mbk-2

id: Q9XTF3
gene_symbol: mbk-2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: 'MBK-2 (minibrain kinase 2) is a DYRK (Dual-specificity tyrosine phosphorylation-Regulated
  Kinase) family member that serves as a master regulator of the oocyte-to-embryo
  transition in C. elegans. As a dual-specificity kinase, MBK-2 phosphorylates both
  serine/threonine and tyrosine residues on key substrate proteins. Its primary functions
  include: (1) promoting the degradation of oocyte proteins (MEI-1/katanin, OMA-1,
  OMA-2) during meiotic maturation by marking them for proteasomal destruction, (2)
  regulating P granule dynamics by phosphorylating MEG-1 and MEG-3 to promote granule
  disassembly in the anterior cytoplasm during zygote polarization, (3) priming MEX-5
  and MEX-6 for polo kinase-dependent phosphorylation to regulate embryonic polarity,
  and (4) contributing to spindle positioning and asymmetric cell division in early
  embryos. MBK-2 is activated during oocyte maturation by CDK-1-dependent phosphorylation
  and is sequestered at the cell cortex by the pseudophosphatases EGG-3, EGG-4, and
  EGG-5 until the meiotic divisions. The human ortholog DYRK3 has analogous functions
  in dissolving stress granules and mitotic condensates.'
core_functions:
  - molecular_function:
      id: GO:0004712
      label: protein serine/threonine/tyrosine kinase activity
    directly_involved_in:
      - id: GO:1903864
        label: P granule disassembly
      - id: GO:0032436
        label: positive regulation of proteasomal ubiquitin-dependent protein 
          catabolic process
      - id: GO:0045167
        label: asymmetric protein localization involved in cell fate 
          determination
    locations:
      - id: GO:0005737
        label: cytoplasm
      - id: GO:0005938
        label: cell cortex
    description: MBK-2 is a DYRK family kinase with demonstrated 
      dual-specificity activity. In vitro kinase assays show it phosphorylates 
      substrates including MEI-1, OMA-1, MEX-5/6, and MEG-1/3 at 
      serine/threonine residues (PMID:16338136, PMID:16289132, PMID:18199581, 
      PMID:25535836). MBK-2 also autophosphorylates at tyrosine-621 in its YTY 
      activation motif (PMID:19879842). Through phosphorylation of substrates, 
      MBK-2 regulates P granule disassembly, oocyte protein degradation during 
      the oocyte-to-embryo transition, and asymmetric localization of cell fate 
      determinants.
existing_annotations:
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: MBK-2 localizes to the cytoplasm after release from cortical 
        anchoring during meiotic divisions. Multiple studies document 
        cytoplasmic localization (PMID:12967564, PMID:16338136, PMID:17869113).
      action: ACCEPT
      reason: IBA annotation is well-supported by experimental literature. MBK-2
        translocates from the cortex to the cytoplasm during meiotic anaphase 
        and functions in the cytoplasm to phosphorylate its substrates.
      supported_by:
        - reference_id: PMID:16338136
          supporting_text: A GFP:MBK-2 fusion relocalizes from the cortex to the
            cytoplasm during the meiotic divisions
        - reference_id: PMID:17869113
          supporting_text: During the meiotic divisions, EGG-3 is internalized 
            and degraded in an APC/C (anaphase-promoting 
            complex/cyclosome)-dependent manner
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: MBK-2 has experimentally demonstrated Ser/Thr kinase activity on 
        multiple substrates including MEI-1, OMA-1, MEX-5/6, and MEG-1/3. It 
        phosphorylates MEI-1 at S92 (PMID:16338136), OMA-1 at T239 
        (PMID:16289132), and MEG proteins at serine-rich motifs (PMID:25535836).
      action: ACCEPT
      reason: Core molecular function well-supported by multiple IDA 
        annotations. This is the primary enzymatic activity of MBK-2.
      supported_by:
        - reference_id: PMID:16338136
          supporting_text: we demonstrate that MBK-2 directly phosphorylates 
            MEI-1 and OMA-1 in vitro and that this activity is essential for 
            degradation in vivo
        - reference_id: PMID:25535836
          supporting_text: We demonstrate that MEG-1 and MEG-3 are substrates of
            the kinase MBK-2/DYRK and the phosphatase PP2A
  - term:
      id: GO:0005856
      label: cytoskeleton
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: MBK-2 localizes to the mitotic spindle and centrosomes 
        (PMID:16338136, PMID:12967564) and regulates microtubule-based processes
        through phosphorylation of MEI-1/katanin.
      action: ACCEPT
      reason: MBK-2 associates with cytoskeletal structures including the 
        mitotic spindle, as documented by IDA evidence.
      supported_by:
        - reference_id: PMID:32412594
          supporting_text: Katanin is readily expressed during embryogenesis, 
            where it is actively recruited to the centrosomes and chromosomes 
            during mitosis
        - reference_id: PMID:12967564
          supporting_text: MBK-2 distribution changes dramatically after 
            fertilization during the meiotic divisions
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: While MBK-2 is primarily cytoplasmic and cortical in C. elegans 
        early embryos, this IBA annotation likely reflects nuclear localization 
        observed in orthologous DYRK family members in other species.
      action: KEEP_AS_NON_CORE
      reason: The IBA annotation reflects phylogenetic inference from other DYRK
        family members. In C. elegans, MBK-2 is predominantly at the cortex, 
        cytoplasm, and on mitotic structures rather than in the nucleus. 
        However, the annotation is not incorrect for the broader DYRK family.
  - term:
      id: GO:0000166
      label: nucleotide binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: As a protein kinase, MBK-2 binds ATP. This is a parent term of 
        ATP binding which is more appropriate.
      action: ACCEPT
      reason: General term that is accurate for a kinase. However, ATP binding 
        (GO:0005524) is more specific and also annotated. This IEA based on 
        keyword is correct but less informative.
  - term:
      id: GO:0004672
      label: protein kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: General kinase activity term. MBK-2 is a well-characterized 
        protein kinase.
      action: ACCEPT
      reason: Accurate parent term derived from InterPro domain annotation. More
        specific child terms (protein serine/threonine kinase activity, protein 
        tyrosine kinase activity) are also annotated with experimental evidence.
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: IEA annotation consistent with multiple experimental annotations 
        for the same term.
      action: ACCEPT
      reason: Keyword-based annotation that agrees with multiple IDA annotations
        for this term. MBK-2 phosphorylates serine/threonine residues on MEI-1, 
        OMA-1, MEX-5/6, and MEG proteins.
