cdc2

UniProt ID: P04551
Organism: Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Review Status: DRAFT
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Gene Description

Cdc2 (p34cdc2, Cdk1) is the founding cyclin-dependent serine/threonine protein kinase and the master regulator of the fission-yeast cell cycle, driving both the G1/S and G2/M transitions of the mitotic cycle as well as the meiotic divisions. It is catalytically inert as a monomer and becomes an active kinase only when bound to a B-type cyclin (chiefly the mitotic cyclin Cdc13, with Cig1/Cig2/Puc1 acting at G1/S) together with the small Suc1/Cks1 subunit, forming the cyclin-dependent kinase holoenzyme (MPF). Its activity is further controlled by activating phosphorylation of Thr167 in the activation loop by CAK (Csk1/Mcs6), by inhibitory phosphorylation of Tyr15 (and Thr14) by the Wee1/Mik1 kinases, by activating Tyr15 dephosphorylation by the Cdc25 phosphatase, and by the CDK inhibitor Rum1 that restrains it during G1. Active Cdc2-cyclin phosphorylates Ser/Thr-Pro motifs on more than 200 substrates, and a single rising CDK activity is sufficient to order cell-cycle events through substrate-specific activity thresholds. Through these substrates it controls DNA replication initiation and prevents re-replication, chromosome condensation and segregation, spindle and kinetochore dynamics, mitotic exit, cytokinesis timing, and meiotic progression. Cdc2 acts mainly in the nucleus, at spindle pole bodies, spindles, kinetochores and on chromatin, and its inactivation by checkpoint signaling enforces cell-cycle arrest in response to DNA damage and replication stress.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000307 cyclin-dependent protein kinase holoenzyme complex
IBA
GO_REF:0000033
ACCEPT
Summary: Cdc2 is the catalytic subunit of the cyclin-dependent protein kinase holoenzyme, a cyclin(Cdc13/Cig2)-Cdc2-Suc1(Cks1) complex.
Reason: Core cellular component; Cdc2 forms a holoenzyme with a cyclin and the Suc1/Cks1 subunit.
GO:0000086 G2/M transition of mitotic cell cycle
IBA
GO_REF:0000033
ACCEPT
Summary: Cdc2 drives the G2/M transition (mitotic entry); the rate-limiting cdc2 function classically defined by the requirement in G2 for control of mitosis and by Tyr15 phospho-regulation of mitotic entry.
Reason: Core cell-cycle driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
Supporting Evidence:
PMID:27984725
a single genetically engineered cyclin-CDK chimera between the mitotic B-type cyclin Cdc13 and the CDK Cdc2 (Cdc13-L-Cdc2) can substitute for the four cyclin-CDK complexes acting during the mitotic cell
PMID:11486016
Cdc2 kinase is a master regulator of cell cycle progression in the fission yeast Schizosaccharomyces pombe. Our data indicate that Cdc2 phosphorylates replication factor Orp2, a subunit of the origin recognition complex (ORC).
GO:0004672 protein kinase activity
IEA
GO_REF:0000002
MODIFY
Summary: General protein kinase activity; correct ancestor term but uninformative for a CDK.
Reason: Over-general parent; replace with the specific cyclin-dependent ser/thr kinase activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0005524 ATP binding
IEA
GO_REF:0000002
ACCEPT
Summary: ATP binding is required for and intrinsic to the kinase catalytic activity; the ATP-binding pocket (Gly-rich loop, Tyr15) is well characterized.
Reason: Correct supporting molecular function for a protein kinase.
GO:0005634 nucleus
IEA
GO_REF:0000117
ACCEPT
Summary: Active Cdc2-cyclin pool localizes to the nucleus, consistent with phosphorylation of nuclear/chromatin substrates.
Reason: Electronic localization consistent with abundant experimental nuclear data for active Cdc2.
GO:0005737 cytoplasm
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Cdc2 is also present in the cytoplasm; a substantial cytoplasmic pool exists in addition to nuclear/SPB pools.
Reason: Valid localization but secondary to the functionally critical nuclear/SPB/chromatin pools.
GO:0106310 protein serine kinase activity
IEA
GO_REF:0000116
MARK AS OVER ANNOTATED
Summary: Protein serine kinase activity is a Rhea/ISS electronic term; CDK1 is a Ser/Thr kinase, so this captures only part of the activity.
Reason: Partial/over-narrow electronic import; the dual-specificity Ser/Thr activity is correctly captured by GO:0004693/GO:0004674.
GO:0005515 protein binding
IPI
PMID:8552194
Interaction of Cdc2 and Cdc18 with a fission yeast ORC2-like...
MARK AS OVER ANNOTATED
Summary: Records a physical interaction with Orc2/Orp2 (ORC subunit). "protein binding" is uninformative; the biologically meaningful relationships are captured by the holoenzyme complex term and specific downstream/regulatory BP terms.
Reason: Bare protein binding adds no functional information; partner-specific function is better represented elsewhere (cyclin binding, holoenzyme complex, substrate-process terms).
GO:0005515 protein binding
IPI
PMID:9115279
Pch1(+), a second essential C-type cyclin gene in Schizosacc...
MARK AS OVER ANNOTATED
Summary: Records a physical interaction with cyclin Pch1. "protein binding" is uninformative; the biologically meaningful relationships are captured by the holoenzyme complex term and specific downstream/regulatory BP terms.
Reason: Bare protein binding adds no functional information; partner-specific function is better represented elsewhere (cyclin binding, holoenzyme complex, substrate-process terms).
GO:0005515 protein binding
IPI
PMID:9303310
p25rum1 promotes proteolysis of the mitotic B-cyclin p56cdc1...
MARK AS OVER ANNOTATED
Summary: Records a physical interaction with CDK inhibitor Rum1. "protein binding" is uninformative; the biologically meaningful relationships are captured by the holoenzyme complex term and specific downstream/regulatory BP terms.
