Slp1 is the fission-yeast ortholog of Cdc20/p55CDC/Fizzy, a WD40 beta-propeller substrate-recognition co-activator of the anaphase-promoting complex/cyclosome (APC/C), the multi-subunit RING E3 ubiquitin ligase that drives mitotic and meiotic progression. Slp1 binds the APC/C and, by recognizing destruction (D-box) and KEN-box degrons on substrates, activates the APC/C at the metaphase-to-anaphase transition. The principal Slp1-APC/C substrates are securin (Cut2) and mitotic cyclin B (Cdc13): their ubiquitin-dependent degradation by the 26S proteasome triggers separase (Cut1) activation, cleavage of cohesin, sister-chromatid separation, and inactivation of Cdk1, leading to anaphase and mitotic exit. Slp1 is the key target of the spindle assembly checkpoint: when kinetochores are unattached or lack tension, the mitotic checkpoint complex (Mad2-Mad3-Slp1, with Bub3 in many other species) binds and inhibits Slp1, obstructing its substrate-degron recognition sites and displacing it from the APC/C until correct bi-orientation is achieved. Slp1 is also the only APC/C coactivator essential for meiosis I progression, and its activity is fine-tuned during meiosis by the meiosis-specific inhibitor/substrate Mes1. Slp1 acts predominantly in the nucleus and associates with mitotic structures (spindle, spindle pole body) and the kinetochore where checkpoint signalling occurs.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005680 anaphase-promoting complex | IBA GO_REF:0000033 | ACCEPT | Summary: Slp1/Cdc20 is the substrate-recognition coactivator that associates with the APC/C; it cofractionates with the APC/C and is the recruited activator early in mitosis. As a transiently bound coactivator rather than a constitutive core subunit, "part_of APC/C" is conventionally used for Cdc20 family activators. ACCEPT. Reason: Phylogenetic inference is fully consistent with strong experimental data that Slp1 is the APC/C activator that binds the complex. Supporting Evidence: PMID:18556659 In order for the APC/C to become active, it must interact with a transiently available activator; early in mitosis, this is Slp1/Cdc20, and later in mitosis and in G1, it switches to Ste9/Cdh1 |
| GO:1905786 positive regulation of anaphase-promoting complex-dependent catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: As the APC/C coactivator, Slp1 positively regulates APC/C-dependent ubiquitination and degradation of mitotic substrates. Core function; well supported. ACCEPT. Reason: Consistent with experimental demonstration that Slp1 activates APC/C-mediated ubiquitination of securin/Cut2 and cyclin B/Cdc13. Supporting Evidence: PMID:26882497 Anaphase onset is initiated by an E3 ubiquitin ligase, known as the anaphase promoting complex or cyclosome (APC/C), and its activating co-factor Cdc20Slp1 |
| GO:0010997 anaphase-promoting complex binding | IBA GO_REF:0000033 | ACCEPT | Summary: Slp1 binds the APC/C as its coactivator. This is a core molecular function directly supported by experimental data (Slp1 cofractionates with APC/C; the slp1-362 mutant fails to bind APC/C). ACCEPT. Reason: Phylogenetic inference corroborated by direct biochemical evidence of Slp1-APC/C association. Supporting Evidence: PMID:18556659 Pools of Mad2, Mad3-GFP, and Cdc20/Slp1-HA were seen to co-fractionate with Lid1-TAP |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Slp1 is required for APC/C-dependent ubiquitin-mediated degradation of securin and cyclin B. Core biological process; ACCEPT. Reason: Consistent with experimental IDA/IMP/EXP annotations for the same process. Supporting Evidence: PMID:26882497 Cdc20Slp1-APC/C targets the separase inhibitor securin and the CDK1 activating subunit cyclin B for destruction by the 26S proteasome |
| GO:1990757 ubiquitin ligase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: Slp1 activates the APC/C ubiquitin ligase. This is the core molecular function and is also supported by direct biochemical (IDA/EXP) evidence. ACCEPT. Reason: Phylogenetic inference matches in vitro demonstration that Cdc20Slp1-APC/C ubiquitinates securin/Cut2. Supporting Evidence: PMID:26882497 a corresponding decrease in Cdc20 Slp1-APC/C dependent ubiquitination of the radio-labelled securinCut2 substrate was observed |
