Sid2 is the NDR/LATS-family serine/threonine protein kinase (EC 2.7.11.1) that serves as the most downstream effector of the Septation Initiation Network (SIN), a Spg1-GTPase-regulated kinase cascade that controls the execution of cytokinesis in fission yeast. Sid2 functions as an obligate complex with its regulatory subunit Mob1, which is required for both its spindle pole body (SPB) localization and its kinase activity. Sid2-Mob1 associates with spindle pole bodies and transiently with the cell-division site and actomyosin contractile ring during late mitosis, when its cytokinetic kinase activity peaks. During late mitosis, Sid2 promotes contractile ring constriction and septum formation by phosphorylating multiple substrates: the Cdc14-family phosphatase Clp1/Flp1 (creating 14-3-3/Rad24 binding sites that retain Clp1 in the cytoplasm), the cytokinetic formin Cdc12 (inhibiting its multimerization), the anillin-like protein Mid1 (driving it from the membrane at constriction onset), the SIN scaffold Cdc11 (a positive-feedback loop establishing SIN asymmetry), and the MOR-pathway kinase Nak1 (coordinating cytokinesis with cell separation). A cytoplasmic G2 Sid2-Mob1 pool activates the NIMA-related kinase Fin1, modulating mitotic commitment through the Pom1/Cdr1/Cdr2-Wee1 axis independently of the rest of the SIN. Sid2 also phosphorylates the kinesin-14 Klp2, inhibiting its Mal3-dependent microtubule association to promote anaphase spindle elongation and maintain nuclear positioning when cytokinesis is delayed. The SIN, including Sid2, is additionally required for forespore membrane and spore formation during meiosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005816 spindle pole body | IBA GO_REF:0000033 | ACCEPT | Summary: SPB localization is experimentally supported, with cell-cycle and reporter context. Sid2-GFP was observed at interphase SPBs, whereas antibody detection of untagged Sid2 supports a cytoplasmic G2 population. Reason: Retain the phylogenetic localization assertion because SPB association is supported; do not extrapolate tagged interphase localization to constitutive residence of untagged Sid2. Supporting Evidence: PMID:10459013 Sid2p is a component of the spindle pole body at all stages of the cell cycle and localizes transiently to the cell division site during medial ring constriction and septation. |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. Sid2 is an NDR/Dbf2-family Ser/Thr protein kinase; kinase activity has been demonstrated directly by in vitro assay and is the basis of all of its biological roles. Reason: Directly supported by multiple experimental kinase assays and conserved across the family. Supporting Evidence: PMID:10459013 We have established an in vitro assay for measuring Sid2p kinase activity, and found that Sid2p kinase activity peaks during medial ring constriction and septation. |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Sid2 is the terminal kinase of the SIN signaling cascade, transducing the signal from the SPB to the division site. The term is correct but general; the more specific 'septation initiation signaling' captures the core role. Reason: Accurate but generic parent process; the specific septation initiation signaling term is the core annotation. Supporting Evidence: PMID:10459013 The Sid2p kinase is one of several proteins that function as part of a novel signaling pathway required for initiation of medial ring constriction and septation. |
| GO:0007096 regulation of exit from mitosis | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: The inherited mitotic-exit process is a poor fit to the experimentally established role of S. pombe Sid2 in cytokinesis initiation. The cached PAINT assertion at PTN008614896 cites CGD:CAL0000197161; it is not a verified pairwise transfer from S. cerevisiae Dbf2. Reason: Experimental studies distinguish Sid2-dependent cytokinesis initiation from MEN-like control of mitotic exit. This target-specific functional distinction supports marking the process as over-annotated. Neither source count nor source database is evidence against an IBA; the cached assertion identities were checked, but the ancestral placement was not independently re-evaluated from a tree and alignment. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN008614896 · PTN008614896 UNRESOLVED Cached PAINT IBD identifies this ancestral assertion and CGD:CAL0000197161 as its source for GO:0007096. Sid2-specific experimental evidence motivates the mitotic-exit concern, but the source experiment and ancestral tree/MSA placement were not independently re-evaluated; no source failure or precise propagation mechanism is asserted. Supporting Evidence: PMID:10837231 Mob1p associates with the Sid2p kinase and like Sid2p, Mob1p is required for the initiation of cytokinesis, but not for mitotic exit. PMID:22684255 whereas the fission yeast equivalent, the septum initiation network (SIN), controls only the execution of cytokinesis. |