  - term:
      id: GO:0004712
      label: protein serine/threonine/tyrosine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: MBK-2 is a DYRK (Dual-specificity tyrosine-Regulated Kinase) with
        dual specificity for Ser/Thr and Tyr residues. It autophosphorylates at 
        Tyr-621 in the YTY activation motif.
      action: ACCEPT
      reason: This is the most accurate MF term for MBK-2 as a DYRK family
        member. UniProt EC 2.7.12.1 annotation correctly classifies it as
        dual-specificity kinase.
      additional_reference_ids:
        - file:worm/mbk-2/mbk-2-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:19879842
          supporting_text: DYRKs are kinases that self-activate in vitro by
            autophosphorylation of a YTY motif in the kinase domain
        - reference_id: PMID:17869113
          supporting_text: Regulation of MBK-2/Dyrk kinase by dynamic cortical
            anchoring during the oocyte-to-zygote transition
        - reference_id: file:worm/mbk-2/mbk-2-deep-research-falcon.md
          supporting_text: |-
            maternally supplied DYRK-family dual-specificity protein kinase that is activated during the oocyte-to-embryo transition
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: MBK-2 has tyrosine kinase activity demonstrated by 
        autophosphorylation at the YTY motif (Y619, Y621) in its activation 
        loop.
      action: ACCEPT
      reason: Accurate annotation. While MBK-2 primarily phosphorylates Ser/Thr 
        on substrates, it autophosphorylates tyrosine residues during its own 
        activation.
      supported_by:
        - reference_id: PMID:19879842
          supporting_text: The pseudotyrosine phosphatases EGG-4 and EGG-5 
            sequester activated MBK-2 until the meiotic divisions by binding to 
            the YTY motif
  - term:
      id: GO:0005524
      label: ATP binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: As a protein kinase, MBK-2 binds and hydrolyzes ATP as a 
        phosphate donor.
      action: ACCEPT
      reason: Essential for kinase function. UniProt annotates ATP binding at 
        positions 467-475 and K490.
      supported_by:
        - reference_id: PMID:19879842
          supporting_text: MBK-2 is activated during oocyte maturation by 
            CDK-1-dependent phosphorylation of serine 68
  - term:
      id: GO:0005938
      label: cell cortex
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: MBK-2 is sequestered at the cell cortex before meiotic divisions 
        by the cortical anchor EGG-3 and the pseudophosphatases EGG-4/5.
      action: ACCEPT
      reason: Key localization for MBK-2 regulation. It is maintained at the 
        cortex in oocytes and released during meiosis.
      supported_by:
        - reference_id: PMID:17869113
          supporting_text: Prior to the meiotic divisions, MBK-2 is tethered at 
            the cortex by EGG-3, an oocyte protein required for egg activation
        - reference_id: PMID:19879842
          supporting_text: The pseudotyrosine phosphatases EGG-4 and EGG-5 
            sequester activated MBK-2 until the meiotic divisions
  - term:
      id: GO:0016301
      label: kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: General parent term for kinase activity.
      action: ACCEPT
      reason: Accurate but uninformative parent term. More specific child terms 
        are annotated.
  - term:
      id: GO:0016740
      label: transferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Very general parent term for kinases as phosphotransferases.
      action: ACCEPT
      reason: Accurate but highly general. More specific terms provide better 
        functional information.
  - term:
      id: GO:0106310
      label: protein serine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000116
    review:
      summary: MBK-2 phosphorylates serine residues on substrates including 
        MEI-1 (S92), OMA-1 (part of T239 is threonine), and MEG proteins at 
        serine-rich regions.
      action: ACCEPT
      reason: RHEA-based annotation that is accurate. MBK-2 phosphorylates MEI-1
        at S90, S92, S113, S137 (PMID:32412594).
      supported_by:
        - reference_id: PMID:32412594
          supporting_text: This analysis showed that MBK-2 phosphorylates MEI-1 
            at S92, consistent with a previous report (Stitzel et al., 2006), 
            but also at S90, S113, and S137
  - term:
      id: GO:0001556
      label: oocyte maturation
    evidence_type: NAS
    original_reference_id: PMID:19879842
    review:
      summary: MBK-2 is activated during oocyte maturation by CDK-1-dependent 
        phosphorylation and is essential for the oocyte-to-embryo transition.
      action: ACCEPT
      reason: MBK-2 plays a key role in coordinating oocyte maturation events.
        Falcon deep research emphasizes that MBK-2 activation is tightly coupled
        to meiotic progression.
      additional_reference_ids:
        - file:worm/mbk-2/mbk-2-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:19879842
          supporting_text: MBK-2 is activated during oocyte maturation by
            CDK-1-dependent phosphorylation of serine 68
        - reference_id: file:worm/mbk-2/mbk-2-deep-research-falcon.md
          supporting_text: |-
            MBK-2 activation is tightly coupled to meiotic progression via regulated cortical sequestration (EGG-3/EGG-4/EGG-5), CDK-1 phosphorylation, and APC/C-dependent release
  - term:
      id: GO:0005938
      label: cell cortex
    evidence_type: NAS
    original_reference_id: PMID:19879842
    review:
      summary: NAS annotation for cortical localization based on PMID:19879842.
      action: ACCEPT
      reason: Correct localization, supported by experimental evidence in the
        same and other papers. MBK-2 cortical sequestration is integral to its
        cell-cycle-gated activation, as synthesized by falcon deep research.
      additional_reference_ids:
        - file:worm/mbk-2/mbk-2-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:19879842
          supporting_text: Regulation of MBK-2/DYRK by CDK-1 and the
            pseudophosphatases EGG-4 and EGG-5 during the oocyte-to-embryo
            transition.
