id: O94235
gene_symbol: mph1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:284812
  label: Schizosaccharomyces pombe (strain 972 / ATCC 24843)
description: >-
  Mph1 (Mps1p-like pombe homolog; also called Mps1) is the fission-yeast member of
  the Mps1 family of dual-specificity protein kinases and an apical kinase of the
  spindle assembly checkpoint (SAC). It localizes to kinetochores, becoming enriched
  at unattached/tensionless kinetochores during mitosis, where it phosphorylates the
  conserved MELT repeats of the outer-kinetochore scaffold Spc7 (KNL1/Blinkin
  homolog). MELT phosphorylation creates a docking mark that recruits the Bub1-Bub3
  complex and, downstream, Mad1-Mad2 and Mad3, generating the "wait-anaphase" signal
  that delays the metaphase-to-anaphase transition until all chromosomes are
  bioriented. Mph1 is the most upstream SAC protein in the kinetochore recruitment
  hierarchy (with Aurora B/Ark1), and tethering Mph1 to the kinetochore is sufficient
  to recruit Bub1 and to impose a checkpoint-dependent arrest. Mph1 kinase activity is
  also required for the mitotic checkpoint complex (Mad2-Mad3-Cdc20/Slp1) to bind and
  inhibit the anaphase-promoting complex (APC/C); Mph1 directly phosphorylates Mad2 and
  Mad3 to stabilize MCC-APC/C and maintain the arrest. Beyond the checkpoint, Mph1 is
  required for accurate chromosome biorientation and segregation, and mph1 deletion
  elevates chromosome loss even without spindle perturbation. Unlike S. cerevisiae
  Mps1, Mph1 is dispensable for spindle pole body duplication and for viability. Mph1
  also acts in meiosis I, where it is required to prevent homolog non-disjunction.
  (Note: this Mps1-family kinase is unrelated to the budding-yeast/human MPH1 DNA
  helicase.)
existing_annotations:
- term:
    id: GO:0004712
    label: protein serine/threonine/tyrosine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: |-
      Mph1 is a member of the Mps1 family of dual-specificity protein kinases, so the
      dual-specificity (Ser/Thr/Tyr) molecular function inferred from orthologs is correct.
      The directly demonstrated substrates in S. pombe are phosphorylated on Ser/Thr
      (Spc7 MELT threonines, Mad2/Mad3 sites), consistent with the family assignment.
    action: ACCEPT
    reason: Phylogenetic inference matches the documented dual-specificity nature of the Mps1 kinase family and the demonstrated kinase activity of Mph1.
    supported_by:
    - reference_id: PMID:9601094
      supporting_text: Mph1, a member of the Mps1-like family of dual specificity protein kinases, is required for the spindle checkpoint in S. pombe.
      reference_section_type: TITLE
- term:
    id: GO:0007094
    label: mitotic spindle assembly checkpoint signaling
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: |-
      The mitotic SAC is the core biological process of Mph1, supported by phylogenetic
      inference and by extensive direct experimental evidence in fission yeast (mph1Delta
      and kinase-dead alleles are checkpoint defective).
    action: ACCEPT
    reason: Core function; the IBA inference is strongly corroborated by direct fission-yeast experiments.
    supported_by:
    - reference_id: PMID:22281223
      supporting_text: The mph1-kd mutant was unable to arrest in mitosis, like mad2Δ and mph1Δ strains (Figure 1C). We conclude that Mph1 kinase activity is required for checkpoint arrest.
      reference_section_type: RESULTS
- term:
    id: GO:0007059
    label: chromosome segregation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: |-
      Mph1 contributes to accurate chromosome segregation; mph1 deletion and kinase-dead
      alleles elevate chromosome loss even without spindle perturbation. This high-level
      term is correct but general; the more specific mitotic SAC and biorientation terms
      capture the mechanistic core.
    action: KEEP_AS_NON_CORE
    reason: Accurate but a broad parent term; retained as a non-core descriptor of the downstream consequence of Mph1 function.
    supported_by:
    - reference_id: PMID:22281223
      supporting_text: These experiments demonstrate that Mph1 kinase has important chromosome segregation function(s), even when there are no extrinsic perturbations of spindle microtubules.
      reference_section_type: RESULTS
- term:
    id: GO:0000776
    label: kinetochore
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: |-
      Mph1 acts at the kinetochore, where it phosphorylates Spc7/KNL1 MELT motifs. This is
      confirmed directly by immunolocalization in fission yeast (IDA), so the phylogenetic
      inference is correct and represents a core localization.