| GO:0034973 Sid2-Mob1 complex | IBA GO_REF:0000033 | ACCEPT | Summary: Sid2 is the kinase component of the Sid2-Mob1 complex. Phylogenetic inference is corroborated by direct experimental co-precipitation with Mob1. Reason: Complex membership directly demonstrated and conserved. Supporting Evidence: PMID:10769201 we also demonstrate that mob1p can be precipitated from cells in a complex with the septation regulating kinase sid2p. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based annotation of generic protein kinase activity. Correct but subsumed by the more specific, experimentally supported serine/threonine kinase activity. Reason: Redundant general parent; the specific protein serine/threonine kinase activity term should be used. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:10459013 We have established an in vitro assay for measuring Sid2p kinase activity, and found that Sid2p kinase activity peaks during medial ring constriction and septation. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation of Ser/Thr kinase activity from EC 2.7.11.1 / InterPro. Correct and corroborated by direct experimental evidence. Reason: Consistent with experimentally demonstrated kinase activity. Supporting Evidence: PMID:10459013 We have established an in vitro assay for measuring Sid2p kinase activity, and found that Sid2p kinase activity peaks during medial ring constriction and septation. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding is a standard, well-supported function for a protein kinase. Sid2 has a canonical kinase ATP-binding motif (residues 214-222, K237), and a kinase-dead K238R ATP-binding mutant abolishes function. Reason: Conserved kinase ATP-binding site; supported by mutational analysis of the ATP-binding lysine. Supporting Evidence: PMID:10459013 Site-directed mutagenesis was employed to create a point mutation in the sid2 gene at a site that would alter the proposed ATP-binding domain of the kinase (K238 to R). |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization is supported; Sid2 has a diffuse cytoplasmic pool in addition to its SPB and division-site concentrations, and a functional G2 cytoplasmic pool of Sid2-Mob1 activates Fin1. General but correct. Reason: Correct location; corroborated by experimental detection of a functional cytoplasmic Sid2-Mob1 pool. Supporting Evidence: PMID:22684255 The S. pombe cytokinesis NDR kinase Sid2 activates Fin1 NIMA kinase to control mitotic commitment through Pom1/Wee1. |
| GO:0005816 spindle pole body | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic (UniProt subcellular-location mapping) annotation of SPB localization, redundant with the experimentally supported SPB annotations. Reason: Consistent with direct experimental localization to the SPB. Supporting Evidence: PMID:10459013 Sid2p is a component of the spindle pole body at all stages of the cell cycle and localizes transiently to the cell division site during medial ring constriction and septation. |
| GO:0010564 regulation of cell cycle process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Sid2 regulates cell-cycle processes through cytokinesis signaling and a G2 role in mitotic commitment. This broad electronic annotation is biologically supported. Reason: Breadth alone does not make this true parent process an over-annotation. Direct Sid2-Fin1 regulation of mitotic commitment and the established cytokinesis role support the term, but more specific cell-cycle terms capture Sid2's core outputs. Supporting Evidence: PMID:22684255 acts independently of the other known SIN components in G2 phase of the cell cycle to control the timing of mitotic commitment. |
