meg-2

id: Q21127
gene_symbol: meg-2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: MEG-2 (Maternal Effect Germ cell defective 2) is a highly intrinsically
  disordered protein (87% disordered residues) that localizes to P granules during
  C. elegans embryogenesis. It functions redundantly with MEG-1 to regulate P granule
  dynamics through phase separation mechanisms. MEG-2 has an acidic predicted pI of
  6.04 and a serine-rich N-terminus characteristic of MEG proteins. Phosphorylation
  of MEG-1/2 by kinase MBK-2 promotes P granule disassembly in the anterior cytoplasm,
  while dephosphorylation by PP2A promotes P granule assembly in the posterior. This
  asymmetric regulation ensures proper segregation of P granules to the germline during
  early embryonic divisions. Loss of meg-2 in combination with meg-1 causes sterility
  and P granule mis-segregation to somatic blastomeres.
existing_annotations:
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14704431
  review:
    summary: High-throughput yeast two-hybrid screen identified interaction between
      MEG-2 and EYA-1 (O17670). The publication describes a large-scale interactome
      mapping effort detecting over 4000 interactions. While the interaction may be
      real, the generic 'protein binding' term provides no functional insight. No
      specific functional context for this interaction is established in the literature.
    action: REMOVE
    reason: The 'protein binding' term is uninformative as a GO annotation per curation
      guidelines. High-throughput Y2H interactions without validation or functional
      characterization should not be annotated with this generic term. The MEG-2/EYA-1
      interaction has no established biological significance in germline development
      or P granule function.
    supported_by:
    - reference_id: PMID:14704431
      supporting_text: more than 4000 interactions were identified from high-throughput,
        yeast two-hybrid (HT=Y2H) screens
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19123269
  review:
    summary: This is from a second high-throughput yeast two-hybrid mapping effort
      (Worm Interactome 2007). The publication describes quality-controlled protein-protein
      interaction mapping detecting the same MEG-2/EYA-1 interaction. While the interaction
      was detected in two independent screens, no functional context is established.
    action: REMOVE
    reason: Same rationale as the previous annotation - 'protein binding' is uninformative
      and does not capture any specific molecular function. The duplicate annotation
      from a related interactome study adds no additional functional information.
      If a more specific binding function were established (e.g., specific role in
      P granule assembly), a more informative MF term should be used.
    supported_by:
    - reference_id: PMID:19123269
      supporting_text: We present an expanded C. elegans protein-protein interaction
        network, or 'interactome' map, derived from testing a matrix of approximately
        10,000 x approximately 10,000 proteins
- term:
    id: GO:1903864
    label: P granule disassembly
  evidence_type: IGI
  original_reference_id: PMID:25535836
  review:
    summary: Well-supported annotation based on genetic interaction evidence. Wang
      et al. (2014) demonstrated that MEG-1 and MEG-2 are required for P granule dynamics
      in embryos. The publication shows that phosphorylation of MEG proteins by MBK-2/DYRK
      kinase promotes granule disassembly in the anterior cytoplasm (PMID:25535836).
    action: ACCEPT
    reason: This annotation accurately captures a core molecular function of MEG-2.
      The IGI evidence from PMID:25535836 demonstrates that simultaneous loss of meg-1
      and meg-2 causes defects in P granule disassembly, with P granules failing to
      disassemble properly in the anterior cytoplasm of the P1 blastomere.
    supported_by:
    - reference_id: PMID:25535836
      supporting_text: Phosphorylation of the MEGs promotes granule disassembly and
        dephosphorylation promotes granule assembly
- term:
    id: GO:0043186
    label: P granule
  evidence_type: IDA
  original_reference_id: PMID:18202375
  review:
    summary: Cellular component annotation demonstrating MEG-2 localization to P granules
      during embryogenesis. Leacock and Reinke (2008) showed that MEG-1 and MEG-2
      are embryo-specific P granule components that localize to P granules from the
      4-8 cell stage through subsequent P cell divisions (PMID:18202375).
    action: ACCEPT
    reason: This is a core cellular localization for MEG-2. The IDA evidence from
      direct observation of MEG-2 localization to P granules in embryos is well-established.
      MEG-2 is one of the defining embryo-specific components of P granules.
    supported_by:
    - reference_id: PMID:18202375
      supporting_text: encode proteins that localize exclusively to P granules during
        embryonic germline segregation
- term:
    id: GO:1903863
    label: P granule assembly
  evidence_type: IGI
  original_reference_id: PMID:25535836
  review:
    summary: Proposed new annotation based on evidence from Wang et al. (2014) showing
      that dephosphorylated MEG-1/MEG-2 promotes P granule assembly in the posterior
      cytoplasm. The literature establishes a dual role for MEG proteins in both assembly
      and disassembly depending on phosphorylation state.
    action: NEW
    reason: 'The existing annotations only capture the disassembly function, but MEG-2
      also has a documented role in promoting P granule assembly when dephosphorylated.