    action: ACCEPT
    reason: Kinetochore localization is directly demonstrated and is where Mph1 carries out its apical SAC function.
    supported_by:
    - reference_id: PMID:22660415
      supporting_text: MPS1/Mph1 kinase locating at the unattached kinetochores initially creates a mark, which is crucial for SAC activation and chromosome bi-orientation.
      reference_section_type: ABSTRACT
- term:
    id: GO:0033316
    label: meiotic spindle assembly checkpoint signaling
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: |-
      Mph1 has a documented meiosis I role (preventing homolog non-disjunction), consistent
      with a meiotic checkpoint contribution inferred from orthologs. However, the fission
      yeast meiotic SAC is reportedly attenuated, and the experimentally demonstrated meiotic
      phenotype is homolog non-disjunction rather than a classical meiotic checkpoint assay.
      Retained as a plausible but non-core, meiosis-specific function.
    action: KEEP_AS_NON_CORE
    reason: Meiosis-specific role inferred phylogenetically; real but peripheral to the central mitotic SAC function and not directly demonstrated as a meiotic checkpoint in the cached literature.
    supported_by:
    - reference_id: PMID:23370392
      supporting_text: Mph1, a member of the Mps1 family of spindle assembly checkpoint kinases, is required to prevent meiosis I homolog non-disjunction.
      reference_section_type: ABSTRACT
- term:
    id: GO:0034501
    label: protein localization to kinetochore
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: |-
      Mph1 drives recruitment of downstream SAC proteins to the kinetochore by phosphorylating
      Spc7 MELT motifs (recruiting Bub1-Bub3, and downstream Mad1-Mad2/Mad3). Centromere-tethered
      Mph1 is sufficient to recruit Bub1, directly supporting this inferred process.
    action: ACCEPT
    reason: Mph1 is required for, and sufficient to drive, recruitment of SAC proteins to kinetochores; well supported by experiment.
    supported_by:
    - reference_id: PMID:22184248
      supporting_text: localization of Mph1 at centromeres/kinetochores is sufficient to recruit Bub1
      reference_section_type: ABSTRACT
    - reference_id: PMID:22521786
      supporting_text: phosphorylation of the conserved MELT motifs in Spc7 by Mph1 (Mps1) recruits Bub1 and Bub3 to the kinetochore and that this is required to maintain the SAC signal.
      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: |-
      Generic protein kinase activity from InterPro domain mapping is correct (Mph1 has a
      bona fide protein kinase domain and demonstrated activity), but it is subsumed by the
      more specific protein serine/threonine kinase activity (IDA) and dual-specificity terms.
    action: MARK_AS_OVER_ANNOTATED
    reason: Correct but redundant generic parent term; the experimentally supported, more specific kinase-activity terms should be preferred.
    supported_by:
    - reference_id: PMID:22281223
      supporting_text: Mph1 is an active kinase that can phosphorylate itself and Mad2 in vitro
      reference_section_type: RESULTS
- term:
    id: GO:0004712
    label: protein serine/threonine/tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: |-
      Dual-specificity (Ser/Thr/Tyr) kinase activity from EC 2.7.12.1 mapping is consistent with
      the Mps1 family classification and UniProt EC assignment. Direct pombe substrates are
      Ser/Thr, but the dual-specificity family property is well established.
    action: ACCEPT
    reason: EC-based inference agrees with the documented dual-specificity family assignment and UniProt EC 2.7.12.1.
    supported_by:
    - reference_id: PMID:9601094
      supporting_text: Mph1, a member of the Mps1-like family of dual specificity protein kinases, is required for the spindle checkpoint in S. pombe.
      reference_section_type: TITLE
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: |-
      Protein tyrosine kinase activity is derived from the EC 2.7.12.1 / RHEA tyrosine
      autophosphorylation reaction mapping. Mph1 belongs to the dual-specificity Mps1 family,
      for which tyrosine (auto)phosphorylation is a recognized property, but no specific
      tyrosine substrate has been demonstrated in S. pombe in the cached literature.
    action: KEEP_AS_NON_CORE
    reason: Supported by the dual-specificity family classification and EC/RHEA mapping; retained as non-core because direct tyrosine-substrate evidence in fission yeast is lacking.
    supported_by:
    - reference_id: PMID:9601094
      supporting_text: Mph1, a member of the Mps1-like family of dual specificity protein kinases, is required for the spindle checkpoint in S. pombe.
