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FLASH GENE
Symbol DCLK1 contributors: mct/npt - updated : 25-01-2023
HGNC name doublecortin-like kinase 1
HGNC id 2700
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an N terminal region homologous to DCX (doublecortin) and to a rat Ca2+/calmodulin dependent kinase CPG16 at C terminus
  • two doublecortin domains
  • C-terminal serine/threonine kinase domain
    • HOMOLOGY
    interspecies ortholog to murine Dcamkl1 (98.4pc)
    intraspecies homolog to calcium/calmodulin-dependent protein kinase 1
    paralog to DCX
    Homologene
    FAMILY
  • Ser/Thr protein kinase family
  • CaMK subfamily
  • family of microtubule-associated proteins
  • neuronal microtubule-associated doublecortin (DCX) family
    • CATEGORY signaling , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    text
  • localized in mitotic cells, radial glial cells and radial processes
  • the kinase fragment of DCLK1 is translocated into the nucleus upon hyperosmotic stresses and the kinase efficiently phosphorylates JDP2, a possible target in the nucleus, with the aid of histones
  • in human intestinal epithelium, DLCK1-positive cells form a subpopulation of non-proliferating neuroendocrine cells with apical brush border similar to that in enterocytes
    • basic FUNCTION
  • participating in functions of the mature nervous system
  • involved in a calcium-signaling pathway controlling neuronal migration in the developing brain
  • acting as a protein serine/threonine kinase
  • acting as a receptor signaling protein
  • may have a role in migrating neurons
  • critically involved in dynamic rearrangement of the cytoskeletal machinery that allow migration
  • playing a unique role in mitotic spindle integrity during early neurogenesis in radial glial cell proliferation and their radial process stability
  • is a functionally pertinent gene involved in human memory and cognitive functions
  • unique roles for DCLK1 in adult neurogenesis
  • role for DCX and DCLK1 in enabling microtubules to overcome retrograde actin-based forces, thereby facilitating the ability of the growth cone to carry out its crucial path-finding functions
  • is a physiologically relevant regulator of anabolic bone formation
  • CDH13, GRM8, ANK2, SLC16A6, ARSG, RIMBP2 and DCLK1 having role in hearing function
  • importance of DCLK1 function in tumorigenesis and cancer (PMIDC:
  • functions in multiple stages of neural development including radial migration and axon growth of cortical neurons
  • DCLK1 kinase activity negatively regulates microtubule polymerization
  • is a microtubule-associated kinase
  • tuft cells, via DCLK1, are important responders to bacterial-induced colitis by enhancing epithelial repair responses, which in turn limits bacterial infiltration into the mucosa
  • DCLK1 autophosphorylates a residue within its C-terminal tail to restrict its kinase activity and prevent aberrant hyperphosphorylation within its microtubule-binding domain
  • DCLK1 modulates likely its kinase activity to tune its microtubule-binding affinity
  • roles of DCLK1 in augmenting SARS-CoV-2 viremia, inflammatory cytokine expression, and dysregulation of immune cells involved in innate immunity
  • DCLK1 regulates tumorigenesis and epithelial&
    • 8209;mesenchymal transformation via several important pathways, such as NOTCH1, WNT/CTNNB1, RAS and multiple microRNAs
    CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS development , nervous system , cellular trafficking transport
    text
  • central nervous system development
  • endosome transport
    • PATHWAY
    metabolism
    signaling signal transduction
    intracellular signaling cascade
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
    • protein
  • DCX to form a potentially mutually regulatory network linking calcium signaling and microtubule dynamics
  • represses osteoblast activation by antagonizing RUNX2, the master transcription factor in osteoblasts
  • guides KIF1A-mediated cargo transport to dendrites
  • MAP7D1 is a novel substrate of DCLK1, and DCLK1 phosphorylates MAP7D1 on Ser 315 to facilitate axon elongation of cortical neurons
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in many cancers including colorectal cancer (CRC)
    tumoral     --over  
    may be responsible for the increased metastatic features in breast cancer cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • DCLK1 may serve as an independent predictor for Colo-rectal cancer prognosis
  • evaluating high serum DCLK1 is a biomarker for detection of hepatocellular carcinoma (HCC)
    • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    therapeutic target for eradicating HCC
    cancerdigestivecolon
    potential therapeutic target for the treatment of colorectal cancer
    cancerbrainglioma/neuroblstoma
    silencing DCLK1 induces apoptosis in NB cells
    cancerdigestivecolon
    potential for developing a therapy for colorectal cancer based on targeting DCLK1-positive tumor stem cells (TSCs)
    cancer  
    potential anti‑tumor target via the glucose metabolism pathway
    immunologyinfectious 
    DCLK1 could be a potential therapeutic target for COVID-19, especially in patients with underlying comorbid diseases associated with DCLK1 expression
    cancerreproductivebreast
    targeting DCLK1 may become a therapeutic option for breast cancer metastasis
    ANIMAL & CELL MODELS
  • mice with a targeted disruption of Dcamkl1 displayed elevated bone mass secondary to increased bone formation by osteoblasts