Cig2 (also called Cyc17) is the major S-phase B-type cyclin of the fission yeast Schizosaccharomyces pombe, a member of the cyclin A/B subfamily. It has no catalytic activity of its own: it binds the single cell-cycle cyclin-dependent kinase Cdc2 (CDK1) and activates it, and the Cig2-Cdc2 kinase, which appears after mitosis and peaks during S phase, is the principal activity that carries cells through Start and into DNA replication. cig2 is not essential because Cig1, Puc1 and above all the mitotic cyclin Cdc13 can supply the G1 CDK activity in its absence; cig2 deletion delays S-phase entry, particularly in small cells, in sensitised cdc2 backgrounds and on recovery from nitrogen starvation, and in cdc13-deleted re-replicating cells loss of Cig2 severely delays re-replication while loss of both Cig1 and Cig2 abolishes it. cig2 transcription is driven at G1/S by the MBF transcription factor (Cdc10-Res1-Res2); the Cig2-Cdc2 kinase then binds Res2 and promotes phosphorylation of Res1, switching off MBF-dependent transcription (including its own) in a negative feedback loop that shapes the G1/S transcriptional pulse. In G1 the CDK inhibitor Rum1 binds and restrains the Cig2-Cdc2 kinase (and, more strongly, Cdc13-Cdc2) until cells reach the critical size for Start, and mating pheromone inhibits the Cig2-Cdc2 kinase to impose G1 arrest. Cig2 abundance is confined to a spike at S phase by two ubiquitin ligases: the APC/C destroys it (via an N-terminal destruction box) in anaphase and G1, and SCF-Pop1/Pop2 ubiquitylates phosphorylated Cig2 in G2 and M. Because Cig2-Cdc2 activity opposes the G1 arrest that sexual differentiation requires, cig2 deletion enhances conjugation even in nitrogen-replete medium, whereas cig2 overexpression blocks conjugation and suppresses pat1-driven entry into meiosis. Cig2 acts in the nucleus, where the S-phase cyclin-Cdc2 kinase associates with chromatin at replication origins, and a pool of the protein is also detected at the mitotic spindle pole body. During meiosis Cig2-dependent CDK phosphorylation of the forkhead factor Fkh2 releases it from mid-meiotic gene promoters so that Mei4 can activate them, and cig2 deletion modestly reduces meiotic double-strand-break formation and gene conversion. Although its UniProt name is 'G2/mitotic-specific cyclin', Cig2 shows no mitotic cyclin activity in wild-type cells; only when inhibitory Cdc2 tyrosine phosphorylation and Cdc13 are removed can deregulated Cig2-Cdc2 drive mitosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: IBA propagation of G1/S transition of the mitotic cell cycle from the deep cyclin node PTN000019791 (human cyclins D/E/A/B, budding-yeast Cln3/Clb5/Clb6, fission-yeast cyclins). Cig2 is the fission-yeast S-phase cyclin: Cig2 protein and Cig2-associated Cdc2 kinase appear after mitosis and peak in S, cig2 deletion delays S-phase onset, and in re-replicating cdc13-deleted cells loss of Cig2 severely delays replication. Reason: Sound node placement for this member: G1/S transition is precisely the process Cig2-Cdc2 drives (passage through Start and onset of DNA replication), and the target carries its own IMP/IGI evidence for the child term positive regulation of G1/S transition. Core function. Supporting Evidence: PMID:8657126 These studies indicate that Cig2 is the primary S-phase-promoting cyclin in S. pombe but that Cdc13 can effectively substitute for Cig2 in deltacig2 cells. PMID:8657126 Cig2 protein and Cig2-associated kinase activity appear soon after the completion of M and peak during S, as well as the observation that S is delayed in deltacig2 cells as they recover from a G1 arrest induced by nitrogen starvation. PMID:8631306 Further deletion of cig1 and puc1 had no effect, but deletion of cig2/cyc17 caused a severe delay in re-replication. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | EXP PMID:9552380 Regulation of G1 progression in fission yeast by the rum1+ g... | ACCEPT | Summary: PomBase EXP annotation from the Martin-Castellanos & Moreno 1996 review of rum1 and G1 control, whose abstract describes the cdc2/cig2 complex as one of the two B-cyclin-Cdc2 complexes that Rum1 holds inactive in G1. The underlying primary data (Cig2-HA immunoprecipitates carry Cdc2-dependent histone H1 kinase activity; Martin-Castellanos et al. 1996 EMBO J) are summarised in the deep-research report. Reason: Cig2 is the regulatory subunit of a Cdc2 holoenzyme; every functional assay of Cig2 measures the Cig2-Cdc2 complex and Cdc2 binding is required for its function (UniProt mutagenesis of R169/E170/I171 abolishes Cdc2 binding). Complex membership is correct and core, although the cited reference is a review rather than a primary paper. Supporting Evidence: PMID:9552380 the rum1 inhibitor, a protein present exclusively in G1, prevents premature activation of the cdc2/cig2 and the cdc2/cdc13 complexes until cells have reached the critical cell size required to pass Start and initiate a new cell cycle. PMID:9552380 cig2 is the major G1 cyclin while cdc13 is the principal mitotic cyclin. file:SCHPO/cig2/cig2-deep-research-falcon.md