Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol DLK1 contributors: mct - updated : 06-01-2016
HGNC name delta-like 1 homolog (Drosophila)
HGNC id 2907
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Endocrineadrenal glandcortex  highly
 neuroendocrinepituitary  highly
 pancreas    
Reproductivefemale systemovary  highly
 female systemplacenta  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
cell lineage nascent hair cells of inner ear, highly in preadipocytes
cell lines tumor with neuroendocrine features
fluid/secretion
at STAGE
physiological period embryo, pregnancy
Text placenta, and widely during embryonic development
IMPRINTING paternally
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