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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | 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). 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. Supporting Evidence: PMID:16338136 A GFP:MBK-2 fusion relocalizes from the cortex to the cytoplasm during the meiotic divisions PMID:17869113 During the meiotic divisions, EGG-3 is internalized and degraded in an APC/C (anaphase-promoting complex/cyclosome)-dependent manner |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | 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). Reason: Core molecular function well-supported by multiple IDA annotations. This is the primary enzymatic activity of MBK-2. Supporting Evidence: PMID:16338136 we demonstrate that MBK-2 directly phosphorylates MEI-1 and OMA-1 in vitro and that this activity is essential for degradation in vivo PMID:25535836 We demonstrate that MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2A |
| GO:0005856 cytoskeleton | IBA GO_REF:0000033 | ACCEPT | 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. Reason: MBK-2 associates with cytoskeletal structures including the mitotic spindle, as documented by IDA evidence. Supporting Evidence: PMID:32412594 Katanin is readily expressed during embryogenesis, where it is actively recruited to the centrosomes and chromosomes during mitosis PMID:12967564 MBK-2 distribution changes dramatically after fertilization during the meiotic divisions |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | 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. 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. |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: As a protein kinase, MBK-2 binds ATP. This is a parent term of ATP binding which is more appropriate. 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. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: General kinase activity term. MBK-2 is a well-characterized protein kinase. 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. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation consistent with multiple experimental annotations for the same term. 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. |
| GO:0004712 protein serine/threonine/tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | 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. 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. Supporting Evidence: PMID:19879842 DYRKs are kinases that self-activate in vitro by autophosphorylation of a YTY motif in the kinase domain PMID:17869113 Regulation of MBK-2/Dyrk kinase by dynamic cortical anchoring during the oocyte-to-zygote transition file:worm/mbk-2/mbk-2-deep-research-falcon.md maternally supplied DYRK-family dual-specificity protein kinase that is activated during the oocyte-to-embryo transition |
| GO:0004713 protein tyrosine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: MBK-2 has tyrosine kinase activity demonstrated by autophosphorylation at the YTY motif (Y619, Y621) in its activation loop. Reason: Accurate annotation. While MBK-2 primarily phosphorylates Ser/Thr on substrates, it autophosphorylates tyrosine residues during its own activation. Supporting Evidence: PMID:19879842 The pseudotyrosine phosphatases EGG-4 and EGG-5 sequester activated MBK-2 until the meiotic divisions by binding to the YTY motif |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: As a protein kinase, MBK-2 binds and hydrolyzes ATP as a phosphate donor. Reason: Essential for kinase function. UniProt annotates ATP binding at positions 467-475 and K490. Supporting Evidence: PMID:19879842 MBK-2 is activated during oocyte maturation by CDK-1-dependent phosphorylation of serine 68 |
| GO:0005938 cell cortex | IEA GO_REF:0000044 | ACCEPT | Summary: MBK-2 is sequestered at the cell cortex before meiotic divisions by the cortical anchor EGG-3 and the pseudophosphatases EGG-4/5. Reason: Key localization for MBK-2 regulation. It is maintained at the cortex in oocytes and released during meiosis. Supporting Evidence: PMID:17869113 Prior to the meiotic divisions, MBK-2 is tethered at the cortex by EGG-3, an oocyte protein required for egg activation PMID:19879842 The pseudotyrosine phosphatases EGG-4 and EGG-5 sequester activated MBK-2 until the meiotic divisions |
| GO:0016301 kinase activity | IEA GO_REF:0000043 | ACCEPT | Summary: General parent term for kinase activity. Reason: Accurate but uninformative parent term. More specific child terms are annotated. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Very general parent term for kinases as phosphotransferases. Reason: Accurate but highly general. More specific terms provide better functional information. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | 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. Reason: RHEA-based annotation that is accurate. MBK-2 phosphorylates MEI-1 at S90, S92, S113, S137 (PMID:32412594). Supporting Evidence: PMID:32412594 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 |
