id: P62714
gene_symbol: PPP2CB
product_type: PROTEIN
status: IN_PROGRESS
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
existing_annotations:
- term:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8206937
      supporting_text: "Methylation of PP2Ac subunit, in vitro, increases its activity
        toward both phosphorylase a and a phosphopeptide."
    - reference_id: PMID:2849765
      supporting_text: "The nucleotide sequence of the cDNA encoding the human lung
        protein phosphatase 2A beta catalytic subunit."
- term:
    id: GO:0000278
    label: mitotic cell cycle
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:27880917
      supporting_text: "complementary affinity purification and proximity-based interaction
        proteomics approaches to generate a physical interactome for 140 human proteins
        harboring phosphatase catalytic domains"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16541025
      supporting_text: "PP2A colocalizes with shugoshin at centromeres and is required
        for centromeric protection."
- term:
    id: GO:0000775
    label: chromosome, centromeric region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16541025
      supporting_text: "a specific subtype of serine/threonine protein phosphatase
        2A (PP2A) associating with human shugoshin. PP2A colocalizes with shugoshin
        at centromeres"
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      IEA from UniProt subcellular location. UniProt states PP2A is found at
      spindle poles during mitosis, based on PMID:16541025.
    action: ACCEPT
    reason: >-
      Spindle pole localization during mitosis is documented in UniProt
      subcellular location, which cites PMID:16541025. Consistent with PP2A
      role in mitotic regulation.
    supported_by:
    - reference_id: PMID:16541025
      supporting_text: "crucial--particularly at centromeres--for proper chromosome
        segregation in mitosis and meiosis"
- term:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    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.
    action: ACCEPT
    reason: >-
      Correct core function. This IEA annotation is consistent with the more
      authoritative IBA and TAS annotations for the same GO term.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16541025
      supporting_text: "PP2A colocalizes with shugoshin at centromeres and is required
        for centromeric protection"
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation for cytoplasm localization. Broader than cytosol but still
      correct. PPP2CB is well established as a cytoplasmic protein.
    action: ACCEPT
    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.
- term:
    id: GO:0016787
    label: hydrolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    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.
    action: ACCEPT
    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.
- term:
    id: GO:0090443
    label: FAR/SIN/STRIPAK complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      IEA from ARBA machine learning model predicting STRIPAK complex
      membership. This is consistent with experimental evidence from
      PMID:18782753 (IDA annotation also present).
    action: ACCEPT
    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.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10698523
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:10698523
      supporting_text: "the heterodimeric form of protein phosphatase 2A (PP2A) directly
        bound to Axin, and PP2A complexed with Axin dephosphorylated APC phosphorylated
        by GSK-3beta"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16085932
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:16085932
      supporting_text: "Using a combination of tandem affinity purification tagging
        and mass spectrometry, we characterized a novel, evolutionarily conserved
        protein phosphatase 4 (PP4)-containing complex"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18782753
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:18782753
      supporting_text: "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"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19156129
  review:
    summary: >-
      IPI for interaction with IGBP1 (P78318) from an integrated PP2A
      interaction proteomics workflow. This is a well-characterized PP2A
      regulatory interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. IGBP1/alpha4 is a known PP2A
      chaperone/regulatory protein. Better captured by complex membership
      annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20969868
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:20969868
      supporting_text: "FHL1B was demonstrated to interact with the beta catalytic
        subunit (Cbeta) of a type 2A protein phosphatase (PP2A) by yeast two-hybrid
        screening"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25531779
  review:
    summary: >-
      IPI for interaction with STRIP1 (Q5VSL9) from STRIPAK complex study on
      cancer cell migration and metastasis. High-throughput proteomics study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. STRIP1 interaction is part of STRIPAK
      complex, better captured by GO:0090443.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26496610
  review:
    summary: >-
      IPI for interactions with IGBP1 (P78318) and STRIP1 (Q5VSL9) from
      quantitative human interactome study. Large-scale proteomics.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. Both are known PP2A complex components.
      High-throughput study; interactions better captured by complex annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27880917
  review:
    summary: >-
      IPI for interactions with TIPRL (O75663) and IGBP1 (P78318) from
      comprehensive phosphatase interactome profiling. Study identified
      diverse mitotic regulators among phosphatase interactors.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:27880917
      supporting_text: "complementary affinity purification and proximity-based interaction
        proteomics approaches to generate a physical interactome for 140 human proteins
        harboring phosphatase catalytic domains"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  review:
    summary: >-
      IPI for interaction with STRIP1 (Q5VSL9) from architecture of the human
      interactome study. Large-scale proteomics.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. STRIP1 is a STRIPAK component.
