TTK

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000280 nuclear division	IEA GO_REF:0000117	MODIFY	Summary: ARBA machine-learning annotation to the very broad process "nuclear division". TTK does act during mitosis, but its participation is specific: it generates the spindle assembly checkpoint signal at unattached kinetochores and destabilises improper kinetochore-microtubule attachments. Reason: Not wrong, but far too general to convey what TTK does; the mitotic-specific descendants already carried by GOA (mitotic spindle assembly checkpoint signaling, repair of mitotic kinetochore microtubule attachment defect) are the informative terms and are recommended in its place. Proposed replacements: mitotic spindle assembly checkpoint signaling repair of mitotic kinetochore microtubule attachment defect Supporting Evidence: PMID:18243099 monopolar spindle 1 (Mps1) kinase, which is essential for the mitotic checkpoint, also controls correction of improper chromosome attachments
GO:0000776 kinetochore	IBA GO_REF:0000033	ACCEPT	Summary: Kinetochore is the site of action of TTK. Human Mps1 cycles between the cytoplasm and unattached or mal-oriented kinetochores, is recruited by direct binding to the NDC80 complex, and its autophosphorylation and substrate phosphorylation are highest at unattached kinetochores. Reason: Core localization, supported by extensive direct evidence in human cells and by the PAINT judgment that kinetochore activity is ancestral to the Mps1 family (fly, mouse, fission and budding yeast donors). Supporting Evidence: PMID:28441529 Mps1 cycles between the cytoplasm and unattached or mal-oriented kinetochores, but is largely excluded from bi-oriented kinetochores PMID:26068854 We found that the checkpoint protein kinase monopolar spindle 1 (Mps1) directly bound to Ndc80C through two independent interactions.
GO:0000776 kinetochore	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl Compara transfer of the mouse Ttk kinetochore annotation. Duplicates the IBA row and is fully supported by human data. Reason: Kinetochore localization is the core site of action; redundant evidence lines for the same correct term are acceptable. Supporting Evidence: PMID:28441529 While Mps1 was recruited to unattached and tensionless kinetochores with similar efficiency, its auto-phosphorylation and trans-phosphorylation of substrates were significantly higher at the former
GO:0004672 protein kinase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO mapping from the Ser/Thr kinase active-site signature. TTK is a catalytically active protein kinase (autophosphorylation and phosphorylation of Borealin, KNL1, SKA3, MCRS1 and MAD1 are all documented). Reason: Correct parent of the more specific serine/threonine kinase annotations; a broad IEA that is consistent with the experimental rows is acceptable. Supporting Evidence: PMID:1639825 Escherichia coli expressing the complete kinase domain of TTK contain markedly elevated levels of phosphoserine and phosphothreonine as well as slightly increased levels of phosphotyrosine
GO:0004674 protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Serine/threonine kinase activity is the physiologically relevant catalytic activity of TTK: every established substrate (Borealin, KNL1 MELT threonines, BUB1 Thr461, MAD1 Thr716, SKA3 Ser34, MCRS1 Ser64/65) is phosphorylated on Ser or Thr. TTK's own IDA annotations are among the descendant evidences behind the PAINT node. Reason: Core molecular function; the phylogenetic inference is corroborated by direct in vitro kinase assays with human TTK. Supporting Evidence: PMID:18243099 Borealin/DasraB, a member of the complex that regulates the Aurora B kinase, is directly phosphorylated by Mps1 on residues that are crucial for Aurora B activity and chromosome alignment PMID:30785839 Mps1 efficiently phosphorylated MCRS1
GO:0004674 protein serine/threonine kinase activity	IDA PMID:18243099 Mps1 phosphorylates Borealin to control Aurora B activity an...	ACCEPT	Summary: Jelluma et al. showed that human Mps1 directly phosphorylates Borealin/CDCA8 on residues required for Aurora B activity and chromosome alignment, and that phosphomimetic Borealin rescues Mps1-depleted cells. Reason: Direct demonstration of Ser/Thr phosphorylation of a physiological substrate by human TTK; core molecular function. Note that a later study (PMID:28441529) found that Mps1 can destabilise attachments even when Aurora B is inhibited, so the Borealin route is one of several TTK outputs at the kinetochore, but the kinase activity itself is not in question. Supporting Evidence: PMID:18243099 Borealin/DasraB bearing phosphomimetic mutations restores Aurora B activity and alignment in Mps1-depleted cells