| GO:0035974 meiotic spindle pole body | IEA GO_REF:0000117 | ACCEPT | Summary: The SIN proteins, including Sid2, localize to the SPB in meiosis, where the SIN is required for forespore membrane and spore formation. Supported by direct experimental IDA annotations (PMID:16787941). Reason: Meiotic SPB localization is experimentally documented for the SIN, including Sid2. Supporting Evidence: PMID:16787941 The SIN proteins localise to the spindle pole body in meiosis. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Sid2 directly phosphorylates protein serine residues, as shown by phosphoamino acid analysis of the Clp1 substrate. Reason: The original Clp1 study establishes serine phosphorylation specifically, rather than merely a generic kinase assay or EC mapping. Supporting Evidence: PMID:18951025 Phosphoamino acid analysis of in vitro phosphorylated Clp1 showed that it was phosphorylated exclusively on serine residues (Figure 1C). |
| GO:0005515 protein binding | IPI PMID:10769201 The S. pombe orthologue of the S. cerevisiae mob1 gene is es... | REMOVE | Summary: The curated IPI record captures the experimentally supported Sid2-Mob1 interaction, but the generic protein binding term carries no functional specificity. Reason: Co-precipitation supports the interaction, and removal does not imply that the Sid2-Mob1 interaction is false. The interaction is captured more informatively by the accepted Sid2-Mob1 complex annotation. Supporting Evidence: PMID:10769201 we also demonstrate that mob1p can be precipitated from cells in a complex with the septation regulating kinase sid2p. |
| GO:0005816 spindle pole body | IDA PMID:15060149 Initiation of cytokinesis is controlled through multiple mod... | ACCEPT | Summary: Direct localization of the Sid2-Mob1 complex to the SPB; the N-terminal Mob1- binding region of Sid2 mediates SPB targeting. Reason: Direct experimental evidence for SPB localization and its molecular basis. Supporting Evidence: PMID:15060149 We identified a region at the amino terminus of Sid2p that is required for Mob1p binding and spindle pole body (SPB) localization. |
| GO:0031028 septation initiation signaling | NAS PMID:15060149 Initiation of cytokinesis is controlled through multiple mod... | ACCEPT | Summary: Septation initiation signaling is the core biological process of Sid2 as the terminal SIN kinase. Well established across the literature. Reason: Core process; Sid2 is the most downstream effector of the SIN that triggers septation. Supporting Evidence: PMID:15060149 The Sid2p-Mob1p kinase complex is an important component of the septation initiation network (SIN) in the fission yeast Schizosaccharomyces pombe. |
| GO:0034973 Sid2-Mob1 complex | IPI PMID:10769201 The S. pombe orthologue of the S. cerevisiae mob1 gene is es... | ACCEPT | Summary: Direct co-precipitation establishes Sid2 as a member of the Sid2-Mob1 complex. Reason: Directly demonstrated physical complex with Mob1. Supporting Evidence: PMID:10769201 we also demonstrate that mob1p can be precipitated from cells in a complex with the septation regulating kinase sid2p. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:24972934 Cross talk between NDR kinase pathways coordinates cytokines... | ACCEPT | Summary: Sid2 kinase activity assayed in the context of phosphorylating MOR component Nak1 to coordinate cytokinesis with cell separation. Reason: Experimentally supported kinase activity (substrate Nak1). Supporting Evidence: PMID:24972934 the SIN inhibiting the MOR during cytokinesis through phosphorylation of the MOR component Nak1 by the SIN Sid2 kinase. |
| GO:0035974 meiotic spindle pole body | IDA PMID:16787941 The Schizosaccharomyces pombe septation initiation network (... | ACCEPT | Summary: Sid2/SIN localizes to the meiotic SPB, where it functions in spore formation. Reason: Direct experimental localization to the meiotic SPB. Supporting Evidence: PMID:16787941 The SIN proteins localise to the spindle pole body in meiosis. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:10837231 Mob1p interacts with the Sid2p kinase and is required for cy... | ACCEPT | Summary: Kinase activity of the Sid2 complex characterized alongside Mob1; Mob1 is required for Sid2 function in cytokinesis initiation. Reason: Experimentally supported kinase activity in the cytokinesis-initiation context. Supporting Evidence: PMID:10837231 Mob1p associates with the Sid2p kinase and like Sid2p, Mob1p is required for the initiation of cytokinesis, but not for mitotic exit. |