| GO:0010997 anaphase-promoting complex binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO electronic annotation of APC/C binding, duplicating the well-supported IBA and IPI annotations for the same term. Correct. ACCEPT. Reason: InterPro Cdc20/Fizzy signature maps appropriately to APC/C binding; concordant with experimental evidence. Supporting Evidence: PMID:18556659 Pools of Mad2, Mad3-GFP, and Cdc20/Slp1-HA were seen to co-fractionate with Lid1-TAP |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning electronic annotation, duplicating experimentally supported IDA/IMP/EXP annotations for this process. Correct. ACCEPT. Reason: Concordant with strong experimental evidence for the same process. Supporting Evidence: PMID:26882497 Cdc20Slp1-APC/C targets the separase inhibitor securin and the CDK1 activating subunit cyclin B for destruction by the 26S proteasome |
| GO:0097027 ubiquitin-protein transferase activator activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO term essentially equivalent to ubiquitin ligase activator activity (GO:1990757), which has stronger experimental (IDA/EXP) support and is the preferred term for APC/C activation. The annotation is not wrong but is redundant with the better-supported term. MODIFY to GO:1990757. Reason: The APC/C is a RING E3 ubiquitin ligase; "ubiquitin ligase activator activity" (GO:1990757) is the more precise and experimentally supported term for Slp1's coactivator role. Proposed replacements: ubiquitin ligase activator activity Supporting Evidence: PMID:26882497 a corresponding decrease in Cdc20 Slp1-APC/C dependent ubiquitination of the radio-labelled securinCut2 substrate was observed |
| GO:0005515 protein binding | IPI PMID:15791259 Fission yeast Mes1p ensures the onset of meiosis II by block... | KEEP AS NON CORE | Summary: IPI capturing the interaction between Slp1 and the meiosis-specific APC/C inhibitor/substrate Mes1 (P41005). The interaction is real and specific, but the bare "protein binding" term is uninformative. Kept as non-core; the underlying function (APC/C coactivator/adaptor) is captured by GO:1990757 and GO:0010997. Reason: Bare protein binding is uninformative per curation guidelines; the Slp1-Mes1 interaction is biologically meaningful but better represented by the coactivator MF terms. Supporting Evidence: PMID:18331722 Mes1 directly binds the WD40 domain of the Fizzy family of APC/C activators |
| GO:0005515 protein binding | IPI PMID:22437499 Structure of the mitotic checkpoint complex. | KEEP AS NON CORE | Summary: IPI capturing the Slp1(Cdc20)-Mad2 interaction within the mitotic checkpoint complex, defined by the S. pombe MCC crystal structure. Real and structurally defined, but bare "protein binding" is uninformative; the MCC membership is captured by GO:0033597. Kept as non-core. Reason: Specific, structurally defined interaction but the generic term adds little; MCC component annotation conveys the biology. Supporting Evidence: PMID:22437499 the crystal structure of Schizosaccharomyces pombe MCC (a complex of mitotic spindle assembly checkpoint proteins Mad2, Mad3 and APC/C co-activator protein Cdc20) |
| GO:0005515 protein binding | IPI PMID:9461438 Fission yeast Slp1: an effector of the Mad2-dependent spindl... | KEEP AS NON CORE | Summary: IPI capturing the Slp1-Mad2 interaction shown by Kim et al. (1998); disrupting it (Slp1 131-132 AF->PY) abolishes the spindle checkpoint. Real and important, but bare "protein binding" is uninformative. Kept as non-core. Reason: The interaction underlies SAC control of Slp1 but the generic term is uninformative; the checkpoint role is captured by GO:0007094 and GO:0033597. Supporting Evidence: PMID:9461438 Mad2 formed a complex with Slp1, a WD (tryptophan-aspartic acid)-repeat protein essential for the onset of anaphase. When the physical interaction between the two proteins was disrupted, the spindle checkpoint was no longer functional |
| GO:0033597 mitotic checkpoint complex | IDA PMID:22437499 Structure of the mitotic checkpoint complex. | ACCEPT | Summary: Slp1(Cdc20) is a defined subunit of the mitotic checkpoint complex (Mad2-Mad3-Cdc20), as shown by the S. pombe MCC crystal structure. Core cellular-component annotation. ACCEPT. Reason: Direct structural evidence that Cdc20/Slp1 is a component of the MCC. Supporting Evidence: PMID:22437499 the crystal structure of Schizosaccharomyces pombe MCC (a complex of mitotic spindle assembly checkpoint proteins Mad2, Mad3 and APC/C co-activator protein Cdc20) |
