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FLASH GENE
Symbol TTBK2 contributors: mct - updated : 11-04-2019
HGNC name tau tubulin kinase 2
HGNC id 19141
Corresponding disease
SCA11 spinocerebellar ataxia 11
Location 15q15.2      Physical location : 43.036.541 - 43.213.007
Synonym name tau-tubulin kinase
Synonym symbol(s) KIAA0847, TTBK, SCA11
EC.number 2.7.11.1
DNA
TYPE functioning gene
STRUCTURE 176.47 kb     14 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
MAPKBP1 15q14 likely ortholog of mouse mitogen activated protein kinase binding proten 1 PLA2G4B 15q11.2-q21.3 phospholipase A2, group IVB (cytosolic) SPTBN5 15q21 spectrin, beta, non-erythrocytic 5 EHD4 15q11.1-q15 EH-domain containing 4 FLJ45651 15q14 FLJ45651 protein LOC388117 15 LOC388117 cPLA2delta LOC255189 15q14 hypothetical protein LOC255189 VPS39 15q14-q15 vacuolar protein sorting 39 (yeast) DKFZP564G2022 15q14 DKFZP564G2022 protein GANC 15q15.1-q15.2 glucosidase, alpha; neutral C CAPN3 15q15.1-q15.3 calpain 3, (p94) ZFP106 15q14 zinc finger protein 106 homolog (mouse) SNAP23 15q14-q15.1 synaptosomal-associated protein, 23kDa FLJ36812 15q14 hypothetical protein FLJ36812 FLJ10460 15q14 hypothetical protein FLJ10460 LOC390579 15 similar to myosin regulatory light chain-like LOC388118 15 similar to kinesin-like protein STARD9 15q14 START domain containing 9 CDAN1 15q14-q15 congenital dyserythropoietic anemia, type I TTBK2 15q14 tau tubulin kinase 2 LOC390580 15 similar to Ac2-125 UBR1 15q15-q21.1 ubiquitin protein ligase E3 component n-recognin 1 LOC146053 15q14 similar to ribosomal protein S3a; 40S ribosomal protein S3a; v-fos transformation effector protein 1 LOC255320 15q15.1 similar to Microsomal signal peptidase 25 kDa subunit (SPase 25 kDa subunit) (SPC25) FLJ23375 15q15.1 hypothetical protein FLJ23375 CCNDBP1 15q14-q15 cyclin D-type binding-protein 1 EPB42 15q15 erythrocyte membrane protein band 4.2 TGM5 15q15.2 transglutaminase 5 LOC390581 15 similar to ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d; ATP synthase, H+ transporting, mitochondrial F1F0, subunit d TGM7 15q15.2 similar to ATP synthase, H+ transporting, mitochondrial F0 complex, subunit d; ATP synthase, H+ transporting, mitochondrial F1F0, subunit d LCMT2 15q14 leucine carboxyl methyltransferase 2 LOC161823 15q15.1 similar to Adenosine deaminase CG11994-PA FLJ35867 15q15.1 hypothetical protein FLJ35867 76P 15q15 gamma tubulin ring complex protein (76p gene) TP53BP1 15q15-q21 tumor protein p53 binding protein, 1 MAP1A 15q13-qter microtubule-associated protein 1A KIAA0377 15q15-q21.2 microtubule-associated protein 1A CKMT1 15q15 creatine kinase, mitochondrial 1 (ubiquitous) STRC 15q15.3 stereocilin CATSPER2 15q13-q15 cation channel, sperm associated 2
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
14 - 5635 - 1244 - 2007 18037885
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestiveliver    
Endocrinethyroid   highly
Nervousbrainhindbraincerebellum highly
 brainlimbic systemhippocampus highly
 brainmidbrainsubstantia nigra highly
Reproductivefemale systemuteruscervix highly
 male systemtestis  highly
Urinarykidney    
cells
SystemCellPubmedSpeciesStageRna symbol
NervousPurkinje cell
cell lineage
cell lines
fluid/secretion
at STAGE
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