Cdc13 (p56cdc13) is the major mitotic B-type cyclin (cyclin AB subfamily) of the fission yeast Schizosaccharomyces pombe. It is the essential regulatory partner of the cyclin-dependent kinase Cdc2 (CDK1); together the Cdc13-Cdc2 complex constitutes M-phase-promoting factor (MPF), the principal driver of mitotic entry and progression. Cdc13 levels rise steadily through G2 and the complex is activated at the G2/M transition (requiring Cdc25 and CAK/Thr167 phosphorylation of Cdc2), then Cdc13 is abruptly destroyed at anaphase by APC/C-mediated, destruction-box-dependent proteolysis, behaving as a classic cyclin. Cdc13 binding also dictates the catalytic properties, substrate selection and subcellular localization of Cdc2: the complex concentrates in the nucleus, is enriched at the spindle pole body (SPB, the centrosome equivalent) in G2 via the cyclin hydrophobic patch and a Polo-kinase-dependent mechanism, and decorates the mitotic spindle and spindle midzone during mitosis. Cdc13-Cdc2 also associates stably with ORC-bound replication origins, enforcing the dependence of S phase on an intervening mitosis and preventing re-replication, and it contributes to the mitotic DNA damage response, chromosome bi-orientation and merotelic-attachment correction. A single Cdc13-Cdc2 complex is sufficient to drive both the mitotic and the meiotic cell cycle; in meiosis the stability of Cdc13 is specifically controlled (stabilized by Mes1 between meiosis I and II to permit MII, then degraded by the Mfr1-activated APC/C at the end of meiosis II to license sporulation). Cdc13 is negatively regulated during G1 by the CDK inhibitor Rum1, which promotes its proteolysis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005815 microtubule organizing center | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) annotation to the microtubule organizing center. Cdc13-Cdc2 is genuinely enriched at the spindle pole body (the fungal MTOC/centrosome equivalent) in G2 and mitosis, so the term is correct, though the more specific experimentally supported terms (mitotic spindle pole body) are preferred. Reason: Localization to the SPB/MTOC is well supported experimentally but is a context for the core kinase-regulator function rather than a core function itself; a more specific SPB term is available. Supporting Evidence: PMID:32084401 the hydrophobic patch targets Cdc13 to the yeast centrosome equivalent, the spindle pole body (SPB) |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IBA GO_REF:0000033 | ACCEPT | Summary: Cdc13 is a B-type cyclin that forms a stable complex with the catalytic subunit Cdc2 (CDK1); this complex is the cyclin-dependent protein kinase holoenzyme. The IBA assignment is strongly supported by direct experimental evidence. Reason: Direct biochemical evidence shows Cdc13 forms a stable kinase-active complex with Cdc2, consistent with the CDK holoenzyme complex. Supporting Evidence: PMID:2569363 The products of the cdc13+ and cdc2+ genes form a stable complex that displays protein kinase activity in vitro. |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. As the mitotic B-type cyclin, Cdc13 binds Cdc2 and regulates both its catalytic activity and localization, the defining function of a cyclin. Strongly supported by both phylogenetic inference and direct experiment. Reason: The cyclin regulatory function of Cdc13 toward the Cdc2 CDK is the central, well-established function of this gene product. Supporting Evidence: PMID:2569363 These observations suggest that the cdc13+-encoded cyclin acts to regulate both the catalytic properties and the localization of the protein kinase of which it is a subunit. |