Cig2 supplies the regulatory cyclin subunit of a complex with Cdc2, the single major cell-cycle CDK in fission yeast. |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA part_of cyclin-dependent protein kinase holoenzyme complex from node PTN000019791; cig2 (PomBase:SPAPB2B4.03) is itself one of the experimental donors, which is expected because PomBase carries the EXP row above. Reason: The cyclin fold is the defining regulatory component of a CDK holoenzyme and Cig2 forms an active complex with Cdc2. Sound phylogenetic transfer grounded on the target itself; core. Supporting Evidence: PMID:9552380 the rum1 inhibitor, a protein present exclusively in G1, prevents premature activation of the cdc2/cig2 and the cdc2/cdc13 complexes until cells have reached the critical cell size required to pass Start and initiate a new cell cycle. file:SCHPO/cig2/cig2-deep-research-falcon.md Cig2 supplies the regulatory cyclin subunit of a complex with Cdc2, the single major cell-cycle CDK in fission yeast. |
| GO:0000785 chromatin | IDA PMID:12419251 Stable association of mitotic cyclin B/Cdc2 to replication o... | ACCEPT | Summary: PomBase IDA is_active_in chromatin from Wuarin et al. 2002, which used chromatin immunoprecipitation to show that B-cyclin/Cdc2 kinase associates with ORC-bound replication origins in vivo. The cached record is abstract-only and foregrounds the mitotic cyclin Cdc13; the Cig2 origin-association data on which the cig2 annotation rests are in the uncached full text. Reason: Association of the S-phase Cig2-Cdc2 kinase with origin chromatin is exactly where the kinase would be expected to act when it triggers replication, and the PomBase curator read the full text. Per project rules an experimental annotation is not overruled because the cached abstract names a paralog. Accepted as the chromatin-level site of the core function; the more informative statement is that the association is at replication origins during S phase. Supporting Evidence: PMID:12419251 We show that in fission yeast the mitotic B type cyclin Cdc13/Cdc2 kinase associates with replication origins in vivo. This association is dependent on the origin recognition complex (ORC), is established as chromosomes are replicated, and is maintained during G2 and early mitosis. PMID:8657126 These studies indicate that Cig2 is the primary S-phase-promoting cyclin in S. pombe but that Cdc13 can effectively substitute for Cig2 in deltacig2 cells. |
| GO:0005515 protein binding | IPI PMID:11781565 Feedback regulation of the MBF transcription factor by cycli... | MODIFY | Summary: PomBase IPI with Res2 (SPAC22F3.09c), one of the two DNA-binding subunits of the MBF (Cdc10-Res1-Res2) G1/S transcription factor. Ayte et al. 2001 showed that cig2 transcription depends on MBF and that Cig2 in turn binds Res2, promotes phosphorylation of Res1 and inhibits MBF-dependent transcription, closing a negative feedback loop. Reason: Bare protein binding carries no functional information. The cited paper supports a more informative molecular function: the cyclin docks the Cdc2 kinase onto the MBF complex through Res2 so that Res1 is phosphorylated and MCB-driven transcription is shut off after G1/S, which is the substrate-targeting facet of cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538, already carried by IBA/IEA rows). The Res2 interaction itself is not disputed (UniProt IntAct NbExp=3). Proposed replacements: cyclin-dependent protein serine/threonine kinase regulator activity Supporting Evidence: PMID:11781565 Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. PMID:11781565 Cig2p thus forms an autoregulating feedback-inhibition loop with MBF which is important for normal regulation of the cell cycle. PMID:11781565 We report here that the cell-cycle-regulated expression of the cyclin cig2 gene is dependent on MBF. |
| GO:0005515 protein binding | IPI PMID:11781565 Feedback regulation of the MBF transcription factor by cycli... | MODIFY | Summary: IntAct-derived IPI with Res1 (P33520), the Cdc10-associated MBF subunit whose phosphorylation Cig2 promotes. Same paper as the Res2 row: Cig2 associates with the MBF complex and drives Res1 phosphorylation to inhibit MBF-dependent transcription. Reason: Res1 is the substrate whose phosphorylation Cig2-Cdc2 promotes, so the informative molecular function supported by this interaction is the cyclin's kinase-regulator (substrate-targeting) activity rather than generic protein binding; GO:0016538 is proposed as the replacement. Interaction not disputed (IntAct NbExp=3). Proposed replacements: cyclin-dependent protein serine/threonine kinase regulator activity Supporting Evidence: PMID:11781565 Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. PMID:11781565 Cig2p thus forms an autoregulating feedback-inhibition loop with MBF which is important for normal regulation of the cell cycle. |
