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FLASH GENE
Symbol TTBK2 contributors: mct - updated : 11-04-2019
HGNC name tau tubulin kinase 2
HGNC id 19141
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminus encodeing a serine-threonine-tyrosine kinase domain
  • C-terminal region showing homology to TTBK1, and the C-terminal tail was required to recruit TTBK2 to the centriole, and the kinase domain was required to promote ciliogenesis
    • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • CK1 Ser/Thr protein kinase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,intermed filament
    intracellular,nucleus
    text
  • TTBK2 is localized to the distal end of the mother centriole, where it promotes ciliogenesis through the displacement of the negative regulator CCP110 and the enrichment of IFT complex components at the base of the cilium
    • basic FUNCTION
  • playing an important role in the tau cascade and in spinocerebellar degeneration
  • having a role in preventing tau toxicity
  • Ser/Thr kinase that putatively phosphorylates residues Ser208 and Ser210 (numbered according to a 441-AA human tau isoform) in tau protein
  • key biochemical functions of TTBK2 are required for ciliogenesis
  • protein kinase important for transitioning centrioles from the cell cycle to postmitotic assembly of axonemes
  • is a dedicated regulator of the initiation of ciliogenesis
  • is not required for the formation of mature basal bodies, but is required to initiate assembly of the ciliary axoneme
  • TTBK2 activity at the centrosome may lead to the removal of CCP110, either directly or indirectly, in order to prime the basal body for cilia formation
  • TTBK2 also acts upstream of CEP164, contributing to the assembly of distal appendages
  • is essential for regulating the growth of axonemal microtubules in ciliogenesis
  • is a multifunctional kinase involved in important cellular processes and demands augmented efforts in investigating its function
  • TTBK2 with MAPRE1/MAPRE3 phosphorylates KIF2A and antagonizes KIF2A-induced depolymerization at microtubules plus ends for cell migration
  • is a key regulator of the assembly of primary cilia
  • new functions for TTBK2 after cilia initiation in the control of cilia length, trafficking of a subset of SHH pathway components, including Smoothened (SMO), and cilia stability
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • is recruited to the centriole and transition zone near the ciliary base, and causes the loss of CCP110, an inhibitor of axonemal growth
  • cell-cycle regulators target TTBK2 to the basal body, where it modifies specific targets to initiate ciliogenesis
  • TTBK2 acts upstream of IFT and is required for the recruitment or retention of IFT complexes at the basal body prior to cilia assembly
  • one of the major functions of CEP164 in ciliogenesis is to recruit active TTBK2 to centrioles
  • TTBK2 has the potential to effectively phosphorylate CEP164 and CEP97 and inhibits the interaction between CEP164 and its binding partner DVL3 (an important regulator of ciliogenesis) in a kinase activity-dependent manner
  • unlike NDE1, MCRS1 played a positive role for the initiation of ciliogenesis, possibly through its interaction with TTBK2
  • TTBK2 down-regulates GRIK2 activity by decreasing the receptor protein abundance in the cell membrane via RAB5A-dependent endocytosis, an effect that may protect against neuroexcitotoxicity
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SCA11
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS