id: P30154
gene_symbol: PPP2R1B
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: '1'
  id: P30154-1
- name: '2'
  id: P30154-2
  sequence_note: VSP_036460
- name: '3'
  id: P30154-3
  sequence_note: VSP_043379, VSP_036460
- name: '4'
  id: P30154-4
  sequence_note: VSP_045275
- name: '5'
  id: P30154-5
  sequence_note: VSP_046684
existing_annotations:
- term:
    id: GO:0000159
    label: protein phosphatase type 2A complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:17540176
      supporting_text: >-
        PP2A holoenzymes are composed of three subunits, a catalytic C subunit, a
        structural A subunit,
        and a regulatory B subunit
    - reference_id: PMID:17540176
      supporting_text: >-
        the WT PP2A Abeta subunit formed heterotrimers with the catalytic Calpha and
        each of the
        regulatory B subunits tested

- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16456541
      supporting_text: >-
        PP2A complexes composed of B56α, B56β and B56ɛ localize to the cytoplasm,
        whereas
        those composed of B56δ and B56γ are concentrated in the nucleus

- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:17540176
      supporting_text: >-
        both RalA and Aβ were found in membrane fraction of HEK TER-Aβ cells
    - reference_id: PMID:16456541
      supporting_text: >-
        PP2A complexes composed of B56α, B56β and B56ɛ localize to the cytoplasm

- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      PP2A complexes are present in the cytosol. The IBA annotation is supported by
      phylogenetic evidence
      from fly, mouse, and plant orthologs.
    action: ACCEPT
    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.

- term:
    id: GO:0019888
    label: protein phosphatase regulator activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:17540176
      supporting_text: >-
        the phosphatase activity associated with mutant Aβ (P65S, V545A, G8R, K343E
        or D504G)
        immune complexes was reduced by 48±5%, 70±7%, 68±9%, 52±4%, or 71±9% respectively,
        compared to the activity levels found with the WT Aβ subunit

- term:
    id: GO:0051225
    label: spindle assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.

- term:
    id: GO:0051754
    label: meiotic sister chromatid cohesion, centromeric
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16456541
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:16456541
      supporting_text: >-
        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

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17540176
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:17540176
      supporting_text: >-
        the WT PP2A Abeta subunit formed heterotrimers with the catalytic Calpha and
        each of the
        regulatory B subunits tested
    - reference_id: PMID:17540176
      supporting_text: >-
        the small GTPase protein RalA was the only protein that specifically formed
        complexes with
        Abeta subunit

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18715871
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:18715871
      supporting_text: >-
        PP4R4 displays weak sequence homology with the A (scaffolding) subunit of
        the PP2A holoenzyme

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18782753
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:18782753
      supporting_text: >-
        we generated a high density interaction map surrounding the protein phosphatase
        2A catalytic
        subunit

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19156129
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:19156129
      supporting_text: >-
        We identified a total of 197 protein interactions
        with high reproducibility, showing the coexistence of distinct classes of
        phosphatase complexes

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21172653
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:21172653
      supporting_text: >-
        UNC5H2/B recruits a protein complex that includes PR65beta and DAPk and retains
        PP2A activity

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23555304
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:23555304
      supporting_text: >-
        we identified 109 novel PPIs among circadian clock proteins via a yeast-two-hybrid
        approach

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:26496610
      supporting_text: >-
        The organization of a cell emerges from the interactions in protein networks

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28330616
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:28330616
      supporting_text: >-
        we used quantitative affinity proteomics to assay protein-protein interactions
        for 54
        phosphatases

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    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.
    action: MODIFY
    reason: >-
      Genuine PP2A complex interactions from a large-scale interactome. "Protein binding"
      is
      uninformative. Already captured by more specific annotations.
    proposed_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: >-
        Dual proteome-scale networks reveal cell-specific remodeling of the human
        interactome

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    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.
    action: MODIFY
    reason: >-
      Genuine PP2A core dimer interaction from a high-quality endogenous tagging study.
      "Protein
      binding" is uninformative. Already captured by more specific annotations.
    proposed_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: >-
        Endogenous tagging for the cartography of human cellular organization

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity

- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:8392071
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0019888
      label: protein phosphatase regulator activity
    supported_by:
    - reference_id: PMID:8392071
      supporting_text: >-
        The trimeric form of protein phosphatase 2A consisting of 36-, 65-, and 72-kDa
        subunits

- term:
    id: GO:0045202
    label: synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: ACCEPT
    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.

- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: ACCEPT
    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.

- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:23533145
      supporting_text: >-
        exosome preparations were characterized by a shotgun proteomics procedure

- term:
    id: GO:2001241
    label: positive regulation of extrinsic apoptotic signaling pathway in absence
      of ligand
  evidence_type: IMP
  original_reference_id: PMID:21172653
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:21172653
      supporting_text: >-
        we identified the structural subunit PR65beta of the holoenzyme protein phosphatase
        2A (PP2A)
    - reference_id: PMID:21172653
      supporting_text: >-
        PP2A activity is required for UNC5H2/B-induced apoptosis, since it activates
        DAPk by
        triggering its dephosphorylation

- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: IDA
  original_reference_id: PMID:21172653
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:21172653
      supporting_text: >-
        UNC5H2/B recruits a protein complex that includes PR65beta and DAPk and retains
        PP2A activity