Reason: Bare protein binding adds no functional information; partner-specific function is better represented elsewhere (cyclin binding, holoenzyme complex, substrate-process terms).
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:41354344
The mitotic functions of a fission yeast CK1 enzyme are regu...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004674 protein serine/threonine kinase activity
IDA
PMID:21965289
Nsk1 ensures accurate chromosome segregation by promoting as...
MODIFY
Summary: General protein serine/threonine kinase activity; correct but less informative than the cyclin-dependent term GO:0004693.
Reason: Accurate but over-general for a CDK; the cyclin-dependent ser/thr kinase term is the informative core MF.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:39174851
CDK phosphorylation of Sfr1 downregulates Rad51 function in ...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0106310 protein serine kinase activity
ISS
GO_REF:0000024
MARK AS OVER ANNOTATED
Summary: Protein serine kinase activity is a Rhea/ISS electronic term; CDK1 is a Ser/Thr kinase, so this captures only part of the activity.
Reason: Partial/over-narrow electronic import; the dual-specificity Ser/Thr activity is correctly captured by GO:0004693/GO:0004674.
GO:0051292 nuclear pore complex assembly
EXP NOT
PMID:35354597
Quantitative analysis of nuclear pore complex organization i...
ACCEPT
Summary: Cdc2 is NOT involved in nuclear pore complex assembly; quantitative NPC analysis found no role.
Reason: Negated annotation appropriately documents absence of a role.
GO:1904547 regulation of cellular response to glucose starvation
IMP
PMID:37128864
CDK actively contributes to establishment of the stationary ...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in regulation of cellular response to glucose starvation / stationary-phase establishment, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0140602 nucleolar peripheral inclusion body
IDA
PMID:37128864
CDK actively contributes to establishment of the stationary ...
KEEP AS NON CORE
Summary: Active CDK localizes to a nucleolar peripheral inclusion body during stationary phase establishment.
Reason: Specialized stationary-phase localization; valid but non-core.
GO:0004674 protein serine/threonine kinase activity
EXP
PMID:36408846
Differential phosphorylation of Clr4(SUV39H) by Cdk1 accompa...
MODIFY
Summary: General protein serine/threonine kinase activity; correct but less informative than the cyclin-dependent term GO:0004693.
Reason: Accurate but over-general for a CDK; the cyclin-dependent ser/thr kinase term is the informative core MF.
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: Experimentally supported role of Cdc2-cyclin in mitotic DNA damage checkpoint signaling, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0071957 old mitotic spindle pole body
IDA
PMID:1699136
Distinct nuclear and spindle pole body population of cyclin-...
KEEP AS NON CORE
Summary: Active Cdc2-cyclin localizes to the spindle pole body (old/new mitotic SPB; meiotic SPB), a major mitotic/meiotic substrate platform.
Reason: Genuine localization of active kinase but a specialized sub-pool, not the core MF.
GO:0071958 new mitotic spindle pole body
IDA
PMID:1699136
Distinct nuclear and spindle pole body population of cyclin-...
KEEP AS NON CORE
Summary: Active Cdc2-cyclin localizes to the spindle pole body (old/new mitotic SPB; meiotic SPB), a major mitotic/meiotic substrate platform.
Reason: Genuine localization of active kinase but a specialized sub-pool, not the core MF.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:34810257
Ccp1-Ndc80 switch at the N terminus of CENP-T regulates kine...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:1905561 positive regulation of kinetochore assembly
EXP
PMID:34810257
Ccp1-Ndc80 switch at the N terminus of CENP-T regulates kine...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of kinetochore assembly, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0072687 meiotic spindle
IDA
PMID:12606573
Function of Cdc2p-dependent Bub1p phosphorylation and Bub1p ...
KEEP AS NON CORE
Summary: Active Cdc2-cyclin localizes to the mitotic/meiotic spindle and spindle midzone where it phosphorylates spindle substrates.
Reason: Genuine sub-localization of active kinase, peripheral to the core catalytic-activity annotation.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:12606573
Function of Cdc2p-dependent Bub1p phosphorylation and Bub1p ...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:34402513
Phosphorylation in the intrinsically disordered region of F-...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:1902413 negative regulation of mitotic cytokinesis
EXP
PMID:34402513
Phosphorylation in the intrinsically disordered region of F-...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of mitotic cytokinesis, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:34133210
Cdk1 phosphorylation of fission yeast paxillin inhibits its ...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0005515 protein binding
IPI
PMID:1655416
Phosphorylation at Thr167 is required for Schizosaccharomyce...
MARK AS OVER ANNOTATED
Summary: Records a physical interaction with cyclin Cdc13 (Thr167-dependent association). "protein binding" is uninformative; the biologically meaningful relationships are captured by the holoenzyme complex term and specific downstream/regulatory BP terms.
Reason: Bare protein binding adds no functional information; partner-specific function is better represented elsewhere (cyclin binding, holoenzyme complex, substrate-process terms).