      reference_section_type: TITLE
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: |-
      ATP binding is correct: Mph1 has a canonical protein kinase ATP-binding pocket (glycine-rich
      loop residues 322-330 and invariant Lys345) and uses ATP to phosphorylate substrates in vitro.
    action: ACCEPT
    reason: A required molecular function for this active protein kinase, supported by the conserved ATP-binding motif and demonstrated kinase activity.
    supported_by:
    - reference_id: PMID:22281223
      supporting_text: Affinity-purified Mph1-SZZ kinase was incubated with γ-[32P]ATP and recombinant Mad2 substrate
      reference_section_type: RESULTS
- term:
    id: GO:0007094
    label: mitotic spindle assembly checkpoint signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: |-
      Same core mitotic SAC process as the experimentally supported annotations, here generated by
      an ARBA machine-learning rule. Correct and redundant with the IMP/EXP/IBA annotations.
    action: ACCEPT
    reason: Correct core function; consistent with multiple experimental annotations to the same term.
    supported_by:
    - reference_id: PMID:9601094
      supporting_text: mph1 functions upstream of mad2, a previously characterized component of the spindle checkpoint.
      reference_section_type: ABSTRACT
- term:
    id: GO:0098813
    label: nuclear chromosome segregation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: |-
      Nuclear chromosome segregation (ARBA rule) is correct but a general parent of the more specific
      mitotic SAC and biorientation roles. Mph1 acts in the closed mitosis of fission yeast on nuclear
      chromosomes, so the term is accurate but non-core.
    action: KEEP_AS_NON_CORE
    reason: Accurate broad descriptor of the downstream consequence; the specific SAC/biorientation terms capture the mechanism.
    supported_by:
    - reference_id: PMID:22281223
      supporting_text: These experiments demonstrate that Mph1 kinase has important chromosome segregation function(s), even when there are no extrinsic perturbations of spindle microtubules.
      reference_section_type: RESULTS
- term:
    id: GO:0106310
    label: protein serine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: |-
      Protein serine kinase activity (RHEA mapping) is correct and directly demonstrated: Mph1
      phosphorylates serine and threonine residues of its substrates (e.g., Mad2/Mad3 sites). It is
      a more specific component of the dual-specificity activity.
    action: ACCEPT
    reason: Consistent with experimentally demonstrated Ser/Thr phosphorylation of Mph1 substrates.
    supported_by:
    - reference_id: PMID:22281223
      supporting_text: Mph1 is an active kinase that can phosphorylate itself and Mad2 in vitro
      reference_section_type: RESULTS
- term:
    id: GO:0000776
    label: kinetochore
  evidence_type: IDA
  original_reference_id: PMID:22660415
  qualifier: is_active_in
  review:
    summary: |-
      Direct experimental evidence places Mph1 at the kinetochore, enriched at unattached
      kinetochores, where it phosphorylates Spc7. This is a core localization for Mph1.
    action: ACCEPT
    reason: Directly demonstrated kinetochore localization at the site of Mph1 catalytic function.
    supported_by:
    - reference_id: PMID:22660415
      supporting_text: MPS1/Mph1 kinase locating at the unattached kinetochores initially creates a mark, which is crucial for SAC activation and chromosome bi-orientation.
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:22660415
  qualifier: enables
  review:
    summary: |-
      Mph1 directly phosphorylates Spc7/KNL1 on the threonine residues of MELT motifs, demonstrating
      protein serine/threonine kinase activity. This is a core molecular function.
    action: ACCEPT
    reason: Directly demonstrated Ser/Thr kinase activity on a physiological substrate (Spc7 MELT motifs).
    supported_by:
    - reference_id: PMID:22660415
      supporting_text: fission yeast Mph1 (MPS1 homologue) phosphorylates the kinetochore protein Spc7 (KNL1/Blinkin homologue) at the MELT repeat sequences.
      reference_section_type: ABSTRACT
- term:
    id: GO:0007094
    label: mitotic spindle assembly checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:22825872
  qualifier: involved_in
  review:
    summary: |-
      Mph1 kinetochore recruitment is crucial and upstream for a stable SAC arrest; an Mph1 mutant
      that loses kinetochore enrichment abolishes SAC signaling, and forced kinetochore recruitment
      restores it. Strong support for the core mitotic SAC function.
    action: ACCEPT
    reason: Direct mutant-phenotype evidence that Mph1 is the apical kinetochore kinase required for the mitotic SAC.
    supported_by:
    - reference_id: PMID:22825872
      supporting_text: An Mph1 mutant that eliminates kinetochore enrichment abolishes SAC signaling, whereas forced recruitment of this mutant to kinetochores restores SAC signaling.
