id: P41892
gene_symbol: cdc7
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:284812
  label: Schizosaccharomyces pombe (strain 972 / ATCC 24843)
description: >-
  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.
existing_annotations:
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Cdc7 is a bona fide Ser/Thr protein kinase, so the phylogenetically
      inferred molecular function is correct and represents a core activity.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:8039497
      supporting_text: >-
        We have cloned the cdc7 gene and show that it encodes a protein kinase
        which is essential for cell division.
      reference_section_type: ABSTRACT
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: PMID:15933715
      supporting_text: >-
        ring constriction is triggered by the septum initiation network (SIN),
        an SPB-associated GTPase-regulated kinase cascade that coordinates exit
        from mitosis with cytokinesis
      reference_section_type: ABSTRACT
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0004674
      label: protein serine/threonine kinase activity
    supported_by:
    - reference_id: PMID:12546793
      supporting_text: >-
        We demonstrate that mitotic hyperphosphorylation of cdc11p requires the
        activity of cdc7p
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      The EC-to-GO mapping is correct and corroborated by experimental kinase
      assays.
    supported_by:
    - reference_id: PMID:9420333
      supporting_text: >-
        Spg1p activity is required for localization of Cdc7p in vivo but not for
        its kinase activity in vitro.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      Conserved kinase ATP-binding motifs are present and the protein has
      demonstrated kinase activity, which requires ATP.
    supported_by:
    - reference_id: PMID:8039497
      supporting_text: >-
        We have cloned the cdc7 gene and show that it encodes a protein kinase
        which is essential for cell division.
      reference_section_type: ABSTRACT
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    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).
    action: ACCEPT
    reason: >-
      Consistent with the dual Ser and Thr catalytic-activity statements in
      UniProt and with the Ser/Thr kinase family assignment.
    supported_by:
    - reference_id: PMID:9420333
      supporting_text: >-
        Spg1p activity is required for localization of Cdc7p in vivo but not for
        its kinase activity in vitro.
      reference_section_type: ABSTRACT
- term:
    id: GO:0035974
    label: meiotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:16787941
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Direct cytological evidence places Cdc7 at the meiotic SPB; the SIN is
      required for spore formation.
    supported_by:
    - reference_id: PMID:16787941
      supporting_text: >-
        The protein kinases Sid1p and Cdc7p do not associate with the spindle
        pole body until meiosis II, when forespore membrane deposition begins.
      reference_section_type: ABSTRACT
- term:
    id: GO:0035974
    label: meiotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:24838944
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Direct cytological observation of Cdc7 at the meiotic SPB during meiosis.
    supported_by:
    - reference_id: PMID:24838944
      supporting_text: >-
        the degradation of Cdc7p, Cdc11p and Sid4p occurs after the second
        meiotic division and depends upon the ubiquitin ligase Dma1p
      reference_section_type: ABSTRACT
- term:
    id: GO:0071957
    label: old mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:15933715
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Consistent with direct cytological evidence for Cdc7 at the mitotic SPB;
      Cdc7 is found transiently at both poles before becoming asymmetric.
    supported_by:
    - reference_id: PMID:15933715
      supporting_text: >-
        The protein kinase Cdc7p is asymmetrically recruited to the SPB that
        maintains the activated form of Spg1p
      reference_section_type: INTRODUCTION
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:12546793
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      Experimental demonstration that Cdc7 activity drives phosphorylation of a
      SIN substrate in vivo.
    supported_by:
    - reference_id: PMID:12546793
      supporting_text: >-
        We demonstrate that mitotic hyperphosphorylation of cdc11p requires the
        activity of cdc7p and that its dephosphorylation at the end of mitosis
        requires PP2A-par1p.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031028
    label: septation initiation signaling
  evidence_type: EXP
  original_reference_id: PMID:12546793
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Experimental evidence directly links Cdc7 activity to activation of SIN
      signaling.
    supported_by:
    - reference_id: PMID:12546793
      supporting_text: >-
        We conclude that cdc11p hyperphosphorylation correlates with activation
        of the SIN and that this may be mediated primarily by cdc7p in vivo.
      reference_section_type: ABSTRACT
- term:
    id: GO:0044732
    label: mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:12546793
  qualifier: is_active_in
  review:
    summary: >-
      Cdc7 signals from the mitotic SPB, where SIN proteins bind in a
      cell-cycle-dependent manner via the Sid4-Cdc11 scaffold. Core localization.
