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FLASH GENE
Symbol CLK2 contributors: mct - updated : 13-09-2018
HGNC name CDC-like kinase 2
HGNC id 2069
Location 1q22      Physical location : 155.232.659 - 155.243.281
Synonym name
  • dual specificity protein kinase CLK2
  • CLK kinase
  • Synonym symbol(s) HCLK2, MGC61500
    EC.number 2.7.12.1
    DNA
    TYPE functioning gene
    STRUCTURE 10.66 kb     13 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 2203 59.8 498 - 2016 27126587
    12 - 2115 - 271 - 2016 27126587
    13 - 2200 - 498 - 2016 27126587
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbraindiencephalonhypothalamus   Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadiposebrown   Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies homolog to murine Clk2 (97.0pc)
    homolog to rattus Clk2 (97.2pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • CLK family of dual specificity protein kinases
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    basic FUNCTION
  • dual specificity protein kinase involved in cell cycle progression, apoptosis, and telomere length regulation
  • stabilizes CHEK1
  • is required for activity of ATR, stimulating its autophosphorylation and contributes to ATR checkpoint signalling (Danielsen 2009)
  • is an insulin-regulated suppressor of hepatic gluconeogenesis and glucose output
  • CLK2 suppresses fatty acid oxidation and ketone body production during diet-induced obesity
  • importance of CLK2 in the regulation of fatty acid metabolism
  • RNA splicing that ultimately controls multiple physiological processes
  • in the hypothalamus is necessary to maintain energy homeostasis
  • is a regulatory component of diet-induced thermogenesis in brown adipose tissue (BAT) through increased CREB-dependent expression of UCP1
  • CELLULAR PROCESS nucleotide, RNA splicing
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • role for regulation of the CLK2 kinase as a component of hepatic insulin signaling and glucose metabolism
  • a component
  • forms a complex with ATR-ATRIP and the ATR activator TOPBP1 (Danielsen 2009)
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • interacting with and inducing the nuclear redistribution of SR proteins SFRS* (see symbols)
  • is a new substrate of AKT1 activation which elucidated its role in cell survival to ionizing radiation
  • AKT1 activation controls cell survival to ionizing radiation by phosphorylating CLK2, revealing an important regulatory mechanism required for promoting cell survival
  • phosphorylates PPP2R5B, which is a critical regulatory step in the assembly of the PP2A holoenzyme complex on AKT1 leading to dephosphorylation of both S473 and T308 AKT1 sites
  • CLK2 plays likely a critical role in controlling the cell cycle and survival of glioblastoma via FOXO3/CDKN1B
  • HIPK1-phosphorylated PAGE4 (HIPK1-PAGE4) potentiates JUN, whereas CLK2-phosphorylated PAGE4 (CLK2-PAGE4) attenuates JUN activity
  • hyperphosphorylation of PAGE4 by CLK2 attenuates this interaction with JUN
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    obesity  
    may be a promising molecule for new therapeutic approaches for obesity and diabetes
    diabete  
    may be a promising molecule for new therapeutic approaches for obesity and diabetes
    cancerreproductivebreast
    therapeutic targeting of CLK2 may be used to modulate EMT splicing patterns and to inhibit breast tumor growth
    digestiveliver 
    inhibition of hepatic CLK2 could provide new therapies in the treatment of fatty liver disease
    ANIMAL & CELL MODELS
  • mice lacking CLK2 in adipose tissue exhibit exacerbated obesity and decreased energy expenditure during high-fat diet intermittent fasting
  • CLK2 inhibition restored normal sociability in a Shank3-deficient mouse model