GO:0004674 protein serine/threonine kinase activity	IDA PMID:28441529 Mps1 Regulates Kinetochore-Microtubule Attachment Stability ...	ACCEPT	Summary: Quantitative phosphoproteomics after kinetochore targeting or inhibition of Mps1 identified Mps1-dependent Ser/Thr sites on KNL1, ROD, SKA3 (Ser34) and on Mps1 itself (autophosphorylation clusters pT33/pS37 and pT360/pS363), verified with phospho-specific antibodies. Reason: Direct experimental support for Ser/Thr kinase activity of human TTK against outer-kinetochore substrates; core molecular function. Supporting Evidence: PMID:28441529 we saw strong inhibition of Mps1 (TTK) autophosphorylation at multiple sites PMID:28441529 we generated antibodies against two separate clusters of Mps1 autophosphorylation sites (pT33/pS37 and pT360/pS363), as well as the newly identified phosphosites in KNL1 (pS1831/pS1834), Rod (pT13/pS15), and Ska3 (pS34)
GO:0004674 protein serine/threonine kinase activity	TAS PMID:7737118 Yeast spindle pole body duplication gene MPS1 encodes an ess...	ACCEPT	Summary: TAS annotation citing the cloning of budding-yeast MPS1, which showed that Mps1p phosphorylates serine, threonine and tyrosine in vitro. The assertion is correct for human TTK, but the cited paper is about the S. cerevisiae orthologue and the human evidence lives in the IDA rows. Reason: The function is correct and is a core activity of TTK; the reference is a weak (orthologue-based) source of support, so the IDA annotations from PMID:18243099 and PMID:28441529 should be regarded as the primary evidence. Supporting Evidence: PMID:7737118 Phosphoamino acid analysis of substrates phosphorylated by Mps1p indicates that this kinase can phosphorylate serine, threonine and tyrosine residues, identifying Mps1p as a dual specificity protein kinase.
GO:0004712 protein serine/threonine/tyrosine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Dual-specificity (Ser/Thr/Tyr) kinase activity is the family-level description of Mps1 kinases: the yeast enzyme phosphorylates all three hydroxyamino acids, and the TTK kinase domain expressed in E. coli produces phosphoserine, phosphothreonine and a small amount of phosphotyrosine. Reason: Consistent with the Mps1-family PAINT node and with the original characterisation of TTK as a "phosphotyrosine-picked threonine kinase". Physiological outputs are Ser/Thr, which is captured by the sibling GO:0004674 rows. Supporting Evidence: PMID:1639825 expression of TTK, a previously unidentified member of the family of kinases which can phosphorylate serine, threonine, and tyrosine hydroxyamino acids, is associated with cell proliferation
GO:0004712 protein serine/threonine/tyrosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation from the Mps1 catalytic-domain InterPro entry, EC 2.7.12.1 (dual-specificity kinase) and the mouse orthologue. Duplicates the IBA row. Reason: Consistent with the family-level dual-specificity assignment; redundant evidence lines are acceptable. Supporting Evidence: PMID:7737118 identifying Mps1p as a dual specificity protein kinase
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000116	MARK AS OVER ANNOTATED	Summary: Rhea-derived annotation from the tyrosine-phosphorylation half-reaction of EC 2.7.12.1. Tyrosine phosphorylation by TTK is a minor in vitro activity (the recombinant kinase domain yields only "slightly increased" phosphotyrosine) and no physiological tyrosine substrate is known. Reason: Presenting tyrosine kinase activity as a stand-alone molecular function overstates a weak in vitro activity and risks classifying TTK alongside true tyrosine kinases. The dual-specificity term GO:0004712 already records this capability at the appropriate level; the physiological activity is Ser/Thr kinase activity. Supporting Evidence: PMID:1639825 Escherichia coli expressing the complete kinase domain of TTK contain markedly elevated levels of phosphoserine and phosphothreonine as well as slightly increased levels of phosphotyrosine file:human/TTK/TTK-deep-research-falcon.md The nomenclature therefore should not be taken to mean that tyrosine phosphorylation is equally prominent in its established SAC function.