      High-throughput study.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: "Interactome Mapping Provides a Network of Neurodegenerative
        Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: >-
      IPI for interactions with IGBP1 (P78318) and STRIP1 (Q5VSL9) from dual
      proteome-scale cell-specific interactome study.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. Both are established PP2A complex
      members. High-throughput study.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: >-
      IPI for interactions with IGBP1 (P78318) and STRIP1 (Q5VSL9) from the
      OpenCell endogenous tagging study. Large-scale proteomics.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Protein binding is uninformative. Both are known PP2A/STRIPAK complex
      members. High-throughput study.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9647778
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:9647778
      supporting_text: "alpha 4, a previously identified phosphoprotein, associates
        constitutively with the catalytic subunits of PP4, PP6, and both isoforms
        of PP2A"
- term:
    id: GO:0000159
    label: protein phosphatase type 2A complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: ACCEPT
    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).
- term:
    id: GO:0004721
    label: phosphoprotein phosphatase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: ACCEPT
    reason: >-
      Technically correct as PPP2CB does have phosphoprotein phosphatase
      activity. More specific GO:0004722 annotations are also present. This
      broader IEA is acceptable.
- term:
    id: GO:0010288
    label: response to lead ion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0031113
    label: regulation of microtubule polymerization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:10640627
      supporting_text: "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"
- term:
    id: GO:0044325
    label: transmembrane transporter binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: UNDECIDED
    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.
- term:
    id: GO:0046580
    label: negative regulation of Ras protein signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: >-
      IDA from HPA immunofluorescence data. PPP2CB was detected in
      nucleoplasm by immunofluorescence. Consistent with UniProt subcellular
      location annotation showing nuclear localization.
    action: ACCEPT
    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.
- term:
    id: GO:1902996
    label: regulation of neurofibrillary tangle assembly
  evidence_type: TAS
  original_reference_id: PMID:16262633
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:16262633
      supporting_text: "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"
- term:
    id: GO:0043124
    label: negative regulation of canonical NF-kappaB signal transduction
  evidence_type: IGI
  original_reference_id: PMID:28159925
  review:
    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).
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:28159925
      supporting_text: "Knock-down of PPP2CB significantly increased RELA expression"
    - reference_id: PMID:28159925
      supporting_text: "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"
- term:
    id: GO:0090443
    label: FAR/SIN/STRIPAK complex
  evidence_type: IDA
  original_reference_id: PMID:18782753
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:18782753
      supporting_text: "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"
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IGI
  original_reference_id: PMID:28159925
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:28159925
      supporting_text: "knock-down of PPP2CB in combination with TNFalpha stimulation
        phenocopied the miR-1246-enhanced transcriptional response of IL-6"
- term:
    id: GO:0010629
    label: negative regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:28159925
  review:
    summary: >-
      IMP annotation showing PPP2CB is involved in negative regulation of
      gene expression, based on the same miR-1246 study in MSCs.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:28159925
      supporting_text: "knock-down of PPP2CB significantly decreased releases of IL-6
        and CCL2"
- term:
    id: GO:0010804
    label: negative regulation of tumor necrosis factor-mediated signaling
      pathway
  evidence_type: IGI
  original_reference_id: PMID:28159925
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:28159925
      supporting_text: "knock-down of PPP2CB in combination with TNFalpha stimulation
        phenocopied the miR-1246-enhanced transcriptional response of IL-6 in combination
        with TNFalpha"
- term:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  evidence_type: TAS
  original_reference_id: PMID:8206937
  review:
    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.
    action: ACCEPT
    reason: >-
      Core molecular function, directly supported by the cited publication
      which demonstrated PP2Ac enzymatic activity.
    supported_by:
    - reference_id: PMID:8206937
      supporting_text: "Methylation of PP2Ac subunit, in vitro, increases its activity
        toward both phosphorylase a and a phosphopeptide"
- term:
    id: GO:0048156
    label: tau protein binding
  evidence_type: NAS
  original_reference_id: PMID:28386764
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:28386764
      supporting_text: "Tau is well established as a microtubule-associated protein
        in neurons"
    - reference_id: PMID:16262633
      supporting_text: "PP2A is the major tau phosphatase that regulates its phosphorylation
        at multiple sites in human brain"
- term:
    id: GO:0010288
    label: response to lead ion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
- term:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: >-
      ISS annotation transferred from rat PPP2CB (P62716). Core phosphatase
      activity, redundant with other annotations for the same term.
    action: ACCEPT
    reason: >-
      Correct core function. ISS transfer from rat is fully appropriate
      given near-100% sequence identity between human and rat PPP2CB.
