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FLASH GENE
Symbol TTK contributors: mct/pgu - updated : 27-05-2014
HGNC name TTK protein kinase
HGNC id 12401
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
Lymphoid/Immunethymus   highly
Reproductivemale systemtestis  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text stem cells
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • unstructured C-terminal tail of TTK is largely dispensable for autophosphorylation but necessary for optimal substrate phosphorylation, and is required for spindle checkpoint activation
  • HOMOLOGY
    interspecies homolog to yeast Mps1and CDC20/Slp1
    Homologene
    FAMILY SER/THR family of protein kinases
    CATEGORY enzyme , receptor membrane serine/threonine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text
  • levels of TTK are relatively low in cells during interphase but elevated in mitosis or upon activation of the spindle checkpoint
  • localize to both centrosomes and kinetochores
  • basic FUNCTION
  • functioning at the mitotic spindle checkpoint
  • required for progression of mitosis
  • essential for the mitotic checkpoint, and also controls correction of improper chromosome attachments
  • coordinating attachment error correction and checkpoint signaling, two crucial responses to unproductive chromosome attachments
  • crucial for the spindle assembly checkpoint and for chromosome biorientation on the mitotic spindle
  • required for the correction of improper chromosome-microtubule attachments
  • having a function in procentriole assembly
  • is required for spindle checkpoint activation
  • critical kinase, and its activity is required for both normal chromosome alignment and for regulating the spindle checkpoint
  • its kinase activity is required for proper chromosome segregation during mitosis through its involvements in microtubule-chromosome attachment error correction and the mitotic checkpoint
  • release of TTK from kinetochores is essential for mitotic checkpoint silencing and a fast metaphase-to-anaphase transition
  • TTK-dependent phosphorylation of CETN2 stimulates the canonical centriole assembly pathway)
  • may participate in cytokinesis via the regulation of SPECC1L
  • conserved protein kinase critical for spindle pole body (the functional equivalent of the centrosome) duplication, spindle checkpoint, kinetochore biorientation, and chromosome-microtubule attachment
  • but what role it plays in SPECC1L function remains to be discovered
  • novel role for AURKB-NDC80-TTK signaling axis in governing accurate chromosome segregation in mitosis
  • is a mitotic checkpoint kinase responsible for sensing the unattached and tensionless kinetochore
  • CELLULAR PROCESS cell cycle
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • phosphorylating CDCA8 to control Aurora B activity and chromosome alignment
  • interaction between TTK and TACC2 established provides new avenue to study centrosome and spindle dynamics underlying cell divisional control
  • regulatory loop between TTK and CHEK2 whereby DNA damage-activated CHEK2 may facilitate the stabilization of TTK, therefore maintaining the checkpoint control
  • phoshorylates the N-terminal domain of TP53 at Thr18, and this phosphorylation disrupts the interaction with MDM2 and abrogates MDM2-mediated TP53 ubiquitination
  • OAZ1 binds to TTK via the TTK degradation signal and modulates the function of TTK in centrosome overproduction
  • interacting with SPECC1L
  • is a target of the UBE4B enzyme (UBE4B-mediated TTK degradation is conserved in humans and is important for mitotic progression)
  • VDAC3 is present at the mother centriole and modulates centriole assembly by recruiting TTK to centrosomes
  • NDC80 interacts with TTK and specifies its kinetochore localization via its calponin homology (CH) domain and N-terminal 80 amino acids
  • CHEK2 contributes to chromosomal stability through TTK
  • CHEK2 stabilizes TTK and phosphorylates AURKB-serine 331 to prevent mitotic exit when most kinetochores are unattached
  • PPP2R5D opposes TTK phosphorylation of CASC5 and thereby promotes spindle assembly checkpoint silencing
  • competition between TTK and microtubules for NDC80C binding thus constitutes a direct mechanism for the detection of unattached kinetochores
  • cell & other
    REGULATION
    inhibited by reversine, a potent mitotic inhibitor of TTK
    Other regulated throughout the cell cycle by the anaphase-promoting complex (APC) E3
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    small molecule inhibitors that target the C-terminus of TTK, might be used alone or in conjunction with other therapeutics (e.g. taxol) to selectively kill tumor cells
    ANIMAL & CELL MODELS