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:9430640
Regulation of the G1 phase of the cell cycle by periodic sta...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
IMP
PMID:9430640
Regulation of the G1 phase of the cell cycle by periodic sta...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of proteasomal ubiquitin-dependent protein catabolism, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:16920624
CDC2 phosphorylation of the fission yeast dis1 ensures accur...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0031568 mitotic G1 cell size control checkpoint signaling
IGI
PMID:9398669
A WD repeat protein controls the cell cycle and differentiat...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in mitotic G1 cell size control checkpoint signaling, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0031568 mitotic G1 cell size control checkpoint signaling
IMP
PMID:8121488
Regulation of progression through the G1 phase of the cell c...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in mitotic G1 cell size control checkpoint signaling, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:32878942
Phosphoregulation of the cytokinetic protein Fic1 contribute...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:2000099 regulation of establishment or maintenance of bipolar cell polarity
IDA
PMID:32878942
Phosphoregulation of the cytokinetic protein Fic1 contribute...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in regulation of bipolar cell polarity (Fic1), reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:23333317
Removal of centrosomal PP1 by NIMA kinase unlocks the MPF fe...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:31644361
A mechanism for how Cdr1/Nim1 kinase promotes mitotic entry ...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:20739936
Phosphorylation of the CPC by Cdk1 promotes chromosome bi-or...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
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: Experimentally supported role of Cdc2-cyclin in positive regulation of mitotic sister chromatid biorientation, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0110045 negative regulation of cell cycle switching, mitotic to meiotic cell cycle
IMP
PMID:17804800
Mei4p coordinates the onset of meiosis I by regulating cdc25...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of mitotic-to-meiotic cell cycle switching, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:11781565
Feedback regulation of the MBF transcription factor by cycli...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:19686686
Phospho-regulated interaction between kinesin-6 Klp9p and mi...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:1904514 positive regulation of initiation of premeiotic DNA replication
IMP
PMID:7498766
The role of cdc2 and other genes in meiosis in Schizosacchar...
ACCEPT
Summary: Cdc2 is essential for initiation of premeiotic DNA replication.
Reason: Core meiotic function supported by classic genetic analysis.
Supporting Evidence:
PMID:7498766
The cdc2 gene, which is required for the initiation of both mitotic S-phase and M-phase, is essential for premeiotic DNA synthesis and meiosis II.
GO:0005515 protein binding
IPI
PMID:10581266
The identification of Wos2, a p23 homologue that interacts w...
MARK AS OVER ANNOTATED
Summary: Records a physical interaction with Wos2 (p23 homologue). "protein binding" is uninformative; the biologically meaningful relationships are captured by the holoenzyme complex term and specific downstream/regulatory BP terms.
Reason: Bare protein binding adds no functional information; partner-specific function is better represented elsewhere (cyclin binding, holoenzyme complex, substrate-process terms).
GO:1905757 negative regulation of primary cell septum biogenesis
IMP
PMID:29813053
Specific detection of fission yeast primary septum reveals s...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of primary cell septum biogenesis, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0062123 regulation of linear element maturation
IMP
PMID:30640914
CDK contribution to DSB formation and recombination in fissi...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in regulation of linear element maturation (meiosis), reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:1905263 positive regulation of meiotic DNA double-strand break formation involved in reciprocal meiotic recombination
IMP
PMID:30640914
CDK contribution to DSB formation and recombination in fissi...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of meiotic DSB formation, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0072441 response to meiotic DNA replication checkpoint signaling
EXP
PMID:10521402
Meiotic DNA replication checkpoint control in fission yeast.
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in response to meiotic DNA replication checkpoint signaling, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:9353247
Regulation of the replication initiator protein p65cdc18 by ...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IMP
PMID:9353247
Regulation of the replication initiator protein p65cdc18 by ...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IMP
PMID:9303310
p25rum1 promotes proteolysis of the mitotic B-cyclin p56cdc1...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:9755169
Cdc18 transcription and proteolysis couple S phase to passag...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0045732 positive regulation of protein catabolic process
EXP
PMID:9755169