| GO:0007089 traversing start control point of mitotic cell cycle | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA annotation to passage through Start (G1/S commitment). Cdc13 is the mitotic cyclin whose endogenous role is the G2/M transition; in wild-type cells Start and G1/S are executed by the G1/S cyclins Cig1, Cig2 and Puc1. Although an engineered single Cdc13-Cdc2 complex can drive S phase when it is the only cyclin, this does not reflect the normal Start function of Cdc13 and is best treated as an over-annotation for the endogenous protein. Reason: The native function of Cdc13 is at G2/M, not at Start; G1/S commitment is normally carried out by other cyclins, so the phylogenetically transferred Start annotation overstates the endogenous role. Supporting Evidence: PMID:32084401 Although, in wild-type cells, the G1/S cyclins Cig1 and Cig2 are expressed in G1 to execute DNA replication, in this situation, Cdc13 is expressed in G1 and compensates for their loss |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation to nucleus from UniProt subcellular location mapping. Cdc13 is a well-established nuclear protein (with the Cdc2 complex localized to a nuclear domain distinct from chromatin), so this is correct and redundant with multiple experimental nucleus annotations below. Reason: Nuclear localization is directly demonstrated experimentally. Supporting Evidence: PMID:2534559 both cdc13 and cdc2 are nuclear proteins in S. pombe. |
| GO:0005816 spindle pole body | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation to spindle pole body from UniProt mapping. Cdc13-Cdc2 is experimentally enriched at the SPB in G2 and mitosis; the mitotic spindle pole body term (GO:0044732) is more specific and also annotated experimentally below. Reason: SPB localization is directly supported by experimental imaging. Supporting Evidence: PMID:11683390 Cdc2-YFP and cdc13-YFP are highly enriched on the spindle pole body of cells in late G2 or arrested at S phase. |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated InterPro-based annotation of the core cyclin regulator activity. This duplicates the well-supported IBA/experimental molecular function and is accepted. Reason: Redundant with the experimentally supported core kinase-regulator function. Supporting Evidence: PMID:2569363 These observations suggest that the cdc13+-encoded cyclin acts to regulate both the catalytic properties and the localization of the protein kinase of which it is a subunit. |
| GO:0044772 mitotic cell cycle phase transition | IEA GO_REF:0000002 | MODIFY | Summary: Automated InterPro annotation to mitotic cell cycle phase transition. This is correct but general; Cdc13 specifically drives the G2/M transition, which is captured by the more precise experimental annotations (GO:0010389, GO:0010971). Reason: The general term is correct but a more specific term reflecting the G2/M role is preferred and is supported experimentally. Proposed replacements: regulation of G2/M transition of mitotic cell cycle Supporting Evidence: PMID:2908246 required for the control of the G2 to M transition |
| GO:0005515 protein binding | IPI PMID:9303310 p25rum1 promotes proteolysis of the mitotic B-cyclin p56cdc1... | MARK AS OVER ANNOTATED | Summary: IPI annotation from the Cdc13-Rum1 interaction. Rum1 is the CDK inhibitor that binds the Cdc13-Cdc2 complex and promotes Cdc13 proteolysis during G1. The bare protein binding term is uninformative per curation guidelines; the biology (being subject to regulation by the inhibitor Rum1) is captured by the kinase-regulator function and the G1 proteolysis biology rather than by GO:0005515. Reason: Bare protein binding is uninformative; the Rum1 interaction is better represented as part of Cdc13 regulation, not as an independent molecular function. Supporting Evidence: PMID:9303310 p25rum1 associates with the CDK p34cdc2/p56cdc13 during G1 in normally cycling cells and is required for the rapid proteolysis of p56cdc13 |
| GO:0005515 protein binding | IPI PMID:9472012 The Cdk inhibitors p25rum1 and p40SIC1 are functional homolo... | MARK AS OVER ANNOTATED | Summary: IPI from the Rum1/SIC1 study, again reflecting binding of the Rum1 CDK inhibitor to the B-cyclin Cdc2 complex. Bare protein binding is uninformative. Reason: Uninformative bare protein binding; the interaction is between the CDK inhibitor and the Cdc13-Cdc2 complex. Supporting Evidence: PMID:9472012 p25rum1 and p40SIC1 are specific inhibitors of p34(cdc2/CDC28) kinase complexes with B-type cyclins |