| GO:0034973 Sid2-Mob1 complex | IPI PMID:10837231 Mob1p interacts with the Sid2p kinase and is required for cy... | ACCEPT | Summary: Sid2 associates with Mob1 (SPBC428.13c) in the Sid2-Mob1 complex. Reason: Directly demonstrated complex membership. Supporting Evidence: PMID:10837231 Mob1p associates with the Sid2p kinase and like Sid2p, Mob1p is required for the initiation of cytokinesis, but not for mitotic exit. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22419817 The fission yeast septation initiation network (SIN) kinase,... | ACCEPT | Summary: Sid2 kinase activity demonstrated by phosphorylation of the SIN scaffold Cdc11 in a positive-feedback loop. Reason: Experimentally supported kinase activity (substrate Cdc11). Supporting Evidence: PMID:22419817 we show that the last protein kinase in the signaling cascade, Sid2, feeds back to phosphorylate Cdc11 during mitosis. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:23087209 The kinesin-14 Klp2 is negatively regulated by the SIN for p... | ACCEPT | Summary: The original study directly assayed Sid2 phosphorylation of recombinant Klp2 and identified Klp2 phosphosites S113 and S123. Reason: Full text is available in the publication cache. Purified Sid2 phosphorylated recombinant Klp2, and phosphosite analysis connects the kinase activity to the Klp2 regulatory mechanism. Supporting Evidence: PMID:23087209 Klp2 was specifically phosphorylated by Sid2 (Figure 2A), showing that the SIN might inhibit Klp2 through direct phosphorylation by Sid2. |
| GO:0044732 mitotic spindle pole body | IDA PMID:25501814 The septation initiation network controls the assembly of no... | ACCEPT | Summary: Retain the curated Sid2 mitotic SPB annotation. The original paper studies SIN-dependent node dispersal, while its abstract localization statement specifically names Cdc7. Reason: Do not present the Cdc7 abstract statement as a Sid2 localization assay. Sid2 SPB localization is independently established in PMID:10459013; retain the curated record on that corroborating evidence without inventing paper-specific imaging details. Supporting Evidence: PMID:10459013 Sid2p is a component of the spindle pole body at all stages of the cell cycle and localizes transiently to the cell division site during medial ring constriction and septation. |
| GO:0110085 mitotic actomyosin contractile ring | IDA PMID:25501814 The septation initiation network controls the assembly of no... | ACCEPT | Summary: Retain the curated mitotic contractile-ring location, consistent with the established Sid2-Mob1 cytokinesis function. Reason: The original abstract supports SIN-dependent node dispersal, rather than directly describing a Sid2 imaging experiment. Its full-text introduction describes Sid2-Mob1 movement to the ring, and independent division-site localization is established in PMID:10459013; distinguish this corroboration from re-verification of the particular curated assay. Supporting Evidence: PMID:10459013 Sid2p is a component of the spindle pole body at all stages of the cell cycle and localizes transiently to the cell division site during medial ring constriction and septation. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:10459013 Sid2p, a spindle pole body kinase that regulates the onset o... | ACCEPT | Summary: Foundational demonstration of Sid2 kinase activity by in vitro assay, peaking during ring constriction and septation. Reason: Primary experimental demonstration of Sid2 kinase activity. Supporting Evidence: PMID:10459013 We have established an in vitro assay for measuring Sid2p kinase activity, and found that Sid2p kinase activity peaks during medial ring constriction and septation. |
| GO:0005737 cytoplasm | IDA PMID:22684255 The S. pombe cytokinesis NDR kinase Sid2 activates Fin1 NIMA... | ACCEPT | Summary: Antibody detection distinguishes an untagged cytoplasmic G2 Sid2 population from the interphase SPB signal of Sid2-GFP. This pool activates cytoplasmic Fin1. Reason: The original full text directly supports the cytoplasmic location and its G2 function; the abstract alone is not the localization evidence. Supporting Evidence: PMID:22684255 Thus, it is a cytoplasmic population of Sid2 that is activated mid-way through G2 to regulate a cytoplasmic population of Fin1. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:22684255 The S. pombe cytokinesis NDR kinase Sid2 activates Fin1 NIMA... | ACCEPT | Summary: Sid2-Mob1 directly activates (phosphorylates) the NIMA kinase Fin1, again demonstrating kinase activity. Reason: Experimentally supported kinase activity (substrate Fin1). Supporting Evidence: PMID:22684255 Sid2-Mob1 promotes mitotic commitment by directly activating the NIMA (Never In Mitosis)-related kinase Fin1. |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IMP PMID:22684255 The S. pombe cytokinesis NDR kinase Sid2 activates Fin1 NIMA... | ACCEPT | Summary: Through G2 activation of Fin1 and the Pom1/Cdr1/Cdr2-Wee1 network, Sid2-Mob1 promotes mitotic commitment, a moonlighting role distinct from its canonical cytokinesis function. Supported by mutant phenotype. Reason: Experimentally demonstrated role in promoting mitotic commitment via Fin1. Supporting Evidence: PMID:22684255 This spike of Fin1 activation modulates the activity of the Pom1/Cdr1/Cdr2 geometry network towards Wee1. |