Cdc18 transcription and proteolysis couple S phase to passag...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of protein catabolic process (Cdc18 turnover), reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
IMP
PMID:9034336
Fission yeast pheromone blocks S-phase by inhibiting the G1 ...
ACCEPT
Summary: Cdc2 (as G1/S cyclin-CDK) positively regulates the G1/S transition.
Reason: Core cell-cycle function consistent with Cdc2 driving S-phase entry.
GO:0005634 nucleus
IDA
PMID:29123917
The telomere bouquet facilitates meiotic prophase progressio...
ACCEPT
Summary: Active Cdc2-cyclin pool localizes to the nucleus, consistent with phosphorylation of nuclear/chromatin substrates.
Reason: Experimentally supported nuclear localization of active kinase.
GO:1903500 negative regulation of mitotic actomyosin contractile ring assembly
IMP
PMID:29343550
Cdk1-dependent phosphoinhibition of a formin-F-BAR interacti...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of mitotic actomyosin contractile ring assembly, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:29343550
Cdk1-dependent phosphoinhibition of a formin-F-BAR interacti...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:26804917
Spatiotemporal Control of Forkhead Binding to DNA Regulates ...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0110044 regulation of cell cycle switching, mitotic to meiotic cell cycle
IDA
PMID:26804917
Spatiotemporal Control of Forkhead Binding to DNA Regulates ...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in regulation of mitotic-to-meiotic cell cycle switching, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0140445 chromosome, telomeric repeat region
EXP
PMID:29123917
The telomere bouquet facilitates meiotic prophase progressio...
KEEP AS NON CORE
Summary: Cdc2-cyclin associates with chromatin (including telomeric repeat regions), e.g. stable association with replication origins that prevents endoreduplication.
Reason: Genuine chromatin localization linked to replication control; peripheral to core MF.
GO:0097472 cyclin-dependent protein kinase activity
IDA
PMID:22665807
Multisite phosphoregulation of Cdc25 activity refines the mi...
ACCEPT
Summary: Cyclin-dependent protein kinase activity is a valid but slightly less specific statement of the core CDK catalytic activity captured more precisely by GO:0004693.
Reason: Correct and core; GO:0004693 is the preferred more specific term but this parent is also accurate.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:27984725
CDK Substrate Phosphorylation and Ordering the Cell Cycle.
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0042307 positive regulation of protein import into nucleus
IMP
PMID:10485849
Fission yeast condensin complex: essential roles of non-SMC ...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of protein import into nucleus, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0031536 positive regulation of exit from mitosis
IMP
PMID:16950791
Role of Hcn1 and its phosphorylation in fission yeast anapha...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of exit from mitosis, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:1905785 negative regulation of anaphase-promoting complex-dependent catabolic process
IMP
PMID:10921878
Fission yeast Fizzy-related protein srw1p is a G(1)-specific...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of APC-dependent catabolic process, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IMP
PMID:19523829
Phosphorylation state defines discrete roles for monopolin i...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0140429 positive regulation of mitotic sister chromatid biorientation
IMP
PMID:19523829
Phosphorylation state defines discrete roles for monopolin i...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of mitotic sister chromatid biorientation, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:1902845 negative regulation of mitotic spindle elongation
IMP
PMID:19523829
Phosphorylation state defines discrete roles for monopolin i...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of mitotic spindle elongation, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:1903380 positive regulation of mitotic chromosome condensation
IMP
PMID:10485849
Fission yeast condensin complex: essential roles of non-SMC ...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of mitotic chromosome condensation (Cut3/SMC4), reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:1903467 negative regulation of mitotic DNA replication initiation
IMP
PMID:11486016
Control of DNA rereplication via Cdc2 phosphorylation sites ...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of mitotic DNA replication initiation (anti-rereplication), reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
Supporting Evidence:
PMID:11486016
Cdc2 phosphorylation of Orp2 appears to be one of multiple mechanisms by which Cdc2 prevents DNA rereplication in a single cell cycle.
GO:1903467 negative regulation of mitotic DNA replication initiation
IMP
PMID:9436991
Negative regulation of Cdc18 DNA replication protein by Cdc2...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of mitotic DNA replication initiation (anti-rereplication), reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0000776 kinetochore
EXP
PMID:11683390
In vivo localisation of fission yeast cyclin-dependent kinas...
KEEP AS NON CORE
Summary: Active Cdc2-cyclin localizes to the kinetochore, consistent with phosphorylation of kinetochore substrates (Nsk1, CENP-T/Cnp20, Bub1).
Reason: Genuine sub-localization, peripheral to the core MF.
GO:0005634 nucleus
EXP
PMID:11683390
In vivo localisation of fission yeast cyclin-dependent kinas...
ACCEPT