GO:0004713 protein tyrosine kinase activity	TAS PMID:7737118 Yeast spindle pole body duplication gene MPS1 encodes an ess...	MARK AS OVER ANNOTATED	Summary: TAS from the budding-yeast MPS1 paper, whose phosphoamino-acid analysis detected tyrosine phosphorylation by yeast Mps1p in vitro. As for the Rhea-derived row, this is a minor, orthologue-derived in vitro activity. Reason: Same reasoning as the IEA row: tyrosine phosphorylation is a marginal in vitro capability, not a physiological function of human TTK, and is already captured by the dual-specificity term GO:0004712. Supporting Evidence: PMID:7737118 this kinase can phosphorylate serine, threonine and tyrosine residues
GO:0005515 protein binding	IPI PMID:19273613 Spatiotemporal control of mitosis by the conserved spindle m...	REMOVE	Summary: IPI with TPR (Megator orthologue). Lince-Faria et al. showed that Tpr, Mad1, Mad2 and Mps1 co-immunoprecipitate from nocodazole-arrested HeLa extracts and that Mps1, like Tpr, localizes to the nuclear pore complex in interphase; Tpr/Megator promotes timely recruitment of Mad2 and Mps1 to unattached kinetochores. Reason: A bare "protein binding" annotation carries no functional information. The paper characterises TPR as a spatial regulator that delivers Mps1 to kinetochores, not a molecular activity of TTK, so no more informative MF term can be justified from it. The interaction itself is not disputed (UniProt records it), and the interphase nuclear-pore localization it reports is noted under the nucleus annotation. Supporting Evidence: PMID:19273613 Tpr, Mad1, Mad2, and Mps1 coimmunoprecipitate in mitotic enriched HeLa cell extracts prepared in the presence of nocodazole
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO from the protein-kinase domain and ATP-binding-site signatures. TTK has a canonical ATP-binding kinase domain (residues 525-791; Lys553 anchors ATP) and is inhibited by ATP-competitive compounds such as SP600125 and reversine. Reason: Correct and implied by the demonstrated kinase activity; ATP-competitive inhibition confirms a functional nucleotide-binding site. Supporting Evidence: PMID:30785839 this phosphorylation was decreased by the presence of the Mps1 inhibitor, reversine, indicating its specificity
GO:0005634 nucleus	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: PAINT inference from a deep node (PTN000540737) that includes plant, fly, worm, trypanosome and other mammalian kinases. Human TTK does have an interphase nuclear pool: it localizes with TPR, MAD1 and MAD2 at the nuclear pore complex, and a nuclear role in the DNA-damage response has been proposed. Its defining activity, however, is exerted on kinetochores after nuclear envelope breakdown. Reason: The localization is real (interphase NPC/nucleoplasmic pool) but is not where TTK's characterised checkpoint and error-correction functions are executed; retained as a non-core cellular component. Supporting Evidence: PMID:19273613 Like Tpr, Mad1, Mad2, and Mps1 localize at the NPC during interphase in human cells.
GO:0005737 cytoplasm	IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	KEEP AS NON CORE	Summary: IDA from a proteomic E-cadherin proximity-labelling study in which candidate proteins were GFP-tagged to determine their subcellular localization. Cytoplasmic localization of TTK is independently well established: during mitosis the kinase cycles between the cytoplasm and unattached kinetochores. Reason: Correct but broad; the cytoplasmic pool is the reservoir from which TTK is recruited to kinetochores rather than a site of characterised function. The cited study does not implicate TTK in adherens-junction biology. Supporting Evidence: PMID:25468996 by tagging identified proteins with GFP (green fluorescent protein), we determined the subcellular localization of 83 putative E-cadherin-proximal proteins PMID:28441529 Mps1 cycles between the cytoplasm and unattached or mal-oriented kinetochores
GO:0005819 spindle	TAS PMID:10366450 Characterization of MAD2B and other mitotic spindle checkpoi...	MODIFY	Summary: TAS citing a 1999 Genomics paper that mapped the chromosomal loci of spindle checkpoint genes (including TTK) and screened them for mutations in colorectal tumours. The paper contains no localization data; the annotation appears to derive from the general description of TTK as a spindle-checkpoint gene. Reason: The structure on which TTK acts is the kinetochore, not the spindle proper, and the cited reference does not support spindle localization. The kinetochore term is the accurate cellular component (already annotated by IBA/IEA) and is proposed as the replacement. Proposed replacements: kinetochore Supporting Evidence: PMID:10366450 We determined the chromosomal localization of it and other spindle checkpoint genes, including MAD1L1, MAD2, BUB3, TTK (MPS1L1), and CDC20. PMID:26068854 Competition between Mps1 and microtubules for Ndc80C binding thus constitutes a direct mechanism for the detection of unattached kinetochores.
