Serine/threonine protein kinase that initiates the Septation Initiation Network (SIN), the spindle pole body (SPB)-associated, GTPase-regulated kinase cascade that triggers cytokinesis and division septum formation in fission yeast. Cdc7 sits at the top of the SIN kinase cascade (Cdc7 -> Sid1-Cdc14 -> Sid2-Mob1): it is recruited to the SPB by the GTP-bound Spg1 GTPase, which is anchored there on the Sid4-Cdc11 scaffold, and its activity is required to hyperphosphorylate the scaffold protein Cdc11 and to propagate signaling that ultimately relocates the Sid2-Mob1 kinase to the cell division site to drive contractile-ring constriction and septum deposition. Cdc7 shows no discrete interphase localization; it associates with both SPBs early in mitosis and then becomes restricted to one (the new/daughter) SPB during anaphase B, an asymmetry that contributes to correct timing and inactivation of the SIN. Loss of cdc7 function blocks septum formation and produces multinucleate cells, whereas overexpression causes repeated rounds of septation without cell cleavage; DNA replication and mitosis are unaffected. During meiosis the SIN, including Cdc7, acts in forespore membrane formation/spore formation, and Cdc7 associates with the meiotic SPB. Despite its name, this protein is unrelated in function to the Dbf4-dependent (DDK) replication-initiation kinase, whose fission-yeast ortholog is Hsk1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Cdc7 is a bona fide Ser/Thr protein kinase, so the phylogenetically inferred molecular function is correct and represents a core activity. Reason: The kinase activity is independently supported by experimental evidence (in vitro kinase assays and kinase-dead phenotypes), and Cdc7 belongs to the protein kinase superfamily Ser/Thr CDC7 subfamily. Supporting Evidence: PMID:8039497 We have cloned the cdc7 gene and show that it encodes a protein kinase which is essential for cell division. |
| GO:0000165 MAPK cascade | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Cdc7 is not a component of a MAPK cascade. It is the apical kinase of the Septation Initiation Network (SIN), a GTPase-regulated kinase cascade that is distinct from MAP kinase signaling. This IBA is over-propagated from the PANTHER STE20/SPS1-PAK family, some members of which feed MAPK cascades. Reason: The SIN is not a MAPK cascade; Cdc7 is neither a MAPKKK/MAP2K/MAPK nor a regulator of one. The correct, experimentally supported pathway annotation is septation initiation signaling (GO:0031028). The MAPK-cascade inference reflects family-level homology rather than the demonstrated biology. Supporting Evidence: PMID:15933715 ring constriction is triggered by the septum initiation network (SIN), an SPB-associated GTPase-regulated kinase cascade that coordinates exit from mitosis with cytokinesis |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Correct but less precise. Cdc7 is specifically a serine/threonine protein kinase (GO:0004674), so this general parent term is subsumed by the more informative experimentally supported annotation. Reason: The InterPro-based parent term is accurate but should be specialized to protein serine/threonine kinase activity, for which there is direct experimental evidence. Proposed replacements: protein serine/threonine kinase activity Supporting Evidence: PMID:12546793 We demonstrate that mitotic hyperphosphorylation of cdc11p requires the activity of cdc7p |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC 2.7.11.1 maps to protein serine/threonine kinase activity, consistent with the UniProt catalytic activity annotation and experimental data. Core molecular function. Reason: The EC-to-GO mapping is correct and corroborated by experimental kinase assays. Supporting Evidence: PMID:9420333 Spg1p activity is required for localization of Cdc7p in vivo but not for its kinase activity in vitro. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding is expected and correct for this active protein kinase, which has a conserved glycine-rich ATP-binding loop (residues 15-23) and an invariant lysine (K38). Core molecular function supporting catalysis. Reason: Conserved kinase ATP-binding motifs are present and the protein has demonstrated kinase activity, which requires ATP. Supporting Evidence: PMID:8039497 We have cloned the cdc7 gene and show that it encodes a protein kinase which is essential for cell division. |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Correct. The RHEA-based serine-kinase reaction annotation is accurate; Cdc7 is a Ser/Thr kinase and so also phosphorylates serine residues. It is a partial/companion of the fuller Ser/Thr term (GO:0004674). Reason: Consistent with the dual Ser and Thr catalytic-activity statements in UniProt and with the Ser/Thr kinase family assignment. Supporting Evidence: PMID:9420333 Spg1p activity is required for localization of Cdc7p in vivo but not for its kinase activity in vitro. |
| GO:0035974 meiotic spindle pole body | IDA PMID:16787941 The Schizosaccharomyces pombe septation initiation network (... | ACCEPT | Summary: During meiosis the SIN, including Cdc7, localizes to the spindle pole body; Cdc7 specifically associates with the meiotic SPB in meiosis II coincident with forespore membrane formation. Supports a meiotic SPB localization. Reason: Direct cytological evidence places Cdc7 at the meiotic SPB; the SIN is required for spore formation. Supporting Evidence: PMID:16787941 The protein kinases Sid1p and Cdc7p do not associate with the spindle pole body until meiosis II, when forespore membrane deposition begins. |
| GO:0035974 meiotic spindle pole body | IDA PMID:24838944 Dma1-dependent degradation of SIN proteins during meiosis in... | ACCEPT | Summary: This study of meiotic SIN regulation documents Cdc7 at the meiotic SPB and its stage-specific, Dma1-dependent degradation after meiosis II, corroborating the meiotic SPB localization. Reason: Direct cytological observation of Cdc7 at the meiotic SPB during meiosis. Supporting Evidence: PMID:24838944 the degradation of Cdc7p, Cdc11p and Sid4p occurs after the second meiotic division and depends upon the ubiquitin ligase Dma1p |
| GO:0071957 old mitotic spindle pole body | IDA PMID:15933715 Etd1p is a novel protein that links the SIN cascade with cyt... | ACCEPT | Summary: Cdc7 localizes to mitotic SPBs as part of SIN signaling. During anaphase Cdc7 is retained on the SPB that maintains active Spg1; this paper reviews and uses Cdc7 SPB localization in characterizing SIN-driven cytokinesis. Reason: Consistent with direct cytological evidence for Cdc7 at the mitotic SPB; Cdc7 is found transiently at both poles before becoming asymmetric. Supporting Evidence: PMID:15933715 The protein kinase Cdc7p is asymmetrically recruited to the SPB that maintains the activated form of Spg1p |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:12546793 Mitotic hyperphosphorylation of the fission yeast SIN scaffo... | ACCEPT | Summary: Direct in vivo evidence that Cdc7 kinase activity is required for mitotic hyperphosphorylation of the SIN scaffold Cdc11, identifying Cdc11 as a functional substrate. Core molecular function. Reason: Experimental demonstration that Cdc7 activity drives phosphorylation of a SIN substrate in vivo. Supporting Evidence: PMID:12546793 We demonstrate that mitotic hyperphosphorylation of cdc11p requires the activity of cdc7p and that its dephosphorylation at the end of mitosis requires PP2A-par1p. |
| GO:0031028 septation initiation signaling | EXP PMID:12546793 Mitotic hyperphosphorylation of the fission yeast SIN scaffo... | ACCEPT | Summary: Core biological process. Cdc7 mediates SIN signaling; mitotic hyperphosphorylation of the SIN scaffold Cdc11 correlates with and requires SIN activation by Cdc7 in vivo. Reason: Experimental evidence directly links Cdc7 activity to activation of SIN signaling. Supporting Evidence: PMID:12546793 We conclude that cdc11p hyperphosphorylation correlates with activation of the SIN and that this may be mediated primarily by cdc7p in vivo. |