| GO:0001556 oocyte maturation | NAS PMID:19879842 Regulation of MBK-2/DYRK by CDK-1 and the pseudophosphatases... | ACCEPT | Summary: MBK-2 is activated during oocyte maturation by CDK-1-dependent phosphorylation and is essential for the oocyte-to-embryo transition. 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. Supporting Evidence: PMID:19879842 MBK-2 is activated during oocyte maturation by CDK-1-dependent phosphorylation of serine 68 file:worm/mbk-2/mbk-2-deep-research-falcon.md 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 |
| GO:0005938 cell cortex | NAS PMID:19879842 Regulation of MBK-2/DYRK by CDK-1 and the pseudophosphatases... | ACCEPT | Summary: NAS annotation for cortical localization based on PMID:19879842. 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. Supporting Evidence: PMID:19879842 Regulation of MBK-2/DYRK by CDK-1 and the pseudophosphatases EGG-4 and EGG-5 during the oocyte-to-embryo transition. file:worm/mbk-2/mbk-2-deep-research-falcon.md 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 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:32412594 Phosphorylation of the microtubule-severing AAA+ enzyme Kata... | ACCEPT | 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. 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. Supporting Evidence: PMID:32412594 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 file:worm/mbk-2/mbk-2-deep-research-falcon.md S92 is the principal site for degradation targeting, while phosphorylation of N-terminal sites suppresses MT-stimulated ATPase activity file:worm/mbk-2/mbk-2-deep-research-falcon.md MEI-1 S90, S92, S113, S137; MEI-2 T32, S68, S86 (MEI-2 phosphorylation requires MEI-1) |
| GO:0005737 cytoplasm | IDA PMID:17869113 Regulation of MBK-2/Dyrk kinase by dynamic cortical anchorin... | ACCEPT | Summary: IDA evidence for cytoplasmic localization after release from cortex during meiosis. 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. Supporting Evidence: PMID:17869113 EGG-3 internalization and degradation correlate with MBK-2 release from the cortex and MEI-1 phosphorylation in the cytoplasm file:worm/mbk-2/mbk-2-deep-research-falcon.md 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 |
| GO:0004672 protein kinase activity | IDA PMID:19879842 Regulation of MBK-2/DYRK by CDK-1 and the pseudophosphatases... | ACCEPT | Summary: IDA evidence from Cheng et al. 2009 demonstrating MBK-2 kinase activity and its regulation. 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. Supporting Evidence: PMID:19879842 MBK-2 is activated during oocyte maturation by CDK-1-dependent phosphorylation of serine 68 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:16289132 DYRK2 and GSK-3 phosphorylate and promote the timely degrada... | ACCEPT | Summary: IDA evidence showing MBK-2 phosphorylates OMA-1 at T239 (threonine), a serine/threonine kinase substrate. Reason: Direct demonstration of Ser/Thr kinase activity on physiological substrate OMA-1. Supporting Evidence: PMID:16289132 OMA-1 protein is directly phosphorylated at T239 by the DYRK kinase MBK-2 file:worm/mbk-2/mbk-2-deep-research-falcon.md 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 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:16338136 The C. elegans DYRK Kinase MBK-2 Marks Oocyte Proteins for D... | ACCEPT | Summary: IDA evidence showing MBK-2 directly phosphorylates MEI-1 (katanin) and OMA-1 in vitro. Reason: Key paper demonstrating MBK-2 kinase activity on oocyte substrates. Supporting Evidence: PMID:16338136 we demonstrate that MBK-2 directly phosphorylates MEI-1 and OMA-1 in vitro and that this activity is essential for degradation in vivo |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:18199581 Polo kinases regulate C. elegans embryonic polarity via bind... | ACCEPT | Summary: IDA evidence showing MBK-2 phosphorylates MEX-5 at T186 to prime it for polo kinase binding. Reason: Demonstrates MBK-2 kinase activity on polarity regulators MEX-5/6. Supporting Evidence: PMID:18199581 We also show that MBK-2, a developmentally regulated DYRK2 kinase activated at meiosis II, primes T(186) for subsequent polo kinase-dependent phosphorylation |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | ACCEPT | Summary: IDA evidence showing MBK-2 phosphorylates MEG-1 and MEG-3 to regulate P granule dynamics. Reason: Demonstrates MBK-2 kinase activity on P granule components. Key paper for P granule regulation function. Supporting Evidence: PMID:25535836 We demonstrate that MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2A |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IMP PMID:16343905 The Conserved Kinases CDK-1, GSK-3, KIN-19, and MBK-2 Promot... | ACCEPT | Summary: IMP evidence showing MBK-2 promotes OMA-1 destruction during the oocyte-to-embryo transition via ubiquitin-mediated proteolysis. 