GO:0007051 spindle organization	TAS PMID:10366450 Characterization of MAD2B and other mitotic spindle checkpoi...	MODIFY	Summary: TAS from the same gene-mapping paper, which provides no functional data on spindle organization. A role for TTK in spindle organization is nonetheless supported by later work: Mps1 phosphorylates MCRS1 to regulate KIF2A at spindle microtubule minus ends and spindle morphology. Reason: The process is plausible but the generic term should be replaced by the mitosis-specific descendant that GOA already carries, and the supporting reference should be PMID:30785839 rather than the mapping paper. Regarded as a secondary (non-core) function. Proposed replacements: mitotic spindle organization Supporting Evidence: PMID:30785839 Mps1 binds and phosphorylates MCRS1. This mechanism enables KIF2A localization to the minus end of spindle microtubules.
GO:0007052 mitotic spindle organization	TAS PMID:7737118 Yeast spindle pole body duplication gene MPS1 encodes an ess...	KEEP AS NON CORE	Summary: TAS citing the budding-yeast MPS1 paper, where Mps1 is essential for spindle pole body duplication. Whether human TTK is required for centrosome duplication has been contested, but a mitotic spindle-organization role in human cells is supported by the MCRS1/KIF2A work (Mps1 regulates spindle morphology through MCRS1). Reason: The term is supported in human cells by PMID:30785839, but it is a secondary role relative to checkpoint signalling and attachment error correction; the cited yeast reference is orthologue evidence only. Supporting Evidence: PMID:30785839 our study reveals a novel role of Mps1 in regulating the dynamics of the minus end of microtubules and expands the functions of Mps1 in genome maintenance PMID:7737118 The MPS1 gene has been previously identified by a mutant allele that shows defects in spindle pole body (SPB) duplication and cell cycle control.
GO:0007059 chromosome segregation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: TTK ensures accurate chromosome segregation through checkpoint signalling and attachment error correction; loss or inhibition causes lagging chromosomes, missegregation and aneuploidy. The term is correct but describes the downstream outcome rather than the mechanism. Reason: Accurate high-level parent supported by the PAINT node and human data, retained as a non-core descriptor; the mechanistic core is captured by GO:0007094 and GO:0140273. Supporting Evidence: PMID:28441529 Our results reveal how Mps1 dynamically modifies kinetochores to correct improper attachments and ensure faithful chromosome segregation.
GO:0007094 mitotic spindle assembly checkpoint signaling	IBA GO_REF:0000033	ACCEPT	Summary: The mitotic SAC is the primary function of TTK, established in human cells and across fungi and metazoa: TTK is the apical checkpoint kinase that phosphorylates KNL1 MELT motifs, BUB1 and MAD1 to assemble the mitotic checkpoint complex. TTK's own experimental annotation is among the descendant evidences for the PAINT node. Reason: Core biological process; phylogenetic inference and direct human evidence agree. Supporting Evidence: PMID:22660415 MPS1 is an evolutionarily conserved protein kinase required for the SAC and chromosome bi-orientation. PMID:28441529 Bub1 and BubR1 interact with Mps1-phosphorylated MELT motifs in KNL1 (CASC5), a large scaffold protein at the kinetochore file:human/TTK/TTK-deep-research-falcon.md It phosphorylates KNL1, BUB1, and MAD1 in sequence, thereby catalyzing production of the mitotic checkpoint complex (MCC).
GO:0007094 mitotic spindle assembly checkpoint signaling	IDA PMID:18243099 Mps1 phosphorylates Borealin to control Aurora B activity an...	ACCEPT	Summary: Jelluma et al. describe Mps1 as essential for the mitotic checkpoint and show that it additionally coordinates attachment error correction through Borealin phosphorylation. Reason: Direct human-cell evidence for the core process. Supporting Evidence: PMID:18243099 Mps1 thus coordinates attachment error correction and checkpoint signaling, two crucial responses to unproductive chromosome attachments.
GO:0007094 mitotic spindle assembly checkpoint signaling	IEA GO_REF:0000120	ACCEPT	Summary: Automated annotation (ARBA plus Ensembl transfer from mouse Ttk) to the core process; duplicates the IBA and IDA rows. Reason: Consistent with the experimental and phylogenetic evidence for TTK's primary function. Supporting Evidence: PMID:26068854 Elimination of one such interaction in human cells caused checkpoint defects expected from a failure to detect unattached kinetochores.
GO:0007094 mitotic spindle assembly checkpoint signaling	TAS PMID:10366450 Characterization of MAD2B and other mitotic spindle checkpoi...	ACCEPT	Summary: TAS from the Genomics paper that lists TTK (MPS1L1) among the spindle checkpoint genes whose chromosomal loci were mapped. The paper supplies no mechanistic data, but the statement it makes is correct. Reason: The assertion is right and is the core process of TTK; the mechanistic support is provided by the IDA and IBA rows and their references. Supporting Evidence: PMID:10366450 We determined the chromosomal localization of it and other spindle checkpoint genes, including MAD1L1, MAD2, BUB3, TTK (MPS1L1), and CDC20.
GO:0008284 positive regulation of cell population proliferation	TAS PMID:1639825 Expression of TTK, a novel human protein kinase, is associat...	REMOVE	Summary: The original TTK cloning paper reported that TTK mRNA is present in proliferating tissues (testis, thymus), tumours and rapidly proliferating cell lines, and absent from most quiescent tissues. This is an expression correlation with proliferation, not evidence that TTK positively regulates proliferation. Reason: The cited evidence is a correlation of transcript abundance with proliferative state (as expected for a mitotic kinase), which the annotation has converted into a regulatory function. TTK's established role is to restrain anaphase until chromosomes are attached and to correct faulty attachments; no step of a proliferation-promoting process is executed by TTK. Removal does not dispute the reported expression pattern. Supporting Evidence: PMID:1639825 all rapidly proliferating cell lines tested expressed TTK mRNA
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: High-throughput membrane proteomics of the NK-like cell line YTS identified 1843 proteins, of which only about 40% were predicted membrane proteins; the authors state that the remainder were likely transiently associated with membranes. TTK has no transmembrane segment, signal peptide or lipid anchor and no described membrane function. Reason: A single HTP detection in a membrane fraction, with no orthogonal support and no known membrane role, is best regarded as over-annotation (contaminant or transient association) rather than a genuine localization of TTK. Supporting Evidence: PMID:19946888 The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes.
GO:0033316 meiotic spindle assembly checkpoint signaling	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: PAINT inference from fly and mouse Mps1, both of which function in the oocyte spindle assembly checkpoint. There is no direct human evidence, but the mechanism (kinetochore Mps1 recruiting checkpoint proteins) is the same one TTK performs in mitosis and is expected to operate in human meiosis. Reason: Reasonable phylogenetic inference from well-characterised metazoan orthologues; retained as non-core because the human evidence base is mitotic and the meiotic role is context-specific. Supporting Evidence: PMID:22660415 MPS1 is an evolutionarily conserved protein kinase required for the SAC and chromosome bi-orientation.
GO:0042802 identical protein binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ensembl transfer from mouse Ttk. Mps1 activation involves dimerisation-dependent trans-autophosphorylation, so self-association is a genuine property, though it is a mechanism of activation rather than a distinct function. Reason: Self-association is consistent with the trans-autophosphorylation mode of activation documented in human cells, but is a low-information term that does not describe a core activity. Supporting Evidence: PMID:28441529 thereby enabling ligand-dependent relocalization (Fig. S1) and activation of Mps1 via trans autophosphorylation
GO:0043515 kinetochore binding	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl transfer from mouse Ttk. Human Mps1 binds the NDC80 complex directly through two interactions that use the microtubule-binding surfaces of NDC80C and are inhibited by microtubules; this competitive binding is the attachment-sensing mechanism of the checkpoint. Reason: Direct kinetochore binding (via NDC80C) is demonstrated in human cells and is mechanistically central to how TTK senses unattached kinetochores. Supporting Evidence: PMID:26068854 Both interactions involved the microtubule-binding surfaces of Ndc80C and were directly inhibited in the presence of microtubules.
