Cln1 is one of the two closely related G1/S cyclins (Cln1 and Cln2) of the budding yeast Saccharomyces cerevisiae and, with the upstream G1 cyclin Cln3, forms the trio of Cln proteins of which at least one is required for passage through Start, the point in late G1 at which the cell commits to a new division cycle. Cln1 has no catalytic activity of its own: it is a cyclin-box protein (Pfam Cyclin_N; the Cln-type Cyclin_CLN family) that binds the sole essential cyclin-dependent kinase Cdc28 (Cdk1) and converts it into an active protein serine/threonine kinase, the curated Cln1-Cdc28 complex. CLN1 is transcribed in late G1 by the SBF (Swi4-Swi6) transcription factor downstream of Cln3-Cdc28, and both its mRNA and protein are strongly cell cycle periodic, peaking in G1 and falling as cells enter S phase; the protein is short-lived, with a PEST-rich C-terminal half and ubiquitylation by SCF(Grr1). Among the three Cln proteins Cln1 belongs with Cln2 to the abundant, periodic, high-activity tier rather than with the rare, constitutively expressed cell-size sensor Cln3, and the division of labour matches that split: Cln3-Cdc28 initiates Start transcription, whereas Cln1-Cdc28 and Cln2-Cdc28 execute the downstream Start events, including bud emergence and the onset of DNA synthesis, and sharpen the transcriptional switch by phosphorylating the SBF co-regulator Stb1. Cln1-Cdc28 reaches a cyclin-class-specific set of substrates through LP docking motifs, including the mating MAP kinase scaffold Ste5 and the kinase Ste20, which are phosphorylated by Cln1 and Cln2 but not by Cln3 or the B-type cyclins, and which is how cells past Start become refractory to pheromone. Together with the Pho85 cyclins Pcl1 and Pcl2, Cln1 and Cln2 supply the late-G1 cyclin-CDK burst required for cell morphogenesis - septin ring assembly and polarisation of the bud site - but not for DNA replication. Cln1 is distributed between the nucleus and the cytoplasm. Genetically the CLN genes are mutually redundant yet collectively essential: cln1 single mutants are viable, cln1 cln2 double mutants are delayed in budding and DNA synthesis, and cln1 cln2 cln3 triple mutants arrest as unbudded cells at Start; conditional expression of CLN1 was the experiment that first confined the essential Cln requirement to G1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (PAINT) annotation of the G1/S transition to the G1 cyclin clade (node PTN000019791), whose experimental descendants include metazoan cyclin D and cyclin E, fission-yeast Puc1/Cig1 and the budding-yeast cyclins Cln2, Cln3 and Clb5/6. Cln1 is a canonical member: Cln1-Cdc28 is one of the three G1 cyclin-CDK complexes any one of which suffices to carry cells through Start into S phase. Reason: The IBD node placement is sound - driving the G1/S transition is the ancestral function of the G1 cyclin-CDK clade - and Cln1 has independent experimental grounding for the same biology in this gene (the GO:0007089 IGI rows below, and the Cln1-Cdc28 kinase assays). Neither CLN1 (SGD:S000004812) nor its paralog CLN2 (SGD:S000006177) is in this row's WITH/FROM, but CLN3 (SGD:S000000038) and the S-phase cyclins Clb5 (SGD:S000006324) and Clb6 (SGD:S000003341) are, along with human cyclin E1 (UniProtKB:P24864) and cyclin D1 (UniProtKB:P24385), so the node is seeded by G1/S cyclins across the clade and the transfer is consistent with CLN1's own evidence. Supporting Evidence: PMID:8387915 the G1 cyclins Cln1, Cln2 and Cln3 regulate entry into the cell cycle (Start) by activating the Cdc28 protein kinase PMID:2574633 Mutational elimination of the CLN1, CLN2, and DAF1/WHI1 products leads to cell cycle arrest independent of cell type, while expression of any one of the genes allows cell proliferation |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT transfer of the cyclin-dependent protein kinase holoenzyme complex to the G1 cyclin clade (node PTN000019791). Correct for Cln1, whose Cdc28-bound complex is directly documented. Reason: Cln1 is a cyclin: its entire molecular function is exerted as the regulatory subunit of a Cdc28 holoenzyme, so the complex term is not peripheral but part of the core description. The complex is curated in its own right as ComplexPortal CPX-1699 (CLN1-CDC28 kinase complex), and Cln1-Cdc28 has been immunoprecipitated from yeast extracts and shown to be an active kinase. CLN1 (SGD:S000004812) appears in this row's WITH/FROM, which is expected and not circular: its