| GO:0005515 protein binding | IPI PMID:11781565 Feedback regulation of the MBF transcription factor by cycli... | MODIFY | Summary: IntAct-derived IPI with Res2 (P41412), duplicating the PomBase row for the same interaction from Ayte et al. 2001: Cig2 binds Res2 and thereby inhibits MBF-dependent transcription. Reason: As for the PomBase Res2 row: the paper supports the more informative cyclin-dependent protein serine/threonine kinase regulator activity (docking Cdc2 on MBF via Res2), so GO:0016538 is proposed in place of uninformative protein binding. Proposed replacements: cyclin-dependent protein serine/threonine kinase regulator activity Supporting Evidence: PMID:11781565 Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. PMID:11781565 We report here that the cell-cycle-regulated expression of the cyclin cig2 gene is dependent on MBF. |
| GO:0005515 protein binding | IPI PMID:14970237 Requirement of the SCFPop1/Pop2 Ubiquitin Ligase for Degrada... | REMOVE | Summary: IPI with Pop1 (P87060), an F-box/WD-repeat substrate adaptor of the SCF ubiquitin ligase. Yamano et al. 2004 showed that Pop1 binds Cig2 in vivo through a 93-residue region of the cyclin box, that binding requires Cig2 phosphorylation, and that SCF-Pop1/Pop2 (with the APC/C in anaphase/G1) degrades Cig2 to restrict it to an S-phase spike. Reason: In this interaction Cig2 is the ubiquitylation substrate and Pop1 is the recognition subunit; the paper supports no molecular function of Cig2 beyond being recognised for degradation, so there is no more informative MF term to modify to. Per project policy a bare GO:0005515 row that conveys no functional information is removed. Removal does not dispute the interaction (IntAct NbExp=4), which is important regulatory biology and is recorded in the notes and description. Supporting Evidence: PMID:14970237 Pop1 binds Cig2 in vivo. An in vitro binding assay shows that an internal 93 amino acid residues comprising a part of the cyclin box are necessary and sufficient for this binding. Cig2 phosphorylation is also required for interaction with Pop1. PMID:14970237 Here we show that fission yeast S phase cyclin Cig2 is ubiquitylated and degraded via both the SCF and the APC/C. Cig2 instability during G(2) and M phase is dependent upon the SCF complex, whereas the APC/C is responsible for Cig2 destruction during anaphase and G(1), thereby ensuring a spike pattern of Cig2 levels, peaking only at S phase. |
| GO:0005515 protein binding | IPI PMID:8455610 Two fission yeast B-type cyclins, cig2 and Cdc13, have diffe... | MODIFY | Summary: IPI with Cdc2 (P04551), the catalytic subunit of the sole fission-yeast cell-cycle CDK, from the paper that discovered cig2 and concluded that Cdc13 and Cig2 each interact with Cdc2 to carry out distinct functions. The 1993 interpretation of a mitotic role was superseded by later work placing Cig2 at G1/S, but the Cig2-Cdc2 interaction itself is the foundation of everything Cig2 does. Reason: The partner is the CDK catalytic subunit and cyclin binding is what generates and regulates the kinase, so the informative molecular function supported by this evidence is cyclin-dependent protein serine/threonine kinase regulator activity (GO:0016538; the activator child GO:0061575 is carried by IDA rows from later papers), not bare protein binding. Interaction not disputed. Proposed replacements: cyclin-dependent protein serine/threonine kinase regulator activity Supporting Evidence: PMID:8455610 These data indicate that Cdc13 and Cig2 interact with Cdc2 to carry out different functions in mitosis. file:SCHPO/cig2/cig2-deep-research-falcon.md Cig2 supplies the regulatory cyclin subunit of a complex with Cdc2, the single major cell-cycle CDK in fission yeast. |
| GO:0005515 protein binding | IPI PMID:9614176 Cyclin B proteolysis and the cyclin-dependent kinase inhibit... | REMOVE | Summary: IPI with Rum1 (P40380), the fission-yeast CDK inhibitor, from Stern & Nurse 1998 (full text cached): Rum1 binds both Cdc13 and Cig2 but is specifically required for Cdc13 proteolysis during pheromone-induced G1 arrest, whereas Cig2 is degraded by the cyclosome independently of Rum1. Reason: Here Cig2-Cdc2 is the target of a CKI; the functional relationship (inhibition of CDK activity) belongs on the rum1 side as CDK inhibitor activity, and the paper attributes no additional molecular function to Cig2. A bare GO:0005515 row therefore conveys nothing and is removed per project policy. The physical interaction is not disputed and is described in the notes. Supporting Evidence: PMID:9614176 it binds both cdc13p and cig2p and is specifically required for cdc13p proteolysis PMID:9614176 cig2p cyclin degradation does not require rum1p, even though rum1p can associate with cig2p |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: High-throughput localization from the Matsuyama et al. 2006 ORFeome YFP screen (about 90% of the proteome imaged); PomBase recorded Cig2-YFP as nuclear and at the mitotic spindle pole body. Reason: Consistent with everything known about Cig2 function (MBF regulation, origin association, Cdc2 activation for S phase) and with the UniProt subcellular-location statement; the nucleus is where Cig2-Cdc2 acts. Core location. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein. PMID:11781565 Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA is_active_in nucleus from the deep cyclin node PTN000019791 with cyclins from plants, animals and fungi as donors (fission-yeast donors are cdc13 and crs1). Cig2 is nuclear by the ORFeome screen and its substrates (Res1/MBF, origin-associated replication factors, Fkh2) are nuclear. Reason: Concordant with the HDA row and with the nuclear site of the core G1/S function; sound propagation. Supporting Evidence: PMID:11781565 Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. PMID:12419251 We show that in fission yeast the mitotic B type cyclin Cdc13/Cdc2 kinase associates with replication origins in vivo. This association is dependent on the origin recognition complex (ORC), is established as chromosomes are replicated, and is maintained during G2 and early mitosis. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location keyword mapping (Nucleus) to GO nucleus. Reason: Correct and corroborated by the HDA and IBA rows. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA is_active_in cytoplasm from the deep cyclin node. The donors include mitotic cyclins with well-documented cytoplasmic pools (human cyclin B1/B2, budding-yeast Clb2, fission-yeast cdc13). For Cig2 the only localization data are nuclear plus a mitotic spindle pole body signal in the ORFeome screen, and no cytoplasm-specific Cig2-Cdc2 activity has been described. Reason: Not challenged as wrong (Cig2 is synthesised in the cytoplasm and the SPB is at the nuclear envelope, so some cytoplasmic pool is plausible), but the functional site of the S-phase cyclin is the nucleus; graded non-core rather than accepted as core, in line with the treatment of the same propagation for budding-yeast Clb5. Supporting Evidence: file:SCHPO/cig2/cig2-deep-research-falcon.md The retrieved primary evidence did not provide high-resolution Cig2 microscopy, nuclear-to-cytoplasmic concentration measurements, or evidence for localization to replication origins, spindle-pole bodies, or other subnuclear structures. PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein. |
| GO:0005815 microtubule organizing center | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA is_active_in microtubule organizing center from sub-node PTN007424001, seeded by the mitotic cyclins cdc13, Clb2, human cyclin B1/B2 and cyclin F plus fission-yeast crs1. For Cig2 the ORFeome screen recorded a mitotic spindle pole body signal (HDA row below), so the propagated MTOC location has target-specific support. Reason: The location is supported for Cig2 itself (mitotic SPB, HDA), so the node placement is not argued with; but the SPB pool is a context for the mitotic cyclins' function and no SPB-dependent role of the S-phase cyclin has been demonstrated, so it is retained as non-core rather than as a core site of action. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein. file:SCHPO/cig2/cig2-deep-research-falcon.md The retrieved primary evidence did not provide high-resolution Cig2 microscopy, nuclear-to-cytoplasmic concentration measurements, or evidence for localization to replication origins, spindle-pole bodies, or other subnuclear structures. |
| GO:0005816 spindle pole body | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular-location keyword mapping (spindle pole body) to GO, derived from the ORFeome localization data. Reason: Consistent with the HDA mitotic spindle pole body row; a documented but functionally uncharacterised pool of the S-phase cyclin, so non-core. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein. |
| GO:0007089 traversing start control point of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: IBA involved_in traversing start control point of mitotic cell cycle from node PTN000808767, whose only listed donor is cig2 itself (PomBase IGI row below). The term describes commitment to S phase via positive feedback between G1/S transcription and G1 CDK activity, which is the MBF-cig2-Cdc2 circuit. Reason: The target's own experimental annotation seeds the node, which is expected and marks that the function is inherited within this fission-yeast clade rather than lineage-specific. Cig2-Cdc2 is the kinase that Rum1 restrains until Start and that passes Start once cells reach the critical size; core. Supporting Evidence: PMID:9552380 the rum1 inhibitor, a protein present exclusively in G1, prevents premature activation of the cdc2/cig2 and the cdc2/cdc13 complexes until cells have reached the critical cell size required to pass Start and initiate a new cell cycle. PMID:9552380 cig2 is the major G1 cyclin while cdc13 is the principal mitotic cyclin. PMID:11781565 We report here that the cell-cycle-regulated expression of the cyclin cig2 gene is dependent on MBF. |