        - reference_id: file:worm/mbk-2/mbk-2-deep-research-falcon.md
          supporting_text: |-
            it autophosphorylates on a YTY motif during translation, CDK-1 phosphorylates S68, and APC/C-dependent release/degradation of EGG proteins allows active MBK-2 to access cytoplasmic substrates
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:32412594
    review:
      summary: IDA evidence from Joly et al. 2020 showing MBK-2 phosphorylates 
        MEI-1 (katanin) at multiple serine residues to regulate its stability 
        and activity.
      action: ACCEPT
      reason: Strong experimental evidence showing phosphorylation of MEI-1 by
        MBK-2 at a single serine (S92) is both necessary and sufficient to
        target MEI-1 for degradation. Falcon deep research adds that MBK-2
        phosphorylation of the N-terminal regulatory sites also abolishes
        microtubule-stimulated katanin ATPase activity, linking degradation
        control to direct enzymatic regulation of katanin.
      additional_reference_ids:
        - file:worm/mbk-2/mbk-2-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:32412594
          supporting_text: This analysis showed that MBK-2 phosphorylates MEI-1
            at S92, consistent with a previous report (Stitzel et al., 2006),
            but also at S90, S113, and S137
        - reference_id: file:worm/mbk-2/mbk-2-deep-research-falcon.md
          supporting_text: |-
            S92 is the principal site for degradation targeting, while phosphorylation of N-terminal sites suppresses MT-stimulated ATPase activity
        - reference_id: file:worm/mbk-2/mbk-2-deep-research-falcon.md
          supporting_text: |-
            MEI-1 S90, S92, S113, S137; MEI-2 T32, S68, S86 (MEI-2 phosphorylation requires MEI-1)
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:17869113
    review:
      summary: IDA evidence for cytoplasmic localization after release from 
        cortex during meiosis.
      action: ACCEPT
      reason: Experimentally demonstrated localization showing EGG-3
        internalization correlates with MBK-2 release from the cortex. Falcon
        deep research describes the relocalization as a two-step,
        meiosis-driven event culminating in cytoplasmic access to substrates.
      additional_reference_ids:
        - file:worm/mbk-2/mbk-2-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:17869113
          supporting_text: EGG-3 internalization and degradation correlate with
            MBK-2 release from the cortex and MEI-1 phosphorylation in the
            cytoplasm
        - reference_id: file:worm/mbk-2/mbk-2-deep-research-falcon.md
          supporting_text: |-
            MBK-2 relocalizes in a two-step, cell-cycle-dependent manner from uniform cortex to cortical puncta and then into cytoplasm; progression through meiosis, not fertilization, is the trigger
  - term:
      id: GO:0004672
      label: protein kinase activity
    evidence_type: IDA
    original_reference_id: PMID:19879842
    review:
      summary: IDA evidence from Cheng et al. 2009 demonstrating MBK-2 kinase 
        activity and its regulation.
      action: ACCEPT
      reason: Core molecular function with strong experimental support. The 
        paper shows MBK-2 kinase activity is regulated by CDK-1 phosphorylation 
        and EGG-4/5 inhibition.
      supported_by:
        - reference_id: PMID:19879842
          supporting_text: MBK-2 is activated during oocyte maturation by 
            CDK-1-dependent phosphorylation of serine 68
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:16289132
    review:
      summary: IDA evidence showing MBK-2 phosphorylates OMA-1 at T239 
        (threonine), a serine/threonine kinase substrate.
      action: ACCEPT
      reason: Direct demonstration of Ser/Thr kinase activity on physiological
        substrate OMA-1.
      additional_reference_ids:
        - file:worm/mbk-2/mbk-2-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:16289132
          supporting_text: OMA-1 protein is directly phosphorylated at T239 by
            the DYRK kinase MBK-2
        - reference_id: file:worm/mbk-2/mbk-2-deep-research-falcon.md
          supporting_text: |-
            MBK-2 directly phosphorylates OMA-1 at T239; this acts as a molecular switch promoting later degradation and enabling OMA-1 functional transition; T239 phosphorylation primes subsequent GSK-3 phosphorylation at T339
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:16338136
    review:
      summary: IDA evidence showing MBK-2 directly phosphorylates MEI-1 
        (katanin) and OMA-1 in vitro.
      action: ACCEPT
      reason: Key paper demonstrating MBK-2 kinase activity on oocyte 
        substrates.
      supported_by:
        - reference_id: PMID:16338136
          supporting_text: we demonstrate that MBK-2 directly phosphorylates 
            MEI-1 and OMA-1 in vitro and that this activity is essential for 
            degradation in vivo
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:18199581
    review:
      summary: IDA evidence showing MBK-2 phosphorylates MEX-5 at T186 to prime 
        it for polo kinase binding.
      action: ACCEPT
      reason: Demonstrates MBK-2 kinase activity on polarity regulators MEX-5/6.
      supported_by:
        - reference_id: PMID:18199581
          supporting_text: We also show that MBK-2, a developmentally regulated 
            DYRK2 kinase activated at meiosis II, primes T(186) for subsequent 
            polo kinase-dependent phosphorylation
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:25535836
    review:
      summary: IDA evidence showing MBK-2 phosphorylates MEG-1 and MEG-3 to 
        regulate P granule dynamics.
      action: ACCEPT
      reason: Demonstrates MBK-2 kinase activity on P granule components. Key 
        paper for P granule regulation function.
      supported_by:
        - reference_id: PMID:25535836
          supporting_text: We demonstrate that MEG-1 and MEG-3 are substrates of
            the kinase MBK-2/DYRK and the phosphatase PP2A
  - term:
      id: GO:0032436
      label: positive regulation of proteasomal ubiquitin-dependent protein 
        catabolic process
    evidence_type: IMP
    original_reference_id: PMID:16343905
    review:
      summary: IMP evidence showing MBK-2 promotes OMA-1 destruction during the 
        oocyte-to-embryo transition via ubiquitin-mediated proteolysis.
      action: ACCEPT
      reason: Core biological function of MBK-2. Mutations in mbk-2 cause
        stabilization of OMA-1 protein indicating MBK-2 normally promotes OMA-1
        degradation. Falcon deep research clarifies that MBK-2 acts as a
        temporal activator conferring degradation competence on specific
        substrates after meiosis, rather than triggering global proteolysis.
      additional_reference_ids:
        - file:worm/mbk-2/mbk-2-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:16343905
          supporting_text: Mutations in four conserved protein kinase
            genes-mbk-2/Dyrk, kin-19/CK1alpha, gsk-3, and cdk-1/CDC2-cause
            stabilization of OMA-1 protein
        - reference_id: file:worm/mbk-2/mbk-2-deep-research-falcon.md
          supporting_text: |-
            MBK-2 functions as a temporal activator of maternal protein degradation during the egg-to-embryo transition, likely by phosphorylation that creates degradation competence after meiotic progression
  - term:
      id: GO:0005938
      label: cell cortex
    evidence_type: IDA
    original_reference_id: PMID:20971008
    review:
      summary: IDA evidence for MBK-2 cortical localization in the context of 
        eggshell formation and polyspermy block.