| GO:1903473 positive regulation of mitotic actomyosin contractile ring contraction | IMP PMID:31041892 Fission yeast type 2 node proteins Blt1p and Gef2p cooperate... | ACCEPT | Summary: Sid2 (NDR kinase) localizes to the contractile ring to promote ring constriction, septation and completion of cell division; its recruitment depends on type-2 node proteins Blt1p/Gef2p. Reason: Core process; Sid2 promotes contractile ring constriction, supported by mutant analysis. Supporting Evidence: PMID:31041892 The conserved NDR-family kinase Sid2p localizes to the contractile ring during fission yeast cytokinesis to promote ring constriction, septation, and completion of cell division. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:30853434 NDR Kinase Sid2 Drives Anillin-like Mid1 from the Membrane t... | ACCEPT | Summary: Sid2 phosphorylates anillin-like Mid1, demonstrating kinase activity toward a contractile-ring substrate. Reason: Experimentally supported kinase activity (substrate Mid1). Supporting Evidence: PMID:30853434 We report that the terminal SIN kinase, Sid2 [6], phosphorylates Mid1 to drive its removal from the cortex at CR constriction onset. |
| GO:0140325 negative regulation of protein localization to medial cortex | EXP PMID:30853434 NDR Kinase Sid2 Drives Anillin-like Mid1 from the Membrane t... | ACCEPT | Summary: Sid2 phosphorylation of Mid1 drives Mid1 (and downstream node components) off the medial cortex at the onset of ring constriction. A specific, well-supported process. Reason: Directly supported; Sid2 removes Mid1 from the medial cortex/membrane. Supporting Evidence: PMID:30853434 A Mid1 mutant that cannot be phosphorylated by Sid2 remains cortical during cytokinesis. |
| GO:1905758 positive regulation of primary cell septum biogenesis | IMP PMID:29813053 Specific detection of fission yeast primary septum reveals s... | ACCEPT | Summary: The SIN (Sid2) promotes primary septum formation; this study specifically detects primary septum and furrow ingression during anaphase. Consistent with Sid2's septation role. Reason: Consistent with Sid2's established role in triggering septum formation, supported by mutant analysis. Supporting Evidence: PMID:29813053 Specific detection of fission yeast primary septum reveals septum and cleavage furrow ingression during early anaphase independent of mitosis completion. |
| GO:0032956 regulation of actin cytoskeleton organization | IMP PMID:20805322 The mitosis-to-interphase transition is coordinated by cross... | KEEP AS NON CORE | Summary: The SIN, via Sid2, inhibits the MOR pathway (Orb6/Nak1) to coordinate cytoskeletal remodeling at the mitosis-to-interphase transition, controlling actin polarization. A genuine but non-core regulatory output. Reason: Real role via SIN-MOR antagonism affecting actin organization, but peripheral to the core cytokinesis function. Supporting Evidence: PMID:20805322 the SIN inhibits MOR signaling in mitosis by interfering with Nak1 kinase-mediated activation of the most downstream MOR component, the NDR family kinase Orb6. |
| GO:0120105 mitotic actomyosin contractile ring, intermediate layer | IDA PMID:28914606 Nanoscale architecture of the Schizosaccharomyces pombe cont... | ACCEPT | Summary: Super-resolution mapping places Sid2 in the intermediate accessory-protein layer (80-160 nm from the membrane) of the contractile ring. Reason: Direct nanoscale localization within the contractile ring intermediate layer. Supporting Evidence: PMID:28914606 An intermediate layer (80-160 nm) consists of a network of cytokinesis accessory proteins as well as multiple |