- term:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  evidence_type: TAS
  original_reference_id: PMID:10640627
  review:
    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.
    action: ACCEPT
    reason: >-
      Core molecular function. The study directly demonstrated PP2A
      phosphatase activity toward MAP substrates.
    supported_by:
    - reference_id: PMID:10640627
      supporting_text: "PP2A might be the major PP that participates in regulation
        of the phosphorylation of MAP1b and MAP2 and their biological activities"
- term:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  evidence_type: TAS
  original_reference_id: PMID:16262633
  review:
    summary: >-
      TAS annotation from the tau phosphorylation study. PP2A accounts for
      ~71% of tau phosphatase activity in human brain.
    action: ACCEPT
    reason: >-
      Core molecular function. The study quantitatively demonstrated PP2A
      phosphatase activity toward tau.
    supported_by:
    - reference_id: PMID:16262633
      supporting_text: "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"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1295599
  review:
    summary: >-
      TAS from Reactome pathway for SPRY2 translocation to plasma membrane.
      Places PPP2CB in cytosol as part of Spry regulation of FGF signaling.
    action: ACCEPT
    reason: >-
      Cytosol localization is correct and well-supported. Reactome annotation
      reflects PPP2CB involvement in SPRY2/FGF signaling regulation in the
      cytosol.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1295609
  review:
    summary: >-
      TAS from Reactome pathway for SRC phosphorylation of SPRY2. Places
      PPP2CB in cytosol.
    action: ACCEPT
    reason: >-
      Cytosol localization is correct. Redundant with other cytosol
      annotations but valid from Reactome evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1295613
  review:
    summary: >-
      TAS from Reactome pathway for SPRY2-GRB2 binding. Places PPP2CB in
      cytosol.
    action: ACCEPT
    reason: >-
      Cytosol localization is correct. Redundant with other cytosol
      annotations but valid.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1295622
  review:
    summary: >-
      TAS from Reactome pathway for SPRY2-CBL binding. Places PPP2CB in
      cytosol.
    action: ACCEPT
    reason: >-
      Cytosol localization is correct. Redundant with other cytosol
      annotations but valid.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1295632
  review:
    summary: >-
      TAS from Reactome pathway for PP2A dephosphorylation of SPRY2. This
      directly reflects PP2A phosphatase activity in the cytosol acting on
      the SPRY2 substrate.
    action: ACCEPT
    reason: >-
      Cytosol localization is correct and directly relevant to PP2A function.
      This Reactome entry describes the actual dephosphorylation reaction
      catalyzed by PP2A on SPRY2.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1549564
  review:
    summary: >-
      TAS from Reactome pathway for PTPN11 dephosphorylation of SPRY2.
      Places PPP2CB in cytosol.
    action: ACCEPT
    reason: >-
      Cytosol localization is correct. Redundant with other cytosol
      annotations.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-934559
  review:
    summary: >-
      TAS from Reactome pathway for SPRY2 phosphorylation by MNK1. Places
      PPP2CB in cytosol.
    action: ACCEPT
    reason: >-
      Cytosol localization is correct. Redundant with other cytosol
      annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21784977
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:21784977
      supporting_text: "Zinc finger protein tristetraprolin (TTP) modulates macrophage
        inflammatory activity by destabilizing cytokine mRNAs"
- term:
    id: GO:0000159
    label: protein phosphatase type 2A complex
  evidence_type: TAS
  original_reference_id: PMID:8206937
  review:
    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.
    action: ACCEPT
    reason: >-
      Core annotation. PPP2CB is a defining component of the PP2A complex.
      The study directly worked with PP2A holoenzyme complexes.
    supported_by:
    - reference_id: PMID:8206937
      supporting_text: "Treatment of extracts from human breast cancer (MCF7) cells
        with either alkali or ethanol increased immunoreactivity of PP2Ac subunit
        severalfold"
- term:
    id: GO:0006470
    label: protein dephosphorylation
  evidence_type: TAS
  original_reference_id: PMID:2849765
  review:
    summary: >-
      TAS annotation from the original cDNA cloning paper for human PPP2CB.