Summary: Active Cdc2-cyclin pool localizes to the nucleus, consistent with phosphorylation of nuclear/chromatin substrates.
Reason: Experimentally supported nuclear localization of active kinase.
GO:0035974 meiotic spindle pole body
EXP
PMID:11683390
In vivo localisation of fission yeast cyclin-dependent kinas...
KEEP AS NON CORE
Summary: Active Cdc2-cyclin localizes to the spindle pole body (old/new mitotic SPB; meiotic SPB), a major mitotic/meiotic substrate platform.
Reason: Genuine localization of active kinase but a specialized sub-pool, not the core MF.
GO:0044732 mitotic spindle pole body
EXP
PMID:11683390
In vivo localisation of fission yeast cyclin-dependent kinas...
KEEP AS NON CORE
Summary: Active Cdc2-cyclin localizes to the spindle pole body (old/new mitotic SPB; meiotic SPB), a major mitotic/meiotic substrate platform.
Reason: Genuine localization of active kinase but a specialized sub-pool, not the core MF.
GO:0072686 mitotic spindle
EXP
PMID:11683390
In vivo localisation of fission yeast cyclin-dependent kinas...
KEEP AS NON CORE
Summary: Active Cdc2-cyclin localizes to the mitotic/meiotic spindle and spindle midzone where it phosphorylates spindle substrates.
Reason: Genuine sub-localization of active kinase, peripheral to the core catalytic-activity annotation.
GO:0005737 cytoplasm
EXP
PMID:11683390
In vivo localisation of fission yeast cyclin-dependent kinas...
KEEP AS NON CORE
Summary: Cdc2 is also present in the cytoplasm; a substantial cytoplasmic pool exists in addition to nuclear/SPB pools.
Reason: Valid localization but secondary to the functionally critical nuclear/SPB/chromatin pools.
GO:0072435 response to mitotic G2 DNA damage checkpoint signaling
IMP
PMID:9278510
Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in response to mitotic G2 DNA damage checkpoint signaling, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0045842 positive regulation of mitotic metaphase/anaphase transition
IMP
PMID:7774573
Dominant mutants identify new roles for p34cdc2 in mitosis.
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of mitotic metaphase/anaphase transition, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0005515 protein binding
IPI
PMID:26131711
Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and ...
MARK AS OVER ANNOTATED
Summary: Records a physical interaction with a Cdc2 interactor. "protein binding" is uninformative; the biologically meaningful relationships are captured by the holoenzyme complex term and specific downstream/regulatory BP terms.
Reason: Bare protein binding adds no functional information; partner-specific function is better represented elsewhere (cyclin binding, holoenzyme complex, substrate-process terms).
GO:0072435 response to mitotic G2 DNA damage checkpoint signaling
IPI
PMID:26131711
Two Distinct Cdc2 Pools Regulate Cell Cycle Progression and ...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in response to mitotic G2 DNA damage checkpoint signaling, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0001100 negative regulation of exit from mitosis
EXP
PMID:16950131
Phospho-regulation of the Cdc14/Clp1 phosphatase delays late...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of exit from mitosis, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IMP
PMID:10485849
Fission yeast condensin complex: essential roles of non-SMC ...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:1903465 positive regulation of mitotic cell cycle DNA replication
EXP
PMID:11937031
CDK phosphorylation of Drc1 regulates DNA replication in fis...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of mitotic cell cycle DNA replication, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:1902845 negative regulation of mitotic spindle elongation
IMP
PMID:19686686
Phospho-regulated interaction between kinesin-6 Klp9p and mi...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of mitotic spindle elongation, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0072435 response to mitotic G2 DNA damage checkpoint signaling
IGI
PMID:9042863
Cdc2 tyrosine phosphorylation is required for the DNA damage...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in response to mitotic G2 DNA damage checkpoint signaling, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:9436991
Negative regulation of Cdc18 DNA replication protein by Cdc2...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0005634 nucleus
IDA
PMID:11084332
Cut8, essential for anaphase, controls localization of 26S p...
ACCEPT
Summary: Active Cdc2-cyclin pool localizes to the nucleus, consistent with phosphorylation of nuclear/chromatin substrates.
Reason: Experimentally supported nuclear localization of active kinase.
GO:1990023 mitotic spindle midzone
IDA
PMID:11084332
Cut8, essential for anaphase, controls localization of 26S p...
KEEP AS NON CORE
Summary: Active Cdc2-cyclin localizes to the mitotic/meiotic spindle and spindle midzone where it phosphorylates spindle substrates.
Reason: Genuine sub-localization of active kinase, peripheral to the core catalytic-activity annotation.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
EXP
PMID:25487150
A PP1-PP2A phosphatase relay controls mitotic progression.
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:7957097
Phosphorylation of dis2 protein phosphatase at the C-termina...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:16950791
Role of Hcn1 and its phosphorylation in fission yeast anapha...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0000785 chromatin
IDA
PMID:12419251
Stable association of mitotic cyclin B/Cdc2 to replication o...
KEEP AS NON CORE