    action: ACCEPT
    reason: >-
      Direct localization of Cdc7 to the mitotic SPB is consistent with this and
      multiple other studies.
    supported_by:
    - reference_id: PMID:12546793
      supporting_text: >-
        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.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031028
    label: septation initiation signaling
  evidence_type: IMP
  original_reference_id: PMID:8039497
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Loss- and gain-of-function phenotypes demonstrate Cdc7's role in initiating
      septum formation/septation signaling.
    supported_by:
    - reference_id: PMID:8039497
      supporting_text: >-
        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.
      reference_section_type: ABSTRACT
- term:
    id: GO:0071957
    label: old mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:9420333
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Direct cytological observation of Cdc7 on both spindle poles early in
      mitosis.
    supported_by:
    - reference_id: PMID:9420333
      supporting_text: >-
        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.
      reference_section_type: ABSTRACT
- term:
    id: GO:0071958
    label: new mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:9420333
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Direct cytological observation of asymmetric Cdc7 retention on one
      (new/daughter) spindle pole during anaphase.
    supported_by:
    - reference_id: PMID:9420333
      supporting_text: >-
        Furthermore, staining with this antibody shows that asymmetric
        distribution of Cdc7p may be mediated by inactivation of Spg1p on one
        spindle pole.
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:9420333
  qualifier: enables
  review:
    summary: >-
      Direct experimental evidence that Cdc7 has in vitro kinase activity,
      measured independently of its localization. Core molecular function.
    action: ACCEPT
    reason: >-
      In vitro kinase activity of Cdc7 was demonstrated and shown to be
      independent of Spg1-dependent SPB recruitment.
    supported_by:
    - reference_id: PMID:9420333
      supporting_text: >-
        Spg1p activity is required for localization of Cdc7p in vivo but not for
        its kinase activity in vitro.
      reference_section_type: ABSTRACT
- term:
    id: GO:0071958
    label: new mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:10381387
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Direct immunofluorescence of Cdc7 across the mitotic cell cycle supports
      asymmetric retention on one (new) SPB.
    supported_by:
    - reference_id: PMID:10381387
      supporting_text: >-
        cdc7p is located on both spindle pole bodies early in mitosis, but only
        on one during the later stages of anaphase.
      reference_section_type: ABSTRACT
- term:
    id: GO:0044732
    label: mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:10799520
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Direct localization study showing regulated recruitment of Cdc7 to mitotic
      SPBs.
    supported_by:
    - reference_id: PMID:10799520
      supporting_text: >-
        As cells enter mitosis, Spg1 accumulates in an active, GTP-bound form and
        binds the Cdc7 protein kinase to cause Cdc7 translocation to SPBs.
      reference_section_type: ABSTRACT
- term:
    id: GO:0044732
    label: mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:19736319
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Live-cell/cytological work confirms regulated Cdc7 localization to the
      mitotic SPB.
    supported_by:
    - reference_id: PMID:19736319
      supporting_text: >-
        Once activated, Spg1-GTP binds the Cdc7 kinase and recruits it to the
        spindle pole body (SPB; Sohrmann et al., 1998).
      reference_section_type: INTRODUCTION
- term:
    id: GO:0071958
    label: new mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:19736319
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Direct observation of asymmetric Cdc7/Spg1 retention on one spindle pole
      during cytokinesis.
    supported_by:
    - reference_id: PMID:19736319
      supporting_text: >-
        Spg1 is active at just one of the two SPBs during cytokinesis.
      reference_section_type: ABSTRACT
- term:
    id: GO:0031028
    label: septation initiation signaling
  evidence_type: EXP
  original_reference_id: PMID:11676915
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: >-
      The study defines the SIN scaffold that recruits Cdc7 and is required for
      septation initiation signaling.
    supported_by:
    - reference_id: PMID:11676915
      supporting_text: >-
        cdc11p is required for the localization of all the known SIN components,
        except sid4p, to the SPB.
      reference_section_type: ABSTRACT
- term:
    id: GO:0044732
    label: mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:25501814
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Live-cell imaging directly visualizes Cdc7-GFP at the SPB.
    supported_by:
    - reference_id: PMID:25501814
      supporting_text: >-
        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.
      reference_section_type: ABSTRACT
- term:
    id: GO:0071958
    label: new mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:19942852
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:9420333
      supporting_text: >-
        as the spindle extends, is seen on only one pole of the spindle during
        anaphase B.
      reference_section_type: ABSTRACT
- term:
    id: GO:0071958
    label: new mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:16325501
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16325501
      supporting_text: >-
        it is recruited to one of the two spindle pole bodies during anaphase and
        to the division site during cytokinesis.