| GO:0044732 mitotic spindle pole body | IDA PMID:12546793 Mitotic hyperphosphorylation of the fission yeast SIN scaffo... | ACCEPT | Summary: Cdc7 signals from the mitotic SPB, where SIN proteins bind in a cell-cycle-dependent manner via the Sid4-Cdc11 scaffold. Core localization. Reason: Direct localization of Cdc7 to the mitotic SPB is consistent with this and multiple other studies. Supporting Evidence: PMID:12546793 SIN proteins signal from the spindle pole body (SPB), to which they bind in a cell cycle-dependent manner, via the scaffold proteins sid4p and cdc11p. |
| GO:0031028 septation initiation signaling | IMP PMID:8039497 The cdc7 protein kinase is a dosage dependent regulator of s... | ACCEPT | Summary: Foundational genetic evidence: loss of cdc7 prevents initiation of the division septum, while overexpression drives repeated septation, establishing Cdc7 as a key inducer of septation initiation signaling. Core biological process. Reason: Loss- and gain-of-function phenotypes demonstrate Cdc7's role in initiating septum formation/septation signaling. Supporting Evidence: PMID:8039497 In the absence of cdc7 function, spore germination, DNA synthesis and mitosis are unaffected, but cells are unable to initiate formation of the division septum. |
| GO:0071957 old mitotic spindle pole body | IDA PMID:9420333 Asymmetric segregation on spindle poles of the Schizosacchar... | ACCEPT | Summary: Cdc7 associates with both SPBs early in mitosis (thus including the old SPB) before becoming restricted to one pole during anaphase B. Direct immunofluorescence evidence supports SPB (including old SPB) localization. Reason: Direct cytological observation of Cdc7 on both spindle poles early in mitosis. Supporting Evidence: PMID:9420333 early in mitosis it associates with both spindle pole bodies and, as the spindle extends, is seen on only one pole of the spindle during anaphase B. |
| GO:0071958 new mitotic spindle pole body | IDA PMID:9420333 Asymmetric segregation on spindle poles of the Schizosacchar... | ACCEPT | Summary: In late anaphase Cdc7 becomes asymmetric and is retained on the new (daughter) SPB that maintains active Spg1. Direct evidence supports the new SPB localization. Core to SIN asymmetry. Reason: Direct cytological observation of asymmetric Cdc7 retention on one (new/daughter) spindle pole during anaphase. Supporting Evidence: PMID:9420333 Furthermore, staining with this antibody shows that asymmetric distribution of Cdc7p may be mediated by inactivation of Spg1p on one spindle pole. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:9420333 Asymmetric segregation on spindle poles of the Schizosacchar... | ACCEPT | Summary: Direct experimental evidence that Cdc7 has in vitro kinase activity, measured independently of its localization. Core molecular function. Reason: In vitro kinase activity of Cdc7 was demonstrated and shown to be independent of Spg1-dependent SPB recruitment. Supporting Evidence: PMID:9420333 Spg1p activity is required for localization of Cdc7p in vivo but not for its kinase activity in vitro. |
| GO:0071958 new mitotic spindle pole body | IDA PMID:10381387 Asymmetry of the spindle pole bodies and spg1p GAP segregati... | ACCEPT | Summary: Confirms Cdc7 on both SPBs early in mitosis and on only one pole later; Cdc7 is retained on the pole with active Spg1 (the new/daughter SPB). Supports new SPB localization. Reason: Direct immunofluorescence of Cdc7 across the mitotic cell cycle supports asymmetric retention on one (new) SPB. Supporting Evidence: PMID:10381387 cdc7p is located on both spindle pole bodies early in mitosis, but only on one during the later stages of anaphase. |