      action: ACCEPT
      reason: Demonstrates cortical localization of MBK-2 as part of the 
        CHS-1/MBK-2/EGG-3 complex at the oocyte cortex.
      supported_by:
        - reference_id: PMID:20971008
          supporting_text: Loss of CBD-1 or EGG-1/2 disrupts oocyte cortical 
            distribution of CHS-1, as well as MBK-2 and EGG-3
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IMP
    original_reference_id: PMID:17869113
    review:
      summary: IMP evidence based on MBK-2's role in phosphorylating MEI-1, with
        its activity dependent on dual-specificity nature including tyrosine 
        autophosphorylation.
      action: ACCEPT
      reason: While MBK-2 primarily phosphorylates substrates on Ser/Thr, it 
        autophosphorylates on tyrosine (Y621) as part of its activation 
        mechanism. This is characteristic of DYRK family kinases.
      supported_by:
        - reference_id: PMID:17869113
          supporting_text: Regulation of MBK-2/Dyrk kinase by dynamic cortical 
            anchoring during the oocyte-to-zygote transition
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19879147
    review:
      summary: MBK-2 interacts with EGG-3, EGG-4, and EGG-5 pseudophosphatases 
        at the oocyte cortex.
      action: MODIFY
      reason: The generic "protein binding" term is uninformative. MBK-2 has 
        specific functional interactions with the EGG pseudophosphatase family 
        that regulate its localization and activity. More specific terms should 
        be used.
      proposed_replacement_terms:
        - id: GO:0140663
          label: pseudophosphatase binding
      supported_by:
        - reference_id: PMID:19879147
          supporting_text: EGG-4 and EGG-5 Link Events of the Oocyte-to-Embryo 
            Transition with Meiotic Progression in C.
  - term:
      id: GO:0005938
      label: cell cortex
    evidence_type: IDA
    original_reference_id: PMID:17869113
    review:
      summary: IDA evidence showing MBK-2 is tethered at the cortex by EGG-3 
        before meiosis.
      action: ACCEPT
      reason: Key localization showing dynamic regulation of MBK-2.
      supported_by:
        - reference_id: PMID:17869113
          supporting_text: Prior to the meiotic divisions, MBK-2 is tethered at 
            the cortex by EGG-3, an oocyte protein required for egg activation
  - term:
      id: GO:0018108
      label: peptidyl-tyrosine phosphorylation
    evidence_type: IMP
    original_reference_id: PMID:17869113
    review:
      summary: MBK-2 as a DYRK autophosphorylates at tyrosine residues in its 
        activation loop (Y619, Y621).
      action: ACCEPT
      reason: Characteristic of DYRK family kinases. MBK-2 autophosphorylates at
        the YTY motif for activation.
      supported_by:
        - reference_id: PMID:19879842
          supporting_text: DYRKs are kinases that self-activate in vitro by 
            autophosphorylation of a YTY motif in the kinase domain
        - reference_id: PMID:17869113
          supporting_text: Regulation of MBK-2/Dyrk kinase by dynamic cortical 
            anchoring during the oocyte-to-zygote transition.
  - term:
      id: GO:0000793
      label: condensed chromosome
    evidence_type: IDA
    original_reference_id: PMID:16338136
    review:
      summary: MBK-2 localizes to condensed chromosomes during meiosis.
      action: ACCEPT
      reason: Documented localization. MBK-2 associates with meiotic chromosomes
        as part of its function in the oocyte-to-embryo transition.
      supported_by:
        - reference_id: PMID:32412594
          supporting_text: Katanin is readily expressed during embryogenesis, 
            where it is actively recruited to the centrosomes and chromosomes 
            during mitosis
        - reference_id: PMID:16338136
          supporting_text: Dec 15. The C. elegans DYRK Kinase MBK-2 Marks Oocyte
            Proteins for Degradation in Response to Meiotic Maturation.
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:16343905
    review:
      summary: IDA evidence for MBK-2 kinase activity in context of OMA-1 
        phosphorylation and degradation.
      action: ACCEPT
      reason: Additional experimental support for core molecular function.
      supported_by:
        - reference_id: PMID:16343905
          supporting_text: Mutations in four conserved protein kinase 
            genes-mbk-2/Dyrk, kin-19/CK1alpha, gsk-3, and cdk-1/CDC2-cause 
            stabilization of OMA-1 protein, and their phenotypes are partially 
            suppressed by an oma-1 loss-of-function mutation
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:16338136
    review:
      summary: IDA evidence for MBK-2 cytoplasmic localization after release 
        from cortex.
      action: ACCEPT
      reason: Key localization for MBK-2 function.
      supported_by:
        - reference_id: PMID:16338136
          supporting_text: A GFP:MBK-2 fusion relocalizes from the cortex to the
            cytoplasm during the meiotic divisions
  - term:
      id: GO:0005938
      label: cell cortex
    evidence_type: IDA
    original_reference_id: PMID:16338136
    review:
      summary: IDA evidence for MBK-2 cortical localization before meiotic 
        divisions.
      action: ACCEPT
      reason: Key localization showing MBK-2 is sequestered at cortex before 
        activation.
      supported_by:
        - reference_id: PMID:16338136
          supporting_text: Dec 15. The C. elegans DYRK Kinase MBK-2 Marks Oocyte
            Proteins for Degradation in Response to Meiotic Maturation.
  - term:
      id: GO:0072686
      label: mitotic spindle
    evidence_type: IDA
    original_reference_id: PMID:16338136
    review:
      summary: MBK-2 localizes to the mitotic spindle in early embryos.
      action: ACCEPT
      reason: Important localization for MBK-2 function in spindle positioning 
        and substrate phosphorylation.
      supported_by:
        - reference_id: PMID:32412594
          supporting_text: Katanin is readily expressed during embryogenesis, 
            where it is actively recruited to the centrosomes and chromosomes 
            during mitosis
        - reference_id: PMID:16338136
          supporting_text: Dec 15. The C. elegans DYRK Kinase MBK-2 Marks Oocyte
            Proteins for Degradation in Response to Meiotic Maturation.
