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FLASH GENE
Symbol TLK2 contributors: mct/npt - updated : 16-07-2018
HGNC name tousled-like kinase 2
HGNC id 11842
Corresponding disease
BPTID blepharophimosis, telecanthus, intellectual disability
Location 17q23.2      Physical location : 60.556.385 - 60.692.839
Synonym name serine/threonine-protein kinase tousled-like 2
Synonym symbol(s) PRKUA, PKU-ALPHA, MGC44450
EC.number 2.7.11.1
DNA
TYPE functioning gene
SPECIAL FEATURE head to head
STRUCTURE 144.57 kb     22 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
TBX2 17q23 T-box 2 LOC388407 17 hypothetical gene supported by BC046200 TBX4 17q23 T-box 4 MGC71999 17q23.3 alpha-NAC protein BRIP1 17q22-q24 BRCA1 interacting protein C-terminal helicase 1 KIAA1287 17q23.3 KIAA1287 protein TRAP240 17q23 KIAA1287 protein LOC284167 17q23.3 similar to RPOM_HUMAN LOC388408 17 similar to Ribosomal protein S6 kinase (S6K) (p70-S6K) LOC388409 17 hypothetical gene supported by BC058890 FLJ25818 17q24.1 hypothetical protein FLJ25818 FLJ12760 17q24.1 hypothetical protein FLJ12760 TLK2 17q23 tousled-like kinase 2 MRC2 17q21.1-q23 mannose receptor, C type 2 FLJ35757 17q24.1 hypothetical protein FLJ35757 DKFZP564D166 17q24.1 putative ankyrin-repeat containing protein CYB561 17q11-qter cytochrome b-561 LOC342541 17q24.1 similar to peptidyl-Pro cis trans isomerase ACE 17q23 angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 KCNH6 17q24.2 potassium voltage-gated channel, subfamily H (eag-related), member 6 HAN11 17q24.2 WD-repeat protein
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
21 - 5113 - 718 - 2016 27489360
  • variant B
  • 22 - 5455 - 750 - 2016 27489360
    variant A
    22 - 5762 - 601 - 2016 27489360
    variant D
    23 - 5518 - 772 - 2016 27489360
    EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Lymphoid/Immunetonsils   highly
    Reproductivefemale systembreastmammary gland highly
     male systemtestis  highly
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectiveadipose  highly
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, S
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • serine/threonine kinase with a N terminal nuclear localization signal (NLS)
  • a coiled coil region
  • HOMOLOGY
    interspecies homolog to murine Tlk2
    intraspecies homolog to TLK1
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • nuclear serine/threonine kinase, cell-cylce regulated, displaying maximal activities during S-phase
  • target of the DNA damage checkpoint
  • TLK1, TLK2 appear to be intimately linked to the pattern of resistance to DNA damage, and specifically DSBs
  • is an important regulator of recovery after DNA damage in G2
  • both TLK2 and ASF1A are required to restore histone H3 incorporation into damaged chromatin
  • specific role for TLK2 in placental function during mammalian development and likely TLK1 and TLK2 have largely redundant roles in genome maintenance
  • critical role for TLK1, TLK2 in chromatin replication and suppression of replication stress
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component component of ATM-CHK1-TLK pathway that may regulate processes involved in chromatin assembly
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • regulates the ASF1A histone chaperone in response to DNA damage and depletion of ASF1A also produces a recovery defect
  • TLK2 promotes ASF1A function during the DNA damage response in G2 to allow for proper restoration of chromatin structure at the break site and subsequent recovery from the arrest
  • TLK1 and TLK2, regulate ASF1A, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair
  • TLK1 and TLK2 interact with each other and TLK activity enhances ASF1 histone binding and is inhibited by the DNA damage response
  • key role for SRC signaling in regulating the functions of TLK2
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) BPTID
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in glioblastoma, and such upregulation was associated with poor patient outcomes
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    targeting TLK2 presents an attractive therapeutic strategy for the TLK2-amplified breast cancers that possess enhanced genomic instability and aggressiveness
    ANIMAL & CELL MODELS
  • Tlk2-null mice were embryonically lethal due to placental failure