own experimental evidence for the complex is one of the descendant evidences behind the IBD, and the IBA additionally asserts that the complex is inherited rather than lineage-specific. Supporting Evidence: PMID:10409718 Epitope-tagged cyclins were used to immunoprecipitate Cln1-Cdc28 and Cln2-Cdc28 kinases from yeast extracts |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning rule assigning the CDK holoenzyme complex on family membership. The conclusion is right for Cln1, though the evidence is an unvetted electronic inference. Reason: Correct, and independently supported by the ComplexPortal IPI row and the Cln1-Cdc28 kinase assays. Cln1 is a cyclin: its entire molecular function is exerted as the regulatory subunit of a Cdc28 holoenzyme, so the complex term is not peripheral but part of the core description. The complex is curated in its own right as ComplexPortal CPX-1699 (CLN1-CDC28 kinase complex), and Cln1-Cdc28 has been immunoprecipitated from yeast extracts and shown to be an active kinase. The ARBA rule itself is not cited as support; the direct evidence is. Supporting Evidence: PMID:10409718 Epitope-tagged cyclins were used to immunoprecipitate Cln1-Cdc28 and Cln2-Cdc28 kinases from yeast extracts |
| GO:0000307 cyclin-dependent protein kinase holoenzyme complex | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | ACCEPT | Summary: ComplexPortal annotation of Cln1 as a subunit of the CDK holoenzyme, curated as CPX-1699 CLN1-CDC28 kinase complex. The most direct of the four GO:0000307 rows. Reason: Cln1 is a cyclin: its entire molecular function is exerted as the regulatory subunit of a Cdc28 holoenzyme, so the complex term is not peripheral but part of the core description. The complex is curated in its own right as ComplexPortal CPX-1699 (CLN1-CDC28 kinase complex), and Cln1-Cdc28 has been immunoprecipitated from yeast extracts and shown to be an active kinase. Supporting Evidence: PMID:10409718 Epitope-tagged cyclins were used to immunoprecipitate Cln1-Cdc28 and Cln2-Cdc28 kinases from yeast extracts file:yeast/CLN1/CLN1-uniprot.txt ComplexPortal; CPX-1699; CLN1-CDC28 kinase complex. |
| GO:0005515 protein binding | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | MODIFY | Summary: Bare protein binding from the Ito et al. comprehensive two-hybrid analysis, with CDC28 (UniProtKB:P00546) as the partner. The interaction is real and expected - Cln1 is a Cdc28 cyclin - but the term says nothing about what the interaction accomplishes. Reason: Bare protein binding carries no functional information, and the project's protein-binding policy excludes ACCEPT and KEEP_AS_NON_CORE for it. The informative replacement is GO:0019901 protein kinase binding: the recorded partner is a protein kinase, and binding a CDK is precisely what a cyclin does. The stronger claim that Cln1 *activates* that kinase is asserted separately from the GO:0016538 IDA rows, so GO:0019901 is the right level for an interaction-detection row. Proposed replacements: protein kinase binding Supporting Evidence: PMID:10409718 Epitope-tagged cyclins were used to immunoprecipitate Cln1-Cdc28 and Cln2-Cdc28 kinases from yeast extracts |
| GO:0005515 protein binding | IPI PMID:11805826 Functional organization of the yeast proteome by systematic ... | MODIFY | Summary: Bare protein binding from the Gavin et al. TAP-MS survey of the yeast proteome, with CDC28 (UniProtKB:P00546) as the partner. The interaction is real and expected - Cln1 is a Cdc28 cyclin - but the term says nothing about what the interaction accomplishes. Reason: Bare protein binding carries no functional information, and the project's protein-binding policy excludes ACCEPT and KEEP_AS_NON_CORE for it. The informative replacement is GO:0019901 protein kinase binding: the recorded partner is a protein kinase, and binding a CDK is precisely what a cyclin does. The stronger claim that Cln1 *activates* that kinase is asserted separately from the GO:0016538 IDA rows, so GO:0019901 is the right level for an interaction-detection row. Proposed replacements: protein kinase binding Supporting Evidence: PMID:10409718 Epitope-tagged cyclins were used to immunoprecipitate Cln1-Cdc28 and Cln2-Cdc28 kinases from yeast extracts |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | MODIFY | Summary: Bare protein binding from the Ho et al. systematic complex identification by TAP-MS, with CDC28 (UniProtKB:P00546) as the partner. The interaction is real and