| GO:0007089 traversing start control point of mitotic cell cycle | IGI PMID:9552380 Regulation of G1 progression in fission yeast by the rum1+ g... | ACCEPT | Summary: PomBase IGI with cdc2 from the Martin-Castellanos & Moreno review: B-type cyclins activate Cdc2 to promote onset of DNA replication, Cig2 being the major G1 cyclin, and Rum1 prevents premature activation of Cdc2/Cig2 until the critical size for Start is reached (primary data in Martin-Castellanos et al. 1996, where cdc2-ts cig2 double mutants accumulate in G1). Reason: Cig2-Cdc2 is the G1 CDK activity that commits fission-yeast cells to S phase at Start, and the MBF-dependent transcription of cig2 with feedback on MBF is the positive-feedback loop the term definition describes. Core. Supporting Evidence: PMID:9552380 B-type cyclins in fission yeast regulate the activation of the cdc2 kinase to promote the onset of both DNA replication and mitosis. PMID:9552380 the rum1 inhibitor, a protein present exclusively in G1, prevents premature activation of the cdc2/cig2 and the cdc2/cdc13 complexes until cells have reached the critical cell size required to pass Start and initiate a new cell cycle. file:SCHPO/cig2/cig2-deep-research-falcon.md Deletion of cig2 delays G1 exit, particularly in small cells or sensitized cdc2 backgrounds. |
| GO:0010520 regulation of reciprocal meiotic recombination | IMP PMID:30640914 CDK contribution to DSB formation and recombination in fissi... | KEEP AS NON CORE | Summary: PomBase IMP from Bustamante-Jaramillo et al. 2019 (full text cached): cig2 deletion reduces meiotic gene conversion (non-crossover recombination) by about 27% and DSB formation at the mbs1 hotspot by about 25% (the DSB reduction alone is not statistically significant), with no additive effect in the cig1 cig2 double mutant and no change in crossovers; the meiosis-specific cyclin Crs1 has a stronger effect. CDK activity thus contributes to meiotic DSB formation, with Cig2-Cdc2 as one of the contributing complexes. Reason: A genuine but modest and redundant contribution: Cig2 supplies part of the CDK activity that promotes Rec12-dependent DSB formation, so a regulatory term is appropriate, but the effect is small, partially masked by other cyclins and secondary to the vegetative G1/S role. Retained as non-core. Supporting Evidence: PMID:30640914 Single deletion mutants of cig1 and cig2 were defective in recombination, with a moderate reduction in gene conversion (26% p value 0.004 and 27% p value 0.016, respectively), and without additive effects in the double cig1 cig2 mutant (33% reduction; p value 0.025), suggesting that both cyclins might act in the same genetic pathway PMID:30640914 we have found that cig1 and cig2 cyclin deletion mutants are indeed impaired in meiotic recombination, and NCOs reduced 26% compared to the control levels observed in wild-type strains. Correspondingly, DSB formation is also reduced to a similar extent at the hotspot of reference mbs1, 28% and 25% respectively. PMID:30640914 Similar results were obtained in cig2 deletion mutants with a maximum of breakage of 6.2% (25% reduction, 8.3% maximum control levels; p value 0.210), in this case at 3.5 hr since this mutant showed a delay in S-phase entry and progression |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cyclin-dependent protein serine/threonine kinase regulator activity from node PTN000019791; cig2 is among the donors. Cig2 has no catalytic activity of its own but binds Cdc2 and generates the S-phase-peaking Cig2-Cdc2 kinase; it also directs the kinase to substrates such as the MBF subunit Res1. Reason: Defining molecular function of a cyclin, grounded on the target's own IDA evidence for the activator child term and on the Res2/Res1 substrate-docking data; core. Supporting Evidence: PMID:8657126 Cig2 protein and Cig2-associated kinase activity appear soon after the completion of M and peak during S, as well as the observation that S is delayed in deltacig2 cells as they recover from a G1 arrest induced by nitrogen starvation. PMID:11781565 Cig2p can bind to Res2p, promote the phosphorylation of Res1p and inhibit MBF-dependent gene transcription. file:SCHPO/cig2/cig2-deep-research-falcon.md Cig2 supplies the regulatory cyclin subunit of a complex with Cdc2, the single major cell-cycle CDK in fission yeast. |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro/ARBA electronic mapping of the cyclin A/B-like domain (IPR046965) to CDK regulator activity. Reason: Correct family-level mapping, fully corroborated by the experimental and IBA rows. Supporting Evidence: PMID:8657126 These studies indicate that Cig2 is the primary S-phase-promoting cyclin in S. pombe but that Cdc13 can effectively substitute for Cig2 in deltacig2 cells. |