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:28497540
  qualifier: enables
  review:
    summary: |-
      Mph1 serine/threonine kinase activity in the context of the meiotic Spc7/Bub1 recruitment
      pathway. This study (meikin/Moa1-Plo1-Spc7-Bub1 axis) was full-text reviewed by the PomBase
      curator; the cached version is abstract-only. The Ser/Thr kinase activity assertion is
      consistent with all other evidence for Mph1 and is accepted.
    action: ACCEPT
    reason: Consistent with the well-established Ser/Thr kinase activity of Mph1; defer to PomBase curator who read the full text.
    supported_by:
    - reference_id: PMID:22660415
      supporting_text: fission yeast Mph1 (MPS1 homologue) phosphorylates the kinetochore protein Spc7 (KNL1/Blinkin homologue) at the MELT repeat sequences.
      reference_section_type: ABSTRACT
- term:
    id: GO:0007094
    label: mitotic spindle assembly checkpoint signaling
  evidence_type: EXP
  original_reference_id: PMID:22660415
  qualifier: involved_in
  review:
    summary: |-
      Phosphorylation of Spc7 MELT motifs by Mph1 is required for kinetochore-based SAC activation
      (Mad1-Mad2-Mad3 localization). Core mitotic SAC function with direct experimental support.
    action: ACCEPT
    reason: Direct experimental demonstration of Mph1's role in mitotic SAC activation via Spc7 phosphorylation.
    supported_by:
    - reference_id: PMID:22660415
      supporting_text: This phosphorylation promotes the in vitro binding to the Bub1-Bub3 complex, which is required for kinetochore-based SAC activation (Mad1-Mad2-Mad3 localization) and chromosome alignment.
      reference_section_type: ABSTRACT
- term:
    id: GO:1990813
    label: meiotic centromeric cohesion protection in anaphase I
  evidence_type: IMP
  original_reference_id: PMID:28497540
  qualifier: involved_in
  review:
    summary: |-
      This annotation links Mph1 to protection of centromeric cohesion in meiosis I, via the
      meikin(Moa1)-Plo1-Spc7-Bub1-Sgo1 pathway in which Spc7 phosphorylation accumulates Bub1 to
      promote Sgo1-dependent cohesion protection. The cached file is abstract-only (foregrounds
      Plo1/Moa1), so the specific Mph1 contribution cannot be fully verified here; the PomBase
      curator made this IMP from the full text. Retained as a meiosis-specific, non-core function.
    action: KEEP_AS_NON_CORE
    reason: Meiosis-specific role made by an expert curator from full text not in our cache; consistent with Mph1's Spc7/Bub1 axis. Per curation guidance, defer rather than remove.
    supported_by:
    - reference_id: PMID:28497540
      supporting_text: recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1
      reference_section_type: ABSTRACT
    - reference_id: PMID:23370392
      supporting_text: We thus conclude that Mph1 is required for efficient homolog disjunction during meiosis I.
      reference_section_type: RESULTS
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:27618268
  qualifier: enables
  review:
    summary: |-
      Mph1 Ser/Thr kinase activity in the context of phosphorylating Spc7 MELT motifs to toggle the
      SAC switch. Consistent with all other kinase-activity evidence for Mph1.
    action: ACCEPT
    reason: Consistent with directly demonstrated Ser/Thr kinase activity on Spc7 MELT motifs.
    supported_by:
    - reference_id: PMID:27618268
      supporting_text: Mph1 (Mps1) phosphorylates multiple conserved MELT motifs in the Spc7 (Spc105/KNL1) protein to recruit Bub1, Bub3, and Mad3 (BubR1) to kinetochores
      reference_section_type: ABSTRACT
- term:
    id: GO:0007094
    label: mitotic spindle assembly checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:9601094
  qualifier: involved_in
  review:
    summary: |-
      The founding study identifying mph1 as a spindle checkpoint gene required for checkpoint
      activation in response to spindle defects, acting upstream of mad2. Core mitotic SAC function.
    action: ACCEPT
    reason: Original genetic identification of Mph1 as a SAC gene upstream of mad2; core function.
    supported_by:
    - reference_id: PMID:9601094
      supporting_text: we report the isolation of a new spindle checkpoint gene, mph1 (Mps1p-like pombe homolog), in the fission yeast Schizosaccharomyces pombe, that is required for checkpoint activation in response to spindle defects. mph1 functions upstream of mad2
      reference_section_type: ABSTRACT
- term:
    id: GO:0000776
    label: kinetochore
  evidence_type: IDA
  original_reference_id: PMID:22184248
  qualifier: is_active_in
  review:
    summary: |-
      A second direct demonstration of Mph1 kinetochore/centromere localization; centromere-tethered
      Mph1 is sufficient to recruit Bub1, confirming both the localization and its functional output.