expected - Cln1 is a Cdc28 cyclin - but the term says nothing about what the interaction accomplishes. Reason: Bare protein binding carries no functional information, and the project's protein-binding policy excludes ACCEPT and KEEP_AS_NON_CORE for it. The informative replacement is GO:0019901 protein kinase binding: the recorded partner is a protein kinase, and binding a CDK is precisely what a cyclin does. The stronger claim that Cln1 *activates* that kinase is asserted separately from the GO:0016538 IDA rows, so GO:0019901 is the right level for an interaction-detection row. Proposed replacements: protein kinase binding Supporting Evidence: PMID:10409718 Epitope-tagged cyclins were used to immunoprecipitate Cln1-Cdc28 and Cln2-Cdc28 kinases from yeast extracts |
| GO:0005515 protein binding | IPI PMID:14690591 Assigning function to yeast proteins by integration of techn... | MODIFY | Summary: Bare protein binding from the Hazbun et al. integrated-technology survey, with CDC28 (UniProtKB:P00546) as the partner. The interaction is real and expected - Cln1 is a Cdc28 cyclin - but the term says nothing about what the interaction accomplishes. Reason: Bare protein binding carries no functional information, and the project's protein-binding policy excludes ACCEPT and KEEP_AS_NON_CORE for it. The informative replacement is GO:0019901 protein kinase binding: the recorded partner is a protein kinase, and binding a CDK is precisely what a cyclin does. The stronger claim that Cln1 *activates* that kinase is asserted separately from the GO:0016538 IDA rows, so GO:0019901 is the right level for an interaction-detection row. Proposed replacements: protein kinase binding Supporting Evidence: PMID:10409718 Epitope-tagged cyclins were used to immunoprecipitate Cln1-Cdc28 and Cln2-Cdc28 kinases from yeast extracts |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | MODIFY | Summary: Bare protein binding from the Krogan et al. proteome-modularity survey, with CDC28 (UniProtKB:P00546) as the partner. The interaction is real and expected - Cln1 is a Cdc28 cyclin - but the term says nothing about what the interaction accomplishes. Reason: Bare protein binding carries no functional information, and the project's protein-binding policy excludes ACCEPT and KEEP_AS_NON_CORE for it. The informative replacement is GO:0019901 protein kinase binding: the recorded partner is a protein kinase, and binding a CDK is precisely what a cyclin does. The stronger claim that Cln1 *activates* that kinase is asserted separately from the GO:0016538 IDA rows, so GO:0019901 is the right level for an interaction-detection row. Proposed replacements: protein kinase binding Supporting Evidence: PMID:10409718 Epitope-tagged cyclins were used to immunoprecipitate Cln1-Cdc28 and Cln2-Cdc28 kinases from yeast extracts |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: Bare protein binding from the Breitkreutz et al. kinase-phosphatase interaction network, with CDC28 (UniProtKB:P00546) as the partner. The interaction is real and expected - Cln1 is a Cdc28 cyclin - but the term says nothing about what the interaction accomplishes. Reason: Bare protein binding carries no functional information, and the project's protein-binding policy excludes ACCEPT and KEEP_AS_NON_CORE for it. The informative replacement is GO:0019901 protein kinase binding: the recorded partner is a protein kinase, and binding a CDK is precisely what a cyclin does. The stronger claim that Cln1 *activates* that kinase is asserted separately from the GO:0016538 IDA rows, so GO:0019901 is the right level for an interaction-detection row. Proposed replacements: protein kinase binding Supporting Evidence: PMID:10409718 Epitope-tagged cyclins were used to immunoprecipitate Cln1-Cdc28 and Cln2-Cdc28 kinases from yeast extracts |