| GO:0005515 protein binding | IPI PMID:9614176 Cyclin B proteolysis and the cyclin-dependent kinase inhibit... | MARK AS OVER ANNOTATED | Summary: IPI from the pheromone-induced G1 arrest study (Rum1-dependent Cdc13 proteolysis). Bare protein binding is uninformative and is not retained as a core function. Reason: Uninformative bare protein binding term. Supporting Evidence: PMID:9614176 Cyclin B proteolysis and the cyclin-dependent kinase inhibitor rum1p are required for pheromone-induced G1 arrest in fission yeast. |
| GO:0140602 nucleolar peripheral inclusion body | IDA PMID:37128864 CDK actively contributes to establishment of the stationary ... | KEEP AS NON CORE | Summary: IDA localization of Cdc2/CDK to a nucleolar inclusion compartment during the stationary-phase/CDK study. This reflects a stress/quiescence-associated relocalization rather than a site of mitotic function. Reason: A condition-specific (stationary phase) localization, not part of the core mitotic function. Supporting Evidence: PMID:37128864 Cdc2 accumulates in the nucleolus. |
| GO:0005654 nucleoplasm | IDA PMID:1699136 Distinct nuclear and spindle pole body population of cyclin-... | ACCEPT | Summary: IDA to nucleoplasm consistent with the nuclear (non-SPB) population of the Cdc13-Cdc2 cyclin. Supported by direct localization of two distinct nuclear populations of Cdc13. Reason: Direct evidence for a nucleoplasmic population of Cdc13. Supporting Evidence: PMID:1699136 the presence of two spatially distinct cdc13 cyclin populations in the nucleus of S. pombe, one of which is associated with the mitotic spindle poles |
| GO:0044773 mitotic DNA damage checkpoint signaling | EXP PMID:12023299 Cdc2-cyclin B kinase activity links Crb2 and Rqh1-topoisomer... | KEEP AS NON CORE | Summary: Experimental evidence that Cdc2-cyclin B kinase activity influences recombinational repair of DSBs in G2 and links the checkpoint protein Crb2 to Top3/Rqh1 function. This is a genuine but non-core (process-specific) role of the Cdc13-Cdc2 complex. Reason: Cdc13-Cdc2 contributes to the G2 DNA damage response, but this is a downstream role distinct from its core mitotic-entry function. Supporting Evidence: PMID:12023299 the major Schizosaccharomyces pombe CDK, Cdc2-cyclin B, influences recombinational repair of radiation-induced DSBs during the G(2) phase at two distinct stages |
| GO:0071957 old mitotic spindle pole body | IDA PMID:1699136 Distinct nuclear and spindle pole body population of cyclin-... | ACCEPT | Summary: IDA to the old (pre-existing) SPB, consistent with the SPB-associated population of Cdc13. A fine-grained localization within the broader SPB localization. Reason: Direct evidence for SPB-associated Cdc13; specific SPB sub-localization. Supporting Evidence: PMID:1699136 the presence of two spatially distinct cdc13 cyclin populations in the nucleus of S. pombe, one of which is associated with the mitotic spindle poles |
| GO:0071958 new mitotic spindle pole body | IDA PMID:1699136 Distinct nuclear and spindle pole body population of cyclin-... | ACCEPT | Summary: IDA to the new (newly duplicated) SPB, complementary to the old-SPB annotation. Both reflect the experimentally observed SPB-associated Cdc13 population. Reason: Direct evidence for SPB-associated Cdc13; specific SPB sub-localization. Supporting Evidence: PMID:1699136 the presence of two spatially distinct cdc13 cyclin populations in the nucleus of S. pombe, one of which is associated with the mitotic spindle poles |
| GO:0005515 protein binding | IPI PMID:1655416 Phosphorylation at Thr167 is required for Schizosaccharomyce... | MARK AS OVER ANNOTATED | Summary: IPI to cdc2, reflecting the Cdc13-Cdc2 complex (Thr167 phosphorylation of Cdc2 is required for kinase activity and for association with cyclin B). Bare protein binding is uninformative; the Cdc2 interaction is the substance of the core kinase-regulator function and is captured by GO:0016538. Reason: Uninformative bare protein binding; the Cdc13-Cdc2 interaction is already represented by the cyclin kinase-regulator molecular function. Supporting Evidence: PMID:1655416 Phosphorylation at Thr167 is required for Schizosaccharomyces pombe p34cdc2 function. |