| GO:0000776 kinetochore | NAS PMID:15930132 Spindle checkpoint signaling requires the mis6 kinetochore s... | KEEP AS NON CORE | Summary: Curator-assigned (NAS) kinetochore localization. The cited paper establishes the kinetochore as the platform where Mad2 (and SAC signalling targeting Slp1) operates; Cdc20/Slp1 transiently localizes to kinetochores in many systems. Plausible but based on inference rather than direct Slp1 imaging. Kept as non-core. Reason: Kinetochore is where SAC signalling that controls Slp1 takes place; localization is plausible but supported by NAS rather than direct evidence, and is peripheral to the core APC/C-activating function. Supporting Evidence: PMID:15930132 The Mis6-complex physically interacts with Mad2 under the condition that the Mad2-dependent checkpoint is activated |
| GO:0007094 mitotic spindle assembly checkpoint signaling | NAS PMID:18556659 The spindle checkpoint functions of Mad3 and Mad2 depend on ... | ACCEPT | Summary: Slp1(Cdc20) is the central target/effector of mitotic SAC signalling: the MCC binds and inhibits Slp1 to delay anaphase until kinetochores are correctly attached. Core process. ACCEPT. Reason: Strong evidence that Cdc20/Slp1 is the key SAC target inhibited by Mad2/Mad3 within the MCC. Supporting Evidence: PMID:18556659 Cdc20 is the key target of the SAC (9, 10). The Mad2 and Mad3/BubR1 checkpoint proteins bind to and inhibit Cdc20 |
| GO:0033597 mitotic checkpoint complex | IPI PMID:22437499 Structure of the mitotic checkpoint complex. | ACCEPT | Summary: ComplexPortal IPI assertion that Slp1 is part of the MCC, concordant with the IDA structural evidence above. ACCEPT. Reason: Concordant with structural evidence that Cdc20/Slp1 is an MCC subunit. Supporting Evidence: PMID:22437499 the crystal structure of Schizosaccharomyces pombe MCC (a complex of mitotic spindle assembly checkpoint proteins Mad2, Mad3 and APC/C co-activator protein Cdc20) |
| GO:1990757 ubiquitin ligase activator activity | NAS GO_REF:0000051 | ACCEPT | Summary: PomBase keyword-mapped NAS annotation of the core APC/C-activator molecular function, also supported by IDA/EXP/IBA. ACCEPT. Reason: Core molecular function, redundant with stronger experimental annotations. Supporting Evidence: PMID:26882497 a corresponding decrease in Cdc20 Slp1-APC/C dependent ubiquitination of the radio-labelled securinCut2 substrate was observed |
| GO:0005515 protein binding | IPI PMID:18331722 A mutual inhibition between APC/C and its substrate Mes1 req... | KEEP AS NON CORE | Summary: IPI capturing the Slp1-Mes1 (SPAC5D6.08c) interaction. Mes1 binds the WD40 domain of Fizzy activators including Slp1. Real and specific but bare "protein binding" is uninformative; kept as non-core (coactivator/adaptor function captured elsewhere). Reason: Uninformative generic term; the biologically meaningful WD40-domain substrate/inhibitor interaction is better represented by the coactivator MF terms. Supporting Evidence: PMID:18331722 Mes1 directly binds the WD40 domain of the Fizzy family of APC/C activators |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | IDA PMID:18331722 A mutual inhibition between APC/C and its substrate Mes1 req... | ACCEPT | Summary: Direct evidence (IDA) that Slp1 participates in APC/C-dependent ubiquitin-mediated proteolysis, here shown via APC/C-Slp1 ubiquitylation of Mes1 and substrate degradation in meiosis. Core process. ACCEPT. Reason: Direct biochemical demonstration of APC/C-Slp1-mediated ubiquitylation/degradation. Supporting Evidence: PMID:18331722 a ternary complex, APC/C-Fizzy/Cdc20-Mes1, is stabilized by inhibiting Mes1 ubiquitylation |
| GO:0000776 kinetochore | TAS PMID:15930132 Spindle checkpoint signaling requires the mis6 kinetochore s... | KEEP AS NON CORE | Summary: TAS kinetochore localization, same underlying source as the NAS annotation. Cdc20/Slp1 acting at the kinetochore where SAC signalling occurs is plausible but supported by author statement rather than direct Slp1 evidence. Kept as non-core. Reason: Peripheral to the core APC/C-activator function; supported by author statement, not direct Slp1 imaging. Supporting Evidence: PMID:15930132 The Mis6-complex physically interacts with Mad2 under the condition that the Mad2-dependent checkpoint is activated |
| GO:0005515 protein binding | IPI PMID:28178520 Identification of a Sgo2-Dependent but Mad2-Independent Path... | KEEP AS NON CORE | Summary: IPI from the Sgo2/Klp9 anaphase-timing study, which demonstrates a Mad2-independent Mad3-Slp1(Cdc20) complex that inhibits APC/C, with Mad3 binding Slp1 in a KEN20-dependent manner. The interaction is real and specific, but bare "protein binding" is uninformative; kept as non-core. Reason: Generic term uninformative; the Mad3-Slp1 inhibitory interaction is captured by SAC/MCC process and component annotations. Supporting Evidence: PMID:28178520 Mad3 interacts with Slp1 in a cell cycle- and KEN20-dependent manner |