| GO:0005515 protein binding | IPI PMID:9032248 A family of cyclin-like proteins that interact with the Pho8... | MODIFY | Summary: Bare protein binding with PHO85 (UniProtKB:P17157), the second budding-yeast CDK, as partner. UniProt curates two experiments for this pair. Reason: Bare protein binding carries no functional information, and the project's protein-binding policy excludes ACCEPT and KEEP_AS_NON_CORE for it. The informative replacement is GO:0019901 protein kinase binding: the recorded partner is a protein kinase, and binding a CDK is precisely what a cyclin does. The stronger claim that Cln1 *activates* that kinase is asserted separately from the GO:0016538 IDA rows, so GO:0019901 is the right level for an interaction-detection row. Pho85 is likewise a cyclin-dependent protein kinase, so the same replacement applies. Note that the cited paper is cached abstract-only and its abstract describes the Pcl cyclins rather than the Cln1-Pho85 affinity experiment; the interaction is nonetheless recorded by IntAct and UniProt, and whether a Cln1-Pho85 complex is physiologically meaningful (as opposed to a reflection of shared cyclin-box chemistry) is an open question raised below rather than a reason to doubt the row. Proposed replacements: protein kinase binding Supporting Evidence: file:yeast/CLN1/CLN1-uniprot.txt P20437; P17157: PHO85; NbExp=2; IntAct=EBI-4479, EBI-13327; |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT transfer of nuclear activity to the G1 cyclin clade. Consistent with the direct imaging of Cln1-GFP in this gene, and functionally apt: the Cln1-Cdc28 substrates Stb1 and Whi5 and the SBF/MBF machinery are nuclear. Reason: Supported directly in Cln1 by GFP localisation, and the is_active_in qualifier is appropriate because the nuclear pool is where the Start transcription substrates are. CLN1 appears in this row's WITH/FROM, which simply marks that the target has its own experimental grounding for the term. Supporting Evidence: PMID:11080155 Cln1–GFP as well as Cln2–GFP were localized in both the nucleus and the cytoplasm |
| GO:0005634 nucleus | IDA PMID:11080155 Nuclear-specific degradation of Far1 is controlled by the lo... | ACCEPT | Summary: Direct localisation of Cln1-GFP to the nucleus, imaged alongside Cln2-GFP in the Far1 degradation study. Reason: A clean IDA for Cln1 itself. Nucleus is as specific as this evidence supports; the finer-grained Cln localisation results in the literature (phosphorylation-driven nuclear exclusion, enrichment at polarised growth sites) were obtained with Cln2, not Cln1, so no refinement is proposed here. Supporting Evidence: PMID:11080155 Cln1–GFP as well as Cln2–GFP were localized in both the nucleus and the cytoplasm |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT transfer of cytoplasmic activity to the G1 cyclin clade, matching the direct Cln1-GFP imaging below. Reason: Supported directly in Cln1. The cytoplasmic pool is functionally relevant rather than incidental: the Cln1/Cln2-specific substrates Ste5 and Ste20 act at the plasma membrane and cell cortex. CLN1 appears in this row's WITH/FROM, which is expected given its own IDA. Supporting Evidence: PMID:11080155 Cln1–GFP as well as Cln2–GFP were localized in both the nucleus and the cytoplasm |
| GO:0005737 cytoplasm | IDA PMID:11080155 Nuclear-specific degradation of Far1 is controlled by the lo... | ACCEPT | Summary: Direct localisation of Cln1-GFP to the cytoplasm in the same imaging experiment as the nuclear row. Reason: A clean IDA for Cln1 itself, and cytoplasm is as precise as the Cln1 evidence goes - the published sub-cytoplasmic resolution (sites of polarised growth) is a Cln2 result. Kept rather than refined for that reason. Supporting Evidence: PMID:11080155 Cln1–GFP as well as Cln2–GFP were localized in both the nucleus and the cytoplasm |
| GO:0007089 traversing start control point of mitotic cell cycle | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA rule assigning Start traversal on family membership. The conclusion is correct for Cln1 and is independently established by the two IGI rows below. Reason: Right term, right gene; Start traversal is the defining Cln function. The electronic rule is not cited as support - the classical CLN genetics is. Supporting Evidence: PMID:2147225 These results are consistent with a specific CLN requirement for START transit PMID:2574633 Using strains where CLN1 was expressed conditionally, the essential function of Cln proteins was found to be limited to the G1 phase |
| GO:0007089 traversing start control point of mitotic cell cycle | IGI PMID:2147225 Cell cycle arrest caused by CLN gene deficiency in Saccharom... | ACCEPT | Summary: SGD IGI for Start traversal, inferred from the cln1 cln2 cln3 triple-mutant G1 arrest with CLN3 (SGD:S000000038) and CLN2 (SGD:S000006177) as the interacting genes. The CLN genes are individually dispensable and collectively essential, which is exactly the redundancy the IGI code is designed to capture. Reason: Core function, and the strongest in vivo evidence available for Cln1's biological role. The arrest is at Start and is independent of the pheromone pathway, so the term is not a generic G1 arrest. Supporting Evidence: PMID:2147225 Null mutations in three genes encoding cyclin-like proteins (CLN1, CLN2, and CLN3) in Saccharomyces cerevisiae cause cell cycle arrest in G1 (cln arrest) PMID:2147225 These results are consistent with a specific CLN requirement for START transit |