| GO:0031138 negative regulation of conjugation with cellular fusion | IMP PMID:7909513 A B-type cyclin negatively regulates conjugation via interac... | KEEP AS NON CORE | Summary: PomBase IMP from Obara-Ishihara & Okayama 1994, who isolated cyc17 (cig2) as a multicopy suppressor of pat1-114 and showed that cyc17 deletion markedly enhances conjugation even in the presence of nitrogen and accelerates G1 arrest on starvation, whereas cyc17 overexpression strongly inhibits conjugation; the mating inhibition by res1/res2 overexpression requires cyc17. Reason: The phenotype is robust and the mechanism is understood: Cig2-Cdc2 activity drives cells out of G1, and G1 arrest is a prerequisite for pheromone signalling and conjugation, so the S-phase cyclin acts as a negative regulator of the decision to mate rather than as a component of the conjugation machinery. The regulatory term expresses this upstream role correctly, but it is a consequence of the core G1/S function rather than a separate core function. Supporting Evidence: PMID:7909513 Deletion of cyc17+ markedly enhances conjugation, despite the presence of nitrogen source, and accelerates growth arrest in G1 upon nitrogen starvation. Conversely, overexpression of the cyc17+ gene strongly inhibits conjugation. PMID:9034336 Pheromone inhibits the p34cdc2 kinase associated with both the G1-specific B-type cyclin p45cig2 and the B-type cyclin p56cdc13 and overexpression of p45cig2 or p47cdc13delta90 overcomes the pheromone-induced G1 arrest. |
| GO:0031568 mitotic G1 cell size control checkpoint signaling | IGI PMID:9552380 Regulation of G1 progression in fission yeast by the rum1+ g... | ACCEPT | Summary: PomBase IGI with cdc2 for mitotic G1 cell size control checkpoint signaling, from the review whose abstract states that Rum1 prevents premature activation of Cdc2/Cig2 and Cdc2/Cdc13 until cells reach the critical size required to pass Start. cig2 deletion delays G1 exit particularly in small cells and in cdc2-ts backgrounds (Martin-Castellanos et al. 1996). Reason: Cig2-Cdc2 is the G1 CDK whose activation is gated by cell size through Rum1, and the cig2 cdc2-ts genetic interaction shows it is the kinase that executes the size-dependent Start decision. The term is PomBase's way of capturing the Rum1-B-cyclin-Cdc2 size control and is appropriate for the cyclin; core. Supporting Evidence: PMID:9552380 the rum1 inhibitor, a protein present exclusively in G1, prevents premature activation of the cdc2/cig2 and the cdc2/cdc13 complexes until cells have reached the critical cell size required to pass Start and initiate a new cell cycle. file:SCHPO/cig2/cig2-deep-research-falcon.md Deletion of cig2 delays G1 exit, particularly in small cells or sensitized cdc2 backgrounds. |
| GO:0031568 mitotic G1 cell size control checkpoint signaling | IGI PMID:9552380 Regulation of G1 progression in fission yeast by the rum1+ g... | ACCEPT | Summary: Same annotation with rum1 as the IGI partner: Rum1 is the G1-specific CKI that binds Cig2 and Cdc13 and holds the B-cyclin-Cdc2 kinases inactive until cells reach the critical size for Start; loss of rum1 advances Start in small cells and cig2 deletion partially suppresses rum1-null phenotypes such as the failure to arrest in G1 on nitrogen starvation. Reason: Direct antagonism between the CKI and the Cig2-Cdc2 kinase is the mechanism of the G1 size control; the genetic interaction is well founded (Stern & Nurse 1998 confirm the physical Rum1-Cig2 interaction and the partial suppression). Core. Supporting Evidence: PMID:9552380 the rum1 inhibitor, a protein present exclusively in G1, prevents premature activation of the cdc2/cig2 and the cdc2/cdc13 complexes until cells have reached the critical cell size required to pass Start and initiate a new cell cycle. PMID:9614176 it binds both cdc13p and cig2p and is specifically required for cdc13p proteolysis |
| GO:0044732 mitotic spindle pole body | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: High-throughput ORFeome YFP localization: PomBase recorded Cig2-YFP at the mitotic spindle pole body in addition to the nucleus. Consistent with the UniProt subcellular-location statement. Reason: The SPB signal is a single high-throughput observation with no demonstrated SPB-dependent function for the S-phase cyclin (SPB enrichment is a hallmark of the mitotic Cdc13-Cdc2 complex); kept as a documented non-core location. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein. file:SCHPO/cig2/cig2-deep-research-falcon.md The retrieved primary evidence did not provide high-resolution Cig2 microscopy, nuclear-to-cytoplasmic concentration measurements, or evidence for localization to replication origins, spindle-pole bodies, or other subnuclear structures. |
| GO:0044772 mitotic cell cycle phase transition | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO mapping of the cyclin A/B-like domain to mitotic cell cycle phase transition, a broad ancestor of the experimentally supported G1/S transition. Reason: Correct, if general; the specific transition (G1/S) is captured by the IBA/IMP/IGI rows. Supporting Evidence: PMID:8657126 These studies indicate that Cig2 is the primary S-phase-promoting cyclin in S. pombe but that Cdc13 can effectively substitute for Cig2 in deltacig2 cells. |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IDA PMID:8631306 A single fission yeast mitotic cyclin B p34cdc2 kinase promo... | ACCEPT | Summary: PomBase IDA cyclin-dependent protein serine/threonine kinase activator activity from Fisher & Nurse 1996: in cdc13-deleted re-replicating cells, deletion of cig2/cyc17 severely delays re-replication and cig1 cig2 double deletion abolishes it, and the paper characterises the cyclin-associated