- term:
    id: GO:0060561
    label: apoptotic process involved in morphogenesis
  evidence_type: IMP
  original_reference_id: PMID:21172653
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:21172653
      supporting_text: >-
        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

references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: PMID:16456541
  title: B56-containing PP2A dephosphorylate ERK and their activity is controlled
    by the early gene IEX-1 and ERK.
  findings:
  - statement: B56-containing PP2A holoenzymes dephosphorylate ERK on Thr residue
- id: PMID:17540176
  title: The tumor suppressor PP2A Abeta regulates the RalA GTPase.
  findings:
  - statement: PPP2R1B/Abeta specifically interacts with RalA GTPase, unlike Aalpha
  - statement: PP2A Abeta-containing complexes dephosphorylate RalA at Ser183 and
      Ser194
  - statement: Suppression of Abeta permits cell transformation, confirming tumor
      suppressor role
  - statement: Cancer-associated Abeta mutants fail to form functional PP2A holoenzymes
  - statement: Aalpha does not substitute for Abeta loss of function
- id: PMID:18715871
  title: PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein
    phosphatase 4.
  findings: []
- id: PMID:18782753
  title: A PP2A phosphatase high density interaction network identifies a novel striatin-interacting
    phosphatase and kinase complex linked to the cerebral cavernous malformation 3
    (CCM3) protein.
  findings: []
- id: PMID:19156129
  title: 'An integrated workflow for charting the human interaction proteome: insights
    into the PP2A system.'
  findings: []
- id: PMID:21172653
  title: The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation
    of DAP kinase.
  findings:
  - statement: PR65-beta specifically identified by siRNA screen as required for UNC5H2-induced
      apoptosis
  - statement: UNC5H2/B recruits PP2A complex containing PR65-beta to dephosphorylate
      and activate DAPk
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
- id: PMID:23555304
  title: Dynamic circadian protein-protein interaction networks predict temporal organization
    of cellular functions.
  findings: []
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by stoichiometries
    and abundances.
  findings: []
- id: PMID:28330616
  title: Systematic Analysis of Human Protein Phosphatase Interactions and Dynamics.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
- id: PMID:8392071
  title: Structure and expression of a 72-kDa regulatory subunit of protein phosphatase
    2A. Evidence for different size forms produced by alternative splicing.
  findings: []
- id: PMID:16541025
  title: Shugoshin collaborates with protein phosphatase 2A to protect cohesin.
  findings:
  - statement: PPP2R1B interacts with SGO1 to recruit PP2A to centromeres for cohesion
      protection
core_functions:
- molecular_function:
    id: GO:0019888
    label: protein phosphatase regulator activity
  contributes_to_molecular_function:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  description: >-
    PPP2R1B is the beta isoform of the PP2A scaffold/structural A subunit (PR65-beta).
    It assembles 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), thereby enabling and regulating phosphatase activity. PPP2R1B is
    the
    minor A subunit isoform (~5-10% of total PP2A scaffold), with the dominant isoform
    being PPP2R1A/Aalpha. Despite its lower abundance, PPP2R1B has non-redundant functions;
    Aalpha cannot substitute for Abeta loss. As part of canonical PP2A trimers, it
    contributes to Ser/Thr phosphatase activity on diverse substrates determined by
    the
    associated B subunit.
  directly_involved_in:
  - id: GO:0065003
    label: protein-containing complex assembly
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005634
    label: nucleus
  in_complex:
    id: GO:0000159
    label: protein phosphatase type 2A complex
  supported_by:
  - reference_id: PMID:17540176
    supporting_text: >-
      the WT PP2A Abeta subunit formed heterotrimers with the catalytic Calpha and
      each of the regulatory B subunits tested
  - reference_id: PMID:17540176
    supporting_text: >-
      These cancer-associated PP2A Aβ mutants are defective in binding to B and/or
      C subunits in vitro (Ruediger et al., 2001a)
  - reference_id: PMID:17540176
    supporting_text: >-
      Overexpression of PP2A Aalpha in these cells failed to revert the transformed
      phenotype induced by Abeta suppression
- molecular_function:
    id: GO:0019888
    label: protein phosphatase regulator activity
  contributes_to_molecular_function:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  description: >-
    PPP2R1B-containing PP2A complexes uniquely interact with and dephosphorylate the
    small GTPase RalA at Ser183 and Ser194, inactivating RalA and suppressing
    transformation. This interaction is specific to the Abeta isoform -- PP2A Aalpha
    does not form complexes with RalA. Cancer-associated Abeta mutations disrupt this
    function, permitting constitutive RalA activation and cell transformation. This
    RalA-directed phosphatase activity underlies the tumor suppressor function of
    PPP2R1B.
  directly_involved_in:
  - id: GO:0032485
    label: regulation of Ral protein signal transduction
  - id: GO:0006470
    label: protein dephosphorylation
  substrates:
  - id: UniProtKB:P11233
    label: RALA
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0000159
    label: protein phosphatase type 2A complex
  supported_by:
  - reference_id: PMID:17540176
    supporting_text: >-
      the small GTPase protein RalA was the only protein that specifically formed
      complexes with Abeta subunit
  - reference_id: PMID:17540176
    supporting_text: >-
      PP2A Abeta-containing complexes dephosphorylate RalA at Ser183 and Ser194,
      inactivating RalA
  - reference_id: PMID:17540176
    supporting_text: >-
      suppression of PP2A Abeta expression permits immortalized human cells to
      achieve a tumorigenic state