GO:0060391 positive regulation of SMAD protein signal transduction	TAS PMID:19018011 Holding their own: the noncanonical roles of Smad proteins.	UNDECIDED	Summary: TAS citing a perspective article on noncanonical Smad functions; the cached abstract does not mention TTK, and the underlying primary report (Mps1 phosphorylation of Smad2/3) is a single-study, noncanonical claim that has not been integrated into the TTK literature. Reason: The primary evidence cannot be evaluated from the cached abstract-only perspective article, and the claim is not corroborated elsewhere in the deep research. It would at most be a peripheral activity unrelated to TTK's kinetochore functions; left undecided rather than removed because the primary data have not been read. Supporting Evidence: PMID:19018011 The number of reports demonstrating the interactions of Smads with proteins outside of canonical TGF-beta signaling is increasing, although the functional relevance of these interactions is not known.
GO:0098813 nuclear chromosome segregation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA annotation to nuclear chromosome segregation, a broad outcome-level term. TTK's checkpoint and error-correction activities ensure faithful segregation. Reason: Correct but broad; the mechanistic, informative terms are GO:0007094 and GO:0140273. Retained as a non-core outcome descriptor, consistent with the IBA chromosome segregation row. Supporting Evidence: PMID:28441529 Our results reveal how Mps1 dynamically modifies kinetochores to correct improper attachments and ensure faithful chromosome segregation.
GO:0106310 protein serine kinase activity	EXP PMID:30785839 Mps1 regulates spindle morphology through MCRS1 to promote c...	ACCEPT	Summary: Yang et al. showed by in vitro kinase assay, mass spectrometry and phospho-specific antibody that recombinant Mps1 phosphorylates MCRS1 on Ser64/Ser65, and that this phosphorylation is blocked by the Mps1 inhibitor reversine. Reason: Direct demonstration of serine phosphorylation of a substrate by human TTK; the serine-specific term is a valid descendant of the Ser/Thr kinase activity that is TTK's core molecular function. Supporting Evidence: PMID:30785839 Mps1 efficiently phosphorylated MCRS1 PMID:30785839 the antibody could detect in vitro phosphorylation of wild-type MCRS1 protein after Mps1 kinase assay, but recognized the S65A mutant much less efficiently, indicating that S65 is an Mps1 site in vitro
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: Rhea-derived annotation from the serine-phosphorylation reaction of EC 2.7.12.1. Serine phosphorylation of substrates (MCRS1 Ser64/65, SKA3 Ser34, KNL1 Ser1831/1834, autophosphorylation at Ser37/Ser363) is directly documented. Reason: Consistent with the EXP row and with the broader Ser/Thr kinase annotations. Supporting Evidence: PMID:28441529 the Mps1-regulated phosphorylation site on Ska3 (S34) sits at the hinge of the W-shaped Ska complex
GO:0140273 repair of mitotic kinetochore microtubule attachment defect	IDA PMID:18243099 Mps1 phosphorylates Borealin to control Aurora B activity an...	ACCEPT	Summary: Cells lacking Mps1 kinase activity fail to align chromosomes because improper attachments are left uncorrected; Mps1 phosphorylation of Borealin sustains centromeric Aurora B activity required for error correction. Reason: Direct human-cell evidence that TTK participates in attachment error correction; a core function alongside checkpoint signalling. Supporting Evidence: PMID:18243099 cells lacking Mps1 kinase activity fail to efficiently align chromosomes due to impaired Aurora B function at centromeres, leaving improper attachments uncorrected
GO:0140273 repair of mitotic kinetochore microtubule attachment defect	IDA PMID:28441529 Mps1 Regulates Kinetochore-Microtubule Attachment Stability ...	ACCEPT	Summary: Kinetochore-targeted Mps1 destabilises K-fibres epistatically to (and independently of) Aurora B; Mps1-dependent phosphorylation of SKA3 Ser34 reduces the Ska complex's end-coupled microtubule binding, and this is opposed by PP2A-B56. Mps1 thereby corrects improper attachments and ensures faithful segregation. Reason: Rigorous mechanistic demonstration (chemical epistasis, phosphoproteomics, phosphomimetic mutants, in vitro reconstitution) that TTK executes attachment error correction through direct substrate phosphorylation; core function. Supporting Evidence: PMID:28441529 We also identify the Ska complex as a key effector of Mps1 at the kinetochore-microtubule interface, as mutations that mimic constitutive phosphorylation destabilized K fibers in vivo PMID:28441529 Epistasis experiments reveal that kinetochore-localized Mps1 can destabilize microtubule attachments directly, even if Aurora B is inhibited.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

📚 Additional Documentation

Notes

📄 View Raw YAML