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:8039497
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: >-
      Mutant phenotype analysis demonstrates that Cdc7 kinase activity is
      required for septum induction.
    supported_by:
    - reference_id: PMID:8039497
      supporting_text: >-
        This phenotype, which is similar to that resulting from inactivation of
        cdc16 protein, requires the kinase activity of p120cdc7.
      reference_section_type: ABSTRACT
- term:
    id: GO:0140281
    label: positive regulation of mitotic division septum assembly
  evidence_type: IMP
  original_reference_id: PMID:8039497
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Loss-of-function blocks septum formation while overexpression promotes
      excess septa, directly demonstrating positive regulation of septum
      assembly.
    supported_by:
    - reference_id: PMID:8039497
      supporting_text: >-
        Overexpression of p120cdc7 causes cell cycle arrest; cells complete
        mitosis and then undergo multiple rounds of septum formation without cell
        cleavage.
      reference_section_type: ABSTRACT
- term:
    id: GO:0071958
    label: new mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:22119525
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: >-
      Direct cytological evidence that Cdc7 accumulates asymmetrically at the new
      (newly duplicated) SPB.
    supported_by:
    - reference_id: PMID:22119525
      supporting_text: >-
        Two of the SIN kinases, Cdc7p and Sid1p, localize asymmetrically to the
        newly duplicated SPB in late anaphase.
      reference_section_type: ABSTRACT
- term:
    id: GO:0044732
    label: mitotic spindle pole body
  evidence_type: IDA
  original_reference_id: PMID:9420333
  qualifier: is_active_in
  review:
    summary: >-
      Direct immunofluorescence shows Cdc7 associated with the mitotic SPB,
      transiently on both poles before becoming asymmetric. Core localization.
    action: ACCEPT
    reason: >-
      Direct cytological evidence for Cdc7 at the mitotic SPB.
    supported_by:
    - reference_id: PMID:9420333
      supporting_text: >-
        early in mitosis it associates with both spindle pole bodies
      reference_section_type: ABSTRACT
core_functions:
- description: >-
    Acts as the apical serine/threonine protein kinase of the Septation
    Initiation Network, phosphorylating SIN components (e.g. the scaffold Cdc11)
    to initiate the kinase cascade that triggers cytokinesis.
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0031028
    label: septation initiation signaling
  locations:
  - id: GO:0044732
    label: mitotic spindle pole body
  supported_by:
  - reference_id: PMID:12546793
    supporting_text: >-
      We demonstrate that mitotic hyperphosphorylation of cdc11p requires the
      activity of cdc7p and that its dephosphorylation at the end of mitosis
      requires PP2A-par1p.
    reference_section_type: ABSTRACT
- description: >-
    Positively regulates initiation of division septum formation and
    cytokinesis; required for septum formation while excess Cdc7 drives repeated
    septation.
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0140281
    label: positive regulation of mitotic division septum assembly
  locations:
  - id: GO:0044732
    label: mitotic spindle pole body
  supported_by:
  - reference_id: PMID:8039497
    supporting_text: >-
      These findings indicate that the p120cdc7 protein kinase plays a key role
      in initiation of septum formation and cytokinesis in fission yeast
    reference_section_type: ABSTRACT
- description: >-
    Is recruited by GTP-bound Spg1 to the spindle pole body and becomes
    asymmetrically retained on one (new/daughter) SPB during anaphase,
    contributing to the spatial and temporal regulation of SIN signaling.
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0031028
    label: septation initiation signaling
  locations:
  - id: GO:0071958
    label: new mitotic spindle pole body
  supported_by:
  - reference_id: PMID:9420333
    supporting_text: >-
      Cdc7p shows no discrete localization during interphase, but 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.
    reference_section_type: ABSTRACT
references:
- id: file:interpro/panther/PTHR48012/PTHR48012-review.md
  title: 'PANTHER family review PTHR48012: IBA propagation assessment for cdc7'
  findings: []
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings:
  - statement: >-
      The protein serine/threonine kinase activity IBA is correct, but the MAPK
      cascade IBA is an over-propagation from the PANTHER STE20/SPS1-PAK family;
      Cdc7 functions in the SIN, not a MAPK cascade.
    supporting_text: >-
      ring constriction is triggered by the septum initiation network (SIN), an
      SPB-associated GTPase-regulated kinase cascade that coordinates exit from
      mitosis with cytokinesis
    reference_section_type: ABSTRACT
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: PMID:10381387
  title: Asymmetry of the spindle pole bodies and spg1p GAP segregation during mitosis
    in fission yeast.
  findings:
  - statement: >-
      Cdc7 localizes to both SPBs early in mitosis and to only one pole during
      anaphase; asymmetric Spg1 inactivation by the Cdc16-Byr4 GAP underlies the
      asymmetric retention of Cdc7.
    supporting_text: >-
      cdc7p is located on both spindle pole bodies early in mitosis, but only on
      one during the later stages of anaphase.
    reference_section_type: ABSTRACT
- id: PMID:10799520
  title: Byr4 localizes to spindle-pole bodies in a cell cycle-regulated manner to
    control Cdc7 localization and septation in fission yeast.
  findings:
  - statement: >-
      Active GTP-Spg1 binds Cdc7 and causes its translocation to SPBs; Byr4
      localization to SPBs controls Cdc7 localization and septation.
    supporting_text: >-
      As cells enter mitosis, Spg1 accumulates in an active, GTP-bound form and
      binds the Cdc7 protein kinase to cause Cdc7 translocation to SPBs.
    reference_section_type: ABSTRACT
- id: PMID:11676915
  title: S. pombe cdc11p, together with sid4p, provides an anchor for septation initiation
    network proteins on the spindle pole body.
  findings:
  - statement: >-
      The Sid4-Cdc11 scaffold anchors SIN components, including Cdc7, at the SPB
      and is required for septation initiation signaling.
    supporting_text: >-
      cdc11p is required for the localization of all the known SIN components,
      except sid4p, to the SPB.
    reference_section_type: ABSTRACT
- id: PMID:11859360
  title: The genome sequence of Schizosaccharomyces pombe.
  findings: []
- id: PMID:12546793
  title: Mitotic hyperphosphorylation of the fission yeast SIN scaffold protein cdc11p
    is regulated by the protein kinase cdc7p.
  findings:
  - statement: >-
      Cdc7 kinase activity is required for mitotic hyperphosphorylation of the
      SIN scaffold Cdc11, identifying Cdc11 as a functional substrate and linking
      Cdc7 to SIN activation.
    supporting_text: >-
      We demonstrate that mitotic hyperphosphorylation of cdc11p requires the
      activity of cdc7p and that its dephosphorylation at the end of mitosis
      requires PP2A-par1p.
    reference_section_type: ABSTRACT
- id: PMID:15933715
  title: Etd1p is a novel protein that links the SIN cascade with cytokinesis.
  findings:
  - statement: >-
      The SIN is an SPB-associated GTPase-regulated kinase cascade; Cdc7 is
      asymmetrically recruited to the SPB that maintains active Spg1 and acts
      upstream of Sid1-Cdc14 and Sid2-Mob1 to trigger ring constriction.
    supporting_text: >-
      The protein kinase Cdc7p is asymmetrically recruited to the SPB that
      maintains the activated form of Spg1p
    reference_section_type: INTRODUCTION
- id: PMID:16325501
  title: The fission yeast MO25 protein functions in polar growth and cell separation.
  findings:
  - statement: >-
      SIN-regulated proteins (and Cdc7) are recruited to one of the two SPBs
      during anaphase and to the division site during cytokinesis.
    supporting_text: >-
      it is recruited to one of the two spindle pole bodies during anaphase and
      to the division site during cytokinesis.
    reference_section_type: ABSTRACT
- id: PMID:16787941
  title: The Schizosaccharomyces pombe septation initiation network (SIN) is required
    for spore formation in meiosis.
  findings:
  - statement: >-
      The SIN, including Cdc7, is required for spore formation in meiosis; Cdc7
      associates with the meiotic SPB in meiosis II coincident with forespore
      membrane deposition.
    supporting_text: >-
      The protein kinases Sid1p and Cdc7p do not associate with the spindle pole
      body until meiosis II, when forespore membrane deposition begins.
    reference_section_type: ABSTRACT
- id: PMID:19736319
  title: Proper timing of cytokinesis is regulated by Schizosaccharomyces pombe Etd1.
  findings:
  - statement: >-
      Spg1-GTP binds and recruits Cdc7 to the SPB; SPB-localized Cdc7 promotes
      Sid2 activation, and Spg1/Cdc7 are active at just one SPB during
      cytokinesis.