| GO:0007089 traversing start control point of mitotic cell cycle | IGI PMID:2574633 An essential G1 function for cyclin-like proteins in yeast. | ACCEPT | Summary: Second SGD IGI for Start traversal, from the companion study in which conditional CLN1 expression localised the essential Cln function to G1 phase. Reason: Core function. This row is the CLN1-centred half of the classical genetics: the conditional allele used was CLN1's own, and shutting it off in a cln2 cln3 background arrests cells in G1. A duplicate of the previous row's claim, which reinforces rather than deduplicates it. Supporting Evidence: PMID:2574633 Using strains where CLN1 was expressed conditionally, the essential function of Cln proteins was found to be limited to the G1 phase PMID:2574633 The data are consistent with the hypothesis that Cln proteins activate the Cdc28 protein kinase |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IBA GO_REF:0000033 | MODIFY | Summary: PAINT transfer of CDK regulator activity to the G1 cyclin clade. Right branch and right gene, but the clade-level term is unsigned where Cln1's own evidence shows activation. Reason: The term is correct but one step more general than the evidence supports. GO:0016538 covers regulation of a CDK in either direction, whereas Cln1 specifically *activates* Cdc28: Cln1-Cdc28 immunoprecipitated from yeast is an active serine/threonine kinase on Stb1 and on histone H1, and CLN1 was isolated as a dosage suppressor of a cdc28 temperature-sensitive allele. GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity is the supported is_a descendant, and is the term used for the paralog Cln2's core function. CLN1 appears in this row's WITH/FROM because of its own IDA rows, which is expected; the refinement is a judgment about the term, not about this row's evidence. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000019791 · PTN000019791 SUPPORTS TRANSFER G1 cyclin node. The node-level claim that members regulate a CDK is correct; it is simply unsigned, and every experimentally characterised member listed below activates rather than inhibits. SGD:S000004812 · CLN1 SUPPORTS TRANSFER The target itself, present because its own GO:0016538 IDA rows are among the descendant evidences behind the IBD. Expected, not circular. SGD:S000006177 · CLN2 SUPPORTS TRANSFER Closest paralog; its equivalent rows were modified to GO:0061575 in genes/yeast/CLN2, so the refinement here is consistent across the pair. SGD:S000000038 · CLN3 SUPPORTS TRANSFER Upstream G1 cyclin; also an activator of Cdc28, so the sign is uniform across the yeast Cln members of the node. UniProtKB:P24864 · CCNE1 SUPPORTS TRANSFER Human cyclin E1, a CDK2 activator; confirms that the activating sign is ancestral to the clade rather than a budding-yeast specialisation. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: PMID:10409718 Stb1 was an excellent substrate for both the Cln1-Cdc28 and Cln2-Cdc28 kinases in vitro and was a better in vitro substrate than histone H1 PMID:2569741 Two Saccharomyces cerevisiae genes were isolated based upon their dosage-dependent rescue of a temperature-sensitive mutation of the gene CDC28 |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IDA PMID:10409718 Regulation of transcription at the Saccharomyces cerevisiae ... | MODIFY | Summary: IDA from the Stb1 study: Cln1-Cdc28 complexes immunoprecipitated from yeast phosphorylate recombinant Stb1 better than histone H1, and the in vivo Stb1 phosphoforms are assigned genetically to Cln1/Cln2-Cdc28 rather than Cln3-Cdc28. The best direct molecular-function experiment on Cln1 in the cached literature. Reason: The term is correct but one step more general than the evidence supports. GO:0016538 covers regulation of a CDK in either direction, whereas Cln1 specifically *activates* Cdc28: Cln1-Cdc28 immunoprecipitated from yeast is an active serine/threonine kinase on Stb1 and on histone H1, and CLN1 was isolated as a dosage suppressor of a cdc28 temperature-sensitive allele. GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity is the supported is_a descendant, and is the term used for the paralog Cln2's core function. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: PMID:10409718 Stb1 was an excellent substrate for both the Cln1-Cdc28 and Cln2-Cdc28 kinases in vitro and was a better in vitro substrate than histone H1 PMID:10409718 several observations suggest that Cln1-Cdc28 and Cln2-Cdc28 are the physiological kinases for Stb1 phosphorylation |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IDA PMID:8387915 Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 ... | MODIFY | Summary: IDA from the three-way comparison of Cln proteins, in which Cln1-associated Cdc28 shows strong histone H1 kinase activity (far stronger than Cln3's) and Cln1 protein is abundant and cell cycle periodic. Reason: The term is correct but one step more general than the evidence supports. GO:0016538 covers regulation of a CDK in either direction, whereas Cln1 specifically *activates* Cdc28: Cln1-Cdc28 immunoprecipitated from yeast is an active serine/threonine kinase on Stb1 and on histone H1, and CLN1 was isolated as a dosage suppressor of a cdc28 temperature-sensitive allele. GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity is the supported is_a descendant, and is the term used for the paralog Cln2's core function. This row is also the clearest statement that Cln1 sits in the high-activity, periodic tier of Cln proteins with Cln2, rather than with the rare, constitutive Cln3. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: PMID:8387915 We find that Cln3 is a much rarer protein than Cln1 or Cln2 and has a much weaker associated histone H1 kinase activity PMID:8387915 the G1 cyclins Cln1, Cln2 and Cln3 regulate entry into the cell cycle (Start) by activating the Cdc28 protein kinase |
| GO:0016538 cyclin-dependent protein serine/threonine kinase regulator activity | IEA GO_REF:0000117 | MODIFY | Summary: ARBA rule assigning CDK regulator activity on family membership. Same term-level issue as the other GO:0016538 rows. Reason: The term is correct but one step more general than the evidence supports. GO:0016538 covers regulation of a CDK in either direction, whereas Cln1 specifically *activates* Cdc28: Cln1-Cdc28 immunoprecipitated from yeast is an active serine/threonine kinase on Stb1 and on histone H1, and CLN1 was isolated as a dosage suppressor of a cdc28 temperature-sensitive allele. GO:0061575 cyclin-dependent protein serine/threonine kinase activator activity is the supported is_a descendant, and is the term used for the paralog Cln2's core function. The ARBA rule is not cited as support; the Cln1 kinase assays are. Proposed replacements: cyclin-dependent protein serine/threonine kinase activator activity Supporting Evidence: PMID:10409718 Stb1 was an excellent substrate for both the Cln1-Cdc28 and Cln2-Cdc28 kinases in vitro and was a better in vitro substrate than histone H1 PMID:2569741 Two Saccharomyces cerevisiae genes were isolated based upon their dosage-dependent rescue of a temperature-sensitive mutation of the gene CDC28 |
| GO:1902806 regulation of cell cycle G1/S phase transition | NAS PMID:2569741 A family of cyclin homologs that control the G1 phase in yea... | MODIFY | Summary: ComplexPortal NAS citing the original CLN1/CLN2 cloning paper for regulation of the G1/S phase transition. The underlying biology is right; the term is unsigned. Reason: The claim is true but unsigned, and the sign is not in doubt: Cln1-Cdc28 drives the G1/S transition forward, and loss of all three CLN genes blocks it. GO:1900087 positive regulation of G1/S transition of mitotic cell cycle is the supported term - a sign correction rather than a specificity refinement - and is what the paralog Cln2's equivalent rows were modified to. Keeping an unsigned regulation term alongside a signed one would leave the review saying less than the evidence does. Proposed replacements: positive regulation of G1/S transition of mitotic cell cycle Supporting Evidence: PMID:2569741 Two Saccharomyces cerevisiae genes were isolated based upon their dosage-dependent rescue of a temperature-sensitive mutation of the gene CDC28 PMID:2147225 These results are consistent with a specific CLN requirement for START transit |