| GO:0140602 nucleolar peripheral inclusion body | IDA PMID:33176152 Acute Heat Stress Leads to Reversible Aggregation of Nuclear... | KEEP AS NON CORE | Summary: IDA localization to nucleolar ring/inclusion structures formed upon acute heat stress, which reversibly sequester cell-cycle regulators. This is a stress-induced aggregation phenomenon, not a constitutive functional site. Reason: Heat-stress-induced reversible aggregation; condition-specific localization, not a core functional compartment. Supporting Evidence: PMID:33176152 NuRs sequester essential factors required for nuclear mRNA metabolism and nuclear pore complex function, as well as cell-cycle regulators. |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IMP PMID:32084401 The Hydrophobic Patch Directs Cyclin B to Centrosomes to Pro... | ACCEPT | Summary: IMP showing that the Cdc13 hydrophobic patch (and SPB targeting) is required for the onset of mitosis and that hydrophobic-patch mutant cells arrest in G2. This directly supports a positive role in driving the G2/M transition and is a core function. Reason: Cdc13-Cdc2 is the principal positive driver of the G2/M transition; SPB-targeting mutants fail mitotic entry. Supporting Evidence: PMID:32084401 disruption of this motif prevents both centrosomal localization of Cdc13 and the onset of mitosis but does not prevent S phase |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IMP PMID:32084401 The Hydrophobic Patch Directs Cyclin B to Centrosomes to Pro... | ACCEPT | Summary: IMP supporting that Cdc13 activates Cdc2/CDK for mitotic substrate phosphorylation, with SPB-localized Cdc13-CDK required to reach the high CDK activity needed for mitosis. Core molecular function as the activating cyclin subunit. Reason: Cdc13 is the activating B-type cyclin of the mitotic CDK; loss of correct localization compromises global mitotic CDK phosphorylation. Supporting Evidence: PMID:32084401 Cdc13-CDK localization to the SPB is important for generating the highest levels of CDK activity in these compartments needed for mitosis |
| GO:0044732 mitotic spindle pole body | IMP PMID:32084401 The Hydrophobic Patch Directs Cyclin B to Centrosomes to Pro... | ACCEPT | Summary: IMP localization to the mitotic SPB; the hydrophobic patch targets Cdc13 to the SPB in G2, and this localization is required for mitotic entry. Well supported. Reason: SPB localization of Cdc13-CDK is directly demonstrated and functionally required. Supporting Evidence: PMID:32084401 the hydrophobic patch targets Cdc13 to the yeast centrosome equivalent, the spindle pole body (SPB) |
| GO:0044732 mitotic spindle pole body | EXP PMID:32084401 The Hydrophobic Patch Directs Cyclin B to Centrosomes to Pro... | ACCEPT | Summary: EXP localization to the mitotic SPB (duplicate of the IMP annotation from the same study). Cdc13 is enriched at the SPB in G2 and decorates the mitotic spindle. Reason: Direct experimental SPB localization of Cdc13. Supporting Evidence: PMID:32084401 Wild-type Cdc13 is found in the nucleus, is visibly enriched at the SPB in G2, and decorates the mitotic spindle during mitosis |
| GO:0140429 positive regulation of mitotic sister chromatid biorientation | EXP PMID:20739936 Phosphorylation of the CPC by Cdk1 promotes chromosome bi-or... | KEEP AS NON CORE | Summary: EXP evidence that Cdk1 (Cdc2)-cyclin B phosphorylates the chromosomal passenger complex (Survivin) to promote chromosome bi-orientation. A genuine downstream mitotic process role of Cdc13-Cdc2. Reason: Bi-orientation control is a real role of the Cdc13-Cdc2 kinase but is downstream of its core mitotic-entry function. Supporting Evidence: PMID:20739936 Cdk1 (also known as Cdc2)-cyclin-B-dependent phosphorylation of Survivin |
| GO:0140013 meiotic nuclear division | IMP PMID:25891897 A single cyclin-CDK complex is sufficient for both mitotic a... | ACCEPT | Summary: IMP showing Cdc13 is required for the meiosis I and meiosis II nuclear divisions; a single Cdc13-Cdc2 complex is sufficient to drive the meiotic cell cycle. This is a genuine (not over-annotated) meiotic role of Cdc13. Reason: Direct genetic evidence establishes Cdc13 as required for both meiotic nuclear divisions. Supporting Evidence: PMID:25891897 Cdc13 is required for meiosis I and II, and is not required for premeiotic S-phase unless this function can be achieved by very low Cdc13 protein levels |
