Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol TTK contributors: mct/pgu - updated : 27-05-2014
HGNC name TTK protein kinase
HGNC id 12401
Location 6q14.1      Physical location : 80.714.321 - 80.752.244
Genatlas name monopolar spindle 1-like 1
Synonym name
  • MPS1 protein kinase
  • monopolar spindle 1 (Mps1) kinase
  • phosphotyrosine picked threonine kinase (PYT)
  • Synonym symbol(s) MPS1L1, ESK, PYT, HMPS1, MPS1
    EC.number 2.7.12.1
    DNA
    TYPE functioning gene
    STRUCTURE 37.92 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status confirmed
    Physical map
    HTR1B 6q13 5-hydroxytryptamine (serotonin) receptor 1B IRAK1BP1 6q14-q15 interleukin-1 receptor-associated kinase 1 binding protein 1 PHIP 6q14 pleckstrin homology domain interacting protein HMGN3 6q15 high mobility group nucleosomal binding domain 3 LOC153959 6q14.3 hypothetical LOC153959 DBIL2 6q12-q21 diazepam binding inhibitor-like 2 (a pseudogene) C6orf152 6q14.3 chromosome 6 open reading frame 152 SH3BGRL2 6q13-15 SH3 domain binding glutamic acid-rich protein like 2 ELOVL4 6q14 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 4 LOC391944 6 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) TTK 6q12-q21 TTK protein kinase LOC285786 6q14.3 similar to KIAA1424 protein LOC389412 6 similar to Rho GTPase activating protein 21; Rho-GTPase activating protein 10 BCKDHB 6p22-p21 branched chain keto acid dehydrogenase E1, beta polypeptide (maple syrup urine disease) LOC391945 6 similar to 60S ribosomal protein L17 (L23) LOC340171 6q14.3 hypothetical LOC340171 LOC153956 6q14.3 similar to citrate (si)-synthase (EC 4.1.3.7) precursor - pig C6orf37 6q14 chromosome 6 open reading frame 37 LOC389413 6 LOC389413 IBTK 6q14.3 inhibitor of Bruton agammaglobulinemia tyrosine kinase TPBG 6q14-q15 trophoblast glycoprotein C6orf157 6q15 chromosome 6 open reading frame 157 KIAA1117 6q15 chromosome 6 open reading frame 157 PGM3 6q14.1-q15 phosphoglucomutase 3 RWDD2 6q15 RWD domain containing 2 ME1 6q12 malic enzyme 1, NADP(+)-dependent, cytosolic C6orf158 6q15 chromosome 6 open reading frame 158 SNAP91 6q13 synaptosomal-associated protein, 91kDa homolog (mouse)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 3010 - 857 - 2002 11927556
    22 - 3019 - 856 - 2002 11927556
    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)
  • 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