cdc13

UniProt ID: P10815
Organism: Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Review Status: DRAFT
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Gene Description

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.

Existing Annotations Review

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.
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.

Core Functions

Acts as the mitotic B-type cyclin regulatory subunit that binds and activates the Cdc2 (CDK1) serine/threonine protein kinase, forming M-phase-promoting factor (MPF) and dictating the catalytic activity, substrate selection and localization of the kinase.

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.

Drives the G2/M transition and mitotic progression; Cdc13-Cdc2 accumulates through G2, is activated at mitotic onset, and is required for entry into and completion of mitosis.

Supporting Evidence:
  • PMID:2908246
    required for the control of the G2 to M transition
  • PMID:32084401
    disruption of this motif prevents both centrosomal localization of Cdc13 and the onset of mitosis but does not prevent S phase

Provides the cyclin activity required for the meiotic nuclear divisions; a single Cdc13-Cdc2 complex is sufficient to drive both meiosis I and meiosis II, with its stability specifically controlled between the divisions.

Directly Involved In:
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

Targets the Cdc2 kinase to the spindle pole body (the fungal centrosome equivalent) via the cyclin hydrophobic patch, concentrating CDK activity needed for phosphorylation of SPB/cytoplasmic mitotic substrates and for mitotic entry.

Cellular Locations:
Supporting Evidence:
  • PMID:32084401
    the hydrophobic patch targets Cdc13 to the yeast centrosome equivalent, the spindle pole body (SPB)

References

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Suggested Questions for Experts

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?

Suggested Experiments

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.

πŸ“š Additional Documentation

Notes

(cdc13-notes.md)

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