| GO:0005634 nucleus | IDA PMID:29123917 The telomere bouquet facilitates meiotic prophase progressio... | ACCEPT | Summary: IDA nuclear localization observed during meiotic prophase imaging of CDK1-Cdc13. Consistent with the established nuclear localization of Cdc13-Cdc2. Reason: Direct imaging of nuclear/telomere-bouquet-associated Cdc13 in meiosis. Supporting Evidence: PMID:29123917 delayed accumulation of CDK1Cdc13 at the SPB |
| GO:0140445 chromosome, telomeric repeat region | EXP PMID:29123917 The telomere bouquet facilitates meiotic prophase progressio... | KEEP AS NON CORE | Summary: EXP localization of CDK1-Cdc13 near telomeres during the meiotic telomere bouquet; heterochromatic/telomeric regions act as a platform that delivers CDK to the SPB. A meiosis-specific localization, genuine but non-core. Reason: Telomere-proximal localization is a meiosis-prophase-specific context for CDK delivery to the SPB, not a core mitotic function site. Supporting Evidence: PMID:29123917 CDK1Cdc13 can localise near to the telomeres and therefore to the SPB during the later bouquet stage |
| GO:0005634 nucleus | EXP PMID:11683390 In vivo localisation of fission yeast cyclin-dependent kinas... | ACCEPT | Summary: EXP nuclear localization from in vivo YFP imaging of Cdc13 during mitosis and meiosis. Strongly supported core localization. Reason: Direct in vivo imaging confirms nuclear localization of Cdc13. Supporting Evidence: PMID:11683390 cdc13-YFP is enriched at the nuclear periphery before fluorescence disappears |
| GO:0034399 nuclear periphery | EXP PMID:11683390 In vivo localisation of fission yeast cyclin-dependent kinas... | KEEP AS NON CORE | Summary: EXP localization to the nuclear periphery; Cdc13-YFP becomes enriched at the nuclear periphery in anaphase before being degraded. A genuine cell-cycle-stage-specific localization. Reason: Nuclear-periphery enrichment is a transient late-mitotic localization, accepted as context rather than a core functional compartment. Supporting Evidence: PMID:11683390 cdc13-YFP is enriched at the nuclear periphery before fluorescence disappears |
| GO:0044732 mitotic spindle pole body | EXP PMID:11683390 In vivo localisation of fission yeast cyclin-dependent kinas... | ACCEPT | Summary: EXP localization to the mitotic SPB from in vivo imaging; Cdc2-YFP and Cdc13-YFP are highly enriched on the SPB in late G2 and accumulate on SPBs and spindle in prophase/metaphase. Well supported. Reason: Direct in vivo imaging of Cdc13 at the SPB across mitosis. Supporting Evidence: PMID:11683390 Cdc2-YFP and cdc13-YFP are highly enriched on the spindle pole body of cells in late G2 or arrested at S phase. |
| GO:0072686 mitotic spindle | EXP PMID:11683390 In vivo localisation of fission yeast cyclin-dependent kinas... | ACCEPT | Summary: EXP localization to the mitotic spindle; Cdc13-Cdc2 accumulates on the spindle in prophase/metaphase and leaves the spindle before sister-chromatid separation. Reason: Direct imaging of Cdc13 decorating the mitotic spindle. Supporting Evidence: PMID:11683390 In anaphase, the cdc2p/cdc13p complex leaves the spindle prior to sister chromatid separation |
| GO:0005515 protein binding | IPI PMID:26131711 Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and ... | MARK AS OVER ANNOTATED | Summary: IPI to cdc2 from the study of two Cdc2 pools in the DNA damage response. Bare protein binding is uninformative; the Cdc13-Cdc2 interaction is already represented by the core cyclin kinase-regulator function. Reason: Uninformative bare protein binding; redundant with the Cdc2 kinase-regulator function. Supporting Evidence: PMID:26131711 Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and the DNA Damage Response in the Fission Yeast S.pombe. |