Summary: Cdc2-cyclin associates with chromatin (including telomeric repeat regions), e.g. stable association with replication origins that prevents endoreduplication.
Reason: Genuine chromatin localization linked to replication control; peripheral to core MF.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:22959349
Telomere-nuclear envelope dissociation promoted by Rap1 phos...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:1904537 negative regulation of mitotic telomere tethering at nuclear periphery
IPI
PMID:22959349
Telomere-nuclear envelope dissociation promoted by Rap1 phos...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of mitotic telomere tethering, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:25533340
Cdk1 restrains NHEJ through phosphorylation of XRCC4-like fa...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:2001033 negative regulation of double-strand break repair via nonhomologous end joining
IMP
PMID:25533340
Cdk1 restrains NHEJ through phosphorylation of XRCC4-like fa...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of NHEJ (Xlf1 phosphorylation), reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0005515 protein binding
IPI
PMID:2665944
Regulation of p34cdc2 protein kinase during mitosis.
MARK AS OVER ANNOTATED
Summary: Records a physical interaction with a Cdc2 mitotic interactor. "protein binding" is uninformative; the biologically meaningful relationships are captured by the holoenzyme complex term and specific downstream/regulatory BP terms.
Reason: Bare protein binding adds no functional information; partner-specific function is better represented elsewhere (cyclin binding, holoenzyme complex, substrate-process terms).
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:16950131
Phospho-regulation of the Cdc14/Clp1 phosphatase delays late...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0031138 negative regulation of conjugation with cellular fusion
IMP
PMID:18059475
Cdc2p controls the forkhead transcription factor Fkh2p by ph...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of conjugation with cellular fusion, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IMP
PMID:10921876
APC(ste9/srw1) promotes degradation of mitotic cyclins in G(...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:10921878
Fission yeast Fizzy-related protein srw1p is a G(1)-specific...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:1905785 negative regulation of anaphase-promoting complex-dependent catabolic process
IMP
PMID:10921876
APC(ste9/srw1) promotes degradation of mitotic cyclins in G(...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of APC-dependent catabolic process, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0031573 mitotic intra-S DNA damage checkpoint signaling
IMP
PMID:15297457
On the slowing of S phase in response to DNA damage in fissi...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in mitotic intra-S DNA damage checkpoint signaling, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:9177184
Interaction of the S phase regulator cdc18 with cyclin-depen...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004672 protein kinase activity
IDA
PMID:3516412
The cell cycle control gene cdc2+ of fission yeast encodes a...
MODIFY
Summary: General protein kinase activity; correct ancestor term but uninformative for a CDK.
Reason: Over-general parent; replace with the specific cyclin-dependent ser/thr kinase activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:24920823
Cdk1 promotes cytokinesis in fission yeast through activatio...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0031031 positive regulation of septation initiation signaling
IMP
PMID:24920823
Cdk1 promotes cytokinesis in fission yeast through activatio...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in positive regulation of septation initiation signaling, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0051446 positive regulation of meiotic cell cycle
IMP
PMID:7498766
The role of cdc2 and other genes in meiosis in Schizosacchar...
ACCEPT
Summary: Cdc2 is required to drive the meiotic divisions; essential for premeiotic DNA synthesis and meiosis II.
Reason: Core meiotic cell-cycle function.
Supporting Evidence:
PMID:7498766
The cdc2 gene, which is required for the initiation of both mitotic S-phase and M-phase, is essential for premeiotic DNA synthesis and meiosis II.
GO:0000086 G2/M transition of mitotic cell cycle
IMP
PMID:2665944
Regulation of p34cdc2 protein kinase during mitosis.
ACCEPT
Summary: Cdc2 drives the G2/M transition (mitotic entry); the rate-limiting cdc2 function classically defined by the requirement in G2 for control of mitosis and by Tyr15 phospho-regulation of mitotic entry.
Reason: Core cell-cycle driving function.
Supporting Evidence:
PMID:2682257
Substitution of this tyrosine by phenylalanine advances cells prematurely into mitosis, establishing that tyrosine phosphorylation/dephosphorylation directly regulates pp34 function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:24074952
Phosphorylation-dependent assembly and coordination of the D...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0005634 nucleus
IDA
PMID:2534559
Fission yeast cyclin: subcellular localisation and cell cycl...
ACCEPT
Summary: Active Cdc2-cyclin pool localizes to the nucleus, consistent with phosphorylation of nuclear/chromatin substrates.
Reason: Experimentally supported nuclear localization of active kinase.
GO:0097472 cyclin-dependent protein kinase activity
IDA
PMID:2665944
Regulation of p34cdc2 protein kinase during mitosis.
ACCEPT
Summary: Cyclin-dependent protein kinase activity is a valid but slightly less specific statement of the core CDK catalytic activity captured more precisely by GO:0004693.