  - term:
      id: GO:1903864
      label: P granule disassembly
    evidence_type: IMP
    original_reference_id: PMID:25535836
    review:
      summary: IMP evidence showing mbk-2 RNAi causes P granules to fail to 
        disassemble in anterior cytoplasm during zygote polarization.
      action: ACCEPT
      reason: Core biological function of MBK-2. Phosphorylation of the MEGs 
        promotes granule disassembly.
      supported_by:
        - reference_id: PMID:25535836
          supporting_text: Phosphorylation of the MEGs promotes granule 
            disassembly and dephosphorylation promotes granule assembly
  - term:
      id: GO:1903864
      label: P granule disassembly
    evidence_type: IGI
    original_reference_id: PMID:25535836
    review:
      summary: IGI evidence showing genetic interaction between MBK-2 and MEG 
        proteins in P granule regulation.
      action: ACCEPT
      reason: Supports the role of MBK-2 in P granule dynamics through 
        phosphorylation of MEG substrates.
      supported_by:
        - reference_id: PMID:25535836
          supporting_text: We demonstrate that MEG-1 and MEG-3 are substrates of
            the kinase MBK-2/DYRK and the phosphatase PP2A
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19879842
    review:
      summary: MBK-2 interacts with EGG-3, EGG-4, and EGG-5 as part of a 
        regulatory complex.
      action: MODIFY
      reason: Generic "protein binding" is uninformative. MBK-2 has specific 
        interactions with pseudophosphatases that regulate its activity and 
        localization.
      proposed_replacement_terms:
        - id: GO:0140663
          label: pseudophosphatase binding
      supported_by:
        - reference_id: PMID:19879842
          supporting_text: Regulation of MBK-2/DYRK by CDK-1 and the 
            pseudophosphatases EGG-4 and EGG-5 during the oocyte-to-embryo 
            transition.
  - term:
      id: GO:0000281
      label: mitotic cytokinesis
    evidence_type: IMP
    original_reference_id: PMID:12967564
    review:
      summary: mbk-2 mutants show defects in cytokinesis during early embryonic 
        cell divisions.
      action: KEEP_AS_NON_CORE
      reason: Cytokinesis defects are observed in mbk-2 mutants, but this is 
        likely a downstream consequence of the primary functions (substrate 
        phosphorylation, spindle positioning) rather than a direct role in 
        cytokinesis machinery. The annotation is accurate but represents a 
        phenotypic outcome rather than core function.
      supported_by:
        - reference_id: PMID:12967564
          supporting_text: the C. elegans DYRK family kinase MBK-2 coordinates 
            the degradation of several maternal proteins, and is essential for 
            zygotes to complete cytokinesis and pattern the first embryonic axis
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: ISS
    original_reference_id: PMID:12967564
    review:
      summary: ISS annotation based on sequence similarity to rat DYRK2.
      action: ACCEPT
      reason: Accurate inference. Multiple experimental annotations now provide 
        direct evidence for this function in C. elegans MBK-2.
      supported_by:
        - reference_id: PMID:12967564
          supporting_text: Coordinate activation of maternal protein degradation
            during the egg-to-embryo transition in C.
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: ISS
    original_reference_id: PMID:12967564
    review:
      summary: ISS annotation for tyrosine kinase activity based on DYRK family 
        membership.
      action: ACCEPT
      reason: Accurate for DYRK family. MBK-2 autophosphorylates at tyrosine 
        residues.
      supported_by:
        - reference_id: PMID:12967564
          supporting_text: Coordinate activation of maternal protein degradation
            during the egg-to-embryo transition in C.
  - term:
      id: GO:0005524
      label: ATP binding
    evidence_type: ISS
    original_reference_id: PMID:12967564
    review:
      summary: ISS annotation for ATP binding based on kinase domain 
        conservation.
      action: ACCEPT
      reason: Required for kinase function. Supported by domain structure.
      supported_by:
        - reference_id: PMID:19879842
          supporting_text: MBK-2 is activated during oocyte maturation by 
            CDK-1-dependent phosphorylation of serine 68
        - reference_id: PMID:12967564
          supporting_text: Coordinate activation of maternal protein degradation
            during the egg-to-embryo transition in C.
  - term:
      id: GO:0007017
      label: microtubule-based process
    evidence_type: IMP
    original_reference_id: PMID:12967564
    review:
      summary: mbk-2 mutants have fragmented and disordered microtubules in 
        early embryos.
      action: KEEP_AS_NON_CORE
      reason: MBK-2 affects microtubules primarily through regulating 
        MEI-1/katanin activity. The microtubule phenotype is a consequence of 
        failed katanin regulation rather than a direct role in MT organization.
      supported_by:
        - reference_id: PMID:12967564
          supporting_text: the C. elegans DYRK family kinase MBK-2 coordinates 
            the degradation of several maternal proteins, and is essential for 
            zygotes to complete cytokinesis and pattern the first embryonic axis
  - term:
      id: GO:0009792
      label: embryo development ending in birth or egg hatching
    evidence_type: IMP
    original_reference_id: PMID:12967564
    review:
      summary: mbk-2 mutants show maternal-effect embryonic lethality.
      action: KEEP_AS_NON_CORE
      reason: This is a phenotypic outcome of MBK-2's multiple functions (oocyte
        protein degradation, spindle positioning, P granule regulation) rather 
        than a specific molecular role. Accurate but very general.
      supported_by:
        - reference_id: PMID:12967564
          supporting_text: the C. elegans DYRK family kinase MBK-2 coordinates 
            the degradation of several maternal proteins, and is essential for 
            zygotes to complete cytokinesis and pattern the first embryonic axis
  - term:
      id: GO:0009880
      label: embryonic pattern specification
    evidence_type: IMP
    original_reference_id: PMID:12967564
    review:
      summary: MBK-2 is required for patterning the first embryonic axis through
        regulation of determinant localization.
      action: ACCEPT
      reason: Core developmental function. MBK-2 regulates asymmetric 
        localization of cell fate determinants (PIE-1, POS-1, PGL-1) and primes 
        MEX-5/6 for polo kinase-dependent polarity establishment.
      supported_by:
        - reference_id: PMID:12967564
          supporting_text: mbk-2 is also required for posterior enrichment of 
            the germ plasm before the first cleavage, and degradation of germ 
            plasm components in anterior cells after cleavage
        - reference_id: PMID:18199581
          supporting_text: Polo kinases regulate C. elegans embryonic polarity 
            via binding to DYRK2-primed MEX-5 and MEX-6
  - term:
      id: GO:0045167
      label: asymmetric protein localization involved in cell fate determination
    evidence_type: IMP
    original_reference_id: PMID:12967564
    review:
      summary: MBK-2 is required for posterior localization of germ plasm 
        determinants (PIE-1, POS-1, PGL-1) and asymmetric PLK-1 localization.