| GO:0051447 negative regulation of meiotic cell cycle | IMP PMID:11493649 Fission yeast mfr1 activates APC and coordinates meiotic nuc... | KEEP AS NON CORE | Summary: IMP from the Mfr1/APC study. Persistent high Cdc13-Cdc2 activity delays meiotic exit/sporulation; timely degradation of Cdc13 by the Mfr1-activated APC/C is required to switch off the meiotic cell cycle and license spore formation. Thus Cdc13 activity negatively impacts meiotic exit and its destruction is required for progression. A genuine, evidence-based meiotic regulatory role (non-core). Reason: Cdc13 levels/activity gate meiotic exit; this is a real meiotic regulatory role but peripheral to the core G2/M kinase-cyclin function. Supporting Evidence: PMID:11493649 An mfr1 null mutant completes meiosis II but remains with high levels of cdc13 and cdc2 kinase activity and has considerably delayed spore formation. |
| GO:1990023 mitotic spindle midzone | IDA PMID:19686686 Phospho-regulated interaction between kinesin-6 Klp9p and mi... | KEEP AS NON CORE | Summary: IDA to the mitotic spindle midzone. Cdc2 (CDK)-Cdc13 phosphorylates the midzone kinesin Klp9 and the bundler Ase1 to control anaphase B spindle elongation, placing the active kinase at the midzone. A genuine localization/process context. Reason: Midzone activity in anaphase B is a downstream role of the Cdc13-Cdc2 kinase, not its core mitotic-entry function. Supporting Evidence: PMID:19686686 The cyclin-dependent kinase cdc2p phosphorylates and its antagonist phosphatase clp1p dephosphorylates klp9p and ase1p to control the position and timing of klp9p-ase1p interaction. |
| GO:0044732 mitotic spindle pole body | IDA PMID:11084332 Cut8, essential for anaphase, controls localization of 26S p... | ACCEPT | Summary: IDA SPB localization associated with the Cut8/proteasome study of mitotic cyclin destruction. Cdc13 SPB localization is independently and strongly supported; here it is in the context of where Cdc13 is degraded. Reason: SPB localization of Cdc13 is well supported across multiple studies. Supporting Evidence: PMID:11084332 destruction of mitotic cyclin and Cut2 in the nucleus is dramatically delayed, though polyubiquitination of Cdc13 occurs in cut8 mutant. |
| GO:1990023 mitotic spindle midzone | IMP PMID:11084332 Cut8, essential for anaphase, controls localization of 26S p... | KEEP AS NON CORE | Summary: IMP to spindle midzone from the Cut8 study. Cdc13 localization/degradation is in the nucleus and at the SPB; midzone localization of the active kinase is better supported by the Klp9/Ase1 phospho-regulation study and is a non-core context. Reason: Midzone is a downstream anaphase context for the Cdc13-Cdc2 kinase, not a core function site. Supporting Evidence: PMID:11084332 destruction of mitotic cyclin and Cut2 in the nucleus is dramatically delayed, though polyubiquitination of Cdc13 occurs in cut8 mutant. |
| GO:0000785 chromatin | IDA PMID:12419251 Stable association of mitotic cyclin B/Cdc2 to replication o... | ACCEPT | Summary: IDA localization to chromatin. Cdc13-Cdc2 stably associates with ORC-bound replication origins (chromatin) in vivo, enforcing the dependence of S phase on an intervening mitosis and preventing re-replication. A genuine, functionally important chromatin association. Reason: Direct evidence that Cdc13-Cdc2 associates with chromatin (replication origins) via ORC. Supporting Evidence: PMID:12419251 the mitotic B type cyclin Cdc13/Cdc2 kinase associates with replication origins in vivo. This association is dependent on the origin recognition complex (ORC) |
| GO:0005515 protein binding | IPI PMID:15791259 Fission yeast Mes1p ensures the onset of meiosis II by block... | MARK AS OVER ANNOTATED | Summary: IPI from the Mes1 study (Mes1 binds Slp1/APC activator to block Cdc13 degradation). Bare protein binding is uninformative; the biology is captured by the meiotic regulation annotations. Reason: Uninformative bare protein binding term. Supporting Evidence: PMID:15791259 Mes1p is a factor that suppresses the degradation of cyclin Cdc13p at anaphase I |
| GO:0005634 nucleus | IDA PMID:15791259 Fission yeast Mes1p ensures the onset of meiosis II by block... | ACCEPT | Summary: IDA nuclear localization observed in the Mes1/Cdc13 meiotic study; consistent with the established nuclear localization of Cdc13. Reason: Nuclear localization of Cdc13 is well established across studies. Supporting Evidence: PMID:15791259 Mes1p is a factor that suppresses the degradation of cyclin Cdc13p at anaphase I |