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. Supporting Evidence: PMID:16343905 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 file:worm/mbk-2/mbk-2-deep-research-falcon.md 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 |
| GO:0005938 cell cortex | IDA PMID:20971008 Eggshell chitin and chitin-interacting proteins prevent poly... | ACCEPT | Summary: IDA evidence for MBK-2 cortical localization in the context of eggshell formation and polyspermy block. Reason: Demonstrates cortical localization of MBK-2 as part of the CHS-1/MBK-2/EGG-3 complex at the oocyte cortex. Supporting Evidence: PMID:20971008 Loss of CBD-1 or EGG-1/2 disrupts oocyte cortical distribution of CHS-1, as well as MBK-2 and EGG-3 |
| GO:0004713 protein tyrosine kinase activity | IMP PMID:17869113 Regulation of MBK-2/Dyrk kinase by dynamic cortical anchorin... | ACCEPT | Summary: IMP evidence based on MBK-2's role in phosphorylating MEI-1, with its activity dependent on dual-specificity nature including tyrosine autophosphorylation. 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. Supporting Evidence: PMID:17869113 Regulation of MBK-2/Dyrk kinase by dynamic cortical anchoring during the oocyte-to-zygote transition |
| GO:0005515 protein binding | IPI PMID:19879147 EGG-4 and EGG-5 Link Events of the Oocyte-to-Embryo Transiti... | MODIFY | Summary: MBK-2 interacts with EGG-3, EGG-4, and EGG-5 pseudophosphatases at the oocyte cortex. 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 replacements: pseudophosphatase binding Supporting Evidence: PMID:19879147 EGG-4 and EGG-5 Link Events of the Oocyte-to-Embryo Transition with Meiotic Progression in C. |
| GO:0005938 cell cortex | IDA PMID:17869113 Regulation of MBK-2/Dyrk kinase by dynamic cortical anchorin... | ACCEPT | Summary: IDA evidence showing MBK-2 is tethered at the cortex by EGG-3 before meiosis. Reason: Key localization showing dynamic regulation of MBK-2. Supporting Evidence: PMID:17869113 Prior to the meiotic divisions, MBK-2 is tethered at the cortex by EGG-3, an oocyte protein required for egg activation |
| GO:0018108 peptidyl-tyrosine phosphorylation | IMP PMID:17869113 Regulation of MBK-2/Dyrk kinase by dynamic cortical anchorin... | ACCEPT | Summary: MBK-2 as a DYRK autophosphorylates at tyrosine residues in its activation loop (Y619, Y621). Reason: Characteristic of DYRK family kinases. MBK-2 autophosphorylates at the YTY motif for activation. Supporting Evidence: PMID:19879842 DYRKs are kinases that self-activate in vitro by autophosphorylation of a YTY motif in the kinase domain PMID:17869113 Regulation of MBK-2/Dyrk kinase by dynamic cortical anchoring during the oocyte-to-zygote transition. |
| GO:0000793 condensed chromosome | IDA PMID:16338136 The C. elegans DYRK Kinase MBK-2 Marks Oocyte Proteins for D... | ACCEPT | Summary: MBK-2 localizes to condensed chromosomes during meiosis. Reason: Documented localization. MBK-2 associates with meiotic chromosomes as part of its function in the oocyte-to-embryo transition. Supporting Evidence: PMID:32412594 Katanin is readily expressed during embryogenesis, where it is actively recruited to the centrosomes and chromosomes during mitosis PMID:16338136 Dec 15. The C. elegans DYRK Kinase MBK-2 Marks Oocyte Proteins for Degradation in Response to Meiotic Maturation. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:16343905 The Conserved Kinases CDK-1, GSK-3, KIN-19, and MBK-2 Promot... | ACCEPT | Summary: IDA evidence for MBK-2 kinase activity in context of OMA-1 phosphorylation and degradation. Reason: Additional experimental support for core molecular function. Supporting Evidence: PMID:16343905 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 |
| GO:0005737 cytoplasm | IDA PMID:16338136 The C. elegans DYRK Kinase MBK-2 Marks Oocyte Proteins for D... | ACCEPT | Summary: IDA evidence for MBK-2 cytoplasmic localization after release from cortex. Reason: Key localization for MBK-2 function. Supporting Evidence: PMID:16338136 A GFP:MBK-2 fusion relocalizes from the cortex to the cytoplasm during the meiotic divisions |