      action: ACCEPT
      reason: Core biological function. MBK-2 phosphorylates and primes MEX-5/6 
        for polo kinase binding, which regulates asymmetric protein 
        localization.
      supported_by:
        - reference_id: PMID:12967564
          supporting_text: mbk-2 is also required for posterior enrichment of 
            the germ plasm before the first cleavage, and degradation of germ 
            plasm components in anterior cells after cleavage
        - reference_id: PMID:18199581
          supporting_text: These polo kinases are asymmetrically localized along
            the anteroposterior axis of newly fertilized C. elegans embryos
  - term:
      id: GO:0045732
      label: positive regulation of protein catabolic process
    evidence_type: IMP
    original_reference_id: PMID:12967564
    review:
      summary: MBK-2 promotes degradation of oocyte proteins including MEI-1 and
        OMA-1 during the egg-to-embryo transition.
      action: ACCEPT
      reason: Core function - MBK-2 coordinates degradation of maternal
        proteins. This is a parent term of the more specific GO:0032436 which is
        also annotated.
      additional_reference_ids:
        - file:worm/mbk-2/mbk-2-deep-research-falcon.md
      supported_by:
        - reference_id: PMID:12967564
          supporting_text: the C. elegans DYRK family kinase MBK-2 coordinates
            the degradation of several maternal proteins
        - reference_id: file:worm/mbk-2/mbk-2-deep-research-falcon.md
          supporting_text: |-
            MBK-2 is required for degradation of OMA-1 and MEI-1/MEI-2, and for regulated degradation of PIE-1 (in specific embryonic regions), and is epistatic to PAR-1 for PIE-1 degradation
  - term:
      id: GO:0005694
      label: chromosome
    evidence_type: IDA
    original_reference_id: PMID:12967564
    review:
      summary: MBK-2 localizes to chromosomes during cell division.
      action: ACCEPT
      reason: Documented localization. MBK-2 associates with chromosomes during 
        meiosis and mitosis.
      supported_by:
        - reference_id: PMID:32412594
          supporting_text: Katanin is readily expressed during embryogenesis, 
            where it is actively recruited to the centrosomes and chromosomes 
            during mitosis
        - reference_id: PMID:12967564
          supporting_text: Coordinate activation of maternal protein degradation
            during the egg-to-embryo transition in C.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:12967564
    review:
      summary: IDA evidence for cytoplasmic localization from the original 
        characterization paper.
      action: ACCEPT
      reason: Key localization for MBK-2 function after release from cortex.
      supported_by:
        - reference_id: PMID:12967564
          supporting_text: Coordinate activation of maternal protein degradation
            during the egg-to-embryo transition in C.
  - term:
      id: GO:0005813
      label: centrosome
    evidence_type: IDA
    original_reference_id: PMID:12967564
    review:
      summary: MBK-2 localizes to centrosomes during mitosis.
      action: ACCEPT
      reason: Important localization for spindle-related functions.
      supported_by:
        - reference_id: PMID:32412594
          supporting_text: Katanin is readily expressed during embryogenesis, 
            where it is actively recruited to the centrosomes and chromosomes 
            during mitosis
        - reference_id: PMID:12967564
          supporting_text: Coordinate activation of maternal protein degradation
            during the egg-to-embryo transition in C.
  - term:
      id: GO:0005938
      label: cell cortex
    evidence_type: IDA
    original_reference_id: PMID:12967564
    review:
      summary: MBK-2 localizes to cell cortex, where it is sequestered before 
        meiotic divisions.
      action: ACCEPT
      reason: Key regulatory localization for MBK-2.
      supported_by:
        - reference_id: PMID:12967564
          supporting_text: Coordinate activation of maternal protein degradation
            during the egg-to-embryo transition in C.
  - term:
      id: GO:0043186
      label: P granule
    evidence_type: IDA
    original_reference_id: PMID:12967564
    review:
      summary: MBK-2 localizes to P granules where it phosphorylates MEG 
        proteins to regulate granule dynamics.
      action: ACCEPT
      reason: Relevant localization for P granule disassembly function. MBK-2 
        must access P granule substrates (MEG-1, MEG-3) to phosphorylate them.
      supported_by:
        - reference_id: PMID:25535836
          supporting_text: We demonstrate that MEG-1 and MEG-3 are substrates of
            the kinase MBK-2/DYRK and the phosphatase PP2A
        - reference_id: PMID:12967564
          supporting_text: Coordinate activation of maternal protein degradation
            during the egg-to-embryo transition in C.
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings:
      - statement: IBA annotations from PAINT based on DYRK family phylogeny
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping
    findings: []
  - id: GO_REF:0000116
    title: Automatic Gene Ontology annotation based on Rhea mapping
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:12967564
    title: Coordinate activation of maternal protein degradation during the 
      egg-to-embryo transition in C. elegans.
    findings:
      - statement: MBK-2 coordinates degradation of maternal proteins including 
          MEI-1 and germ plasm components
        supporting_text: the C. elegans DYRK family kinase MBK-2 coordinates the
          degradation of several maternal proteins
      - statement: MBK-2 is required for spindle positioning and cytokinesis in 
          early embryos
        supporting_text: is essential for zygotes to complete cytokinesis and 
          pattern the first embryonic axis
      - statement: MBK-2 localizes to cytoplasm, cortex, centrosomes, 
          chromosomes, and P granules
        supporting_text: MBK-2 distribution changes dramatically after 
          fertilization during the meiotic divisions
  - id: PMID:16289132
    title: DYRK2 and GSK-3 phosphorylate and promote the timely degradation of 
      OMA-1, a key regulator of the oocyte-to-embryo transition in C. elegans.
    findings:
      - statement: MBK-2 phosphorylates OMA-1 at T239 to promote its degradation
        supporting_text: OMA-1 protein is directly phosphorylated at T239 by the
          DYRK kinase MBK-2
      - statement: Phosphorylation at T239 is required for OMA-1 function and 
          degradation timing
        supporting_text: phosphorylation at T239 is required both for OMA-1 
          function in the 1-cell embryo and its degradation after the first 
          mitosis
  - id: PMID:16338136
    title: The C. elegans DYRK Kinase MBK-2 Marks Oocyte Proteins for 
      Degradation in Response to Meiotic Maturation.