| GO:0005730 nucleolus | IDA PMID:8688826 Cyclin B (p56cdc13) localization in the yeast Schizosaccharo... | KEEP AS NON CORE | Summary: IDA from ultrastructural/immunocytochemical localization of p56cdc13. The study mainly shows cytoplasmic and nuclear/perinuclear localization; nucleolar signal is a minor compartment and not a core functional site. Reason: Nucleolar signal is a minor compartment in the EM/IF study; not a core functional site for the mitotic cyclin. Supporting Evidence: PMID:8688826 evidencing cytoplasmic localization of p56cdc13, in addition to the nuclear localization previously observed |
| GO:0005737 cytoplasm | IDA PMID:8688826 Cyclin B (p56cdc13) localization in the yeast Schizosaccharo... | KEEP AS NON CORE | Summary: IDA cytoplasmic localization from improved EM (high-pressure freezing) and immunofluorescence, showing a major cytoplasmic pool of p56cdc13 in interphase that relocalizes to the nucleus in mitosis. A genuine localization, though the functionally dominant compartment is nuclear/SPB. Reason: A cytoplasmic interphase pool exists, but the functionally critical mitotic localization is nuclear and at the SPB. Supporting Evidence: PMID:8688826 evidencing cytoplasmic localization of p56cdc13, in addition to the nuclear localization previously observed |
| GO:0034399 nuclear periphery | IDA PMID:8688826 Cyclin B (p56cdc13) localization in the yeast Schizosaccharo... | KEEP AS NON CORE | Summary: IDA to nuclear periphery from the EM/IF study; consistent with the documented enrichment of Cdc13 at the nuclear periphery during the cell cycle. Non-core compartment. Reason: Transient/contextual perinuclear localization rather than a core function site. Supporting Evidence: PMID:8688826 evidencing cytoplasmic localization of p56cdc13, in addition to the nuclear localization previously observed |
| GO:0072687 meiotic spindle | IDA PMID:15791259 Fission yeast Mes1p ensures the onset of meiosis II by block... | KEEP AS NON CORE | Summary: IDA localization to the meiotic spindle, consistent with Cdc13's established role in meiotic divisions (analogous to its mitotic-spindle association). A genuine meiotic localization. Reason: Meiotic-spindle localization reflects the genuine meiotic role of Cdc13 but is peripheral to its core mitotic function. Supporting Evidence: PMID:15791259 Mes1p is a factor that suppresses the degradation of cyclin Cdc13p at anaphase I |
| GO:0140429 positive regulation of mitotic sister chromatid biorientation | IGI PMID:22264609 A role for metaphase spindle elongation forces in correction... | KEEP AS NON CORE | Summary: IGI evidence that Cdk1 (Cdc2)-Cdc13 regulates metaphase spindle elongation forces to correct merotelic kinetochore attachments (by phosphorylating/inhibiting Klp9), promoting correct bi-orientation. A genuine downstream mitotic role. Reason: Merotelic correction/bi-orientation is a real downstream role of the kinase, not the core mitotic-entry function. Supporting Evidence: PMID:22264609 A role for metaphase spindle elongation forces in correction of merotelic kinetochore attachments. |
| GO:0010389 regulation of G2/M transition of mitotic cell cycle | IMP PMID:2908246 Cloning and sequencing of the cyclin-related cdc13+ gene and... | ACCEPT | Summary: IMP from the original cloning/cytology study establishing that cdc13+ is required for control of the G2-to-M transition. This is the canonical core biological process of Cdc13. Reason: Foundational genetic evidence that Cdc13 controls the G2/M transition; core function. Supporting Evidence: PMID:2908246 required for the control of the G2 to M transition |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IGI PMID:2569363 The fission yeast cdc2/cdc13/suc1 protein kinase: regulation... | ACCEPT | Summary: IGI/experimental support that the Cdc13-encoded cyclin activates the Cdc2 protein kinase and regulates its catalytic activity and localization. Core molecular function. Reason: Cdc13 is the activating cyclin subunit of the Cdc2/CDK1 kinase; the complex is kinase-active in vitro and oscillates in activity through the cell cycle. Supporting Evidence: PMID:2569363 The products of the cdc13+ and cdc2+ genes form a stable complex that displays protein kinase activity in vitro. |