| GO:2000045 regulation of G1/S transition of mitotic cell cycle | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from the IPR014399 Cyclin_CLN family signature to regulation of the G1/S transition. The family assignment is correct for Cln1 - it is the Cln-type cyclin family - but the mapped term is unsigned. Reason: The claim is true but unsigned, and the sign is not in doubt: Cln1-Cdc28 drives the G1/S transition forward, and loss of all three CLN genes blocks it. GO:1900087 positive regulation of G1/S transition of mitotic cell cycle is the supported term - a sign correction rather than a specificity refinement - and is what the paralog Cln2's equivalent rows were modified to. Keeping an unsigned regulation term alongside a signed one would leave the review saying less than the evidence does. The IPR014399 match itself is good evidence for family membership (and so for the cyclin function), which is why this row is refined rather than removed. Proposed replacements: positive regulation of G1/S transition of mitotic cell cycle Supporting Evidence: file:yeast/CLN1/CLN1-uniprot.txt PIRSF; PIRSF001770; Cyclin_CLN; 1. PMID:2147225 These results are consistent with a specific CLN requirement for START transit |
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Download this section (compressed HTML)Q: Are Cln1 and Cln2 genuinely interchangeable, or does Cln1 have private substrates? Every molecular experiment in the cached literature assays the two together and reports them as equivalent, while the published Cln-specific results on nuclear export, LP-motif docking geometry and enrichment at polarised growth sites were obtained with Cln2 alone, so Cln1's individual contribution has never been isolated.
Q: Should the Cln1/Cln2 shut-off of the pheromone pathway be annotated to the cyclins at all? Cln1- and Cln2-Cdk, but not Cln3-, Clb5- or Clb2-Cdk, phosphorylate Ste5 and Ste20, yet no budding-yeast cyclin carries GO:0180040 negative regulation of pheromone response MAPK cascade; SGD instead annotates CLN2 to GO:0000321 re-entry into mitotic cell cycle after pheromone arrest. Is that a deliberate convention, and if so should CLN1 carry a GO:0000321 row too?
Q: Is the curated Cln1-Pho85 interaction (UniProt NbExp=2, from PMID:9032248) physiologically meaningful, or does it reflect shared cyclin-box chemistry between the two budding-yeast CDKs? No phenotype or substrate has been attributed to a Cln1-Pho85 complex.
Q: Within the late-G1 cyclin-CDK burst that CLN1,2 and PCL1,2 jointly supply for septin ring assembly and bud-site polarisation, does Cln1 contribute anything the other three cyclins cannot? The requirement has only been demonstrated for the combined activity, which is why no morphogenesis term is proposed for CLN1 here.
Experiment: In a cyclin-replacement strain where Cdc28 activity in late G1 is supplied by a single inducible cyclin (Cln1 or Cln2 alone), combine analog-sensitive cdc28-as1 with quantitative phosphoproteomics within minutes of cyclin induction in elutriated small G1 cells, and compare the two phosphosite sets directly. Score LP-motif-containing substrates separately to test whether docking preference rather than abundance accounts for any difference.
Hypothesis: Cln1 and Cln2 have distinguishable substrate repertoires despite their redundancy in viability assays.
Experiment: Build NLS- and NES-tethered Cln1 variants at the endogenous locus in a cln2 cln3 background and ask which compartment-restricted form supports Start, Stb1 phosphorylation, bud emergence and recovery from pheromone arrest. The published compartment-partition experiments of this design were done on Cln2, so the Cln1 result is not predictable from them.
Hypothesis: Cln1 has a functionally important nuclear pool distinct from its cytoplasmic pool.
Experiment: Co-immunoprecipitate endogenously tagged Cln1 and Pho85 across a synchronised cell cycle to establish whether the complex forms at native stoichiometry, then test whether any Cln1-dependent phosphorylation event survives in a pho85 deletion and whether Pho85 kinase activity is stimulated by purified Cln1 in vitro.
Hypothesis: The Cln1-Pho85 interaction has no physiological output.
G1 cyclin involved in regulation of the cell cycle; activates Cdc28p kinase to promote the G1 to S phase transition; late G1 specific expression depends on transcription factor complexes, MBF (Swi6p-Mbp1p) and SBF (Swi6p-Swi4p); CLN1 has a paralog, CLN2, that arose from the whole genome duplication; cell cycle arrest phenotype of the cln1 cln2 cln3 triple null mutant is complemented by any of human cyclins CCNA2, CCNB1, CCNC, CCND1, or CCNE1
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