    findings:
      - statement: MBK-2 directly phosphorylates MEI-1 and OMA-1 in vitro
        supporting_text: we demonstrate that MBK-2 directly phosphorylates MEI-1
          and OMA-1 in vitro and that this activity is essential for degradation
          in vivo
      - statement: MBK-2 relocalization from cortex to cytoplasm during meiotic 
          divisions
        supporting_text: A GFP:MBK-2 fusion relocalizes from the cortex to the 
          cytoplasm during the meiotic divisions
      - statement: Phosphorylation of MEI-1 by MBK-2 is essential for 
          degradation in vivo
        supporting_text: this activity is essential for degradation in vivo
  - id: PMID:16343905
    title: The Conserved Kinases CDK-1, GSK-3, KIN-19, and MBK-2 Promote OMA-1 
      Destruction to Regulate the Oocyte-to-Embryo Transition in C. elegans.
    findings:
      - statement: MBK-2 (with CDK-1, GSK-3, KIN-19) promotes OMA-1 destruction
        supporting_text: Mutations in four conserved protein kinase 
          genes-mbk-2/Dyrk, kin-19/CK1alpha, gsk-3, and cdk-1/CDC2-cause 
          stabilization of OMA-1 protein
      - statement: MBK-2 regulates the oocyte-to-embryo transition via protein 
          degradation
        supporting_text: destruction of OMA-1 is needed during the first cell 
          division for the initiation of ZIF-1-dependent proteolysis of 
          cell-fate determinants
  - id: PMID:17869113
    title: Regulation of MBK-2/Dyrk kinase by dynamic cortical anchoring during 
      the oocyte-to-zygote transition.
    findings:
      - statement: MBK-2 is tethered at cortex by EGG-3 before meiotic divisions
        supporting_text: Prior to the meiotic divisions, MBK-2 is tethered at 
          the cortex by EGG-3, an oocyte protein required for egg activation
      - statement: EGG-3 internalization releases MBK-2 for substrate 
          phosphorylation
        supporting_text: EGG-3 internalization and degradation correlate with 
          MBK-2 release from the cortex and MEI-1 phosphorylation in the 
          cytoplasm
      - statement: Cell cycle-regulated release of MBK-2 ensures proper timing 
          of MEI-1 phosphorylation
        supporting_text: precise timing of MEI-1 phosphorylation depends on the 
          cell cycle-regulated release of MBK-2 from the cortex
  - id: PMID:18199581
    title: Polo kinases regulate C. elegans embryonic polarity via binding to 
      DYRK2-primed MEX-5 and MEX-6.
    findings:
      - statement: MBK-2 primes MEX-5 at T186 for polo kinase-dependent 
          phosphorylation
        supporting_text: We also show that MBK-2, a developmentally regulated 
          DYRK2 kinase activated at meiosis II, primes T(186) for subsequent 
          polo kinase-dependent phosphorylation
      - statement: MBK-2 regulates asymmetric PLK-1 localization at 2-cell stage
        supporting_text: These polo kinases are asymmetrically localized along 
          the anteroposterior axis of newly fertilized C. elegans embryos
  - id: PMID:19879147
    title: EGG-4 and EGG-5 Link Events of the Oocyte-to-Embryo Transition with 
      Meiotic Progression in C. elegans.
    findings:
      - statement: MBK-2 interacts with EGG-4 and EGG-5 pseudophosphatases
        supporting_text: EGG-4 and EGG-5 assemble at the oocyte cortex with the 
          previously identified regulators or effectors of the oocyte-to-embryo 
          transition EGG-3, CHS-1, and MBK-2
      - statement: MBK-2 is part of cortical complex with EGG-3, CHS-1, EGG-4, 
          EGG-5
        supporting_text: All of these molecules share a complex interdependence 
          with regards to their dynamics and subcellular localization
  - id: PMID:19879842
    title: Regulation of MBK-2/DYRK by CDK-1 and the pseudophosphatases EGG-4 
      and EGG-5 during the oocyte-to-embryo transition.
    findings:
      - statement: MBK-2 is activated by CDK-1 phosphorylation at S68
        supporting_text: MBK-2 is activated during oocyte maturation by 
          CDK-1-dependent phosphorylation of serine 68
      - statement: EGG-4 and EGG-5 sequester MBK-2 by binding to its YTY motif
        supporting_text: The pseudotyrosine phosphatases EGG-4 and EGG-5 
          sequester activated MBK-2 until the meiotic divisions by binding to 
          the YTY motif
      - statement: MBK-2 autophosphorylates at Y621
        supporting_text: DYRKs are kinases that self-activate in vitro by 
          autophosphorylation of a YTY motif in the kinase domain
      - statement: MBK-2 is part of complex with EGG-3, EGG-4, EGG-5
        supporting_text: EGG-4 and EGG-5 sequester activated MBK-2 until the 
          meiotic divisions
  - id: PMID:20971008
    title: Eggshell chitin and chitin-interacting proteins prevent polyspermy in
      C. elegans.
    findings:
      - statement: MBK-2 cortical distribution is affected by loss of CBD-1 or 
          EGG-1/2
        supporting_text: Loss of CBD-1 or EGG-1/2 disrupts oocyte cortical 
          distribution of CHS-1, as well as MBK-2 and EGG-3
      - statement: MBK-2 is part of CHS-1/MBK-2/EGG-3 cortical complex
        supporting_text: aberrantly clustered CHS-1/MBK-2/EGG-3 may fail to 
          support construction of a continuous eggshell
  - id: PMID:25535836
    title: Regulation of RNA granule dynamics by phosphorylation of serine-rich,
      intrinsically disordered proteins in C. elegans.
    findings:
      - statement: MEG-1 and MEG-3 are substrates of MBK-2/DYRK kinase
        supporting_text: We demonstrate that MEG-1 and MEG-3 are substrates of 
          the kinase MBK-2/DYRK and the phosphatase PP2A
      - statement: MBK-2 phosphorylation of MEGs promotes P granule disassembly
        supporting_text: Phosphorylation of the MEGs promotes granule 
          disassembly and dephosphorylation promotes granule assembly
      - statement: mbk-2 RNAi causes P granules to persist in anterior cytoplasm
        supporting_text: P granules in C. elegans embryos
  - id: PMID:32412594
    title: Phosphorylation of the microtubule-severing AAA+ enzyme Katanin 
      regulates C. elegans embryo development.