| GO:1903473 positive regulation of mitotic actomyosin contractile ring contraction | EXP PMID:24790095 Characterization of the roles of Blt1p in fission yeast cyto... | ACCEPT | Summary: Sid2 (with Blt1p context) promotes contractile ring constriction during cytokinesis. Consistent with its core role in driving ring constriction. Reason: Core process supported experimentally; Sid2 drives ring contraction. Supporting Evidence: PMID:24790095 Spatial and temporal regulation of cytokinesis is essential for cell division, yet the mechanisms that control the formation and constriction of the contractile ring are incompletely understood. |
| GO:0032153 cell division site | IDA PMID:10459013 Sid2p, a spindle pole body kinase that regulates the onset o... | ACCEPT | Summary: Sid2 translocates transiently to the cell-division site during ring constriction and septation, where it executes cytokinesis. Core localization. Reason: Direct experimental evidence for transient division-site localization. Supporting Evidence: PMID:10459013 Sid2p is a component of the spindle pole body at all stages of the cell cycle and localizes transiently to the cell division site during medial ring constriction and septation. |
| GO:0044732 mitotic spindle pole body | IDA PMID:10459013 Sid2p, a spindle pole body kinase that regulates the onset o... | ACCEPT | Summary: Sid2 is a constitutive component of the mitotic SPB, the scaffold of the SIN kinase cascade. Reason: Direct experimental localization to the mitotic SPB. Supporting Evidence: PMID:10459013 Sid2p is a component of the spindle pole body at all stages of the cell cycle and localizes transiently to the cell division site during medial ring constriction and septation. |
| GO:0044878 mitotic cytokinesis checkpoint signaling | IMP PMID:16085489 The 14-3-3 protein rad24p modulates function of the cdc14p f... | ACCEPT | Summary: Sid2 is required for the cytokinesis checkpoint: SIN-dependent (Sid2-dependent) cytoplasmic retention of Clp1/Flp1 via Rad24 maintains the "cytokinesis- competent" delayed state upon ring perturbation. Reason: Experimentally supported role in the cytokinesis monitoring/checkpoint via Clp1-Rad24 retention. Supporting Evidence: PMID:16085489 This physical interaction depends on the function of the SIN component, Sid2p. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:18951025 The SIN kinase Sid2 regulates cytoplasmic retention of the S... | ACCEPT | Summary: Sid2 directly phosphorylates Clp1, demonstrating kinase activity toward a Cdc14-family phosphatase substrate. Reason: Experimentally supported kinase activity (substrate Clp1). Supporting Evidence: PMID:18951025 the most downstream SIN component, the Ndr-family kinase Sid2, maintains Clp1 in the cytoplasm in late mitosis by phosphorylating Clp1 directly and thereby creating binding sites for the 14-3-3 protein Rad24. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:23394829 Identification of SIN pathway targets reveals mechanisms of ... | ACCEPT | Summary: A proteomics screen identified multiple Sid2 substrates (e.g. Nak1, Sog2), confirming kinase activity and revealing SIN-MOR crosstalk. Reason: Experimentally supported kinase activity (multiple substrates including Nak1). Supporting Evidence: PMID:23394829 we developed a proteomics approach that allowed us to identify multiple substrates of the SIN effector kinase Sid2, including the MOR pathway components Nak1 kinase and an associated protein, Sog2. |
| GO:1902846 positive regulation of mitotic spindle elongation | IMP PMID:23087209 The kinesin-14 Klp2 is negatively regulated by the SIN for p... | ACCEPT | Summary: Sid2 promotes anaphase spindle elongation through inhibitory phosphorylation of the minus-end-directed kinesin Klp2. Reason: The original full text reports slower spindle elongation in sid2-250 cells and in cells expressing nonphosphorylatable Klp2. These measurements, together with direct Klp2 phosphorylation, support the positive regulatory process. Supporting Evidence: PMID:23087209 Consistent with SIN-mediated inhibition of Klp2, sid2-250 (SIN off) mutant cells showed 18% slower spindle elongation (n = 23) compared with wild-type cells (n = 29; p < 0.00001; Figure 3G). |