Reason: Correct and core; GO:0004693 is the preferred more specific term but this parent is also accurate.
GO:1990820 response to mitotic DNA integrity checkpoint signaling
IGI
PMID:12186947
A novel chk1-dependent G1/M checkpoint in fission yeast.
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in response to mitotic DNA integrity checkpoint signaling, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:11486016
Control of DNA rereplication via Cdc2 phosphorylation sites ...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:1902424 negative regulation of attachment of mitotic spindle microtubules to kinetochore
IMP
PMID:22065639
Cdk1 phosphorylation of the kinetochore protein Nsk1 prevent...
KEEP AS NON CORE
Summary: Experimentally supported role of Cdc2-cyclin in negative regulation of mitotic spindle MT attachment to kinetochore, reflecting phosphorylation of a specific substrate/process downstream of the master kinase.
Reason: Genuine substrate-specific/downstream phosphoregulatory role, but a peripheral consequence of the single master CDK rather than its core cell-cycle-driving function.
GO:0000307 cyclin-dependent protein kinase holoenzyme complex
IDA
PMID:3322810
p13suc1 acts in the fission yeast cell division cycle as a c...
ACCEPT
Summary: Cdc2 is the catalytic subunit of the cyclin-dependent protein kinase holoenzyme, a cyclin(Cdc13/Cig2)-Cdc2-Suc1(Cks1) complex.
Reason: Core cellular component; Cdc2 forms a holoenzyme with a cyclin and the Suc1/Cks1 subunit.
Supporting Evidence:
PMID:3322810
p13suc1 was found in yeast lysates in a complex with the cdc2+ gene product.
GO:0097472 cyclin-dependent protein kinase activity
IDA
PMID:3322810
p13suc1 acts in the fission yeast cell division cycle as a c...
ACCEPT
Summary: Cyclin-dependent protein kinase activity is a valid but slightly less specific statement of the core CDK catalytic activity captured more precisely by GO:0004693.
Reason: Correct and core; GO:0004693 is the preferred more specific term but this parent is also accurate.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:22065639
Cdk1 phosphorylation of the kinetochore protein Nsk1 prevent...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004672 protein kinase activity
IDA
PMID:2569363
The fission yeast cdc2/cdc13/suc1 protein kinase: regulation...
MODIFY
Summary: General protein kinase activity; correct ancestor term but uninformative for a CDK.
Reason: Over-general parent; replace with the specific cyclin-dependent ser/thr kinase activity.
GO:0005634 nucleus
IDA
PMID:2569363
The fission yeast cdc2/cdc13/suc1 protein kinase: regulation...
ACCEPT
Summary: Active Cdc2-cyclin pool localizes to the nucleus, consistent with phosphorylation of nuclear/chromatin substrates.
Reason: Experimentally supported nuclear localization of active kinase.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IGI
PMID:2569363
The fission yeast cdc2/cdc13/suc1 protein kinase: regulation...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0000082 G1/S transition of mitotic cell cycle
IMP
PMID:7254352
Gene required in G1 for commitment to cell cycle and in G2 f...
ACCEPT
Summary: Cdc2 drives the G1/S transition of the mitotic cell cycle; genetically required in G1 for commitment to the cell cycle (Nurse & Bissett).
Reason: Core cell-cycle driving function, classic genetic evidence.
Supporting Evidence:
PMID:7254352
Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast.
GO:0000086 G2/M transition of mitotic cell cycle
IMP
PMID:7254352
Gene required in G1 for commitment to cell cycle and in G2 f...
ACCEPT
Summary: Cdc2 drives the G2/M transition (mitotic entry); the rate-limiting cdc2 function classically defined by the requirement in G2 for control of mitosis and by Tyr15 phospho-regulation of mitotic entry.
Reason: Core cell-cycle driving function.
Supporting Evidence:
PMID:7254352
Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:18059475
Cdc2p controls the forkhead transcription factor Fkh2p by ph...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:11937031
CDK phosphorylation of Drc1 regulates DNA replication in fis...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
IDA
PMID:9242669
A novel protein, Psp1, essential for cell cycle progression ...
ACCEPT
Summary: Cdc2 is the founding cyclin-dependent serine/threonine protein kinase (CDK1); when activated by a B-type cyclin it phosphorylates S/T-P sites on >200 substrates to drive the cell cycle. This is the defining core molecular function.
Reason: Most informative MF term for Cdc2; directly experimentally demonstrated. Many entries with this term are independent substrate-phosphorylation observations supporting the same core activity.
GO:0005515 protein binding
IPI
PMID:8455610
Two fission yeast B-type cyclins, cig2 and Cdc13, have diffe...
MARK AS OVER ANNOTATED
Summary: Records a physical interaction with cyclin Cig2. "protein binding" is uninformative; the biologically meaningful relationships are captured by the holoenzyme complex term and specific downstream/regulatory BP terms.
Reason: Bare protein binding adds no functional information; partner-specific function is better represented elsewhere (cyclin binding, holoenzyme complex, substrate-process terms).
GO:0000307 cyclin-dependent protein kinase holoenzyme complex
IPI
PMID:2682257
Tyrosine phosphorylation of the fission yeast cdc2+ protein ...
ACCEPT
Summary: Cdc2 is the catalytic subunit of the cyclin-dependent protein kinase holoenzyme, a cyclin(Cdc13/Cig2)-Cdc2-Suc1(Cks1) complex.
Reason: Core cellular component; Cdc2 forms a holoenzyme with a cyclin and the Suc1/Cks1 subunit.