    action: ACCEPT
    reason: Independent direct evidence for kinetochore localization, the core site of Mph1 action.
    supported_by:
    - reference_id: PMID:22184248
      supporting_text: localization of Mph1 at centromeres/kinetochores is sufficient to recruit Bub1
      reference_section_type: ABSTRACT
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:22281223
  qualifier: enables
  review:
    summary: |-
      Affinity-purified Mph1 phosphorylates itself and Mad2 in vitro using ATP, and the D459A
      kinase-dead allele abolishes this activity, directly demonstrating Ser/Thr kinase activity.
    action: ACCEPT
    reason: Direct in vitro demonstration of catalytic kinase activity, abolished by an active-site mutation.
    supported_by:
    - reference_id: PMID:22281223
      supporting_text: Mph1 is an active kinase that can phosphorylate itself and Mad2 in vitro; second, the D459A substitution has “killed” Mph1 kinase activity
      reference_section_type: RESULTS
- term:
    id: GO:0007094
    label: mitotic spindle assembly checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:22281223
  qualifier: involved_in
  review:
    summary: |-
      The mph1 kinase-dead allele is checkpoint defective and fails to assemble/maintain MCC-APC/C
      complexes, showing Mph1 kinase activity is required for the mitotic SAC. Core function.
    action: ACCEPT
    reason: Direct mutant evidence that Mph1 kinase activity is required for mitotic checkpoint arrest and MCC-APC/C formation.
    supported_by:
    - reference_id: PMID:22281223
      supporting_text: Both mph1 mutants failed to assemble significant levels of MCC-APC/C, and both failed to checkpoint arrest, highlighting the importance of Mph1 kinase activity in the spindle checkpoint.
      reference_section_type: RESULTS
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:26882497
  qualifier: enables
  review:
    summary: |-
      Mph1 directly phosphorylates Mad3 (sixteen in vitro sites; the kinase-dead control fails),
      demonstrating Ser/Thr kinase activity on a checkpoint substrate. Core molecular function.
    action: ACCEPT
    reason: Direct in vitro kinase assay with Mad3 substrate confirms Mph1 Ser/Thr kinase activity.
    supported_by:
    - reference_id: PMID:26882497
      supporting_text: we identify Mad3 as a substrate of fission yeast Mps1(Mph1) kinase.
      reference_section_type: ABSTRACT
- term:
    id: GO:0007094
    label: mitotic spindle assembly checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:26882497
  qualifier: involved_in
  review:
    summary: |-
      Mph1-dependent phosphorylation of Mad3 (and Mad2) stabilizes MCC-APC/C binding and is required
      to maintain spindle checkpoint arrests, supporting Mph1's core mitotic SAC role through direct
      substrate modification.
    action: ACCEPT
    reason: Demonstrates Mph1's mitotic SAC function via phosphorylation of the MCC component Mad3.
    supported_by:
    - reference_id: PMID:26882497
      supporting_text: Mps1(Mph1) kinase-dependent modifications of Mad3 and Mad2 act in a concerted manner to maintain spindle checkpoint arrests.
      reference_section_type: ABSTRACT
- term:
    id: GO:0007094
    label: mitotic spindle assembly checkpoint signaling
  evidence_type: IMP
  original_reference_id: PMID:22521786
  qualifier: involved_in
  review:
    summary: |-
      Phosphorylation of Spc7 MELT motifs by Mph1 recruits Bub1-Bub3 to kinetochores and is required
      to maintain the SAC signal; mph1Delta and D459A fail to localize Bub1. Core mitotic SAC function.
    action: ACCEPT
    reason: Direct demonstration that Mph1 kinase activity maintains the SAC via Spc7 MELT phosphorylation and Bub1-Bub3 recruitment.
    supported_by:
    - reference_id: PMID:22521786
      supporting_text: Bub1 fails to form discrete foci during mitosis in either Δmph1 or mph1(D459A) mutants (which are defective for kinase activity [23]), indicating that catalytic activity of Mph1 is required to promote kinetochore association of Bub1
      reference_section_type: RESULTS
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:22521786
  qualifier: enables
  review:
    summary: |-
      Mph1 directly phosphorylates the Spc7 N-terminal half in vitro on MELT-motif threonines,
      demonstrating Ser/Thr kinase activity on a physiological kinetochore substrate.
    action: ACCEPT
    reason: Direct in vitro kinase assay on Spc7 MELT motifs confirms Mph1 Ser/Thr kinase activity.
    supported_by:
    - reference_id: PMID:22521786
      supporting_text: We find that Mph1 phosphorylates Spc7 in vitro on two threonine residues (T453 and T507) which are part of a repetitive motif of unknown function, termed the MELT motif
      reference_section_type: RESULTS
- term:
    id: GO:0007127
    label: meiosis I
  evidence_type: IMP
  original_reference_id: PMID:23370392
  qualifier: involved_in
  review:
    summary: |-
      mph1 deletion causes meiosis I homolog non-disjunction and lagging chromosomes, indicating a
      requirement for Mph1 in proper homolog disjunction during meiosis I (likely via preventing
      precocious anaphase I entry). A genuine but meiosis-specific, non-core function.
    action: KEEP_AS_NON_CORE
    reason: Directly demonstrated meiosis I role, but peripheral relative to Mph1's central mitotic SAC function.
    supported_by:
    - reference_id: PMID:23370392
      supporting_text: We thus conclude that Mph1 is required for efficient homolog disjunction during meiosis I.
      reference_section_type: RESULTS
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:16823372
  qualifier: is_active_in
  review:
    summary: |-
      Genome-wide YFP localization assigned Mph1 a nuclear signal. Fission yeast undergoes closed
      mitosis and Mph1 acts on intranuclear kinetochores and on the nucleoplasmic MCC/APC-C, so a
      nuclear pool is consistent with its biology.
    action: ACCEPT
    reason: High-throughput localization consistent with Mph1 acting on nuclear kinetochores and nucleoplasmic checkpoint complexes in closed mitosis.
    supported_by:
    - reference_id: PMID:16823372
      supporting_text: we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: HDA
  original_reference_id: PMID:16823372
  qualifier: is_active_in
  review:
    summary: |-
      The same genome-wide study reported a cytosolic signal for Mph1. A soluble/cytoplasmic pool is
      plausible (only a fraction of Mph1 is kinetochore-bound at any time), but the functionally
      important pools are the kinetochore and nucleoplasm. Retained as non-core.
    action: KEEP_AS_NON_CORE
    reason: High-throughput cytosolic signal; plausible soluble pool but not the principal functional site.
    supported_by:
    - reference_id: PMID:16823372
      supporting_text: we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.
      reference_section_type: ABSTRACT
core_functions:
- description: >-
    Dual-specificity (predominantly Ser/Thr) protein kinase that, localized at
    unattached kinetochores, phosphorylates the Spc7/KNL1 MELT-motif threonines to
    create a phospho-mark that recruits the Bub1-Bub3 complex and downstream SAC
    proteins, thereby establishing the mitotic spindle assembly checkpoint signal.
  supported_by:
  - reference_id: PMID:22660415
    supporting_text: fission yeast Mph1 (MPS1 homologue) phosphorylates the kinetochore protein Spc7 (KNL1/Blinkin homologue) at the MELT repeat sequences. This phosphorylation promotes the in vitro binding to the Bub1-Bub3 complex, which is required for kinetochore-based SAC activation (Mad1-Mad2-Mad3 localization) and chromosome alignment.
    reference_section_type: ABSTRACT
  - reference_id: PMID:22521786
    supporting_text: phosphorylation of the conserved MELT motifs in Spc7 by Mph1 (Mps1) recruits Bub1 and Bub3 to the kinetochore and that this is required to maintain the SAC signal.
    reference_section_type: ABSTRACT
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0007094
    label: mitotic spindle assembly checkpoint signaling
  locations:
  - id: GO:0000776
    label: kinetochore
- description: >-
    Apical SAC kinase whose kinetochore localization is required and sufficient to
    initiate the checkpoint: tethering Mph1 to the kinetochore recruits Bub1 and
    imposes a checkpoint-dependent metaphase arrest, placing Mph1 at the top of the
    SAC protein recruitment hierarchy.
  supported_by:
  - reference_id: PMID:22825872
    supporting_text: An Mph1 mutant that eliminates kinetochore enrichment abolishes SAC signaling, whereas forced recruitment of this mutant to kinetochores restores SAC signaling.
