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FLASH GENE
Symbol DLK1 contributors: mct - updated : 06-01-2016
HGNC name delta-like 1 homolog (Drosophila)
HGNC id 2907
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • six EGF-like extracellular repeats
  • a unique transmembrane segment
  • a short intracellular region
  • N and O glycosylation sites
    • conjugated GlycoP
    mono polymer monomer
    HOMOLOGY
    interspecies homolog to delta Drosophila-like 1
    homolog to Drosophila Notch
    homolog to murine Dlk (86.2pc)
    homolog to C.elegans mo2g9.2
    homolog to rattus Dlk (85.4pc)
    intraspecies homolog to DLL4
    homolog to DLK2
    Homologene
    FAMILY
  • EGF-like homeotic family
    • CATEGORY regulatory , antigen , tumor suppressor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • secretory vesicles, type I transmembrane protein
  • membrane-bound precursor that is subsequently cleaved to generate the circulating form
  • secretory granules of the beta cells within the islets of Langherans
    • basic FUNCTION
  • NOTCH1 ligand involved in cell differentiation in a justacrine/paracrine manner and in the pathogenesis of NF1
  • participating in the control of cell differentiation of several cell type, including small cell lung cancer lines, immune stem cells, B cells and adrenal glomerulose cells
  • activates the MEK/ERK pathway to inhibit adipocyte differentiation
  • may play a role in the formation or progression of gliomas
  • coordinated expression of DLK1 and DLK2 may modulate adipogenesis
  • have ability to inhibit preadipocyte differentiation, and to regulate the differentiation of several other cell types through unknown mechanisms
  • by inducing Sox9, promotes chondrogenic induction of mesenchymal cells but inhibits differentiation into adipocytes
  • activating the MAPK kinase/ERK pathway
  • enhancing cancer cell stemness and tumorigenicity
  • dispensable during embryonic neurogenesis
  • DLK1 secreted by SVZ (subventricular zone) niche astrocytes regulates in neural stem cells self-renewal, probably in combination with other niche factors
  • neurogenic continuum, initiating at the early postnatal period and being maintained over the lifetime
  • inhibitory role for DLK1 in the regulation of angiogenesis, mediated by antagonism of the NOTCH pathway,
  • role for DLK1 in the post-natal development of hypothalamic functions, most notably those regulated by the arginine-vasopressin and oxytocin systems
  • major dual inhibitory function of DLK1 on adipogenesis, which places DLK1 as a master regulator of preadipocyte homeostasis
  • its expression is not essential for the normal development of beta-cells, somatotrophs and endothelial cells
  • imprinted gene best known for its ability to inhibit adipogenesis, is a crucial regulator of the myogenic program in skeletal muscle
  • dual biological function of DLK1 as an enhancer of muscle development, but as an inhibitor of adult muscle regeneration
    • CELLULAR PROCESS cell life, differentiation
    PHYSIOLOGICAL PROCESS development
    text neuroendocrine differentiation, inner ear development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding NOTCH
  • interacting with GH (regulates GH expression and GH is a DLK1-regulated target gene)
  • novel regulatory mechanism for FGF18 signaling involving GLG1 and DLK1
  • fibronectin FN1) is a DLK1 interacting protein (the inhibitory role of DLK1 is, at least in part, through DLK1 binding to the C-terminal region of fibronectin, which, in turn, activates integrin signaling to result in MEK/ERK activation and the inhibition of adipocyte differentiation)
  • SORT1 binds to DLK1, an inhibitor of adipocyte differentiation, and the overexpression of SORT1 prevents DLK1 downregulation, leading to enhanced inhibition of adipogenesis
  • DLK1 genes may play an important role in the GSK3B-mediated osteoblast apoptosis process
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) UPD14M , UPD14P , DEL14Q32
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in renal cell carcinoma by gain of methylation upstream of the untranslated MEG3 leading to pathological downregulation
    tumoral     --over  
    in GH-secreting (GH-S) pituitary tumors, and in gliomas
    tumoral     --over  
    in hepatocellular carcinoma, through deregulation of genomic DNA methylation of the imprinted domain
    Susceptibility to type 1 diabetes
    Variant & Polymorphism
    Candidate gene
  • associated with child and adolescent obesity
    • Marker
    Therapy target
    ANIMAL & CELL MODELS
  • transgenic mice overexpressing soluble DLK1 in adipose tissue or liver show a marked decrease in adiposity, with reduced adipogenesis and adipocyte marker expression
  • Dlk1(-/-) mice were developmentally retarded in their muscle mass and function owing to inhibition of the myogenic program during embryogenesis