      UniProt annotation states: "Together with dephosphorylated meg-1, promotes the
      assembly and accumulation of zygotic P granules in the posterior cytoplasm of
      pre-gastrulation embryos."'
    supported_by:
    - reference_id: PMID:25535836
      supporting_text: Phosphorylation of the MEGs promotes granule disassembly and
        dephosphorylation promotes granule assembly
- term:
    id: GO:0030719
    label: P granule organization
  evidence_type: IGI
  original_reference_id: PMID:25535836
  review:
    summary: MEG-2 regulates overall P granule organization through its role in controlling
      both assembly and disassembly dynamics. This is more general than the specific
      assembly/disassembly terms and captures the full scope of MEG-2 function.
    action: NEW
    reason: P granule organization (GO:0030719) is the parent term that encompasses
      both assembly and disassembly. MEG-2 participates in both processes depending
      on phosphorylation state, making this term an appropriate annotation.
    supported_by:
    - reference_id: PMID:25535836
      supporting_text: a group of intrinsically disordered, serine-rich proteins regulate
        the dynamics of P granules in C. elegans embryos
- term:
    id: GO:0140693
    label: molecular condensate scaffold activity
  evidence_type: IDA
  original_reference_id: PMID:25535836
  review:
    summary: MEG-2 functions as a scaffold protein for P granule condensates through
      its intrinsically disordered regions. The MEG proteins regulate liquid-like
      P granule dynamics through phase separation mechanisms.
    action: NEW
    reason: MEG-2 is an intrinsically disordered protein that regulates P granule
      condensate dynamics. P granules behave as liquid droplets whose dynamics depend
      on MEG proteins. This molecular function term captures the scaffold role of
      MEG-2 in condensate formation.
    supported_by:
    - reference_id: PMID:25535836
      supporting_text: RNA granules have been likened to liquid droplets whose dynamics
        depend on the controlled dissolution and condensation of internal components
references:
- id: PMID:14704431
  title: A map of the interactome network of the metazoan C. elegans.
  findings:
  - statement: High-throughput yeast two-hybrid screen detected MEG-2 interaction
      with EYA-1
    supporting_text: more than 4000 interactions were identified from high-throughput,
      yeast two-hybrid (HT=Y2H) screens
- id: PMID:18202375
  title: MEG-1 and MEG-2 are embryo-specific P-granule components required for germline
    development in Caenorhabditis elegans.
  findings:
  - statement: MEG-1 and MEG-2 localize exclusively to P granules during embryonic
      germline segregation
    supporting_text: encode proteins that localize exclusively to P granules during
      embryonic germline segregation
  - statement: Loss of meg-1 and meg-2 causes P granule mis-segregation and sterility
    supporting_text: 'meg-1 mutants exhibit multiple germline defects: P-granule mis-segregation
      in embryos, underproliferation and aberrant P-granule morphology in larval germ
      cells, and ultimately, sterility as adults. The penetrance of meg-1 phenotypes
      increases when meg-2 is also absent.'
  - statement: meg-1 and meg-2 are required redundantly for germline development
    supporting_text: The penetrance of meg-1 phenotypes increases when meg-2 is also
      absent.
- id: PMID:19123269
  title: Empirically controlled mapping of the Caenorhabditis elegans protein-protein
    interactome network.
  findings:
  - statement: Independent validation of MEG-2/EYA-1 interaction in WI-2007 interactome
      dataset
    supporting_text: We present an expanded C. elegans protein-protein interaction
      network, or 'interactome' map, derived from testing a matrix of approximately
      10,000 x approximately 10,000 proteins
- id: PMID:25535836
  title: Regulation of RNA granule dynamics by phosphorylation of serine-rich, intrinsically
    disordered proteins in C. elegans.
  findings:
  - statement: MEG proteins are intrinsically disordered with serine-rich regions
    supporting_text: a group of intrinsically disordered, serine-rich proteins regulate
      the dynamics of P granules in C. elegans embryos
  - statement: MEG-1 and MEG-3 are substrates of MBK-2/DYRK kinase and PP2A phosphatase
    supporting_text: "We demonstrate that MEG-1 and MEG-3 are substrates of the kinase\
      \ MBK-2/DYRK and the phosphatase PP2A(PPTR-\xBD)"
  - statement: Phosphorylation promotes P granule disassembly, dephosphorylation promotes
      assembly
    supporting_text: Phosphorylation of the MEGs promotes granule disassembly and
      dephosphorylation promotes granule assembly
  - statement: MEG proteins are required redundantly for fertility
    supporting_text: The MEG (maternal-effect germline defective) proteins are germ
      plasm components that are required redundantly for fertility
core_functions:
- description: MEG-2 is an intrinsically disordered protein that regulates P granule
    dynamics through phase separation. Its phosphorylation state determines whether
    it promotes granule assembly (dephosphorylated) or disassembly (phosphorylated).
  molecular_function:
    id: GO:0140693
    label: molecular condensate scaffold activity
  directly_involved_in:
  - id: GO:0030719
    label: P granule organization
  locations:
  - id: GO:0043186
    label: P granule
  supported_by:
  - reference_id: PMID:25535836
    supporting_text: Phosphorylation of the MEGs promotes granule disassembly and
      dephosphorylation promotes granule assembly
  - reference_id: PMID:18202375
    supporting_text: encode proteins that localize exclusively to P granules during
      embryonic germline segregation
tags:
- caeel-p-granules