      The paper established PPP2CB as a phosphatase catalytic subunit.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:2849765
      supporting_text: "The nucleotide sequence of the cDNA encoding the human lung
        protein phosphatase 2A beta catalytic subunit"
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    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.
    action: NEW
    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.
    supported_by:
    - reference_id: PMID:10318862
      supporting_text: "substitution of glutamine for either of two putative active
        site histidines in the PP2A C subunit results in inactivation of PP2A"
core_functions:
- molecular_function:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  description: >-
    PPP2CB is the beta catalytic subunit of PP2A, a major cellular Ser/Thr phosphatase
    (EC 3.1.3.16). It dephosphorylates phosphoserine and phosphothreonine residues
    on
    protein substrates using a bimetallic Mn2+ active site. PPP2CB functions as the
    catalytic engine of heterotrimeric PP2A holoenzymes (A scaffold + C catalytic
    + B
    regulatory subunit). Substrate specificity is determined by the regulatory B subunit
    incorporated into the holoenzyme. PPP2CB is the minor catalytic isoform (~97%
    identical to PPP2CA but ~10x less abundant), and is predominantly cytoplasmic
    and
    nuclear. C-terminal Leu-309 methylation by LCMT1 (reversed by PME-1) regulates
    holoenzyme assembly and B subunit selection.
  directly_involved_in:
  - id: GO:0006470
    label: protein dephosphorylation
  - id: GO:0000278
    label: mitotic cell cycle
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005654
    label: nucleoplasm
  in_complex:
    id: GO:0000159
    label: protein phosphatase type 2A complex
  supported_by:
  - reference_id: PMID:8206937
    supporting_text: >-
      Methylation of PP2Ac subunit, in vitro, increases its activity toward both
      phosphorylase a and a phosphopeptide.
  - reference_id: PMID:2849765
    supporting_text: >-
      The nucleotide sequence of the cDNA encoding the human lung protein phosphatase
      2A beta catalytic subunit.
  - reference_id: PMID:16262633
    supporting_text: >-
      PP2A accounted for approximately 71% of the total tau phosphatase activity of
      human brain.
    full_text_unavailable: true
- molecular_function:
    id: GO:0004722
    label: protein serine/threonine phosphatase activity
  description: >-
    PPP2CB functions as the catalytic subunit within the STRIPAK complex
    (FAR/SIN/STRIPAK complex), a large signaling assembly that includes PP2A catalytic
    and scaffolding subunits, striatins (B''' regulatory subunits), MOB4, STRIP1/2,
    PDCD10/CCM3, and germinal center kinase III family STE20 kinases. In this context,
    PPP2CB provides phosphatase activity that opposes the kinase activities within
    the
    complex, regulating cell migration, polarity, and cerebral cavernous malformation
    signaling.
  directly_involved_in:
  - id: GO:0006470
    label: protein dephosphorylation
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0090443
    label: FAR/SIN/STRIPAK complex
  supported_by:
  - reference_id: PMID:18782753
    supporting_text: >-
      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, PDCD10, and members of the germinal
      center kinase III family of Ste20 kinases.
    full_text_unavailable: true
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with
    GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping,
    accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
    Location vocabulary mapping, accompanied by conservative changes to GO terms
    applied by UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data
    to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning
    models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:2849765
  title: The nucleotide sequence of the cDNA encoding the human lung protein
    phosphatase 2A beta catalytic subunit.
  findings:
  - statement: Original cDNA cloning and sequencing of human PPP2CB from lung
      tissue.
- id: PMID:8206937
  title: The catalytic subunit of protein phosphatase 2A is carboxyl-methylated
    in vivo.
  findings:
  - statement: Demonstrated carboxyl-methylation of PP2Ac at Leu-309 in vivo;
      methylation increases phosphatase activity.
- id: PMID:9647778
  title: Alpha 4 associates with protein phosphatases 2A, 4, and 6.
  findings:
  - statement: Alpha4/IGBP1 constitutively associates with PP2A, PP4, and PP6
      catalytic subunits.
- id: PMID:10318862
  title: A protein phosphatase methylesterase (PME-1) is one of several novel
    proteins stably associating with two inactive mutants of protein phosphatase
    2A.
  findings:
  - statement: Identified PME-1 as PP2A demethylase; H59Q and H118Q mutations
      inactivate PP2A catalytic activity.
- id: PMID:10640627
  title: Regulation of phosphorylation of neuronal microtubule-associated
    proteins MAP1b and MAP2 by protein phosphatase-2A and -2B in rat brain.
  findings:
  - statement: PP2A is the major phosphatase regulating MAP1b and MAP2
      phosphorylation and microtubule binding activity.
- id: PMID:10698523
  title: GSK-3beta-dependent phosphorylation of adenomatous polyposis coli gene
    product can be modulated by beta-catenin and protein phosphatase 2A
    complexed with Axin.
  findings:
  - statement: PP2A directly binds Axin and dephosphorylates APC phosphorylated
      by GSK-3beta in Wnt signaling.