    reference_section_type: ABSTRACT
  - reference_id: PMID:22184248
    supporting_text: localization of Mph1 at centromeres/kinetochores is sufficient to recruit Bub1
    reference_section_type: ABSTRACT
  directly_involved_in:
  - id: GO:0034501
    label: protein localization to kinetochore
- description: >-
    Maintains the checkpoint arrest by directly phosphorylating the MCC components
    Mad2 and Mad3, stabilizing binding of the mitotic checkpoint complex to and
    inhibition of the Cdc20(Slp1)-APC/C, thereby delaying anaphase onset until
    biorientation is achieved.
  supported_by:
  - reference_id: PMID:22281223
    supporting_text: a kinase-dead allele of the fission yeast MPS1 homolog (Mph1) is checkpoint defective and that levels of APC/C-associated Mad2 and Mad3 are dramatically reduced in this mutant. Thus, MCC binding to fission yeast APC/C is dependent on Mph1 kinase activity.
    reference_section_type: ABSTRACT
  - reference_id: PMID:26882497
    supporting_text: Mps1(Mph1) kinase-dependent modifications of Mad3 and Mad2 act in a concerted manner to maintain spindle checkpoint arrests.
    reference_section_type: ABSTRACT
  molecular_function:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  directly_involved_in:
  - id: GO:0007094
    label: mitotic spindle assembly checkpoint signaling
proposed_new_terms: []
suggested_questions:
- question: >-
    Does Mph1 phosphorylate any physiological tyrosine substrate in fission yeast, or
    is its tyrosine activity restricted to autophosphorylation, as the dual-specificity
    EC assignment would predict?
- question: >-
    What is the relative contribution of kinetochore-localized Mph1 (Spc7 MELT
    phosphorylation) versus nucleoplasmic Mph1 (direct Mad2/Mad3 phosphorylation) to
    establishing versus maintaining the checkpoint arrest?
- question: >-
    Is the meiosis I homolog non-disjunction phenotype of mph1Delta solely a
    consequence of a weakened SAC and precocious anaphase I, or does Mph1 contribute
    directly to the meikin/Bub1/Sgo1 cohesion-protection pathway?
suggested_experiments:
- description: >-
    Use analog-sensitive mph1 (or chemical Mps1 inhibition) combined with quantitative
    phosphoproteomics across synchronized mitosis to define the in vivo Mph1 substrate
    repertoire and distinguish kinetochore from nucleoplasmic targets.
- description: >-
    Reconstitute Mph1 with recombinant Spc7, Bub1-Bub3 and Mad1-Mad2 in vitro to test
    whether MELT phosphorylation is sufficient to assemble a functional checkpoint
    signaling module and to map the order of recruitment events.
- description: >-
    Separate Mph1 mitotic and meiotic functions using meiosis-specific depletion or
    separation-of-function alleles, and score homolog disjunction, Bub1/Sgo1 centromeric
    accumulation, and Rec8 cohesion protection in meiosis I.
references:
- id: file:interpro/panther/PTHR22974/PTHR22974-review.md
  title: 'PANTHER family review PTHR22974: IBA propagation assessment for mph1'
  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: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:16823372
  title: ORFeome cloning and global analysis of protein localization in the fission
    yeast Schizosaccharomyces pombe.
  findings:
  - statement: Genome-wide YFP tagging localized Mph1 to the nucleus and cytosol.
    supporting_text: we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein.
    reference_section_type: ABSTRACT
- id: PMID:22184248
  title: Centromere-tethered Mps1 pombe homolog (Mph1) kinase is a sufficient marker
    for recruitment of the spindle checkpoint protein Bub1, but not Mad1.
  findings:
  - statement: Kinetochore-localized Mph1 is sufficient to recruit Bub1 and to arrest cells in a checkpoint-dependent manner; Mad1 association requires an additional condition.
    supporting_text: We propose that Mph1 is a sufficient marker for recruitment of Bub1. Mad1, in contrast, requires an additional condition/component for stable association with kinetochores.
    reference_section_type: ABSTRACT
- id: PMID:22281223
  title: Kinase activity of fission yeast Mph1 is required for Mad2 and Mad3 to stably
    bind the anaphase promoting complex.
  findings:
  - statement: Mph1 is an active kinase (phosphorylates itself and Mad2 in vitro); D459A abolishes activity; kinase activity is required for the SAC and MCC-APC/C binding.
    supporting_text: a kinase-dead allele of the fission yeast MPS1 homolog (Mph1) is checkpoint defective and that levels of APC/C-associated Mad2 and Mad3 are dramatically reduced in this mutant.