| GO:0044732 mitotic spindle pole body | IDA PMID:10799520 Byr4 localizes to spindle-pole bodies in a cell cycle-regula... | ACCEPT | Summary: Active GTP-Spg1 binds Cdc7 and causes its translocation to mitotic SPBs; Byr4 controls Cdc7 SPB localization. Direct evidence for Cdc7 at the mitotic SPB. Core localization. Reason: Direct localization study showing regulated recruitment of Cdc7 to mitotic SPBs. Supporting Evidence: PMID:10799520 As cells enter mitosis, Spg1 accumulates in an active, GTP-bound form and binds the Cdc7 protein kinase to cause Cdc7 translocation to SPBs. |
| GO:0044732 mitotic spindle pole body | IDA PMID:19736319 Proper timing of cytokinesis is regulated by Schizosaccharom... | ACCEPT | Summary: Spg1-GTP binds and recruits Cdc7 to the SPB, where SPB-localized Cdc7 promotes downstream Sid2 activation. Direct evidence for Cdc7 at the mitotic SPB. Reason: Live-cell/cytological work confirms regulated Cdc7 localization to the mitotic SPB. Supporting Evidence: PMID:19736319 Once activated, Spg1-GTP binds the Cdc7 kinase and recruits it to the spindle pole body (SPB; Sohrmann et al., 1998). |
| GO:0071958 new mitotic spindle pole body | IDA PMID:19736319 Proper timing of cytokinesis is regulated by Schizosaccharom... | ACCEPT | Summary: Spg1 is active at just one (the new/daughter) SPB during cytokinesis and retains Cdc7 there; asymmetric SIN activation is described directly. Supports new SPB localization. Reason: Direct observation of asymmetric Cdc7/Spg1 retention on one spindle pole during cytokinesis. Supporting Evidence: PMID:19736319 Spg1 is active at just one of the two SPBs during cytokinesis. |
| GO:0031028 septation initiation signaling | EXP PMID:11676915 S. pombe cdc11p, together with sid4p, provides an anchor for... | ACCEPT | Summary: SIN signaling requires the Sid4-Cdc11 scaffold, which anchors Cdc7 and the other SIN components at the SPB; this work delineates the SIN organization in which Cdc7 signals septation initiation. Core biological process. Reason: The study defines the SIN scaffold that recruits Cdc7 and is required for septation initiation signaling. Supporting Evidence: PMID:11676915 cdc11p is required for the localization of all the known SIN components, except sid4p, to the SPB. |
| GO:0044732 mitotic spindle pole body | IDA PMID:25501814 The septation initiation network controls the assembly of no... | ACCEPT | Summary: Time-lapse imaging of Cdc7-GFP shows accumulation at spindle pole bodies upon SIN activation. Direct fluorescence evidence for Cdc7 at the mitotic SPB. Core localization. Reason: Live-cell imaging directly visualizes Cdc7-GFP at the SPB. Supporting Evidence: PMID:25501814 Activating the SIN in interphase cells dispersed Cdr2p and anillin Mid1p from type 1 nodes a few min after the SIN kinase Cdc7p-GFP accumulated at spindle pole bodies. |
| GO:0071958 new mitotic spindle pole body | IDA PMID:19942852 Fission yeast Pcp1 links polo kinase-mediated mitotic entry ... | ACCEPT | Summary: This SPB-focused study uses Cdc7 as a marker of the active/new SPB during mitosis. Consistent with direct evidence that Cdc7 marks one (new/daughter) mitotic SPB. Given the paper's primary focus is Pcp1, this specific Cdc7 new-SPB IDA reflects curator reading of the full text; accepted and deferred to PomBase. Reason: PomBase curators assigned this IDA from the full text; Cdc7 asymmetric new-SPB localization is corroborated by multiple independent studies, so the annotation is consistent even though the cached abstract foregrounds Pcp1. Supporting Evidence: PMID:9420333 as the spindle extends, is seen on only one pole of the spindle during anaphase B. |
| GO:0071958 new mitotic spindle pole body | IDA PMID:16325501 The fission yeast MO25 protein functions in polar growth and... | ACCEPT | Summary: This study of Pmo25 reports that, like Cdc7, proteins are recruited to one of the two SPBs during anaphase under SIN control; the curated Cdc7 IDA reflects observation of Cdc7 marking the SPB. Accepted and deferred to PomBase given the cached abstract centers on Pmo25. Reason: PomBase assigned this IDA from the full text; Cdc7 asymmetric new-SPB localization is well established across studies, so the annotation is consistent despite the abstract's focus on Pmo25. Supporting Evidence: PMID:16325501 it is recruited to one of the two spindle pole bodies during anaphase and to the division site during cytokinesis. |