- id: PMID:16085932
  title: A novel, evolutionarily conserved protein phosphatase complex involved
    in cisplatin sensitivity.
  findings:
  - statement: Characterized PP4-containing complex; TIPRL interacts with PP2A
      family catalytic subunits.
- id: PMID:16262633
  title: Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the
    regulation of tau phosphorylation.
  findings:
  - statement: PP2A accounts for ~71% of total tau phosphatase activity in human
      brain; activity decreased in AD brain.
- id: PMID:16541025
  title: Shugoshin collaborates with protein phosphatase 2A to protect cohesin.
  findings:
  - statement: PP2A localizes to centromeres in prometaphase via SGO1
      interaction; also found at spindle poles during mitosis.
- 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:
  - statement: Defined the STRIPAK complex containing PP2A catalytic/scaffolding
      subunits, striatins, MOB4, STRIP1/2, PDCD10, and STE20 kinases.
- id: PMID:19156129
  title: 'An integrated workflow for charting the human interaction proteome: insights
    into the PP2A system.'
  findings:
  - statement: Mapped the PP2A interaction network including IGBP1/alpha4
      binding to PP2A catalytic subunits.
- id: PMID:20969868
  title: "LIM domain protein FHL1B interacts with PP2A catalytic β subunit--a novel
    cell cycle regulatory pathway."
  findings:
  - statement: FHL1B specifically interacts with PPP2CB (not PPP2CA was tested)
      by yeast two-hybrid and co-IP; linked to cell cycle regulation.
- id: PMID:21784977
  title: Zinc finger protein tristetraprolin interacts with CCL3 mRNA and
    regulates tissue inflammation.
  findings:
  - statement: TTP/ZFP36 interacts with PPP2CB; TTP modulates inflammatory
      cytokine mRNA stability.
- id: PMID:25531779
  title: STRIPAK components determine mode of cancer cell migration and
    metastasis.
  findings:
  - statement: STRIPAK complex components including STRIP1 interact with PP2A
      catalytic subunits in cancer cell migration.
- id: PMID:26496610
  title: A human interactome in three quantitative dimensions organized by
    stoichiometries and abundances.
  findings:
  - statement: High-throughput interactome study confirming IGBP1 and STRIP1
      interactions with PPP2CB.
- id: PMID:27880917
  title: Phenotypic and Interaction Profiling of the Human Phosphatases
    Identifies Diverse Mitotic Regulators.
  findings:
  - statement: Comprehensive phosphatase interactome profiling; PPP2CB interacts
      with TIPRL and IGBP1.
- id: PMID:28159925
  title: miRNA-1246 induces pro-inflammatory responses in mesenchymal
    stem/stromal cells by regulating PKA and PP2A.
  findings:
  - statement: PPP2CB is a direct target of miR-1246; knockdown increases
      p65/NF-kappaB and enhances TNF-mediated inflammatory gene expression in
      MSCs.
- id: PMID:28386764
  title: Roles of tau protein in health and disease.
  findings:
  - statement: Review describing PP2A as a major tau phosphatase, with relevance
      to tauopathies.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and
    disease networks.
  findings:
  - statement: Large-scale interactome study confirming STRIP1 interaction with
      PPP2CB.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease
    Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings:
  - statement: Identified PPP2CB-FMR1 interaction in neurodegenerative disease
      protein network.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the
    human interactome.
  findings:
  - statement: Cell-specific interactome confirming IGBP1 and STRIP1
      interactions with PPP2CB.
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings:
  - statement: Endogenous tagging proteomics confirming IGBP1 and STRIP1
      interactions with PPP2CB.
- id: Reactome:R-HSA-1295599
  title: SPRY2 translocates to the plasma membrane
  findings: []
- id: Reactome:R-HSA-1295609
  title: SRC phosphorylates SPRY2 on Y55 and Y227
  findings: []
- id: Reactome:R-HSA-1295613
  title: SPRY2 binds GRB2
  findings: []
- id: Reactome:R-HSA-1295622
  title: SPRY2 binds CBL
  findings: []
- id: Reactome:R-HSA-1295632
  title: PPA2A dephosphorylates SPRY2
  findings: []
- id: Reactome:R-HSA-1549564
  title: PPTN11 dephosphorylates SPRY2
  findings: []
- id: Reactome:R-HSA-934559
  title: SPRY2 is phosphorylated by phosphorylated MNK1
  findings: []