| GO:0045842 positive regulation of mitotic metaphase/anaphase transition | NAS GO_REF:0000051 | ACCEPT | Summary: Slp1 promotes the metaphase-to-anaphase transition by activating APC/C-dependent destruction of securin and cyclin B. Core process; well supported. ACCEPT. Reason: Strongly supported: Slp1-APC/C degradation of securin triggers cohesin cleavage and anaphase onset. Supporting Evidence: PMID:26882497 Once securin is destroyed, cohesin is cleaved and sister chromatids separate and segregate in anaphase |
| GO:1990757 ubiquitin ligase activator activity | IDA PMID:26882497 Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC... | ACCEPT | Summary: Direct in vitro demonstration that Cdc20Slp1-APC/C ubiquitinates securin (Cut2), establishing Slp1's APC/C activator activity. Core molecular function with the strongest evidence. ACCEPT. Reason: Direct biochemical evidence of Slp1-dependent APC/C ubiquitination activity. Supporting Evidence: PMID:26882497 a corresponding decrease in Cdc20 Slp1-APC/C dependent ubiquitination of the radio-labelled securinCut2 substrate was observed |
| GO:1990949 metaphase/anaphase transition of meiosis I | EXP PMID:21389117 Mes1 controls the meiosis I to meiosis II transition by dist... | ACCEPT | Summary: Slp1/Cdc20 is the only APC/C coactivator essential for meiosis I progression; slp1 mutants delay anaphase I and stabilize Cut2/Cdc13. Core meiotic process. ACCEPT. Reason: Experimental evidence that Slp1 is required for the meiosis I metaphase/anaphase transition. Supporting Evidence: PMID:21389117 find that only Slp1/Cdc20 is essential for meiosis I progression |
| GO:0005515 protein binding | IPI PMID:21389117 Mes1 controls the meiosis I to meiosis II transition by dist... | KEEP AS NON CORE | Summary: IPI capturing the Slp1-Mes1 interaction in the meiotic context (Mes1 is a competitive substrate for Slp1). Real and specific but bare "protein binding" is uninformative; kept as non-core. Reason: Generic term uninformative; the meiotic Slp1-Mes1 substrate interaction is captured by the coactivator function and meiotic process terms. Supporting Evidence: PMID:21389117 Mes1 behaves as a pseudosubstrate for Fzr1/Mfr1 but works as a competitive substrate for Slp1 |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | IDA PMID:21389117 Mes1 controls the meiosis I to meiosis II transition by dist... | ACCEPT | Summary: Direct evidence that Slp1-APC/C drives substrate (Cut2/Cdc13) degradation during meiosis. Core process. ACCEPT. Reason: Direct evidence for Slp1-dependent APC/C catabolic activity in meiosis. Supporting Evidence: PMID:21389117 find that only Slp1/Cdc20 is essential for meiosis I progression |
| GO:0031145 anaphase-promoting complex-dependent catabolic process | IMP PMID:21389117 Mes1 controls the meiosis I to meiosis II transition by dist... | ACCEPT | Summary: Mutant-phenotype (IMP) evidence that loss of Slp1 function impairs APC/C-dependent degradation of meiotic substrates. Core process; concordant with the IDA/EXP annotations. ACCEPT. Reason: Loss-of-function evidence consistent with Slp1's role in APC/C-dependent proteolysis. Supporting Evidence: PMID:21389117 find that only Slp1/Cdc20 is essential for meiosis I progression |
| GO:1990757 ubiquitin ligase activator activity | EXP PMID:21389117 Mes1 controls the meiosis I to meiosis II transition by dist... | ACCEPT | Summary: Experimental evidence that Slp1 acts as the essential APC/C coactivator in meiosis I. Core molecular function. ACCEPT. Reason: Concordant with the core APC/C-activator role demonstrated in mitosis and meiosis. Supporting Evidence: PMID:21389117 find that only Slp1/Cdc20 is essential for meiosis I progression |