| GO:0005938 cell cortex | IDA PMID:16338136 The C. elegans DYRK Kinase MBK-2 Marks Oocyte Proteins for D... | ACCEPT | Summary: IDA evidence for MBK-2 cortical localization before meiotic divisions. Reason: Key localization showing MBK-2 is sequestered at cortex before activation. Supporting Evidence: PMID:16338136 Dec 15. The C. elegans DYRK Kinase MBK-2 Marks Oocyte Proteins for Degradation in Response to Meiotic Maturation. |
| GO:0072686 mitotic spindle | IDA PMID:16338136 The C. elegans DYRK Kinase MBK-2 Marks Oocyte Proteins for D... | ACCEPT | Summary: MBK-2 localizes to the mitotic spindle in early embryos. Reason: Important localization for MBK-2 function in spindle positioning and substrate phosphorylation. Supporting Evidence: PMID:32412594 Katanin is readily expressed during embryogenesis, where it is actively recruited to the centrosomes and chromosomes during mitosis PMID:16338136 Dec 15. The C. elegans DYRK Kinase MBK-2 Marks Oocyte Proteins for Degradation in Response to Meiotic Maturation. |
| GO:1903864 P granule disassembly | IMP PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | ACCEPT | Summary: IMP evidence showing mbk-2 RNAi causes P granules to fail to disassemble in anterior cytoplasm during zygote polarization. Reason: Core biological function of MBK-2. Phosphorylation of the MEGs promotes granule disassembly. Supporting Evidence: PMID:25535836 Phosphorylation of the MEGs promotes granule disassembly and dephosphorylation promotes granule assembly |
| GO:1903864 P granule disassembly | IGI PMID:25535836 Regulation of RNA granule dynamics by phosphorylation of ser... | ACCEPT | Summary: IGI evidence showing genetic interaction between MBK-2 and MEG proteins in P granule regulation. Reason: Supports the role of MBK-2 in P granule dynamics through phosphorylation of MEG substrates. Supporting Evidence: PMID:25535836 We demonstrate that MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2A |
| GO:0005515 protein binding | IPI PMID:19879842 Regulation of MBK-2/DYRK by CDK-1 and the pseudophosphatases... | MODIFY | Summary: MBK-2 interacts with EGG-3, EGG-4, and EGG-5 as part of a regulatory complex. Reason: Generic "protein binding" is uninformative. MBK-2 has specific interactions with pseudophosphatases that regulate its activity and localization. Proposed replacements: pseudophosphatase binding Supporting Evidence: PMID:19879842 Regulation of MBK-2/DYRK by CDK-1 and the pseudophosphatases EGG-4 and EGG-5 during the oocyte-to-embryo transition. |
| GO:0000281 mitotic cytokinesis | IMP PMID:12967564 Coordinate activation of maternal protein degradation during... | KEEP AS NON CORE | Summary: mbk-2 mutants show defects in cytokinesis during early embryonic cell divisions. 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. Supporting Evidence: PMID:12967564 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 |
| GO:0004674 protein serine/threonine kinase activity | ISS PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: ISS annotation based on sequence similarity to rat DYRK2. Reason: Accurate inference. Multiple experimental annotations now provide direct evidence for this function in C. elegans MBK-2. Supporting Evidence: PMID:12967564 Coordinate activation of maternal protein degradation during the egg-to-embryo transition in C. |
| GO:0004713 protein tyrosine kinase activity | ISS PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: ISS annotation for tyrosine kinase activity based on DYRK family membership. Reason: Accurate for DYRK family. MBK-2 autophosphorylates at tyrosine residues. Supporting Evidence: PMID:12967564 Coordinate activation of maternal protein degradation during the egg-to-embryo transition in C. |
| GO:0005524 ATP binding | ISS PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: ISS annotation for ATP binding based on kinase domain conservation. Reason: Required for kinase function. Supported by domain structure. Supporting Evidence: PMID:19879842 MBK-2 is activated during oocyte maturation by CDK-1-dependent phosphorylation of serine 68 PMID:12967564 Coordinate activation of maternal protein degradation during the egg-to-embryo transition in C. |
| GO:0007017 microtubule-based process | IMP PMID:12967564 Coordinate activation of maternal protein degradation during... | KEEP AS NON CORE | Summary: mbk-2 mutants have fragmented and disordered microtubules in early embryos. 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. Supporting Evidence: PMID:12967564 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 |
| GO:0009792 embryo development ending in birth or egg hatching | IMP PMID:12967564 Coordinate activation of maternal protein degradation during... | KEEP AS NON CORE | Summary: mbk-2 mutants show maternal-effect embryonic lethality. 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. Supporting Evidence: PMID:12967564 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 |