Cdc2 kinase activities that drive S phase. Reason: Cig2 binds and activates Cdc2 to provide the G1 cyclin-CDK activity that triggers DNA replication; the activator term is the precise molecular function of the cyclin. Core. Supporting Evidence: PMID:8631306 Further deletion of cig1 and puc1 had no effect, but deletion of cig2/cyc17 caused a severe delay in re-replication. PMID:8631306 Deletion of cig1 and cig2/cyc17 together abolished re-replication completely and cells arrested in G1. PMID:8631306 suggests that cdc13 can effectively substitute for the G1 cyclin activity of cig2/cyc17 |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IDA PMID:8657126 Cig2, a B-type cyclin, promotes the onset of S in Schizosacc... | ACCEPT | Summary: PomBase IDA from Mondesert et al. 1996: Cig2 protein and Cig2-associated kinase activity appear soon after mitosis and peak in S, S phase is delayed in cig2-deleted cells recovering from nitrogen starvation, and cdc13 cig2 double mutants cannot re-replicate; Cig2 is the primary S-phase-promoting cyclin. Reason: Direct measurement of Cig2-associated Cdc2 kinase activity peaking at S phase, plus loss-of-function phenotypes, establishes Cig2 as a Cdc2 activator; core. Supporting Evidence: PMID:8657126 Cig2 protein and Cig2-associated kinase activity appear soon after the completion of M and peak during S, as well as the observation that S is delayed in deltacig2 cells as they recover from a G1 arrest induced by nitrogen starvation. PMID:8657126 These studies indicate that Cig2 is the primary S-phase-promoting cyclin in S. pombe but that Cdc13 can effectively substitute for Cig2 in deltacig2 cells. PMID:8657126 Unlike deltacdc13 cells, double-mutant deltacdc13 deltacig2 cells are defective in undergoing multiple rounds of DNA replication. |
| GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity | IGI PMID:9552380 Regulation of G1 progression in fission yeast by the rum1+ g... | ACCEPT | Summary: PomBase IGI with cdc2 from the Martin-Castellanos & Moreno review: B-type cyclins regulate activation of the cdc2 kinase to promote onset of DNA replication and mitosis, cig2 being the major G1 cyclin; the primary genetics (cdc2-ts cig2 synthetic G1 arrest) and biochemistry (Cig2-HA kinase activity lost in cdc2-33) are from Martin-Castellanos et al. 1996. Reason: The genetic interaction with cdc2 and the Cdc2-dependence of Cig2-associated kinase activity support the activator term; core. Supporting Evidence: PMID:9552380 B-type cyclins in fission yeast regulate the activation of the cdc2 kinase to promote the onset of both DNA replication and mitosis. PMID:9552380 cig2 is the major G1 cyclin while cdc13 is the principal mitotic cyclin. file:SCHPO/cig2/cig2-deep-research-falcon.md In synchronized cells, Cig2-associated kinase activity accumulated in G1, peaked as cells entered S phase, and was low in dividing cells. |
| GO:0110044 regulation of cell cycle switching, mitotic to meiotic cell cycle | IMP PMID:26804917 Spatiotemporal Control of Forkhead Binding to DNA Regulates ... | KEEP AS NON CORE | Summary: PomBase IMP from Alves-Rodrigues et al. 2016 (abstract-only cache): during meiosis the forkhead factor Fkh2, which sits on and represses most Mei4-dependent mid-meiotic genes, is phosphorylated in a CDK/Cig2-dependent manner, lowering its DNA affinity and opening a window for Mei4 to activate the meiotic gene program. Together with the pat1-suppressor and conjugation phenotypes of Obara-Ishihara & Okayama, this places Cig2-Cdc2 among the regulators of the mitotic/meiotic programme. Reason: The curator read the full text and the dependence of Fkh2 phosphorylation on Cig2 is stated in the abstract, so the annotation is retained; but the mechanism described (relief of Fkh2 repression of mid-meiotic genes) operates within meiosis on the gene-expression programme rather than at the mitotic-to-meiotic switch itself, and it is a secondary role of the S-phase cyclin. Kept as non-core; whether a meiotic gene-expression term would fit the evidence better is raised in suggested_questions. Supporting Evidence: PMID:26804917 During meiosis, Fkh2 is phosphorylated in a CDK/Cig2-dependent manner, decreasing its affinity for DNA, which creates a window of opportunity for Mei4 binding to its target genes. PMID:26804917 Fkh2 binding preexists in most Mei4-dependent genes, inhibiting their expression. PMID:7909513 Deletion of cyc17+ markedly enhances conjugation, despite the presence of nitrogen source, and accelerates growth arrest in G1 upon nitrogen starvation. Conversely, overexpression of the cyc17+ gene strongly inhibits conjugation. |
