzyme assembly. However, "protein binding" is too generic per curation guidelines. The interaction represents the A subunit scaffolding function. A more informative term would capture the phosphatase regulator activity or complex assembly function. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:16456541 The PP2A holoenzyme is a heterotrimer that consists of a core dimer, composed of a scaffold (A) and a catalytic (C) subunit that associates with a variety of regulatory (B) subunits |
| GO:0005515 protein binding | IPI PMID:17540176 The tumor suppressor PP2A Abeta regulates the RalA GTPase. | MODIFY | Summary: This PMID generated multiple IPI annotations for PPP2R1B interactions with RALA (P11233), PPP2R2A (P63151/B55alpha), PPP2CA (P67775), PPP2R5C (Q13362/B56gamma), PPP2R5D (Q14738/B56delta), PPP2R5A (Q15172/B56alpha), and PPP2R5E (Q16537/B56epsilon). These interactions were detected by co-immunoprecipitation and mass spectrometry in a focused study of PP2A Abeta function (PMID:17540176). The RalA interaction is uniquely specific to the Abeta isoform and does not occur with Aalpha. Reason: The interactions detected in this study are genuine and represent both core PP2A holoenzyme assembly (C subunit, B subunits) and a specific substrate interaction (RalA). However, "protein binding" is uninformative. The holoenzyme assembly interactions are better captured by the phosphatase regulator activity annotation already present, while the RalA interaction represents a specific substrate binding event. A more informative annotation would be preferred. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:17540176 the WT PP2A Abeta subunit formed heterotrimers with the catalytic Calpha and each of the regulatory B subunits tested PMID:17540176 the small GTPase protein RalA was the only protein that specifically formed complexes with Abeta subunit |
| GO:0005515 protein binding | IPI PMID:18715871 PP4R4/KIAA1622 forms a novel stable cytosolic complex with p... | MODIFY | Summary: This IPI annotation reflects interaction between PPP2R1B and PPP2CA (P67775), detected in the context of a study primarily characterizing PP4R4/KIAA1622 and PP4c. The PPP2R1B-PPP2CA interaction is a core PP2A holoenzyme assembly interaction detected as a control/comparison in this study. Reason: The A-C subunit interaction is a core PP2A assembly event. "Protein binding" is too generic. Already captured by phosphatase regulator activity and PP2A complex membership annotations. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:18715871 PP4R4 displays weak sequence homology with the A (scaffolding) subunit of the PP2A holoenzyme |
| GO:0005515 protein binding | IPI PMID:18782753 A PP2A phosphatase high density interaction network identifi... | MODIFY | Summary: This IPI annotation reflects interactions between PPP2R1B and PPP2R1A (P30153), PPP2CA (P67775), and PPP2R5A (Q15172/B56alpha) detected in a high-density PP2A interaction network study using AP-MS. These interactions represent genuine PP2A complex assembly events and possible A-subunit dimerization. Reason: These are genuine PP2A complex interactions detected in a systematic proteomics study. "Protein binding" is uninformative. The interactions with C and B subunits are already captured by the phosphatase regulator activity and PP2A complex annotations. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:18782753 we generated a high density interaction map surrounding the protein phosphatase 2A catalytic subunit |
| GO:0005515 protein binding | IPI PMID:19156129 An integrated workflow for charting the human interaction pr... | MODIFY | Summary: This IPI annotation reflects interaction between PPP2R1B and PPP2CA (P67775), detected by systematic AP-MS in a comprehensive PP2A interaction proteome study. This is a core PP2A scaffold-catalytic subunit interaction. Reason: This is a genuine PP2A A-C core dimer interaction. "Protein binding" is uninformative per curation guidelines. The underlying interaction is already captured by the phosphatase regulator activity and PP2A complex annotations. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:19156129 We identified a total of 197 protein interactions with high reproducibility, showing the coexistence of distinct classes of phosphatase complexes |
| GO:0005515 protein binding | IPI PMID:21172653 The dependence receptor UNC5H2/B triggers apoptosis via PP2A... | MODIFY | Summary: This IPI annotation reflects interaction between PPP2R1B and mouse Unc5b (O08722), detected in the study showing that UNC5H2/B recruits PP2A PR65-beta to mediate DAPk dephosphorylation and apoptosis. This is a specific and biologically meaningful interaction in the dependence receptor signaling pathway. Reason: The interaction with UNC5H2/B (Unc5b) is a specific and functionally important interaction that recruits PP2A to trigger apoptosis. "Protein binding" is too generic. This interaction is better captured by a process-level annotation for the apoptotic signaling pathway. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:21172653 UNC5H2/B recruits a protein complex that includes PR65beta and DAPk and retains PP2A activity |