| GO:0004674 protein serine/threonine kinase activity | IMP PMID:8039497 The cdc7 protein kinase is a dosage dependent regulator of s... | ACCEPT | Summary: The kinase activity of Cdc7 is required for its biological function: the overexpression-induced multiple-septation phenotype requires Cdc7 kinase activity, and cdc7 encodes an essential protein kinase. Core molecular function. Reason: Mutant phenotype analysis demonstrates that Cdc7 kinase activity is required for septum induction. Supporting Evidence: PMID:8039497 This phenotype, which is similar to that resulting from inactivation of cdc16 protein, requires the kinase activity of p120cdc7. |
| GO:0140281 positive regulation of mitotic division septum assembly | IMP PMID:8039497 The cdc7 protein kinase is a dosage dependent regulator of s... | ACCEPT | Summary: Cdc7 positively regulates division septum assembly: it is required to initiate septum formation, and elevated dosage drives multiple rounds of septum formation. Core biological process. Reason: Loss-of-function blocks septum formation while overexpression promotes excess septa, directly demonstrating positive regulation of septum assembly. Supporting Evidence: PMID:8039497 Overexpression of p120cdc7 causes cell cycle arrest; cells complete mitosis and then undergo multiple rounds of septum formation without cell cleavage. |
| GO:0071958 new mitotic spindle pole body | IDA PMID:22119525 SIN-inhibitory phosphatase complex promotes Cdc11p dephospho... | ACCEPT | Summary: Cdc7 (with Sid1) localizes asymmetrically to the newly duplicated SPB in late anaphase; the SIP/PP2A complex propagates this asymmetry by promoting Cdc7 accumulation at the new SPB. Direct evidence for new SPB localization. Reason: Direct cytological evidence that Cdc7 accumulates asymmetrically at the new (newly duplicated) SPB. Supporting Evidence: PMID:22119525 Two of the SIN kinases, Cdc7p and Sid1p, localize asymmetrically to the newly duplicated SPB in late anaphase. |
| GO:0044732 mitotic spindle pole body | IDA PMID:9420333 Asymmetric segregation on spindle poles of the Schizosacchar... | ACCEPT | Summary: Direct immunofluorescence shows Cdc7 associated with the mitotic SPB, transiently on both poles before becoming asymmetric. Core localization. Reason: Direct cytological evidence for Cdc7 at the mitotic SPB. Supporting Evidence: PMID:9420333 early in mitosis it associates with both spindle pole bodies |
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Download this section (compressed HTML)Q: What are the physiological substrates of Cdc7 beyond Cdc11, and how does Cdc7 phosphorylation activate the downstream Sid1-Cdc14 kinase module?
Q: How is Cdc7 kinase activity itself regulated at the SPB, given that Spg1 controls its localization but not its intrinsic in vitro activity?
Q: What is the molecular basis for the asymmetric retention of Cdc7 on the new (daughter) SPB, and why is this asymmetry important for correct SIN timing and inactivation?
Experiment: Quantitative phosphoproteomics comparing wild-type and analog-sensitive cdc7-as cells (with bulky ATP-analog inhibition) to map the in vivo Cdc7 substrate set during anaphase/cytokinesis.
Experiment: Structure-function dissection of the large C-terminal ARM-repeat region of Cdc7 to determine its contribution to SPB recruitment, Spg1 binding, and asymmetric localization.
Experiment: Live-cell imaging of Cdc7-GFP in spg1, cdc16, byr4 and SIP/PP2A mutant backgrounds to dissect how the GAP and phosphatase modules establish and propagate asymmetric Cdc7 localization to the new SPB.
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