| GO:1902854 positive regulation of nuclear migration during mitotic telophase | IMP PMID:23087209 The kinesin-14 Klp2 is negatively regulated by the SIN for p... | ACCEPT | Summary: Sid2-dependent Klp2 inhibition contributes to telophase nuclear positioning, especially when cytokinesis is delayed. Reason: The original full text reports nuclear-positioning defects when SIN regulation of Klp2 is lost, with postanaphase-array microtubules providing an additional contribution. Retain the curated process while specifying the delayed-cytokinesis context; the experiments do not establish the same dependence in every normally dividing cell. Supporting Evidence: PMID:23087209 confirming our hypothesis that SIN inhibition of Klp2 contributes to maintaining proper nuclear positioning when cytokinesis is delayed. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:24115772 SIN-dependent phosphoinhibition of formin multimerization co... | ACCEPT | Summary: Sid2 phosphorylates the cytokinetic formin Cdc12 to inhibit its multimerization, again demonstrating kinase activity toward a key contractile-ring substrate. Reason: Experimentally supported kinase activity (substrate Cdc12 formin). Supporting Evidence: PMID:24115772 we identify the essential cytokinetic formin Cdc12 as a key CR substrate of SIN kinase Sid2. |
| GO:1903501 positive regulation of mitotic actomyosin contractile ring assembly | IMP PMID:24115772 SIN-dependent phosphoinhibition of formin multimerization co... | ACCEPT | Summary: Through phosphoinhibition of Cdc12 multimerization, Sid2 controls contractile ring assembly/maintenance; loss of Sid2-mediated Cdc12 phosphorylation prevents CR assembly without Mid1 and collapses rings when cytokinesis is delayed. Reason: Experimentally supported role in contractile ring assembly via Cdc12 phosphoregulation. Supporting Evidence: PMID:24115772 Eliminating Sid2-mediated Cdc12 phosphorylation leads to persistent Cdc12 clustering, which prevents CR assembly in the absence of anillin-like Mid1 and causes CRs to collapse when cytokinesis is delayed. |
| GO:0031028 septation initiation signaling | IMP PMID:22419817 The fission yeast septation initiation network (SIN) kinase,... | ACCEPT | Summary: Sid2 is essential for SIN signaling, including a positive-feedback loop onto Cdc11 that establishes SIN asymmetry and maximal anaphase signaling. Core process. Reason: Core septation-initiation-signaling role, supported by mutant analysis of the Sid2-Cdc11 feedback loop. Supporting Evidence: PMID:22419817 Sid2 is crucial for the establishment of SIN asymmetry, indicating a positive-feedback loop is an important element of the SIN. |
| GO:0005515 protein binding | IPI PMID:20876564 Antagonistic roles of PP2A-Pab1 and Etd1 in the control of c... | MODIFY | Summary: The curated IPI record captures a two-hybrid interaction of Sid2 with the PP2A regulatory subunit Pab1, which is better represented as phosphatase 2A binding. Reason: The paper explicitly reports Sid2 in Pab1 two-hybrid assays. Replace the contentless protein binding term with the more specific PP2A binding term because Pab1 is a protein phosphatase 2A B-subunit. Proposed replacements: protein phosphatase 2A binding Supporting Evidence: PMID:20876564 Two-hybrid assays indicate that Pab1 physically interacts with Mob1, Sid1, Sid2, and Cdc11, suggesting that the phosphatase 2A B-subunit is a component of the SIN complex. |
| GO:0044732 mitotic spindle pole body | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: The genome-wide localization study used yellow fluorescent protein tagging and supports the curated mitotic SPB localization. Reason: Retain the experimental localization with the correct reporter identity (YFP). This high-throughput record does not justify constitutive interphase localization of untagged Sid2. Supporting Evidence: PMID:16823372 ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe. |
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Download this section (compressed HTML)Q: What is the complete in vivo Sid2 substrate set across the cell cycle, and how is substrate selection spatially restricted between the SPB pool and the division-site pool of Sid2-Mob1?
Q: How is the G2-specific, SIN-independent Sid2-Mob1 activity that activates Fin1 regulated, given that canonical SIN activation is restricted to anaphase?
Experiment: Analog-sensitive (as) Sid2 kinase combined with quantitative phosphoproteomics and rapid kinase inhibition at defined cell-cycle stages to define the stage-specific Sid2 substrate repertoire and distinguish SPB vs division-site outputs.
Experiment: Optogenetic or anchor-away relocalization of Sid2-Mob1 to ectopic sites to test whether forced division-site targeting is sufficient to trigger ring constriction and septation independently of upstream SIN activation.
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