Core Functions

Cyclin-dependent protein serine/threonine kinase activity: as the catalytic subunit of the cyclin-CDK holoenzyme, Cdc2 phosphorylates Ser/Thr-Pro motifs on its substrates.

Supporting Evidence:
  • PMID:11486016
    Cdc2 kinase is a master regulator of cell cycle progression in the fission yeast Schizosaccharomyces pombe. Our data indicate that Cdc2 phosphorylates replication factor Orp2, a subunit of the origin recognition complex (ORC).

Drives the G2/M transition (mitotic entry) of the cell cycle; the rate-limiting mitotic kinase activated by Cdc25-mediated Tyr15 dephosphorylation and restrained by Wee1/Mik1.

Supporting Evidence:
  • PMID:2682257
    Substitution of this tyrosine by phenylalanine advances cells prematurely into mitosis, establishing that tyrosine phosphorylation/dephosphorylation directly regulates pp34 function.

Drives the G1/S transition / commitment to the cell cycle (Start), required in G1 for cell-cycle commitment.

Supporting Evidence:
  • PMID:7254352
    Gene required in G1 for commitment to cell cycle and in G2 for control of mitosis in fission yeast.

Drives the meiotic cell cycle; required for premeiotic DNA synthesis and meiosis II.

Supporting Evidence:
  • PMID:7498766
    The cdc2 gene, which is required for the initiation of both mitotic S-phase and M-phase, is essential for premeiotic DNA synthesis and meiosis II.

References

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Suggested Questions for Experts

Q: Which of the >200 identified Cdc2 substrates are individually rate-limiting for ordering specific cell-cycle events, versus collectively contributing through the activity-threshold model?

Q: To what extent is substrate selection determined by cyclin identity (Cdc13 vs Cig1/Cig2/Puc1) versus simply by total CDK activity level in vivo?

Q: How do the spatially distinct Cdc2 pools (nuclear, spindle pole body, kinetochore, chromatin, cytoplasmic) differ in their substrate repertoire and regulation?

Suggested Experiments

Experiment: Systematic analog-sensitive (as-CDK) chemical-genetic inactivation combined with quantitative phosphoproteomics across synchronized mitotic and meiotic time-courses to map substrate-specific activity thresholds and assign each substrate to a cell-cycle event.

Experiment: Targeted, substrate-non-phosphorylatable (S/T-to-A) allele panels for individual Cdc2 substrates to determine which downstream processes (e.g. condensation, kinetochore assembly, cytokinesis timing) genetically require direct Cdc2 phosphorylation.

Experiment: Live-cell imaging with cyclin-specific tagged Cdc2 complexes to quantify the spatiotemporal dynamics of distinct Cdc2-cyclin pools at SPBs, kinetochores and chromatin during mitosis and meiosis.

πŸ“š Additional Documentation

Notes

(cdc2-notes.md)

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