Dual specificity protein kinase TTK
Also known as: MPS1, MPS1L1, TTK
Function
Involved in mitotic spindle assembly checkpoint signaling, a process that delays anaphase until chromosomes are bioriented on the spindle, and in the repair of incorrect mitotic kinetochore-spindle microtubule attachments. Phosphorylates MAD1L1 to promote the mitotic spindle assembly checkpoint. Phosphorylates CDCA8/Borealin leading to enhanced AURKB activity at the kinetochore. Phosphorylates SKA3 at 'Ser-34' leading to dissociation of the SKA complex from microtubules and destabilization of microtubule-kinetochore attachments. Phosphorylates KNL1, KNTC1 and autophosphorylates. Phosphorylates MCRS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and promotes chromosome alignment.
Classification
- Family (Pfam)
- PF00069 Pkinase
- InterPro
- Kinase-like_dom_sf, Mps1_cat, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS, TPR-like_helical_dom_sf
- Functional cluster
- Protein Serine/Threonine Kinases
Experimental structures · PDB · 78
- 2X9E X-ray 3.10A
- 2ZMC X-ray 3.14A
- 2ZMD X-ray 2.88A
- 3CEK X-ray 2.30A
- 3DBQ X-ray 2.70A
- 3GFW X-ray 2.74A
- 3H9F X-ray 2.60A
- 3HMN X-ray 2.70A
- 3HMO X-ray 2.40A
- 3HMP X-ray 2.30A
- 3VQU X-ray 2.40A
- 3W1F X-ray 2.70A
- … and 66 more
A predicted model is available from AlphaFold.
Gene Ontology · 20
- GO:0005737 cytoplasm
- GO:0000776 kinetochore
- GO:0016020 membrane
- GO:0005634 nucleus
- GO:0005819 spindle
- GO:0005524 ATP binding
- GO:0042802 identical protein binding
- GO:0106310 protein serine kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0004712 protein serine/threonine/tyrosine kinase activity
- GO:0004713 protein tyrosine kinase activity
- GO:0007059 chromosome segregation
- GO:0033316 meiotic spindle assembly checkpoint signaling
- GO:0007094 mitotic spindle assembly checkpoint signaling
- GO:0007052 mitotic spindle organization
- GO:0008284 positive regulation of cell population proliferation
- GO:0060391 positive regulation of SMAD protein signal transduction
- GO:0034501 protein localization to kinetochore
- GO:0140273 repair of mitotic kinetochore microtubule attachment defect
- GO:0007051 spindle organization
Drugs targeting this protein · 2
- BAY-1161909 inhibitor
- BAY-1217389 inhibitor
Related proteins · sequence + function similarity
- Dual specificity protein kinase TTK 0.99
- Dual specificity protein kinase TTK 0.92
- Dual specificity protein kinase Ttk 0.81
- Serine/threonine-protein kinase MPS1 0.67
- Mitotic checkpoint serine/threonine-protein kinase BUB1 0.67
- Serine/threonine-protein kinase Nek5 0.67
- Mitotic checkpoint serine/threonine-protein kinase BUB1 0.66
- Serine/threonine-protein kinase Nek4 0.65
- Anillin 0.62
- Mitotic checkpoint serine/threonine-protein kinase BUB1 beta 0.62
- Insulin receptor substrate 1 0.62
- Protein deadlock 0.62
Co-cited proteins · studied together in the literature
- Borealin 1 shared papers
- Kinesin-like protein KIF2A 1 shared papers
- Mitotic spindle assembly checkpoint protein MAD1 2 shared papers
- Kinetochore-associated protein 1 1 shared papers
- Microspherule protein 1 1 shared papers
- Nucleoprotein TPR 1 shared papers
- SKA complex subunit 1 1 shared papers
- Nucleoprotein TPR 1 shared papers
- Outer kinetochore KNL1 complex subunit KNL1 1 shared papers
- Mitotic spindle assembly checkpoint protein MAD2A 1 shared papers
- Mitotic checkpoint serine/threonine-protein kinase BUB1 beta 1 shared papers
- Cell division cycle protein 20 homolog 1 shared papers
Literature · 23 cited papers
- Mps1 regulates spindle morphology through MCRS1 to promote chromosome alignment. Mol. Biol. Cell · 2019
- Direct interactions of mitotic arrest deficient 1 (MAD1) domains with each other and MAD2 conformers are required for mitotic checkpoint signaling. J. Biol. Chem. · 2018
- Mps1 Regulates Kinetochore-Microtubule Attachment Stability via the Ska Complex to Ensure Error-Free Chromosome Segregation. Dev. Cell · 2017
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci. Signal. · 2009
- Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
- Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
- Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator. J. Cell Biol. · 2009
- Structural and mechanistic insights into Mps1 kinase activation. J. Cell. Mol. Med. · 2009
- … and 11 more in the literature graph
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