    reference_section_type: ABSTRACT
  - statement: Mph1 has chromosome segregation functions independent of extrinsic spindle perturbation.
    supporting_text: These experiments demonstrate that Mph1 kinase has important chromosome segregation function(s), even when there are no extrinsic perturbations of spindle microtubules.
    reference_section_type: RESULTS
- id: PMID:22521786
  title: Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase
    maintains the spindle checkpoint.
  findings:
  - statement: Mph1 phosphorylates Spc7 MELT-motif threonines (e.g. T453, T507) to recruit Bub1-Bub3 to kinetochores and maintain the SAC.
    supporting_text: phosphorylation of the conserved MELT motifs in Spc7 by Mph1 (Mps1) recruits Bub1 and Bub3 to the kinetochore and that this is required to maintain the SAC signal.
    reference_section_type: ABSTRACT
- id: PMID:22660415
  title: MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC
    components.
  findings:
  - statement: Mph1 at unattached kinetochores phosphorylates Spc7 MELT repeats, creating a mark crucial for SAC activation and chromosome biorientation.
    supporting_text: MPS1/Mph1 kinase locating at the unattached kinetochores initially creates a mark, which is crucial for SAC activation and chromosome bi-orientation.
    reference_section_type: ABSTRACT
- id: PMID:22825872
  title: Mph1 kinetochore localization is crucial and upstream in the hierarchy of
    spindle assembly checkpoint protein recruitment to kinetochores.
  findings:
  - statement: Mph1 (with Ark1) is at the top of the kinetochore SAC recruitment hierarchy; loss of Mph1 kinetochore enrichment abolishes SAC signaling and forced recruitment restores it.
    supporting_text: a three-layered hierarchy with Ark1 and Mph1 on top, Bub1 and Bub3 in the middle, and Mad3 as well as the Mad1-Mad2 complex at the lower end of the hierarchy.
    reference_section_type: ABSTRACT
- id: PMID:23370392
  title: A knockout screen for protein kinases required for the proper meiotic segregation
    of chromosomes in the fission yeast Schizosaccharomyces pombe.
  findings:
  - statement: mph1Delta causes meiosis I homolog non-disjunction; Mph1 is required for efficient homolog disjunction during meiosis I.
    supporting_text: Mph1, a member of the Mps1 family of spindle assembly checkpoint kinases, is required to prevent meiosis I homolog non-disjunction.
    reference_section_type: ABSTRACT
- id: PMID:26882497
  title: Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC/C and Maintain
    Spindle Checkpoint Arrests.
  findings:
  - statement: Mad3 is a direct Mph1 substrate; Mph1-dependent modification of Mad3 and Mad2 stabilizes MCC-APC/C binding and maintains the checkpoint arrest.
    supporting_text: Mps1(Mph1) kinase-dependent modifications of Mad3 and Mad2 act in a concerted manner to maintain spindle checkpoint arrests.
    reference_section_type: ABSTRACT
- id: PMID:27618268
  title: Bub3-Bub1 Binding to Spc7/KNL1 Toggles the Spindle Checkpoint Switch by Licensing
    the Interaction of Bub1 with Mad1-Mad2.
  findings:
  - statement: Mph1 phosphorylates Spc7 MELT motifs to recruit Bub1/Bub3/Mad3; multisite Bub3 binding to the MELT array toggles the checkpoint by licensing Bub1-Mad1-Mad2 interaction.
    supporting_text: Mph1 (Mps1) phosphorylates multiple conserved MELT motifs in the Spc7 (Spc105/KNL1) protein to recruit Bub1, Bub3, and Mad3 (BubR1) to kinetochores
    reference_section_type: ABSTRACT
- id: PMID:28497540
  title: Meikin-associated polo-like kinase specifies Bub1 distribution in meiosis
    I.
  findings:
  - statement: In meiosis I, the meikin(Moa1)-Plo1 module phosphorylates Spc7 to accumulate Bub1 at kinetochores, supporting Sgo1-dependent centromeric cohesion protection.
    supporting_text: recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1
    reference_section_type: ABSTRACT
- id: PMID:9601094
  title: Mph1, a member of the Mps1-like family of dual specificity protein kinases,
    is required for the spindle checkpoint in S. pombe.
  findings:
  - statement: mph1 is a spindle checkpoint gene required for checkpoint activation in response to spindle defects, acting upstream of mad2; unlike S. cerevisiae Mps1 it is not required for SPB duplication.
    supporting_text: mph1 functions upstream of mad2, a previously characterized component of the spindle checkpoint.
    reference_section_type: ABSTRACT