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FLASH GENE
Symbol DCLK1 contributors: mct/npt - updated : 30-09-2016
HGNC name doublecortin-like kinase 1
HGNC id 2700
Location 13q13      Physical location : 36.342.789 - 36.705.514
Synonym name
  • doublecortin-like kinase
  • doublecortin and CaM kinase-like 1
  • serine/threonine-protein kinase DCLK1
  • Synonym symbol(s) KIAA0369, DCLK, DCAMKL1, DCDC3A, CL1, CLICK1, DCL
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 363.37 kb     18 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map cen - D13S220 - D13S1197 - D13S805 - DCLK1 - D13S1164 - D13S1174 - D13S1159 - D13S219 - qter
    Authors Sossey-Alaoui (99)
    RNA
    TRANSCRIPTS type messenger
    text
  • type A (AS and AL) and type B (BS and BL) isoforms differ respectively by the presence or absence of the doublecortin domain
  • an alternative splicing occurring in 3' of the mRNA produces the long (L) instead of the short (S) isoforms
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 splicing 7592 - 422 DCLK1-short-A is relatively more strongly expressed than DCLK1-short-B in the subependymal zone 2004 14741399
  • variant 1 - A short
  • DCLK1-short-A and -B control different neuronal processes that overlap with those controlled by CaMKs
  • 18 splicing 8453 81 729 - 2004 14741399
    variant 2 - A long
    3 splicing 5342 - 56 . DCLK1-short-B variant shows stronger expression in the cortex, the ventromedial and dorsomedial hypothalamic nuclei, the arcuate nucleus, the zona incerta and the subincertal nucleus 2004 14741399
  • variant 3 - B short
  • DCLK1-short-A and -B control different neuronal processes that overlap with those controlled by CaMKs
  • 13 splicing 7518 47.6 433 adult, fetal brain 2004 14741399
    variant 4 - B long
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveintestinelarge intestinecolon   Homo sapiens
     stomach     Homo sapiens
    Endocrineneuroendocrinepituitary  predominantly
    Hearing/Equilibriumearinner  highly Homo sapiens
    Lymphoid/Immunespleen   moderately
     thymus    
    Nervousbrain   predominantly Homo sapiens
     nerve   predominantly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  moderately
    Epithelialabsorptive excretorydigestive epithelium (mucosa)   Homo sapiens
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain, lung, liver
    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,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
  • 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
  • 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)
    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
    ANIMAL & CELL MODELS
  • mice with a targeted disruption of Dcamkl1 displayed elevated bone mass secondary to increased bone formation by osteoblasts