    supporting_text: >-
      Once activated, Spg1-GTP binds the Cdc7 kinase and recruits it to the
      spindle pole body (SPB; Sohrmann et al., 1998).
    reference_section_type: INTRODUCTION
- id: PMID:19942852
  title: Fission yeast Pcp1 links polo kinase-mediated mitotic entry to gamma-tubulin-dependent
    spindle formation.
  findings:
  - statement: >-
      Cdc7 is used as a marker of the active/new mitotic SPB in this study of SPB
      function.
    supporting_text: >-
      fission-yeast pericentrin-like Pcp1 regulates multiple functions of the
      spindle pole body (SPB)
    reference_section_type: ABSTRACT
- id: PMID:22119525
  title: SIN-inhibitory phosphatase complex promotes Cdc11p dephosphorylation and
    propagates SIN asymmetry in fission yeast.
  findings:
  - statement: >-
      Cdc7 and Sid1 localize asymmetrically to the newly duplicated SPB in late
      anaphase; the SIP/PP2A complex propagates this asymmetry by promoting Cdc7
      accumulation at the new SPB.
    supporting_text: >-
      Two of the SIN kinases, Cdc7p and Sid1p, localize asymmetrically to the
      newly duplicated SPB in late anaphase.
    reference_section_type: ABSTRACT
- id: PMID:24838944
  title: Dma1-dependent degradation of SIN proteins during meiosis in Schizosaccharomyces
    pombe.
  findings:
  - statement: >-
      During meiosis Cdc7 localizes to the SPB and is degraded after meiosis II
      in a Dma1-dependent manner, reflecting stage-specific SIN regulation.
    supporting_text: >-
      the degradation of Cdc7p, Cdc11p and Sid4p occurs after the second meiotic
      division and depends upon the ubiquitin ligase Dma1p
    reference_section_type: ABSTRACT
- id: PMID:25501814
  title: The septation initiation network controls the assembly of nodes containing
    Cdr2p for cytokinesis in fission yeast.
  findings:
  - statement: >-
      Cdc7-GFP accumulates at spindle pole bodies upon SIN activation, after
      which SIN activity disperses type 1 (Cdr2/Mid1) nodes.
    supporting_text: >-
      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.
    reference_section_type: ABSTRACT
- id: PMID:8039497
  title: The cdc7 protein kinase is a dosage dependent regulator of septum formation
    in fission yeast.
  findings:
  - statement: >-
      cdc7 encodes an essential protein kinase required to initiate division
      septum formation and cytokinesis; DNA synthesis and mitosis are unaffected
      in cdc7 mutants, and the overexpression multiple-septation phenotype
      requires kinase activity.
    supporting_text: >-
      These findings indicate that the p120cdc7 protein kinase plays a key role
      in initiation of septum formation and cytokinesis in fission yeast
    reference_section_type: ABSTRACT
- id: PMID:9203579
  title: The Spg1p GTPase is an essential, dosage-dependent inducer of septum formation
    in Schizosaccharomyces pombe.
  findings:
  - statement: >-
      The Spg1 GTPase interacts with Cdc7 and is an essential, dosage-dependent
      inducer of septum formation, acting upstream of Cdc7 in the SIN.
    supporting_text: >-
      The Spg1p GTPase is an essential, dosage-dependent inducer of septum
      formation in Schizosaccharomyces pombe
    reference_section_type: TITLE
- id: PMID:9420333
  title: Asymmetric segregation on spindle poles of the Schizosaccharomyces pombe
    septum-inducing protein kinase Cdc7p.
  findings:
  - statement: >-
      Cdc7 has no discrete interphase localization, associates with both SPBs
      early in mitosis, then is retained on one pole during anaphase B; Spg1
      activity is required for Cdc7 localization in vivo but not for its in vitro
      kinase activity.
    supporting_text: >-
      Cdc7p shows no discrete localization during interphase, but 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.
    reference_section_type: ABSTRACT
suggested_questions:
- question: >-
    What are the physiological substrates of Cdc7 beyond Cdc11, and how does Cdc7
    phosphorylation activate the downstream Sid1-Cdc14 kinase module?
- question: >-
    How is Cdc7 kinase activity itself regulated at the SPB, given that Spg1
    controls its localization but not its intrinsic in vitro activity?
- question: >-
    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?
suggested_experiments:
- description: >-
    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.
- description: >-
    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.
- description: >-
    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.