| GO:1990950 metaphase/anaphase transition of meiosis II | EXP PMID:21389117 Mes1 controls the meiosis I to meiosis II transition by dist... | KEEP AS NON CORE | Summary: Slp1, together with Fzr1/Mfr1 and regulated by Mes1, contributes to the meiosis I-to-II transition and meiosis II anaphase. Experimental evidence supports involvement. ACCEPT as non-core relative to the primary mitotic/meiosis-I roles. Reason: Slp1 participates in meiosis II, but its activity here is shared with/handed to Fzr1/Mfr1 and is secondary to its essential meiosis I role. Supporting Evidence: PMID:21389117 Mes1 interacts with two coactivators in a different way to control the activity of the APC/C required for the meiosis I/meiosis II transition |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: High-throughput GFP localization places Slp1 in the nucleus, the compartment where APC/C substrates are ubiquitinated and degraded. This is the most biologically central localization. ACCEPT. Reason: Nuclear localization is consistent with Slp1's role as a nuclear APC/C coactivator acting on nuclear substrates. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0032153 cell division site | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: High-throughput localization to the cell division site from a single global ORFeome study. Not a recognized site of Slp1 action; peripheral and not supported by focused studies. Kept as non-core. Reason: Single high-throughput dataset; cell division site is not an established functional location for the APC/C coactivator and may reflect general nuclear/cytoplasmic signal during cytokinesis. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0044732 mitotic spindle pole body | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: High-throughput localization to the mitotic spindle pole body. Consistent with mitotic APC/C action but from a single global dataset and not central to the activator function. Kept as non-core. Reason: Plausible mitotic-apparatus localization but supported only by a single high-throughput study; peripheral to the core coactivator function. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0072686 mitotic spindle | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: High-throughput localization to the mitotic spindle, consistent with mitotic-stage APC/C activity but from a single global dataset. Kept as non-core. Reason: Plausible mitotic localization supported only by a single high-throughput study; peripheral to the core function. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0010997 anaphase-promoting complex binding | IPI PMID:18556659 The spindle checkpoint functions of Mad3 and Mad2 depend on ... | ACCEPT | Summary: IPI evidence (cofractionation with the APC/C subunit Lid1; slp1-362 fails to bind APC/C) that Slp1 binds the APC/C. Core molecular function. ACCEPT. Reason: Direct biochemical evidence of Slp1-APC/C binding. Supporting Evidence: PMID:18556659 Pools of Mad2, Mad3-GFP, and Cdc20/Slp1-HA were seen to co-fractionate with Lid1-TAP |
| GO:0033597 mitotic checkpoint complex | IDA PMID:18556659 The spindle checkpoint functions of Mad3 and Mad2 depend on ... | ACCEPT | Summary: Direct evidence that Slp1(Cdc20) is incorporated into the S. pombe MCC (Mad3-Mad2-Slp1). Core cellular-component annotation. ACCEPT. Reason: Direct biochemical evidence that Cdc20/Slp1 is a component of the mitotic checkpoint complex. Supporting Evidence: PMID:18556659 abolishes incorporation of Mad3 into the mitotic checkpoint complex (Mad3-Mad2-Slp1 in S. pombe, where Slp1 is the Cdc20 homolog |
Loading supporting content…
Download this section (compressed HTML)Q: What are the temporal dynamics of Slp1 protein levels and APC/C association across the mitotic and meiotic cell cycles, and how is Slp1 itself turned over?
Q: Beyond securin (Cut2) and cyclin B (Cdc13), what is the full repertoire of Slp1-specific APC/C substrates, and how does substrate degron preference differ between Slp1 and the Cdh1-type activators Ste9 and Fzr1/Mfr1?
Q: How is the Mad2-independent Mad3-Slp1 inhibitory complex regulated relative to the canonical Mad2-Mad3-Slp1 MCC, and what physiological situations rely on each?
Experiment: Quantitative live-cell imaging of endogenously tagged Slp1 (e.g., GFP knock-in) to determine its subcellular dynamics (nucleus, kinetochore, spindle, SPB) during unperturbed and checkpoint-arrested mitosis, to clarify which of the high-throughput localizations reflect functional sites.
Experiment: Reconstituted in vitro APC/C ubiquitination assays comparing Slp1 versus Ste9/Fzr1 coactivators with defined substrates (Cut2, Cdc13, Mes1) to map activator-specific degron recognition.
Experiment: Proximity labeling (e.g., TurboID) of endogenous Slp1 across mitosis and meiosis to define the in vivo interactome and substrate landscape, including condition-dependent MCC versus Mad3-only inhibitory complexes.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)