    findings:
      - statement: MBK-2 phosphorylates MEI-1 at S92, S90, S113, S137
        supporting_text: This analysis showed that MBK-2 phosphorylates MEI-1 at
          S92, consistent with a previous report (Stitzel et al., 2006), but 
          also at S90, S113, and S137
      - statement: S92 phosphorylation is necessary and sufficient for MEI-1 
          degradation
        supporting_text: phosphorylation of MEI-1 by MBK-2 at a single serine 
          (S92) is both necessary and sufficient to target MEI-1 for degradation
          after meiosis
      - statement: MBK-2-mediated phosphorylation inhibits katanin MT-stimulated
          ATPase activity
        supporting_text: MBK-2, by phosphorylating the catalytic MEI-1 Katanin 
          subunit, inhibits Katanin ATPase activity stimulated by MTs
      - statement: MBK-2 localizes to centrosomes and chromosomes during mitosis
        supporting_text: Katanin is readily expressed during embryogenesis,
          where it is actively recruited to the centrosomes and chromosomes
          during mitosis
  - id: PMID:22872483
    title: The oocyte-to-embryo transition.
    findings:
      - statement: The oocyte-to-embryo transition is coordinated primarily
          through the MBK-2 kinase, whose activation is tied to completion of
          meiosis.
        reference_section_type: ABSTRACT
        supporting_text: |-
          which are coordinated primarily through the MBK-2 kinase, whose activation is intimately tied to completion of meiosis
  - id: PMID:22918246
    title: Emerging role of DYRK family protein kinases as regulators of
      protein stability in cell cycle control.
    findings:
      - statement: MBK-2, the C. elegans DYRK2 ortholog, triggers proteasomal
          destruction of oocyte proteins after meiosis to permit embryonic
          mitotic divisions, exemplifying the DYRK family role in regulating
          protein stability.
        reference_section_type: ABSTRACT
        supporting_text: |-
          The DYRK2 ortholog of C. elegans, MBK-2, triggers the proteasomal destruction of oocyte proteins after meiosis to allow the mitotic divisions in embryo development.
  - id: file:worm/mbk-2/mbk-2-deep-research-falcon.md
    title: Falcon deep research report on mbk-2 (C. elegans)
    findings:
      - statement: |-
          MBK-2 is a maternally supplied DYRK-family dual-specificity kinase activated during the oocyte-to-embryo transition; it phosphorylates maternal regulators to switch their function and mark them for ubiquitin-proteasome-dependent degradation, with best-supported direct substrates OMA-1 (T239) and katanin MEI-1 (S92).
        reference_section_type: OTHER
        supporting_text: |-
          Its best-supported direct substrates are the oocyte RNA-binding protein OMA-1 (phosphorylation at T239) and the meiotic microtubule-severing enzyme katanin catalytic subunit MEI-1 (phosphorylation at S92; plus additional N-terminal sites affecting enzymatic activity).
      - statement: |-
          MBK-2 kinase activity is essential for embryonic viability: kinase-dead MBK-2 fails to rescue mbk-2 maternal mutants.
        reference_section_type: OTHER
        supporting_text: |-
          mbk-2(pk1427) maternal embryos: 0% viability (n=1063); GFP::MBK-2 rescue: 80% viability (n=569); kinase-dead GFP::MBK-2(K196R): 0% viability (n=198)
      - statement: |-
          MBK-2 phosphorylates OMA-1 at T239, priming subsequent GSK-3 phosphorylation at T339 and promoting timely OMA-1 degradation after the first mitosis.
        reference_section_type: OTHER
        supporting_text: |-
          MBK-2 directly phosphorylates OMA-1 at T239; this acts as a molecular switch promoting later degradation and enabling OMA-1 functional transition; T239 phosphorylation primes subsequent GSK-3 phosphorylation at T339
      - statement: |-
          MBK-2 phosphorylates the katanin complex on multiple N-terminal regulatory sites of MEI-1 and MEI-2; S92 is the dominant site for MEL-26/CUL-3-dependent degradation targeting, while N-terminal phosphorylation abolishes microtubule-stimulated katanin ATPase activity.
        reference_section_type: OTHER
        supporting_text: |-
          S92 is the principal site for degradation targeting, while phosphorylation of N-terminal sites suppresses MT-stimulated ATPase activity
      - statement: |-
          MBK-2 acts as a temporal activator that confers degradation competence to specific maternal substrates after meiotic progression, rather than triggering global proteolysis.
        reference_section_type: OTHER
        supporting_text: |-
          MBK-2 functions as a temporal activator of maternal protein degradation during the egg-to-embryo transition, likely by phosphorylation that creates degradation competence after meiotic progression
      - statement: |-
          MBK-2 activation is gated by meiotic cell-cycle events: co-translational YTY autophosphorylation, restraint by EGG-4/EGG-5 pseudophosphatases and cortical EGG-3, CDK-1 phosphorylation of S68, and APC/C-dependent degradation of EGG proteins that releases active MBK-2 into the cytoplasm.
        reference_section_type: OTHER
        supporting_text: |-
          it autophosphorylates on a YTY motif during translation, CDK-1 phosphorylates S68, and APC/C-dependent release/degradation of EGG proteins allows active MBK-2 to access cytoplasmic substrates
      - statement: |-
          MBK-2 relocalizes in a two-step, meiosis-driven manner from the uniform cortex to cortical puncta and then into the cytoplasm; progression through meiosis rather than fertilization is the trigger.
        reference_section_type: OTHER
        supporting_text: |-
          MBK-2 relocalizes in a two-step, cell-cycle-dependent manner from uniform cortex to cortical puncta and then into cytoplasm; progression through meiosis, not fertilization, is the trigger
proposed_new_terms: []
suggested_questions:
  - question: Does MBK-2 have additional substrates beyond MEI-1, OMA-1/2, 
      MEX-5/6, and MEG-1/3?
  - question: How is MBK-2 activity spatially regulated after release from the 
      cortex?
suggested_experiments:
  - description: Phosphoproteomic comparison of wild-type vs mbk-2 mutant 
      embryos to identify novel substrates and proteins with reduced 
      phosphorylation in mbk-2 mutants
  - description: Live imaging of MBK-2 and MEG-3 dynamics with super-resolution 
      microscopy for direct visualization of MBK-2 action on P granule 
      substrates
tags:
  - caeel-p-granules