| GO:0005634 nucleus | IDA PMID:2569363 The fission yeast cdc2/cdc13/suc1 protein kinase: regulation... | ACCEPT | Summary: IDA nuclear localization; Cdc13 and Cdc2 co-localize in the nucleus and Cdc13 is required to localize Cdc2 to the nucleus. Strongly supported core localization. Reason: Direct co-localization evidence; Cdc13 dictates nuclear localization of the complex. Supporting Evidence: PMID:2569363 cdc13 and cdc2 co-localize in the cell nucleus. |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: High-throughput (HDA) nuclear localization from the genome-wide ORFeome localization study. Consistent with the strong experimental consensus for nuclear Cdc13. Reason: Consistent with abundant focused experimental evidence for nuclear localization. Supporting Evidence: PMID:2534559 both cdc13 and cdc2 are nuclear proteins in S. pombe. |
| GO:0044732 mitotic spindle pole body | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: HDA localization to the mitotic SPB from the genome-wide localization study; consistent with focused imaging studies of Cdc13 at the SPB. Reason: Consistent with focused experimental SPB localization data. Supporting Evidence: PMID:11683390 Cdc2-YFP and cdc13-YFP are highly enriched on the spindle pole body of cells in late G2 or arrested at S phase. |
| GO:0072686 mitotic spindle | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: HDA localization to the mitotic spindle from the genome-wide study; consistent with focused imaging showing Cdc13 decorating the spindle during mitosis. Reason: Consistent with focused experimental mitotic-spindle localization data. Supporting Evidence: PMID:11683390 In anaphase, the cdc2p/cdc13p complex leaves the spindle prior to sister chromatid separation |
| GO:0005634 nucleus | IDA PMID:2534559 Fission yeast cyclin: subcellular localisation and cell cycl... | ACCEPT | Summary: IDA nuclear localization from the classic subcellular-localization study; both Cdc13 and Cdc2 are nuclear proteins localized to a nuclear domain distinct from chromatin, and Cdc13 is required to localize Cdc2 to the nucleus. Core localization. Reason: Foundational direct evidence for nuclear localization of Cdc13. Supporting Evidence: PMID:2534559 cdc13 therefore appears to be required to localise cdc2 to the nucleus but not vice versa. |
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Download this section (compressed HTML)Q: What is the full repertoire of Cdc13-Cdc2 substrates whose phosphorylation strictly requires SPB-localized (hydrophobic-patch-dependent) cyclin-CDK versus the nuclear pool, and how does this spatial partitioning order mitotic events?
Q: How is Cdc13 stability differentially controlled in the mitotic versus meiotic cycle (APC/C-Slp1 vs Mes1-protected vs Mfr1-activated APC/C), and what determines the precise timing windows?
Q: To what extent does the ORC-dependent association of Cdc13-Cdc2 with replication origins contribute to re-replication control independently of its kinase activity?
Experiment: Combine analog-sensitive Cdc2 (cdc2as) with rapid Cdc13 degradation and quantitative phosphoproteomics across synchronized mitosis and meiosis to map cyclin-pool-specific substrate phosphorylation and define the boundary between core mitotic-entry substrates and downstream targets (bi-orientation, midzone, DDR).
Experiment: Use endogenously tagged Cdc13 with live-cell super-resolution imaging plus degron-controlled removal of SPB, ORC and telomere-bouquet factors to dissect the sequence and dependencies of Cdc13 localization (nucleus, SPB, replication origins, spindle, midzone) in mitosis and meiosis.
Experiment: Reconstitute APC/C-dependent Cdc13 destruction in vitro with Slp1, Mes1 and Mfr1 to quantify how these regulators set Cdc13 levels at the meiosis I/II boundary and at meiotic exit, correlating with MPF activity and sporulation timing.
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