| GO:1900087 positive regulation of G1/S transition of mitotic cell cycle | IGI PMID:8631306 A single fission yeast mitotic cyclin B p34cdc2 kinase promo... | ACCEPT | Summary: PomBase IGI with cdc13 from Fisher & Nurse 1996: in cdc13-deleted cells cig2/cyc17 deletion severely delays re-replication, and cdc13 can substitute for the G1 cyclin activity of cig2, so the two B-cyclin-Cdc2 kinases are redundant activators of S-phase onset. Reason: The term (a signaling pathway that activates a cell-cycle CDK to promote the G1-to-S switch) is exactly what the S-phase cyclin does, and the cdc13 cig2 genetics define the redundancy. Core. Supporting Evidence: PMID:8631306 Further deletion of cig1 and puc1 had no effect, but deletion of cig2/cyc17 caused a severe delay in re-replication. PMID:8631306 suggests that cdc13 can effectively substitute for the G1 cyclin activity of cig2/cyc17 PMID:8631306 Deletion of cig1 and cig2/cyc17 together abolished re-replication completely and cells arrested in G1. |
| GO:1900087 positive regulation of G1/S transition of mitotic cell cycle | IMP PMID:7909513 A B-type cyclin negatively regulates conjugation via interac... | ACCEPT | Summary: PomBase IMP from Obara-Ishihara & Okayama 1994: cyc17 (cig2) transcripts peak in G1 and S under MBF (res1/res2) control, deletion accelerates G1 arrest on nitrogen starvation and enhances conjugation, and overexpression suppresses pat1-114 and blocks conjugation, i.e. Cig2 promotes progression out of G1. Reason: Loss- and gain-of-function phenotypes show Cig2 pushing cells through G1/S; core function. Supporting Evidence: PMID:7909513 Deletion of cyc17+ markedly enhances conjugation, despite the presence of nitrogen source, and accelerates growth arrest in G1 upon nitrogen starvation. Conversely, overexpression of the cyc17+ gene strongly inhibits conjugation. PMID:7909513 Only the poly(A)+ species is expressed during vegetative growth and periodically with a peak in the G1 and S phases of the cell cycle. |
| GO:1900087 positive regulation of G1/S transition of mitotic cell cycle | IMP PMID:8657126 Cig2, a B-type cyclin, promotes the onset of S in Schizosacc... | ACCEPT | Summary: PomBase IMP from Mondesert et al. 1996: S phase is delayed in cig2-deleted cells recovering from a nitrogen-starvation G1 arrest, and cdc13 cig2 double mutants are defective in re-replication; Cig2 is the primary S-phase-promoting cyclin. Reason: Defining loss-of-function evidence for Cig2 as the positive regulator of the G1/S transition; core. Supporting Evidence: PMID:8657126 Cig2 protein and Cig2-associated kinase activity appear soon after the completion of M and peak during S, as well as the observation that S is delayed in deltacig2 cells as they recover from a G1 arrest induced by nitrogen starvation. PMID:8657126 These studies indicate that Cig2 is the primary S-phase-promoting cyclin in S. pombe but that Cdc13 can effectively substitute for Cig2 in deltacig2 cells. |
| 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: PomBase IMP from Stern & Nurse 1997: mating pheromone blocks S-phase onset by inhibiting the Cdc2 kinase associated with the G1-specific B-cyclin Cig2 (and Cdc13), and overexpression of Cig2 overcomes the pheromone-induced G1 arrest. Reason: Overexpression of Cig2 forcing S-phase entry past a pheromone block is direct gain-of-function evidence that Cig2-Cdc2 activity positively regulates the G1/S transition; core. Supporting Evidence: PMID:9034336 Pheromone inhibits the p34cdc2 kinase associated with both the G1-specific B-type cyclin p45cig2 and the B-type cyclin p56cdc13 and overexpression of p45cig2 or p47cdc13delta90 overcomes the pheromone-induced G1 arrest. PMID:9034336 We suggest that onset of S-phase is controlled by pheromone inhibiting the B-cyclin-associated kinase in G1 |
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Download this section (compressed HTML)Q: Does Cig2 confer substrate specificity on Cdc2 (for example through hydrophobic-patch docking of origin-associated or MBF substrates) or does it act mainly by setting the timing and threshold of total CDK activity, given that Cdc13 can substitute for it at S phase and deregulated Cig2-Cdc2 can drive mitosis?
Q: PomBase records the Cig2-mediated feedback inhibition of MBF (PMID:11781565) only as Res2 protein binding, and neither cig2 nor cdc2 carries a transcription-regulation process term; is this a deliberate convention (the cyclin-CDK regulates the transcription factor rather than transcription itself), and if so should the substrate relationship to Res1/Res2 be captured on cdc2 with has-input rather than on the cyclin?
Q: For PMID:26804917, is 'regulation of cell cycle switching, mitotic to meiotic cell cycle' the intended level, or would a term for regulation of meiotic gene expression better describe CDK/Cig2-dependent phosphorylation of Fkh2 during meiosis?
Experiment: Combine an analogue-sensitive cdc2-as allele with cig2-deleted and hydrophobic-patch-mutant cig2 strains in synchronised cultures and perform phosphoproteomics across G1/S to define the Cdc2 substrates whose phosphorylation depends specifically on Cig2 (candidates: Res1, Cdc18, Cdt1, Sld3/Drc1).
Experiment: Chromatin immunoprecipitation sequencing of endogenously tagged Cig2 and Cdc13 through a synchronous cell cycle, together with live imaging against SPB (Sid4) and origin markers, to resolve when Cig2-Cdc2 occupies replication origins and whether the mitotic SPB pool of Cig2 has any function.
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