| GO:0005515 protein binding | IPI PMID:23555304 Dynamic circadian protein-protein interaction networks predi... | MODIFY | Summary: This IPI annotation reflects interactions between PPP2R1B and mouse Clock (O08785), PPP2R5D (Q14738/B56delta), and PPP2R5E (Q16537/B56epsilon), detected in a yeast-two-hybrid study of circadian protein-protein interactions. The B subunit interactions reflect core PP2A assembly, while the Clock interaction links PP2A to circadian regulation. Reason: The B subunit interactions are genuine PP2A assembly events. The Clock interaction may reflect a role of PP2A in circadian regulation. "Protein binding" is too generic per curation guidelines. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:23555304 we identified 109 novel PPIs among circadian clock proteins via a yeast-two-hybrid approach |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: This IPI annotation reflects interactions between PPP2R1B and PPP2R1A (P30153), PPP2R2A (P63151/ B55alpha), and PPP2R5D (Q14738/B56delta), detected by quantitative IP-MS in a large-scale human interactome study. These represent core PP2A complex interactions. Reason: These are genuine PP2A complex assembly interactions detected by high-quality quantitative proteomics. "Protein binding" is uninformative. Already captured by phosphatase regulator activity and PP2A complex annotations. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:26496610 The organization of a cell emerges from the interactions in protein networks |
| GO:0005515 protein binding | IPI PMID:28330616 Systematic Analysis of Human Protein Phosphatase Interaction... | MODIFY | Summary: This IPI annotation reflects interactions between PPP2R1B and PPP2R2A (P63151/B55alpha) and PPP2CA (P67775), detected in a systematic phosphatase interactome study using AP-MS. These are core PP2A holoenzyme assembly interactions. Reason: Genuine PP2A complex interactions from a focused phosphatase interactomics study. "Protein binding" is uninformative. Already captured by phosphatase regulator activity and PP2A complex annotations. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:28330616 we used quantitative affinity proteomics to assay protein-protein interactions for 54 phosphatases |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: This IPI annotation reflects interactions between PPP2R1B and PPP2R1A (P30153) and PPP2R5A (Q15172/B56alpha), detected in a dual proteome-scale human interactome study (BioPlex). These represent PP2A complex interactions or paralog co-purification. Reason: Genuine PP2A complex interactions from a large-scale interactome. "Protein binding" is uninformative. Already captured by more specific annotations. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: This IPI annotation reflects interaction between PPP2R1B and PPP2CA (P67775), detected in the OpenCell endogenous tagging and proteomics study. This is a core PP2A A-C dimer interaction. Reason: Genuine PP2A core dimer interaction from a high-quality endogenous tagging study. "Protein binding" is uninformative. Already captured by more specific annotations. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:35271311 Endogenous tagging for the cartography of human cellular organization |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: This IPI annotation reflects interaction between PPP2R1B and PPP2R1A (P30153), detected in a multimodal cell mapping study integrating AP-MS and other approaches. This likely represents co-purification of PP2A scaffold subunit paralogs. Reason: The PPP2R1A-PPP2R1B interaction may represent co-purification or genuine A-subunit heterodimerization within the PP2A system. "Protein binding" is uninformative. Already captured by more specific annotations. Proposed replacements: protein phosphatase regulator activity |
| GO:0005515 protein binding | IPI PMID:8392071 Structure and expression of a 72-kDa regulatory subunit of p... | MODIFY | Summary: This IPI annotation reflects interaction between PPP2R1B and PPP2CA (P67775/PP2A catalytic subunit), based on a 1993 study characterizing the PR72 regulatory subunit. PPP2R1B was co-purified with the catalytic subunit in this study. This is a core PP2A holoenzyme interaction. Reason: This represents a core PP2A A-C subunit interaction. "Protein binding" is too generic per curation guidelines. Already captured by phosphatase regulator activity and PP2A complex annotations. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:8392071 The trimeric form of protein phosphatase 2A consisting of 36-, 65-, and 72-kDa subunits |