| GO:0009880 embryonic pattern specification | IMP PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: MBK-2 is required for patterning the first embryonic axis through regulation of determinant localization. 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. Supporting Evidence: PMID:12967564 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 PMID:18199581 Polo kinases regulate C. elegans embryonic polarity via binding to DYRK2-primed MEX-5 and MEX-6 |
| GO:0045167 asymmetric protein localization involved in cell fate determination | IMP PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: MBK-2 is required for posterior localization of germ plasm determinants (PIE-1, POS-1, PGL-1) and asymmetric PLK-1 localization. Reason: Core biological function. MBK-2 phosphorylates and primes MEX-5/6 for polo kinase binding, which regulates asymmetric protein localization. Supporting Evidence: PMID:12967564 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 PMID:18199581 These polo kinases are asymmetrically localized along the anteroposterior axis of newly fertilized C. elegans embryos |
| GO:0045732 positive regulation of protein catabolic process | IMP PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: MBK-2 promotes degradation of oocyte proteins including MEI-1 and OMA-1 during the egg-to-embryo transition. 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. Supporting Evidence: PMID:12967564 the C. elegans DYRK family kinase MBK-2 coordinates the degradation of several maternal proteins file:worm/mbk-2/mbk-2-deep-research-falcon.md 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 |
| GO:0005694 chromosome | IDA PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: MBK-2 localizes to chromosomes during cell division. Reason: Documented localization. MBK-2 associates with chromosomes during meiosis and mitosis. Supporting Evidence: PMID:32412594 Katanin is readily expressed during embryogenesis, where it is actively recruited to the centrosomes and chromosomes during mitosis PMID:12967564 Coordinate activation of maternal protein degradation during the egg-to-embryo transition in C. |
| GO:0005737 cytoplasm | IDA PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: IDA evidence for cytoplasmic localization from the original characterization paper. Reason: Key localization for MBK-2 function after release from cortex. Supporting Evidence: PMID:12967564 Coordinate activation of maternal protein degradation during the egg-to-embryo transition in C. |
| GO:0005813 centrosome | IDA PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: MBK-2 localizes to centrosomes during mitosis. Reason: Important localization for spindle-related functions. Supporting Evidence: PMID:32412594 Katanin is readily expressed during embryogenesis, where it is actively recruited to the centrosomes and chromosomes during mitosis PMID:12967564 Coordinate activation of maternal protein degradation during the egg-to-embryo transition in C. |
| GO:0005938 cell cortex | IDA PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: MBK-2 localizes to cell cortex, where it is sequestered before meiotic divisions. Reason: Key regulatory localization for MBK-2. Supporting Evidence: PMID:12967564 Coordinate activation of maternal protein degradation during the egg-to-embryo transition in C. |
| GO:0043186 P granule | IDA PMID:12967564 Coordinate activation of maternal protein degradation during... | ACCEPT | Summary: MBK-2 localizes to P granules where it phosphorylates MEG proteins to regulate granule dynamics. Reason: Relevant localization for P granule disassembly function. MBK-2 must access P granule substrates (MEG-1, MEG-3) to phosphorylate them. Supporting Evidence: PMID:25535836 We demonstrate that MEG-1 and MEG-3 are substrates of the kinase MBK-2/DYRK and the phosphatase PP2A PMID:12967564 Coordinate activation of maternal protein degradation during the egg-to-embryo transition in C. |
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Download this section (compressed HTML)Q: Does MBK-2 have additional substrates beyond MEI-1, OMA-1/2, MEX-5/6, and MEG-1/3?
Q: How is MBK-2 activity spatially regulated after release from the cortex?
Experiment: Phosphoproteomic comparison of wild-type vs mbk-2 mutant embryos to identify novel substrates and proteins with reduced phosphorylation in mbk-2 mutants
Experiment: Live imaging of MBK-2 and MEG-3 dynamics with super-resolution microscopy for direct visualization of MBK-2 action on P granule substrates
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