| GO:0045202 synapse | IEA GO_REF:0000107 | ACCEPT | Summary: This IEA annotation is based on Ensembl Compara transfer from mouse ortholog Q7TNP2. PP2A complexes are known to function at synapses, where they regulate synaptic transmission and plasticity. However, this annotation may be more relevant to the Aalpha isoform given its greater abundance. Reason: While IEA annotations are automatically transferred and less curated, PP2A does function at synapses. The annotation is based on mouse ortholog data and is not incorrect as a broader localization. PPP2R1B could form PP2A complexes at synapses, even if the dominant A subunit at synapses is likely PPP2R1A. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | ACCEPT | Summary: This IEA annotation is transferred from mouse ortholog Q7TNP2 via Ensembl Compara. It is more specific than the general synapse annotation. PP2A is known to regulate glutamate receptor signaling, but this level of specificity for the Abeta isoform is uncertain. Reason: This is an automated transfer from mouse ortholog data. While PP2A does function at glutamatergic synapses, the specific involvement of the Abeta isoform (as opposed to the much more abundant Aalpha) at glutamatergic synapses is not strongly established. However, the IEA annotation is not incorrect and provides useful context. It is acceptable as a broader IEA annotation even if the IBA or experimental evidence would be primarily for the Aalpha isoform. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: This HDA annotation is based on high-throughput proteomic identification of PPP2R1B in exosomes isolated from expressed prostatic secretions in urine. This is a large-scale proteomics study and the presence of PPP2R1B in exosomes likely reflects its abundance as a cytoplasmic protein rather than a specific functional role in exosomes. Reason: Detection in exosomes by mass spectrometry is common for abundant cytoplasmic proteins and does not necessarily indicate a functional role in exosome biology. While the detection is real, this is not a core function of PPP2R1B. Many PP2A subunits are detected in exosome proteomes. Supporting Evidence: PMID:23533145 exosome preparations were characterized by a shotgun proteomics procedure |
| GO:2001241 positive regulation of extrinsic apoptotic signaling pathway in absence of ligand | IMP PMID:21172653 The dependence receptor UNC5H2/B triggers apoptosis via PP2A... | KEEP AS NON CORE | Summary: This IMP annotation is based on the finding that PPP2R1B (PR65-beta) was identified in a siRNA screen as required for UNC5H2/B-induced apoptosis. In the absence of netrin-1, UNC5H2/B recruits a complex containing PR65-beta and DAPk. PP2A then dephosphorylates DAPk, activating it and triggering apoptosis. This is a specific and experimentally well-supported finding. Reason: The annotation is experimentally well-supported by the Guenebeaud et al. (2010) study, which specifically identified PR65-beta (not PR65-alpha) as required for this pathway. However, this represents a specialized context-dependent function in dependence receptor signaling rather than a core evolved function of PP2A scaffold. The specificity for PPP2R1B (vs PPP2R1A) in this pathway is notable and adds biological value. Supporting Evidence: PMID:21172653 we identified the structural subunit PR65beta of the holoenzyme protein phosphatase 2A (PP2A) PMID:21172653 PP2A activity is required for UNC5H2/B-induced apoptosis, since it activates DAPk by triggering its dephosphorylation |
| GO:0045121 membrane raft | IDA PMID:21172653 The dependence receptor UNC5H2/B triggers apoptosis via PP2A... | KEEP AS NON CORE | Summary: This IDA annotation indicates PPP2R1B was detected in membrane rafts in the context of UNC5H2/B-mediated apoptotic signaling. The dependence receptor UNC5H2/B recruits PP2A (specifically via PR65-beta) to membrane-associated complexes to activate DAPk. Reason: The membrane raft localization is specific to the UNC5H2/B signaling context. While the experimental evidence (IDA) supports the localization, this is a context-dependent localization related to the dependence receptor pathway rather than a constitutive location for PPP2R1B. It is biologically valid but represents a non-core localization. Supporting Evidence: PMID:21172653 UNC5H2/B recruits a protein complex that includes PR65beta and DAPk and retains PP2A activity |
| GO:0060561 apoptotic process involved in morphogenesis | IMP PMID:21172653 The dependence receptor UNC5H2/B triggers apoptosis via PP2A... | KEEP AS NON CORE | Summary: This IMP annotation relates to the role of PPP2R1B in UNC5H2/B-mediated apoptosis, which the study links to angiogenesis regulation. UNC5H2/B-induced apoptosis via PP2A/DAPk is described as important for vascular development. Reason: The study shows that UNC5H2/B-PP2A-DAPk pathway is involved in angiogenesis regulation, but this is a specialized pathway context. The morphogenesis connection comes from the broader role of dependence receptors in developmental apoptosis. This is not a core function of PPP2R1B as a PP2A scaffold but represents a valid downstream biological process. Supporting Evidence: PMID:21172653 in the absence of netrin-1, recruitment of PP2A to UNC5H2/B allows the activation of DAPk via a PP2A-mediated dephosphorylation and that this mechanism is involved in angiogenesis regulation |
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